=95th percentile, respectively. Using triceps SFT, obesity was
defined as SFT > 85th percentile of the NHANES III study. Fifty-seven subjects
(15 boys and 42 girls) had SFT > 85th percentile with a higher prevalence in
girls than boys (6.4% vs. 2.6%, P = 0.001). The prevalence of BMI-defined
overweight and obesity were also higher among girls (11.9% vs. 5.7%, P < 0.001
and 4.7% vs. 2.2%, P = 0.02, respectively). Females of upper socioeconomic class
were more likely to be overweight (16.2% vs. 6.6%, P < 0.0001), obese (6.3% vs.
2.8%, P = 0.03) or have elevated SFT (8.2% vs. 4.2%, P = 0.03) than those of low
socioeconomic status. Forty-seven of 57 subjects (82.5%) with elevated SFT also
had high BMI. The prevalence of obesity is low in the study population but the
much higher prevalence of overweight suggests that steps should be taken to
control fatness before the figures worsen. In more than 80% of subjects, elevated
SFT co-existed with elevated BMI.
PMID- 25586534
TI - Accumulation of amyloid in cognitive impairment after mild traumatic brain
injury.
AB - Recent epidemiology studies have indicated that traumatic brain injury (TBI) can
increase the risk of developing neurodegenerative diseases such as Alzheimer's
disease (AD). Amyloid-beta (Abeta) plaques and neurofibrillary tangles are
pathological indicators of AD. The accumulation of Abeta is considered the first
step of AD pathophysiology. Compelling studies have supported the hypothesis that
TBI accelerates the formation and accumulation of Abeta. These findings could
link TBI with AD, although the research that reported these findings had
limitations, particularly regarding mild TBI (mTBI) patients. The effects of mTBI
on Abeta accumulation remain uncertain because of a lack of mTBI pathology data.
Using amyloid-positron emission tomography (amyloid-PET), researchers can help to
determine whether mTBI increases the accumulation of Abeta, which might be
involved in the pathophysiological mechanisms of mTBI in AD, and could be a
target for the treatment of neurodegenerative diseases associated with TBI. In
this study, we recruited 27 mTBI patients with mTBI in mean 6years before this
study (21 mTBI patients without cognitive impairment, 6 mTBI patients with
cognitive impairment,) and 10 controls. All of them underwent mini-mental state
examination, apolipoprotein E (APOE) genotyping, and amyloid-PET. The results
show an increase of amyloid accumulation and allele frequency of APOE4 in the
mTBI patients with cognitive impairment. These findings indicate that amyloid
accumulation is an important indicator of cognitive impairment, and amyloid-PET
should be a safe and useful tool for diagnosing amyloid-related cognitive
impairment. APOE allele might play a role in the occurrence of cognitive
impairment after mTBI. The contribution of mTBI to the amyloid accumulation
requires further study, and mTBI patients should be recruited for longitudinal
research with repeated amyloid-PET studies.
PMID- 25586535
TI - Wallerian degeneration of the bilateral middle cerebellar peduncles.
PMID- 25586536
TI - Immunological differences between classical phenothypes of multiple sclerosis.
AB - Multiple sclerosis (MS), one of the most serious inflammatory and
neurodegenerative conditions, is characterized by variable clinical courses -
relapsing-remitting (RRMS), primary progressive (PPMS) and secondary progressive
(SPMS). Although PPMS affects only 10-15% of the patient population, its course
and pathophysiological and immunological background are distinct. In this review
we present and discuss main differences between different types of MS, with
particular focus on the underlying immunological mechanisms.
PMID- 25586537
TI - Mitochondrial recessive ataxia syndrome: A neurological rarity not to be missed.
PMID- 25586539
TI - Unusual cerebral white matter change in a Chinese family with Spinocerebellar
ataxia type 12.
AB - In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with
action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing
revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2,
regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the
first report on patients with SCA12 presenting with prominent cerebral white
matter change besides cerebral and/or cerebellar atrophy.
PMID- 25586540
TI - Autotriggering caused by cardiogenic oscillation during pressure support
ventilation.
PMID- 25586541
TI - Mock circulation loop to investigate hemolysis in a pulsatile total artificial
heart.
AB - Hemocompatibility of blood pumps is a crucial parameter that has to be ensured
prior to in vivo testing. In contrast to rotary blood pumps, a standard for
testing a pulsatile total artificial heart (TAH) has not yet been established.
Therefore, a new mock circulation loop was designed to investigate hemolysis in
the left ventricle of the ReinHeart TAH. Its main features are a high
hemocompatibility, physiological conditions, a low priming volume, and the
conduction of blood through a closed tubing system. The mock circulation loop
consists of a noninvasive pressure chamber, an aortic compliance chamber, and an
atrium directly connected to the ventricle. As a control pump, the clinically
approved Medos-HIA ventricular assist device (VAD) was used. The pumps were
operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a
mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min.
Heparinized porcine blood was used. A series of six identical tests were
performed. A test method was established that is comparable to ASTM F 1841, which
is standard practice for the assessment of hemolysis in continuous-flow blood
pumps. The average normalized index of hemolysis (NIH) values of the VAD and the
ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard
deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore,
a single test with a BPX-80 Bio-Pump was performed to verify that the hemolysis
induced by the mock circulation loop was negligible. The performed tests showed a
good reproducibility and statistical significance. The mock circulation loop and
test protocol developed in this study are valid methods to investigate the
hemolysis induced by a pulsatile blood pump.
PMID- 25586538
TI - Candidate pathway-based genetic association study of platinum and platinum-taxane
related toxicity in a cohort of primary lung cancer patients.
AB - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common
toxicity secondary to chemotherapy. Genetic factors may be important in
predisposing patients to this adverse effect. PATIENTS AND METHODS: We studied
950 primary lung cancer patients, who received platinum or platinum-combination
drug chemotherapy and who had DNA available for study. We analyzed
epidemiological risk factors in 279 CIPN patients and 456 non-CIPN patients and
genetic risk factors in 141 CIPN patients and 259 non-CIPN patients. The risk
factors studied included demographic, diagnostic, and treatment data, as well as
174 tag SNPs (single nucleotide polymorphisms) across 43 candidate genes in the
glutathione, cell cycle, DNA repair, cell signaling, and apoptosis pathways.
RESULTS: Patients who had diabetes mellitus were more likely to have CIPN
(p=0.0002). Other epidemiologic risk factors associated with CIPN included number
of cycles (p=0.0004) and type of concurrent chemotherapy (p<0.001). SNPs most
associated with CIPN were in glutathione peroxidase 7 (GPX7) gene (p values
0.0015 and 0.0028, unadjusted and adjusted) and in ATP-binding cassette sub
family C member 4 (ABCC4) gene (p values 0.037 and 0.006, unadjusted and
adjusted). We also found other suggestive associations in methyl-o-guanine-methyl
transferase (MGMT) and glutathione-S-transferase (GST) isoforms. CONCLUSIONS:
Epidemiological and genetic risk factors associated with CIPN in this cohort,
included the type of chemotherapy drug, intensity of chemotherapy treatment, and
genes known to be associated with chemotherapy resistance. These findings suggest
that differentiating between cytotoxic and neurotoxic mechanisms of chemotherapy
drugs is challenging but represents an important step toward individualized
therapy and improving quality of life for patients.
PMID- 25586542
TI - Serotonergic, brain volume and attentional correlates of trait anxiety in
primates.
AB - Trait anxiety is a risk factor for the development and maintenance of affective
disorders, and insights into the underlying brain mechanisms are vital for
improving treatment and prevention strategies. Translational studies in non-human
primates, where targeted neurochemical and genetic manipulations can be made, are
critical in view of their close neuroanatomical similarity to humans in brain
regions implicated in trait anxiety. Thus, we characterised the serotonergic and
regional brain volume correlates of trait-like anxiety in the marmoset monkey.
Low- and high-anxious animals were identified by behavioral responses to a human
intruder (HI) that are known to be sensitive to anxiolytic drug treatment.
Extracellular serotonin levels within the amygdala were measured with in vivo
microdialysis, at baseline and in response to challenge with the selective
serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by
structural magnetic resonance imaging. Anxious individuals showed persistent,
long-term fearful responses to both a HI and a model snake, alongside sustained
attention (vigilance) to novel cues in a context associated with unpredictable
threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin
levels, and smaller volumes in a closely connected prefrontal region, the dorsal
anterior cingulate cortex. These findings highlight behavioral and neural
similarities between trait-like anxiety in marmosets and humans, and set the
stage for further investigation of the processes contributing to vulnerability
and resilience to affective disorders.
PMID- 25586544
TI - The long-term consequences of preterm birth: what do teachers know?
AB - AIM: The knowledge and information needs of education professionals were assessed
to determine how prepared they feel to support the growing number of preterm
children entering schools today. METHOD: In a national survey, 585 teachers and
212 educational psychologists completed the Preterm Birth-Knowledge Scale (PB-KS)
to assess knowledge of outcomes following preterm birth. Total scores (range 0
33) were compared between groups and the impact of demographic characteristics on
knowledge was analysed. Training and information needs were also assessed.
RESULTS: Teaching staff (mean 14.7, SD 5.5) had significantly lower knowledge
scores than educational psychologists (mean 17.1, SD 5.0; p<0.001); both had
significantly lower scores than neonatal clinicians surveyed previously (mean
26.0, SD 3.6; p<0.001). Education professionals' poorest areas of knowledge
related to the most frequent adverse outcomes following preterm birth. Only 16%
of teaching staff had received training about preterm birth and more than 90%
requested more information. Having a special educational needs role and being
employed at least 16 years were associated with higher knowledge scores.
INTERPRETATION: Education professionals have poor knowledge of the needs of
children born preterm and most feel ill-equipped to support them in school. As
teachers have primary responsibility for providing long-term support for children
born preterm, this is of significant public health and educational concern.
PMID- 25586546
TI - Identification of nanoscale ingredients in commercial food products and their
induction of mitochondrially mediated cytotoxic effects on human mesenchymal stem
cells.
AB - Titanium dioxide (E171) and silicon dioxide (E551) are common additives found in
food products, personal-care products, and many other consumer products used in
daily life. Recent studies have reported that these food additives (manufactured
E171 and E551) contain nanosized particles of less than 100 nm. However, the
particle size distribution and morphology of added TiO2 and SiO2 particles are
not typically stated on the package label. Furthermore, there is an increasing
debate regarding health and safety concerns related to the use of synthetic food
additives containing nanosized ingredients in consumer products. In this study,
we identified the size and morphology of TiO2 and SiO2 particles in commercially
available food products by using transmission electron microscope (TEM). In
addition, the in vitro toxicological effects of E171 and E551 on human
mesenchymal stem cells (hMSCs), an adult stem cell-based model, were assessed
using the MTT assay and a flow cytometry-based JC-1 assay. Our TEM results
confirmed the presence of nanoscale ingredients in food products, and the in
vitro toxicology results indicated that the nanoscale E171 and E551 ingredients
induced dose-dependent cytotoxicity, changes in cellular morphology, and the loss
of mitochondrial trans-membrane potential in hMSCs. These preliminary results
clearly demonstrated that the nanoscale E171 and E551 particles had adverse
effects on hMSCs by inducing oxidative stress-mediated cell death. Accordingly,
further studies are needed to identify the specific pathway involved, with an
emphasis on differential gene expression in hMSCs.
PMID- 25586545
TI - Effect of orexin A on apoptosis in BGC-823 gastric cancer cells via OX1R through
the AKT signaling pathway.
AB - Orexins are a class of peptides involved in the regulation of food intake, energy
homeostasis, the sleep-wake cycle and gastrointestinal function. Recent studies
have demonstrated that orexin A may influence apoptosis and proliferation in
numerous types of cancer cells. However, the effect of orexin A on gastric cancer
cells and its mechanisms of action remain elusive. In the present study, BGC-823
gastric cancer cells were treated with orexin A (10-10-10-6 M) in vitro and the
expression levels of orexin receptor 1 (OX1R) protein in cells was then
determined. The proliferation, viability and apoptosis of BGC-823 cells were
detected. In addition, BGC-823 cells were treated with AKT inhibitor PF-04691502
or OX1R-specific antagonist SB334867 in combination with orexin A, in order to
examine the activation of AKT and caspase-3. The results showed that orexin A (10
10-10-6 M) stimulated the OX1R protein expression in BGC-823 cells, which
improved the proliferation and viability of the cells as well as protected them
from apoptosis. Phosphorylated AKT protein was significantly increased in BGC-823
cells following treatment with orexin A. Moreover, 10-8 M orexin A reduced the
proapoptotic activity of caspase-3 (by <=30%). The OX1R antagonist SB334867 (10-6
M) and AKT antagonist PF-04691502 (10-6 M), when used individually or in
combination, abolished the effect of orexin A (10-8 M) on BGC-823 cells. In
conclusion, the results of the present study demonstrated that orexin A inhibited
gastric cancer cell apoptosis via OX1R through the AKT signaling pathway.
PMID- 25586543
TI - The EPA2 adhesin encoding gene is responsive to oxidative stress in the
opportunistic fungal pathogen Candida glabrata.
AB - Candida glabrata has emerged as an important opportunistic pathogen in both
mucosal and bloodstream infections. C. glabrata contains 67 adhesin-like
glycosylphosphatidylinositol-cell-wall proteins (GPI-CWPs), which are classified
into seven groups and the largest is the Epa family. Epa proteins are very
diverse and their expression is differentially regulated. Like many of the EPA
genes, EPA2 is localized in a subtelomeric region where it is subject to
chromatin-based transcriptional silencing and its role remains largely
unexplored. In this study, we show that EPA2 gene is induced specifically in
vitro in the presence of oxidative stress generated by H2O2. This induction is
dependent on both Yap1 and Skn7, whereas Msn4 represses EPA2 expression.
Interestingly, EPA2 is not induced during phagocytosis, but its expression can be
identified in the liver in a murine model of systemic infection. Epa2 has no
effect on the virulence of C. glabrata. The work presented herein provides a
foundation for future studies to dissect the molecular mechanism(s) by which EPA2
of C. glabrata can be induced in the presence of oxidative stress in a region
subject to subtelomeric silencing.
PMID- 25586547
TI - A systematic review and economic evaluation of intraoperative tests [RD-100i one
step nucleic acid amplification (OSNA) system and Metasin test] for detecting
sentinel lymph node metastases in breast cancer.
AB - BACKGROUND: In breast cancer patients, sentinel lymph node biopsy is carried out
at the same time as the removal of the primary tumour to postoperatively test
with histopathology for regional metastases in the sentinel lymph node. Those
patients with positive test results are then operated on 2-4 weeks after primary
surgery to remove the lymph nodes from the axilla (axillary lymph node
dissection, ALND). New molecular tests RD-100i [one-step nucleic acid
amplification (OSNA); based on messenger RNA amplification to identify the
cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin
(using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess
Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an
intraoperative diagnosis, thereby avoiding the need for postoperative
histopathology and, in positive cases, a second operation for ALND. OBJECTIVE: To
evaluate the clinical effectiveness and cost-effectiveness of using OSNA and
Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph
nodes metastases, compared with postoperative histopathology, the current
standard. DATA SOURCES: Electronic databases including MEDLINE, MEDLINE In
Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the
Health Economic Evaluations Database as well as clinical trial registries, grey
literature and conference proceedings were searched up to July 2012. REVIEW
METHODS: A systematic review of the evidence was carried out using standard
methods. Single-gate studies were used to estimate the accuracy of OSNA with
histopathology as the reference standard. The cost-effectiveness analysis adapted
an existing simulation model of the long-term costs and health implications of
early breast cancer diagnostic outcomes. The model accounted for the costs of an
extended first operation with intraoperative testing, the loss of health-related
quality of life (disutility) from waiting for postoperative test results,
disutility and costs of a second operation, and long-term costs and disutility
from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and
metastatic recurrence. RESULTS: A total of 724 references were identified in the
searches, of which 17 studies assessing test accuracy were included in the
review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished.
OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and
specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were
estimated in a meta-analysis of five studies [unadjusted for tissue allocation
bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in
lifetime discounted cost-savings of L498 and a quality-adjusted life-year (QALY)
loss of 0.048 relative to histopathology, that is, L4324 saved per QALY lost. The
most favourable plausible scenario for OSNA in terms of the node-positive rate
(range 10-40%), diagnostic accuracy values (91.3% sensitivity and 94.2%
specificity, from three reports that adjusted for TAB), the costs of
histopathology, OSNA and second surgery, and long-term costs and utilities
resulted in a maximum saving per QALY lost of L10,500; OSNA sensitivity and
specificity would need to be >= 95% for this figure to be >= L20,000.
LIMITATIONS: There is limited evidence on the diagnostic test accuracy of
intraoperative tests. The quality of information on costs of resource utilisation
during the diagnostic pathway is low and no evidence exists on the disutility of
waiting for a second surgery. No comparative studies exist that report clinical
outcomes of intraoperative diagnostic tests. These knowledge gaps have more
influence on the decision than current uncertainty in the performance of
postoperative histopathology in standard practice. CONCLUSIONS: One-step nucleic
acid amplification is not cost-effective for the intraoperative diagnosis of
sentinel lymph node metastases. OSNA is less accurate than histopathology and the
consequent loss of health benefits in this patient group is not compensated for
by health gains elsewhere in the health system that may be obtained with the cost
savings made. The evidence on Metasin is insufficient to evaluate its cost
effectiveness. STUDY REGISTRATION: This study is registered as PROSPERO
CRD42012002889. FUNDING: The National Institute for Health Research Health
Technology Assessment programme.
PMID- 25586549
TI - Comparison of mathematical models for red marrow and blood absorbed dose
estimation in the radioiodine treatment of advanced differentiated thyroid
carcinoma.
AB - Metastatic and recurrent differentiated thyroid carcinoma is preferably treated
with (131)I, whose administered activity is limited by red marrow (RM) toxicity,
originally correlated by Benua to a blood absorbed dose higher than 2 Gy.
Afterward a variety of dosimetric approaches has been proposed. The aim of this
work is to compare the results of the Benua formula with the ones of other three
blood and RM absorbed dose formulae. Materials and methods have been borrowed by
the dosimetric protocol of the Italian Internal Dosimetry group and adapted to
the routine of our centre. Wilcoxon t-tests and percentage differences have been
applied for comparison purposes. Results are significantly different (p < 0.05)
from each other, with an average percentage difference between Benua versus other
results of -22%. The dosimetric formula applied to determine blood or RM absorbed
dose may contribute significantly to increase heterogeneity in absorbed dose and
dose-response results. Standardization should be a major objective.
PMID- 25586548
TI - Concomitant analysis of Helios and Neuropilin-1 as a marker to detect thymic
derived regulatory T cells in naive mice.
AB - Regulatory T (Treg) cells are characterized by the expression of CD4, CD25 and
the intracellular Foxp3. However, these markers do not indicate whether Treg
cells are thymic derived Treg (tTreg) cells or peripherally induced Treg (pTreg)
cells. Recently, Helios and Neuropilin-1 (Nrp1) has been reported as potential
markers for tTreg cells. Herein, we used flow cytometry to examine the proportion
of CD4(+)CD8(-)CD25(+) Treg cells expressing Helios, Nrp1 and Foxp3 in thymus,
pancreatic draining lymph nodes (PDLNs) and spleen of CD-1 mice, and thymus of
NOD and C57BL/6 mice. The frequency of Helios(+) cells was higher than that of
Nrp1(+) cells in CD4(+)CD8(-)CD25(+) and CD4(+)CD8(-)CD25(+)Foxp3(+) Treg cells
in thymus. Interestingly, the proportion of IL-10(+), Ebi3(+)and CTLA-4(+) cells
was higher in Helios(+) than Nrp1(+) tTreg cells. The anti-apoptotic activity of
Helios(+) tTreg cells was higher in thymus compared to Nrp1(+) tTreg cells. Nrp1
seems to be expressed at a later developmental stage compared to Helios and
Foxp3. Furthermore, the expression of Nrp1 in CD4(+)CD25(+) T cells of younger
mice did not increase after stimulating them in vitro with anti-CD3 and -CD28.
Thus, under these conditions, Helios could be considered a more reliable marker
for distinguishing tTreg cells from pTreg cells than Nrp1.
PMID- 25586550
TI - Tethered cord syndrome associated with a thickened filum terminale in a dog.
PMID- 25586551
TI - Newly isolated Penicillium oxalicum A592-4B secretes enzymes that degrade milled
rice straw with high efficiency.
AB - An enzyme producing micro-organism, which can directly saccharify rice straw that
has only been crushed without undergoing the current acid or alkaline
pretreatment, was found. From the homology with the ITS, 28S rDNA sequence, the
strain named A592-4B was identified as Penicillium oxalicum. Activities of the
A592-4B enzymes and commercial enzyme preparations were compared by Novozymes
Cellic CTec2 and Genencore GC220. In the present experimental condition, activity
of A592-4B enzymes was 2.6 times higher than that of CTec2 for degrading milled
rice straw. Furthermore, even when a quarter amount of A592-4B enzyme was applied
to the rice straw, the conversion rate was still higher than that by CTec2. By
utilizing A592-4B enzymes, improved lignocellulose degradation yields can be
achieved without pre-treatment of the substrates; thus, contributing to cost
reduction as well as reducing environmental burden.
PMID- 25586552
TI - Benign-appearing urothelial tissue fragments in noninstrumented voided urine
specimens are associated with low rates of urothelial neoplasia.
AB - BACKGROUND: The presence of urothelial tissue fragments (UTF) in voided urine
(VU) is often considered an abnormal finding that may be associated with the
presence of urothelial papillary neoplasms. In the current study, the authors
reviewed VU specimens containing benign-appearing UTF (BUTF) to determine the
associated rate of urothelial neoplasia at the study institution. METHODS: A
retrospective search of the electronic pathology database system over a 5-year
period (2009-2013) revealed 1131 VU specimens containing UTF. Of these, 459 cases
(40.6%) did not have a recent history of instrumentation. Fifteen cases were
excluded because the slides were not available for review. In the remaining 444
cases, 274 cases (61.7%) had BUTF. A total of 170 cases (38.3%) had UTF with
atypical cytologic features and were therefore excluded. RESULTS: Of the 274
cases, 29 (10.6%) had follow-up surgical pathology specimens available. The
overall rate of urothelial neoplasia on follow-up was 3.6% for low-grade
urothelial neoplasia (10 cases) and 0.7% for high-grade urothelial carcinoma (2
cases). Forty-five cases (16.4%) were determined to have urinary tract stones on
follow-up. CONCLUSIONS: The presence of BUTF in VU specimens requires careful
examination of the medical history because their presence may be explained by
recent instrumentation. If recent instrumentation is not identified, the etiology
of BUTF is not usually determined; in the current study, BUTF were found to be
associated with urinary tract stones in 16.4% of cases. They also present a low
risk of low-grade urothelial neoplasia (3.6%) and high-grade urothelial carcinoma
(0.7%) when compared with the overall benign category at the study institution
(2.3% [P =.15] and 0.7%, respectively).
PMID- 25586553
TI - Novel approach to systematic random sampling in population surveys: Lessons from
the United Arab Emirates National Diabetes Study (UAEDIAB).
AB - BACKGROUND: The prevalence of diabetes has risen rapidly in the Middle East,
particularly in the Gulf Region. However, some prevalence estimates have not
fully accounted for large migrant worker populations and have focused on minority
indigenous populations. The objectives of the UAE National Diabetes and Lifestyle
Study are to: (i) define the prevalence of, and risk factors for, T2DM; (ii)
describe the distribution and determinants of T2DM risk factors; (iii) study
health knowledge, attitudes, and (iv) identify gene-environment interactions; and
(v) develop baseline data for evaluation of future intervention programs.
METHODS: Given the high burden of diabetes in the region and the absence of
accurate data on non-UAE nationals in the UAE, a representative sample of the non
UAE nationals was essential. We used an innovative methodology in which non-UAE
nationals were sampled when attending the mandatory biannual health check that is
required for visa renewal. Such an approach could also be used in other countries
in the region. RESULTS: Complete data were available for 2719 eligible non-UAE
nationals (25.9% Arabs, 70.7% Asian non-Arabs, 1.1% African non-Arabs, and 2.3%
Westerners). Most were men < 65 years of age. The response rate was 68%, and the
non-response was greater among women than men; 26.9% earned less than UAE Dirham
(AED) 24 000 (US$6500) and the most common areas of employment were as managers
or professionals, in service and sales, and unskilled occupations. Most (37.4%)
had completed high school and 4.1% had a postgraduate degree. CONCLUSION: This
novel methodology could provide insights for epidemiological studies in the UAE
and other Gulf States, particularly for expatriates.
PMID- 25586554
TI - Influence of capsule shell composition on the performance indicators of
hypromellose capsule in comparison to hard gelatin capsules.
AB - The purpose of this study was to assess the in vitro performances of "vegetable"
capsules in comparison to hard gelatin capsules in terms of shell weight
variation, reaction to different humidity conditions, resistance to stress in the
absence of moisture, powder leakage, disintegration and dissolution. Two types of
capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling
agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight
variability was relatively low for all tested capsules shells. Although Capsule 1
had the highest moisture content under different humidity conditions, all capsule
types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone
(PVP) powder from surrounding humidity. The initial disintegration for all
Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n
= 18). Dissolution of acetaminophen was better when the deionized water (DIW)
temperature increased from 32 to 42 degrees C in case of Capsule 1, but the
effect of temperature was not significant for the other types of capsules.
Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and
independent of the media pH or contents unlike Capsule 2 which was influenced by
the pH and dissolution medium contents. It is feasible to use hypromellose
capsules shells with or without gelling agent for new lines of pharmaceutical
products, however, there is a window for capsule shells manufacturing companies
to improve the dissolution of their hypromellose capsules to match the
conventional gelatin capsule shells and eventually replace them.
PMID- 25586555
TI - A survey of patient preferences for oral antihyperglycemic therapy in patients
with type 2 diabetes mellitus.
AB - INTRODUCTION: Previous research has demonstrated a correlation among patient
preferences, dosing burden, and medication nonadherence, a well-recognized
challenge in type 2 diabetes mellitus (T2DM). The objective of this study was to
elicit preferences for alternative dosing regimens for oral antihyperglycemic
therapies among patients with T2DM and to quantify differences in dosing
preferences among patients with different characteristics. METHODS: Preferences
for dosing of oral antihyperglycemic drugs (OAD) were evaluated by surveying
patients with T2DM in the United States (US). Survey participants were adult US
patients with T2DM who were taking no or only 1 OAD and no injectable therapies.
Each patient completed a web-enabled discrete-choice experiment (DCE) including a
series of 8 pairs of hypothetical OAD profiles. Each profile was defined by
reductions in average glucose, dosing schedule (e.g., once-weekly, once-daily, or
twice-daily dosing), chance of mild-to-moderate gastrointestinal side effects,
frequency of hypoglycemia, weight change, incremental risk of congestive heart
failure, and cost. Each participant also answered a direct question about dosing
preference. Random-parameters logit was used to analyze the DCE data.
Prespecified subgroups were analyzed. RESULTS: Of 2,262 patients invited to
participate, 923 were included in the analysis (mean age 63 years, 45% male, 79%
white). Reducing dosing frequency was statistically significantly important to
patients; however, it was relatively less important than medication cost or
clinical outcomes. On average, patients preferred once-weekly to once-daily
dosing. Patients not currently taking an OAD had a stronger preference for once
weekly dosing than patients on treatment (P = 0.012). Patients younger than 45
years had a stronger preference for weekly dosing than older patients (P <
0.075). CONCLUSIONS: For younger patients and patients not currently on
treatment, once-weekly dosing may provide additional incentive to initiate and
adhere to antihyperglycemic treatment; however, additional research will be
required to confirm this hypothesis.
PMID- 25586557
TI - Antibody-targeted vaccination to lung dendritic cells generates tissue-resident
memory CD8 T cells that are highly protective against influenza virus infection.
AB - Influenza virus gains entry into the body by inhalation and initiates its
replication cycle within the lung. The early stage of infection, while the virus
is confined to the lung mucosa, provides the ideal window of opportunity for an
effective immune response to control the infection. Tissue-resident memory (Trm)
CD8 T cells, located in a variety of tissues including the lung, are ideally
situated to act during this window and stall the infection. The factors involved
in the differentiation of lung Trm cells remain poorly defined. We demonstrate
that recognition of antigen presented locally by dendritic cells (DCs) and
transforming growth factor-beta (TGFbeta) signaling are both required. We
exploited this knowledge to develop an antibody-targeted vaccination approach to
generate lung Trm cells. Delivering antigen exclusively to respiratory DCs
results in the development of lung CD8 Trm cells that are highly protective
against lethal influenza challenge. Our results describe an effective vaccination
strategy that protects against influenza virus infection.
PMID- 25586556
TI - PPARgamma activation following apoptotic cell instillation promotes resolution of
lung inflammation and fibrosis via regulation of efferocytosis and proresolving
cytokines.
AB - Changes in macrophage phenotype have been implicated in apoptotic cell-mediated
immune modulation via induction of peroxisome proliferator-activated receptor
gamma (PPARgamma). In this study, we characterized PPARgamma induction by
apoptotic cell instillation over the course of bleomycin-induced lung injury in
C57BL/6 mice. Next, the role of PPARgamma activation in resolving lung
inflammation and fibrosis was investigated. Our data demonstrate that apoptotic
cell instillation after bleomycin results in immediate and prolonged enhancement
of PPARgamma mRNA and protein in alveolar macrophages and lung. Moreover,
PPARgamma activity and expression of its target molecules, including CD36,
macrophage mannose receptor, and arginase 1, were persistently enhanced following
apoptotic cell instillation. Coadministration of the PPARgamma antagonist,
GW9662, reversed the enhanced efferocytosis, and the reduced proinflammatory
cytokine expression, neutrophil recruitment, myeloperoxidase activity,
hydroxyproline contents, and fibrosis markers, including type 1 collagen alpha2,
fibronectin and alpha-smooth muscle actin (alpha-SMA), in the lung by apoptotic
cell instillation. In addition, inhibition of PPARgamma activity reversed the
expression of transforming growth factor-beta (TGF-beta), interleukin (IL)-10,
and hepatocyte growth factor (HGF). These findings indicate that one-time
apoptotic cell instillation contributes to anti-inflammatory and antifibrotic
responses via upregulation of PPARgamma expression and subsequent activation,
leading to regulation of efferocytosis and production of proresolving cytokines.
PMID- 25586558
TI - Interleukin (IL)-21 promotes intestinal IgA response to microbiota.
AB - Commensal microbiota-specific T helper type 17 (Th17) cells are enriched in the
intestines, which can convert into T follicular helper (Tfh) in Peyer's patches,
and are crucial for production of intestinal immunoglobulin A (IgA) against
microbiota; however, the role of Th17 and Tfh cytokines in regulating the mucosal
IgA response to enteric microbiota is still not completely known. In this study,
we found that intestinal IgA was impaired in mice deficient in interleukin (IL)
17 or IL-21 signaling. IL-21, but not IL-17, is able to augment B-cell
differentiation to IgA(+) cells as mediated by transforming growth factor beta1
(TGFbeta1) and accelerate IgA class switch recombination (CSR). IL-21 and
retinoic acid (RA) induce IgA(+) B-cell development and IgA production and drives
autocrine TGFbeta1 production to initiate IgA CSR. Repletion of T-cell-deficient
TCRbetaxdelta(-/-) mice with Th17 cells specific for commensal bacterial antigen
increased the levels of IgA(+) B cells and IgA production in the intestine, which
was blocked by neutralizing IL-21. Thus IL-21 functions to strongly augment IgA
production under intestinal environment. Furthermore, IL-21 promotes intestinal B
cell homing through alpha4beta7 expression, alone or with TGFbeta and RA.
Together, IL-21 from microbiota-specific Th17 and/or Tfh cells contributes to
robust intestinal IgA levels by enhancing IgA(+) CSR, IgA production and B-cell
trafficking into the intestine.
PMID- 25586559
TI - Dysbiotic bacteria translocate in progressive SIV infection.
AB - Infection of gut-resident CD4(+) memory T cells during acute human
immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection is
associated with rapid loss of these cells and damage to the epithelial barrier.
Damage to the epithelial barrier allows translocation of microbial products from
the intestinal lumen into the body. Immune activation caused by these microbial
products has been associated with disease progression. Although microbial
translocation has been demonstrated in SIV-infected nonhuman primates, the
identity of translocating bacteria has not been determined. In this study we
examined the communities of bacteria both within the gastrointestinal (GI) tract
and systemic tissues of both healthy and experimentally SIV-infected Asian
macaques. Although there were only modest changes in the GI tract-associated
microbiome resulting from infection, there is substantial dysbiosis after
administration of antiretrovirals. Analysis of bacterial DNA isolated from
tissues of infected animals revealed a preference for the phylum Proteobacteria,
suggesting that they preferentially translocate. Consistent with this finding, we
observed increased metabolic activity of Proteobacterial species within the
colonic lumen of SIV-infected animals. Overall, these data provide insights into
disease progression and suggest that therapies aimed at altering the composition
and metabolic activity of the GI tract microbiome could benefit chronically HIV
infected individuals, particularly those on antiretroviral therapies.
PMID- 25586561
TI - Three-dimensional structures of laccases.
AB - Laccases are phenol oxidases that belong to the family of multi-copper oxidases
and the superfamily of cupredoxins. A number of potential industrial applications
for laccases have led to intensive structure-function studies and an increased
amount of crystal structures has been solved. The objective of this review is to
summarize and analyze available crystal structures of laccases. The experimental
crystallographic data are now easily available from the websites and electron
density maps can be used for the interpretation of the structural models. The
crystal structures can give valuable insights into the functional mechanisms and
may serve as the basis for the development of laccases for industrial
applications.
PMID- 25586560
TI - Laccase engineering by rational and evolutionary design.
AB - Laccases are considered as green catalysts of great biotechnological potential.
This has attracted a great interest in designing laccases a la carte with
enhanced stabilities or activities tailored to specific conditions for different
fields of application. Over 20 years, numerous efforts have been taken to
engineer these multicopper oxidases and to understand their reaction mechanisms
by site-directed mutagenesis, and more recently, using computational calculations
and directed evolution tools. In this work, we review the most relevant
contributions made in the field of laccase engineering, from the comprehensive
study of their structure-function relationships to the tailoring of outstanding
biocatalysts.
PMID- 25586563
TI - Inferring the microscopic surface energy of protein-protein interfaces from
mutation data.
AB - Mutations at protein-protein recognition sites alter binding strength by altering
the chemical nature of the interacting surfaces. We present a simple surface
energy model, parameterized with empirical DeltaDeltaG values, yielding mean
energies of -48 cal mol(-1) A(-2) for interactions between hydrophobic surfaces,
51 to -80 cal mol(-1) A(-2) for surfaces of complementary charge, and 66-83 cal
mol(-1) A(-2) for electrostatically repelling surfaces, relative to the aqueous
phase. This places the mean energy of hydrophobic surface burial at -24 cal mol(
1) A(-2) . Despite neglecting configurational entropy and intramolecular changes,
the model correlates with empirical binding free energies of a functionally
diverse set of rigid-body interactions (r = 0.66). When used to rerank docking
poses, it can place near-native solutions in the top 10 for 37% of the complexes
evaluated, and 82% in the top 100. The method shows that hydrophobic burial is
the driving force for protein association, accounting for 50-95% of the cohesive
energy. The model is available open-source from
http://life.bsc.es/pid/web/surface_energy/ and via the CCharpPPI web server
http://life.bsc.es/pid/ccharppi/.
PMID- 25586564
TI - Estimation of heritability for varied indexes of handedness.
AB - Inconsistent results of the molecular studies for handedness have been reported.
One of the key issues involved could be ways of assessing handedness. The current
study aimed to identify the index of handedness better reveal the genetic
component, which showed higher heritability. We measured handedness using the
Annett's handedness questionnaire. The college students participating in this
study filled the questionnaire in the class while their first-degree relatives
returned questionnaires one to two weeks later. A total of 1,968 subjects
returned their questionnaires, including 640 college students and 1,328 first
degree relatives. Among the 449 college students returning at least one
handedness questionnaire for their parents, a total of 449 fathers, 440 mothers,
and 425 siblings participated in the study. The index of mixed-handedness (e.g.,
Degree of Handedness) showed highest heritability (0.67), followed by the Hand
Preference Index (0.52), and then the Direction of Handedness (0.39). Using an
index of mixed-handedness for future molecular studies was suggested.
PMID- 25586567
TI - The support for newly qualified practitioners and new staff entering the critical
care environment.
PMID- 25586565
TI - Evaluation of a 64Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic
acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin
releasing peptide receptor-expressing prostate cancer xenograft model.
AB - Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human
tumors and in particular, identified to be upregulated in prostate cancers. The
current study aimed to develop clinically translatable BBN analogue-based
radioligands for positron emission tomography (PET) of GRPR-positive tumors. We
developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN
analogues and then investigated their tumor-targeting efficacy in vivo. The
chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was
used to radiolabel the peptides with 64Cu. The peptides were evaluated by
measuring cell-based receptor-binding affinities. Biodistribution experiments and
small animal imaging using PET were performed in nude mice bearing subcutaneous
PC3 human prostate cancer xenografts. The conjugates were radiolabeled with
yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA
galacto-BBN remained stable in both human and mouse serum for 1 h at 37C. PET
images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h
after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h,
low liver uptake, and rapid renal clearance. PET imaging results were also
confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and
[64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate
cancer.
PMID- 25586566
TI - A case of late presenting unicuspid aortic valve in a 62-year-old female.
AB - We describe the case of a 62-year-old female presenting with new onset
progressive dyspnea on exertion and a new diagnosis of aortic stenosis.
Transesophageal echocardiography showed fusion of the aortic valve leaflets
suspicious for bicuspid aortic valve with dilated ascending aorta. Surgical
replacement of the valve revealed a unicuspid aortic valve with one true
commissure at the level of the left and noncoronary cusps. The case is supported
by clinical, echocardiographic and angiographic imaging and discussion of current
imaging modalities used in diagnosis of aortic valve pathology.
PMID- 25586568
TI - 5th International BACCN Conference - delivering high quality and safe critical
care services: a global ambition.
PMID- 25586573
TI - Enterobius vermicularis: an unusual cause of recurrent urinary tract infestation
in a 7-year-old girl: case report and review of the literature.
AB - Enterobius vermicularis, the pinworm, is one of the most prevalent intestinal
parasites in the world. Ectopic infestations in the genital or urinary tracts
rarely occur and chronic enterobiasis of the urinary tract has rarely been
reported. Here we present such a case in a 7-year-old girl presenting with fever,
pain in the abdomen, vomiting and burning micturition. Ultrasonography and
micturating cystourethrogram (MCU) studies were normal. The ova were demonstrated
from both the patient's urine and stool specimen. This child was treated
successfully with Albendazole and Ivermectin.
PMID- 25586574
TI - Acute lower limb ischemia complicating pemetrexed and carboplatin combination
chemotherapy for malignant pleural mesothelioma.
AB - Pemetrexed and Carboplatin are two well-known chemioterapic agents used for the
treatment of many tumors, especially for lung cancer and mesothelioma. Peripheral
ischemic events related to Pemetrexed and Carboplatin are rarely reported. We
herein report a case of lower limb acute ischemia related to combined treatment
of Pemetrexed and Carboplatin. A 68-year-old woman was given the chemiotherapic
treatment with combination of Pemetrexed and Carboplatin after pleural resection
for a malignant pleural mesothelioma. Immediately after the second cycle of
treatment, the patient experienced sudden acute left lower limb ischemia.
Symptoms resolved after an intra-operative thrombolytic and spasmolytic therapy.
PMID- 25586562
TI - Metabolic restructuring and cell fate conversion.
AB - Accumulating evidence implicates mitochondrial and metabolic pathways in the
establishment of pluripotency, as well as in the control of proliferation and
differentiation programs. From classic studies in mouse embryos to the latest
findings in adult stem cells, human embryonic and induced pluripotent stem cells,
an increasing number of evidence suggests that mitochondrial and metabolic
related processes might intertwine with signaling networks and epigenetic
rewiring, thereby modulating cell fate decisions. This review summarizes the
progresses in this exciting field of research. Dissecting these complex
mitochondrial and metabolic mechanisms may lead to a more comprehensive
understanding of stemness biology and to potential improvements in stem cell
applications for biomedicine, cell therapy, and disease modeling.
PMID- 25586575
TI - Alfalfa microsymbionts from different ITS and nodC lineages of Ensifer meliloti
and Ensifer medicae symbiovar meliloti establish efficient symbiosis with alfalfa
in Spanish acid soils.
AB - Alfalfa (Medicago sativa L.) is an important crop worldwide whose cropping in
acid soils is hampered by the poor nodulation and yield commonly attributed to
the sensitivity of its endosymbionts to acid pH. In this work, we isolated
several acid-tolerant strains from alfalfa nodules in three acid soils in
northwestern Spain. After grouping by RAPD fingerprinting, most strains were
identified as Ensifer meliloti and only two strains as Ensifer medicae according
to their 16S-23S intergenic spacer (ITS) sequences that allowed the
differentiation of two groups within each one of these species. The two ITS
groups of E. meliloti and the ITS group I of E. medicae have been previously
found in Medicago nodules; however, the group II of E. medicae has been only
found to date in Prosopis alba nodules. The analysis of the nodC gene showed that
all strains isolated in this study belong to the symbiovar meliloti, grouping
with the type strains of E. meliloti or E. medicae, but some harboured nodC gene
alleles different from those found to date in alfalfa nodules. The strains of E.
medicae belong to the symbiovar meliloti which should be also recognised in this
species, although they harboured a nodC allele phylogenetically divergent to
those from E. meliloti strains. Microcosm experiments showed that inoculation of
alfalfa with selected acid-tolerant strains significantly increased yields in
acid soils representing a suitable agricultural practice for alfalfa cropping in
these soils.
PMID- 25586576
TI - Zebrafish gut colonization by mCherry-labelled lactic acid bacteria.
AB - A critical feature of probiotic microorganisms is their ability to colonize the
intestine of the host. Although the microbial potential to adhere to the human
gut lumen has been investigated in in vitro models, there is still much to
discover about their in vivo behaviour. Zebrafish is a vertebrate model that is
being widely used to investigate various biological processes shared with humans.
In this work, we report on the use of the zebrafish model to investigate the in
vivo colonization ability of previously characterized probiotic lactic acid
bacteria. Lactobacillus plantarum Lp90, L. plantarum B2 and Lactobacillus
fermentum PBCC11.5 were fluorescently tagged by transfer of the pRCR12 plasmid,
which encodes the mCherry protein and which was constructed in this work. The
recombinant bacteria were used to infect germ-free zebrafish larvae. After
removal of bacteria, the colonization ability of the strains was monitored until
3 days post-infection by using a fluorescence stereomicroscope. The results
indicated differential adhesion capabilities among the strains. Interestingly, a
displacement of bacteria from the medium to the posterior intestinal tract was
observed as a function of time that suggested a transient colonization by
probiotics. Based on fluorescence observation, L. plantarum strains exhibited a
more robust adhesion capability. In conclusion, the use of pRCR12 plasmid for
labelling Lactobacillus strains provides a powerful and very efficient tool to
monitor the in vivo colonization in zebrafish larvae and to investigate the
adhesion ability of probiotic microorganisms.
PMID- 25586577
TI - Ammonia-oxidizing bacteria and archaea in wastewater treatment plant sludge and
nearby coastal sediment in an industrial area in China.
AB - Under the increasing pressure of human activities, Hangzhou Bay has become one of
the most seriously polluted waters along China's coast. Considering the excessive
inorganic nitrogen detected in the bay, in this study, the impact of an effluent
from a coastal industrial park on ammonia-oxidizing microorganisms (AOMs) of the
receiving area was interpreted for the first time by molecular technologies.
Revealed by real-time PCR, the ratio of archaeal amoA/bacterial amoA ranged from
5.68 * 10(-6) to 4.79 * 10(-5) in the activated sludge from two wastewater
treatment plants (WWTPs) and 0.54-3.44 in the sediments from the effluent
receiving coastal area. Analyzed by clone and pyrosequencing libraries, genus
Nitrosomonas was the predominant ammonia-oxidizing bacteria (AOB), but no ammonia
oxidizing archaea (AOA) was abundant enough for sequencing in the activated
sludge from the WWTPs; genus Nitrosomonas and Nitrosopumilus were the dominant
AOB and AOA, respectively, in the coastal sediments. The different abundance of
AOA but similar structure of AOB between the WWTPs and nearby coastal area
probably indicated an anthropogenic impact on the microbial ecology in Hangzhou
Bay.
PMID- 25586578
TI - Characterization of an omega-6 linoleate lipoxygenase from Burkholderia
thailandensis and its application in the production of 13-hydroxyoctadecadienoic
acid.
AB - A recombinant putative lipoxygenase from Burkholderia thailandensis with a
specific activity of 26.4 U mg(-1) was purified using HisTrap affinity
chromatography. The native enzyme was a 75-kDa dimer with a molecular mass of 150
kDa. The enzyme activity and catalytic efficiency (k cat/K m) were the highest
for linoleic acid (k cat of 93.7 s(-1) and K m of 41.5 MUM), followed by
arachidonic acid, alpha-linolenic acid, and gamma-linolenic acid. The enzyme was
identified as an omega-6 linoleate lipoxygenase (or a linoleate 13S-lipoxygenase)
based on genetic and HPLC analyses as well as substrate specificity. The reaction
conditions for the enzymatic production of 13-hydroxy-9,11(Z,E)-octadecadienoic
acid (13-HODE) were optimal at pH 7.5, 25 degrees C, 20 g l(-1) linoleic acid,
2.5 g l(-1) enzyme, 0.1 mM Cu(2+), and 6% (v/v) methanol. Under these conditions,
linoleate 13-lipoxygenase from B. thailandensis produced 20.8 g l(-1) 13-HODE
(70.2 mM) from 20 g l(-1) linoleic acid (71.3 mM) for 120 min, with a molar
conversion yield of 98.5% and productivity of 10.4 g l(-1) h(-1). The molar
conversion yield and productivity of 13-HODE obtained using B. thailandensis
lipoxygenase were 151 and 158% higher, respectively, than those obtained using
commercial soybean lipoxygenase under the optimum conditions for each enzyme at
the same concentrations of substrate and enzyme.
PMID- 25586579
TI - Targeted expression of nuclear transgenes in Chlamydomonas reinhardtii with a
versatile, modular vector toolkit.
AB - We present a versatile vector toolkit for nuclear transgene expression in the
model green microalga Chlamydomonas reinhardtii. The vector was designed in a
modular fashion which allows quick replacement of regulatory elements and genes
of interest. The current toolkit comprises two antibiotic resistance markers
(paromomycin and hygromycin B), five codon-optimized light emission reporters,
including the Gaussia princeps luciferase, as well as bright cyan, green, yellow,
and red fluorescent protein variants. The system has demonstrated robust
functional flexibility with signal options to target the protein of interest to
the cytoplasm, the nucleus, cellular microbodies, the chloroplast, mitochondria,
or via the endoplasmic reticulum-Golgi apparatus secretory pathway into the
culture medium. Successful fluorescent reporter protein fusion to C. reinhardtii
Rubisco small subunit 1 was accomplished with this system. Localization of the
fluorescently tagged protein was observed in the chloroplast pyrenoid via live
cell fluorescence microscopy, the first report of heterologous protein
localization to this cellular structure. The functionalities of the vector
toolkit, the individual modular elements, as well as several combinations thereof
are demonstrated in this manuscript. Due to its strategic design, this vector
system can quickly be adapted to individual tasks and should therefore be of
great use to address specific scientific questions requiring nuclear recombinant
protein expression in C. reinhardtii.
PMID- 25586580
TI - The transcriptomic profile of Pseudozyma aphidis during production of
mannosylerythritol lipids.
AB - The basidiomycetous fungus Pseudozyma aphidis is able to convert vegetable oils
to abundant amounts of the biosurfactant mannosylerythritol lipid (MEL) with a
unique product pattern of MEL-A, MEL-B, MEL-C, and MEL-D. To investigate the
metabolism of MEL production, we analyzed the transcriptome of P. aphidis DSM
70725 under MEL-inducing and non-inducing conditions using deep sequencing.
Following manual curation of the previously described in silico gene models based
on RNA-Seq data, we were able to generate an experimentally verified gene
annotation containing 6347 genes. Using this database, our expression analysis
revealed that only four of the five cluster genes required for MEL synthesis were
clearly induced by the presence of soybean oil. The acetyltransferase encoding
gene PaGMAT1 was expressed on a much lower level, which may explain the secretion
of MEL with different degrees of acetylation in P. aphidis. In parallel to MEL
synthesis, microscopic observations showed morphological changes accompanied by
expression of genes responsible for cell development, indicative of a
coregulation between MEL synthesis and cell morphology. In addition a set of
transcription factors was identified which may be responsible for regulation of
MEL synthesis and cell development. The upregulation of genes required for
nitrogen metabolism and other assimilation processes indicate additional
metabolic pathways required under the MEL-inducing conditions used. We also
searched for a conserved gene cluster for cellobiose lipids (CL) but only found
seven genes with limited homology distributed over the genome. However, we
detected characteristic TLC spots in fermentations using P. aphidis DSM 70725,
indicative of CL secretion.
PMID- 25586581
TI - Truncation of domain V of the multidomain glucansucrase GTF180 of Lactobacillus
reuteri 180 heavily impairs its polysaccharide-synthesizing ability.
AB - Glucansucrases are exclusively found in lactic acid bacteria and synthesize a
variety of alpha-glucans from sucrose. They are large multidomain enzymes
belonging to the CAZy family 70 of glycoside hydrolase enzymes (GH70). The
crystal structure of the N-terminal truncated GTF180 of Lactobacillus reuteri 180
(GTF180-DeltaN) revealed that the polypeptide chain follows a U shape course to
form five domains, including domains A, B, and C, which resemble those of family
GH13 enzymes, and two extra and novel domains (domains IV and V), which are
attached to the catalytic core. To elucidate the functional roles of domain V, we
have deleted the domain V fragments from both the N- and C-terminal ends (GTF180
DeltaNDeltaV). Truncation of domain V of GTF180-DeltaN yielded a catalytically
fully active enzyme but with heavily impaired polysaccharide synthesis ability.
Instead, GTF180-DeltaNDeltaV produced a large amount of oligosaccharides. Domain
V is not involved in determining the linkage specificity, and the size of
polysaccharide produced as the polysaccharide produced by GTF180-DeltaNDeltaV was
identical in size and structure with that of GTF180-DeltaN. The data indicates
that GTF180-DeltaNDeltaV acts nonprocessively, frequently initiating synthesis of
a new oligosaccharide from sucrose, instead of continuing the synthesis of a full
size polysaccharide. Mutations L940E and L940F in GTF180-DeltaNDeltaV, which are
involved in the acceptor substrate binding, restored polysaccharide synthesis
almost to the level of GTF180-DeltaN. These results demonstrated that
interactions of growing glucan chains with both domain V and acceptor substrate
binding sites are important for polysaccharide synthesis.
PMID- 25586583
TI - Antimicrobial peptides: an alternative for innovative medicines?
AB - Antimicrobial peptides are small molecules with activity against bacteria,
yeasts, fungi, viruses, bacteria, and even tumor cells that make these molecules
attractive as therapeutic agents. Due to the alarming increase of antimicrobial
resistance, interest in alternative antimicrobial agents has led to the
exploitation of antimicrobial peptides, both synthetic and from natural sources.
Thus, many peptide-based drugs are currently commercially available for the
treatment of numerous ailments, such as hepatitis C, myeloma, skin infections,
and diabetes. Initial barriers are being increasingly overcome with the
development of cost-effective, more stable peptides. Herein, we review the
available strategies for their synthesis, bioinformatics tools for the rational
design of antimicrobial peptides with enhanced therapeutic indices, hurdles and
shortcomings limiting the large-scale production of AMPs, as well as the
challenges that the pharmaceutical industry faces on their use as therapeutic
agents.
PMID- 25586582
TI - A new salicylate synthase AmS is identified for siderophores biosynthesis in
Amycolatopsis methanolica 239(T).
AB - Siderophores are important for the growth of bacteria or the applications in
treatment of iron overload-associated diseases due to the iron-chelating
property. Salicylate synthase played a key role in the biosynthesis of some NRPS
derived siderophores by the providing of an iron coordination moiety as the
initial building block. A new salicylate synthase, namely AmS, was identified in
the biosynthesis pathway of siderophore amychelin in Amycolatopsis methanolica
239(T), since it shunt chorismate, an integrant precursor, from primary to
secondary metabolite flow. The amino acid sequence alignment and phylogenetic
analysis showed that AmS grouped into a new cluster. In vitro assays of AmS
revealed its wide temperature tolerance ranged from 0 to 40 degrees C and narrow
pH tolerant ranged from 7.0 to 9.0. AmS was resistant to organic solvents and non
ionic detergents. Moreover, AmS converted chorismate to salicylate with K m of
129.05 MUM, k cat of 2.20 min(-1) at optimal conditions, indicating its low
substrate specificity and comparable velocity to reported counterparts (Irp9 and
MbtI). These properties of AmS may improve the iron-seizing ability of A.
methanolica to compete with its neighbors growing in natural environments. Most
importantly, serine and cysteine residues were found to be important for the
catalytic activity of AmS. This study presented AmS as a new cluster of
salicylate synthase and the reaction mechanism and potential applications of
salicylate synthase were highlighted as well.
PMID- 25586584
TI - Genomic and chemical insights into biosurfactant production by the mangrove
derived strain Bacillus safensis CCMA-560.
AB - Many Bacillus species can produce biosurfactant, although most of the studies on
lipopeptide production by this genus have been focused on Bacillus subtilis.
Surfactants are broadly used in pharmaceutical, food and petroleum industry, and
biological surfactant shows some advantages over the chemical surfactants, such
as less toxicity, production from renewable, cheaper feedstocks and development
of novel recombinant hyperproducer strains. This study is aimed to unveil the
biosurfactant metabolic pathway and chemical composition in Bacillus safensis
strain CCMA-560. The whole genome of the CCMA-560 strain was previously
sequenced, and with the aid of bioinformatics tools, its biosurfactant metabolic
pathway was compared to other pathways of closely related species. Fourier
transform infrared (FTIR) and high-resolution TOF mass spectrometry (MS) were
used to characterize the biosurfactant molecule. B. safensis CCMA-560 metabolic
pathway is similar to other Bacillus species; however, some differences in amino
acid incorporation were observed, and chemical analyses corroborated the genetic
results. The strain CCMA-560 harbours two genes flanked by srfAC and srfAD not
present in other Bacillus spp., which can be involved in the production of the
analogue gramicidin. FTIR and MS showed that B. safensis CCMA-560 produces a
mixture of at least four lipopeptides with seven amino acids incorporated and a
fatty acid chain with 14 carbons, which makes this molecule similar to the
biosurfactant of Bacillus pumilus, namely, pumilacidin. This is the first report
on the biosurfactant production by B. safensis, encompassing the investigation of
the metabolic pathway and chemical characterization of the biosurfactant
molecule.
PMID- 25586585
TI - Engineering of Escherichia coli for the biosynthesis of poly(3-hydroxybutyrate-co
3-hydroxyhexanoate) from glucose.
AB - The copolymer poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] has
the potential to serve as a biodegradable tissue engineering material. However,
the production of this kind of copolymer still suffers from high cost and
uncertainty. We describe here the design of metabolic pathways to synthesize P(HB
co-HHx) directly from glucose using recombinant Escherichia coli. By combining
the BktB-dependent condensation pathway with the inverted beta-oxidation cycle
pathway, we were able to synthesize a P(HB-co-HHx) copolymer with a 10 mol% HHx
fraction in recombinant E. coli. After optimizing the host strain and employing
thioesterase mutant strains, the engineered E. coli produced 12.9 wt% P(HB-co
HHx) with a 13.2 mol% 3HHx fraction.
PMID- 25586586
TI - The herbal-derived honokiol and magnolol enhances immune response to infection
with methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant
S. aureus (MRSA).
AB - The emergence of antibiotic resistant strains such as methicillin-resistant
Staphylococcus aureus (MRSA) reminds us an urgent need to develop a new immune
modulating agent for preventing S. aureus infection. In this study, we found that
herbal medicines, honokiol and magnolol, caused a significant cellular immune
modulatory effect during S. aureus infection. In mouse macrophages, these
compounds drove upregulation of an antioxidant effect in response to S. aureus,
resulting in a dampened total cellular reactive oxygen species (ROS) production
and decreased production of inflammatory cytokines/chemokines, whereas honokiol
induced increased types I and III interferon messenger RNA (mRNA) expression
levels in response to MSSA infection. Moreover, the internalization of S. aureus
by human alveolar epithelial cells was inhibited by these compounds. Furthermore,
honokiol and magnolol treatment promoted a delay in killing during MSSA infection
in Caenorhabditis elegans, suggesting antimicrobial function in vivo. In
conclusion, honokiol and magnolol may be considered as attractive immune
modulating treatment for S. aureus infection.
PMID- 25586587
TI - Chimpanzees (Pan troglodytes) and human children (Homo sapiens) know when they
are ignorant about the location of food.
AB - Over the last decade, the metacognitive abilities of nonhuman primates and the
developmental emergence of metacognition in children have become topics of
increasing research interest. In the current study, the performance of three
adult chimpanzees (Pan troglodytes; Experiment 1) and forty-four 3.5- and 5.5
year-old human children (Experiment 2) was assessed on a behavioral search
paradigm designed to assess metacognition. Subjects either directly observed the
baiting of a large reward into one cup among an array of four, or had the baiting
occluded from their view. In half of the trials, subjects were also presented
with an additional distinctive cup that was always visibly baited with a small
reward. This cup allowed subjects the opportunity to escape from making a guess
about the location of the bigger reward. All three chimpanzees and both age
groups of children selected the escape cup more often when the baiting of the
large reward was concealed, compared to when it was visible. This demonstrates
that both species can selectively choose a guaranteed smaller reward when they do
not know the location of a larger reward and provides insight into the
development of metacognition.
PMID- 25586588
TI - Osteogenic responses to zirconia with hydroxyapatite coating by aerosol
deposition.
AB - Previously, we found that osteogenic responses to zirconia co-doped with niobium
oxide (Nb2O5) or tantalum oxide (Ta2O5) are comparable with responses to
titanium, which is widely used as a dental implant material. The present study
aimed to evaluate the in vitro osteogenic potential of hydroxyapatite (HA)-coated
zirconia by an aerosol deposition method for improved osseointegration. Surface
analysis by scanning electron microscopy and x-ray diffraction proved that a thin
as-deposited HA film on zirconia showed a shallow, regular, crater-like surface.
Deposition of dense and uniform HA films was measured by SEM, and the contact
angle test demonstrated improved wettability of the HA-coated surface. Confocal
laser scanning microscopy indicated that MC3T3-E1 pre-osteoblast attachment did
not differ notably between the titanium and zirconia surfaces; however, cells on
the HA-coated zirconia exhibited a lower proliferation than those on the uncoated
zirconia late in the culture. Nevertheless, ALP, alizarin red S staining, and
bone marker gene expression analysis indicated good osteogenic responses on HA
coated zirconia. Our results suggest that HA-coating by aerosol deposition
improves the quality of surface modification and is favorable to osteogenesis.
PMID- 25586589
TI - Erythropoietin promotes bone formation through EphrinB2/EphB4 signaling.
AB - Recent studies have demonstrated that erythropoietin (EPO) has extensive
nonhematopoietic biological functions. However, little is known about how EPO
regulates bone formation, although several studies suggested that EPO can affect
bone homeostasis. In this study, we investigated the effects of EPO on the
communication between osteoclasts and osteoblasts through the ephrinB2/EphB4
signaling pathway. We found that EPO slightly promotes osteoblastic
differentiation with the increased expression of EphB4 in ST2 cells. However, EPO
increased the expression of Nfatc1 and ephrinB2 but decreased the expression of
Mmp9 in RAW264.7 cells, resulting in an increase of ephrinB2-expressing
osteoclasts and a decrease in resorption activity. The stimulation of
ephrinB2/EphB4 signaling via ephrinB2-Fc significantly promoted EPO-mediated
osteoblastic differentiation in ST2 cells. EphB4 knockdown through EphB4 shRNA
inhibited EPO-mediated osteoblastic phenotypes. Furthermore, in vivo assays
clearly demonstrated that EPO efficiently induces new bone formation in the
alveolar bone regeneration model. Taken together, these results suggest that
ephrinB2/EphB4 signaling may play an important role in EPO-mediated bone
formation.
PMID- 25586592
TI - Chlorin e6-ZnSe/ZnS quantum dots based system as reagent for photodynamic
therapy.
AB - Stable water-soluble complexes of Cd-free ZnSe/ZnS quantum dots (QDs) and chlorin
e6 complexes have been prepared. These complexes have shown approximately 50%
intracomplex fluorescence resonance energy transfer from QDs to chlorin e6. The
photodynamic therapy (PDT) test of the complexes against the Erlich acsite
carcinoma cell culture demonstrated a two-fold enhancement of the cancer cell
photodynamic destruction as compared to that of free chlorin e6 molecules. It was
shown that the PDT effect was significantly increased due to two factors: the
efficient QD-chlorin e6 photoexcitation energy transfer and the improvement of
cellular uptake of the photosensitizer in the presence of ZnSe/ZnS QDs.
PMID- 25586591
TI - Identification of Toxoplasma gondii antigens associated with different types of
infection by serum antibody profiling.
AB - Acquisition of acute toxoplasmosis during the first trimester of pregnancy can
have catastrophic consequences for the foetus. Diagnosis is routinely based on
the detection of maternal Toxoplasma gondii--antibodies using whole parasite
extracts as detection antigen. While such assays are sensitive, they show no
specificity for the stage of infection. We hypothesized diagnosis might be
improved using recombinant antigens for detection, particularly if antibodies to
certain antigen(s) were associated with early or late stages of infection. To
address this, protein microarrays comprising 1513 T. gondii exon products were
probed with well-characterized sera from seronegative ('N') controls, and acute
('A'), chronic/IgM-persisting ('C/M') and chronic ('C') toxoplasmosis cases from
Turkey. Three reactive exon products recognized preferentially in A infections,
and three recognized preferentially in C/M infections, were expressed in
Escherichia coli and tested for discrimination in IgG ELISAs. The best
discriminators were exon 1 of TGME49_086450 (GRA5) which detected C/M infections
with 70.6% sensitivity and 81.8% specificity, and exon 6 of TGME49_095700
(ubiquitin transferase domain-containing protein) which detected A infections
with 84.8% sensitivity and 82.4% specificity. Overall, the data support a
recombinant protein approach for the development of improved serodiagnostic tests
for toxoplasmosis.
PMID- 25586594
TI - Action spectroscopy of a protonated peptide in the ultraviolet range.
AB - Action spectroscopy of protonated substance P, a model undecapeptide, has been
probed from 5.2 eV to 20 eV. For photon energy above the ionization threshold
measured at 10.3 +/- 0.1 eV, the radical dication is observed along with side
chain losses and abundant formation of all kinds of sequence ions. Below the
photoionization threshold, the photoproducts involve side chain cleavages and
backbone cleavages into a-, b-/y-, and c-sequence ions. Different electronic
excited states appear to produce different fragment ions. Norrish type I and II
reactions are proposed to account for some photoproducts. This study bridges the
gap between laser activation and electron-induced dissociation of peptides.
Moreover, our results report for the first time a comprehensive picture of the
photochemical fragmentation of a gas phase peptide in a wide photon energy range.
PMID- 25586596
TI - Novel method for rapid reversal of drug toxicity: a case report.
AB - Drug toxicity is traditionally treated by reducing the amount of the drug
absorbed, enhancing elimination, and providing supportive care. Once the drug has
been absorbed, there are few methods that help decrease morbidity and mortality
caused by a toxic drug level. Albumin infusion is a new approach that changes
that, as it can rapidly reverse a toxic drug level back to a therapeutic level.
It is believed with most drugs that the toxic effects are related to the total
amount of the free drug. In this method, albumin binds to the free drug and acts
as a reservoir or depot from which the drug is slowly released to the free form,
thereby limiting the effects of drug toxicity. In this case report, an elderly
female patient who experienced phenytoin toxicity was treated with albumin
infusion, after which her phenytoin level returned to a therapeutic level with
corresponding improvements in her symptoms. Based on our calculations, it was
predicted that a small amount of albumin would reverse the patient's toxic
symptoms. With this approach, the patient's toxic symptoms improved when free
phenytoin levels dropped from 15 to 8 MUmol/L. Albumin infusion is a promising
new therapy that can rapidly reverse a toxic drug level back to a therapeutic
level by binding the free drug to albumin.
PMID- 25586597
TI - Educating surgeons on intraoperative disposable supply costs during laparoscopic
cholecystectomy: a regional health system's experience.
AB - BACKGROUND: Surgeons play a crucial role in the cost efficiency of the operating
room through total operative time, use of supplies, and patient outcomes. This
study aimed to examine the effect of surgeon education on disposable supply usage
during laparoscopic cholecystectomy. METHODS: Surgeons were educated about the
cost of disposable equipments without incentives for achieved cost reductions.
Surgical supply costs for laparoscopic cholecystectomy in fiscal year (FY) 2013
were compared with FY 2014. RESULTS: The average disposable supply cost per
laparoscopic cholecystectomy was reduced from $589 (n = 586) in FY 2013 to $531
(n = 428) in FY 2014, representing a 10% reduction in supply costs (P < .001).
Adjustments included reduction in the use of expensive fascial closure devices,
clip appliers, suction irrigators, and specimen retrieval bags. CONCLUSIONS:
Disposable equipment cost for laparoscopic cholecystectomy can be reduced by
surgeon education. These techniques can likely be used to reduce costs in an
array of specialties and procedures.
PMID- 25586593
TI - Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant
myelodysplastic syndrome.
AB - Somatic mutations in the spliceosome gene ZRSR2-located on the X chromosome-are
associated with myelodysplastic syndrome (MDS). ZRSR2 is involved in the
recognition of 3'-splice site during the early stages of spliceosome assembly;
however, its precise role in RNA splicing has remained unclear. Here we
characterize ZRSR2 as an essential component of the minor spliceosome (U12
dependent) assembly. shRNA-mediated knockdown of ZRSR2 leads to impaired splicing
of the U12-type introns and RNA-sequencing of MDS bone marrow reveals that loss
of ZRSR2 activity causes increased mis-splicing. These splicing defects involve
retention of the U12-type introns, while splicing of the U2-type introns remain
mostly unaffected. ZRSR2-deficient cells also exhibit reduced proliferation
potential and distinct alterations in myeloid and erythroid differentiation in
vitro. These data identify a specific role for ZRSR2 in RNA splicing and
highlight dysregulated splicing of U12-type introns as a characteristic feature
of ZRSR2 mutations in MDS.
PMID- 25586598
TI - Prediction models of Medicare 90-day postdischarge deaths, readmissions, and
costs in bowel operations.
AB - BACKGROUND: The 90-day postdischarge morbidity and mortality rates following
elective and emergent bowel surgery remain poorly defined. METHODS: The 2009 to
2011 Medicare inpatient files for patients undergoing elective and emergent small
and large bowel operations in 1,024 hospitals that passed present-on-admission
coding accuracy standards had prediction models designed for inpatient mortality,
prolonged postoperative length of hospital stay (prLOS), 90-day postdischarge
mortality and readmissions, and total hospital costs. RESULTS: Of 118,758
patients studied, there was a 4.7% inpatient mortality rate and 7.3% prLOS among
live discharges. An additional 7,586 deaths and 26,969 readmissions occurred
within 90 days of discharge. Prolonged preoperative and prolonged postoperative
hospitalizations were significant (P < .0001) variables in predicting
postdischarge deaths and readmissions. Total hospital costs were increased by
over $18,000 per adverse outcome. CONCLUSION: Postdischarge deaths and
readmissions are more common than inpatient adverse events of death and prLOS in
elective and emergent Medicare large and small bowel operations.
PMID- 25586599
TI - The derived neutrophil/lymphocyte ratio predicts poor clinical outcome in soft
tissue sarcoma patients.
AB - BACKGROUND: Inflammation plays an important role in tumor proliferation and
survival in cancer patients. The aim of this study was to investigate the
prognostic impact of the pre-operative-derived neutrophil/lymphocyte ratio (dNLR)
in a large cohort of soft tissue sarcoma (STS) patients after curative surgical
resection. METHODS: The impact of preoperative dNLR on disease-free survival
(DFS) and overall survival (OS) in retrospectively evaluated 340 STS patients was
assessed using Kaplan-Meier curves and Cox proportional models. RESULTS: Applying
receiver operating curve analysis, we determined a cut-off value of 2.39 for the
dNLR to be optimal for discrimination of patients' survival in the whole cohort.
Kaplan-Meier curves revealed a dNLR greater than or equal to 2.39 as a marker for
decreased DFS (P = .031) and OS (P = .007, log-rank test) in STS patients. In
multivariate analysis, increased dNLR was significantly associated with poor OS
(hazard ratio 1.60, 95% confidence interval 1.07 to 2.40, P = .022). CONCLUSIONS:
This study demonstrates that preoperative dNLR might represent a well-correlated
surrogate marker for the widely validated NLR. The dNLR is easily obtainable and
can provide important information for individual risk assessment in clinical
trials.
PMID- 25586600
TI - Real-time web-based assessment of total population risk of future emergency
department utilization: statewide prospective active case finding study.
AB - BACKGROUND: An easily accessible real-time Web-based utility to assess patient
risks of future emergency department (ED) visits can help the health care
provider guide the allocation of resources to better manage higher-risk patient
populations and thereby reduce unnecessary use of EDs. OBJECTIVE: Our main
objective was to develop a Health Information Exchange-based, next 6-month ED
risk surveillance system in the state of Maine. METHODS: Data on electronic
medical record (EMR) encounters integrated by HealthInfoNet (HIN), Maine's Health
Information Exchange, were used to develop the Web-based surveillance system for
a population ED future 6-month risk prediction. To model, a retrospective cohort
of 829,641 patients with comprehensive clinical histories from January 1 to
December 31, 2012 was used for training and then tested with a prospective cohort
of 875,979 patients from July 1, 2012, to June 30, 2013. RESULTS: The
multivariate statistical analysis identified 101 variables predictive of future
defined 6-month risk of ED visit: 4 age groups, history of 8 different encounter
types, history of 17 primary and 8 secondary diagnoses, 8 specific chronic
diseases, 28 laboratory test results, history of 3 radiographic tests, and
history of 25 outpatient prescription medications. The c-statistics for the
retrospective and prospective cohorts were 0.739 and 0.732 respectively.
Integration of our method into the HIN secure statewide data system in real time
prospectively validated its performance. Cluster analysis in both the
retrospective and prospective analyses revealed discrete subpopulations of high
risk patients, grouped around multiple "anchoring" demographics and chronic
conditions. With the Web-based population risk-monitoring enterprise dashboards,
the effectiveness of the active case finding algorithm has been validated by
clinicians and caregivers in Maine. CONCLUSIONS: The active case finding model
and associated real-time Web-based app were designed to track the evolving nature
of total population risk, in a longitudinal manner, for ED visits across all
payers, all diseases, and all age groups. Therefore, providers can implement
targeted care management strategies to the patient subgroups with similar
patterns of clinical histories, driving the delivery of more efficient and
effective health care interventions. To the best of our knowledge, this
prospectively validated EMR-based, Web-based tool is the first one to allow real
time total population risk assessment for statewide ED visits.
PMID- 25586603
TI - Novel mutations in the von Hippel-Lindau gene associated with congenital
polycythemia.
PMID- 25586601
TI - PD-1 blockade therapy in renal cell carcinoma: current studies and future
promises.
AB - RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell
infiltrate, unable to control tumor growth. Evasion of immune surveillance, a
process defined immune-editing, leads to malignant progression. The striking
improvement of knowledge in immunology has led to the identification of immune
checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor
immunity. The interaction between PD-1, an inducible inhibitory receptor
expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells,
results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1
axis inhibition by targeted-antibodies, increasing the T-cell proliferation and
cytotoxicity, represents a promising mechanism to stimulate the anti-tumor
activity of the immune system, improving the outcomes of cancer patients. Several
PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing
promising results. The interesting correlation between lymphocytes PD-1
expression and RCC advanced stage, grade and prognosis, as well as the selective
PD-L1 expression by RCC tumor cells and its potential association with worse
clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents,
alone or in combination with anti-angiogenic drugs or other immunotherapeutic
approaches, for the treatment of RCC. In this review we discuss the role of PD
1/PD-L1 in RCC, focusing on the biological rationale, current clinical studies
and promising therapeutic perspectives to target the PD-1 pathway.
PMID- 25586604
TI - Concomitant bone marrow involvement by plasma cell myeloma and primary
myelodysplastic syndrome with biclonal complex chromosome anomalies.
PMID- 25586602
TI - Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older
Adults: A Systematic Review.
AB - A 2012 update of the Beers criteria categorizes selective serotonin reuptake
inhibitors (SSRIs) as potentially inappropriate medications in all older adults
based on fall risk. The application of these recommendations, not only to frail
nursing home residents, but to all older adults, may lead to changes in health
policy or clinical practice with harmful consequences. A systematic review of
studies on the association between SSRIs and falls in older adults was conducted
to examine the evidence for causation. Twenty-six studies met the inclusion
criteria. The majority of studies were observational and suggest an association
between SSRIs and falls. The direction of the relationship--causation or effect-
cannot be discerned from this type of study. Standardized techniques for
determining likely causation were then used to see if there was support for the
hypothesis that SSRIs lead to falls. This analysis did not suggest causation was
likely. There is no Level 1 evidence that SSRIs cause falls. Therefore, changes
in the current treatment guidelines or policies on the use of SSRIs in older
adults based on fall risk may not be justified at this time given the lack of an
established evidence base. Given its significance to public health, well-designed
experimental studies are required to address this question definitively.
PMID- 25586606
TI - Nurse like cells: chronic lymphocytic leukemia associated macrophages.
AB - CD14 + cells are able to differentiate into large and adherent cells if in
contact with chronic lymphocytic leukemia (CLL) cells or healthy B lymphocytes.
In CLL these cells, called CLL-nurse like cells (NLCs), express a very high
amount of CD163 and CD68 and are able to rescue CLL cells through CCL4
production. Adherent cells derived from healthy donors, called HD-NLCs, express
very little CD163 and CD68, do not produce CCL4 and are unable to rescue CCL
cells. This study reveals that CLL-NLCs are the specific nurse cells in CLL,
protecting CLL cells from death.
PMID- 25586605
TI - Asparaginase pharmacokinetics and implications of therapeutic drug monitoring.
AB - Asparaginase is widely used in chemotherapeutic regimens for the treatment of
acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in
cure rates, especially in children. Optimal therapeutic effects depend on a
complete and sustained depletion of serum asparagine. However, pronounced
interpatient variability, differences in pharmacokinetic properties between
asparaginases and the formation of asparaginase antibodies make it difficult to
predict the degree of asparagine depletion that will result from a given dose of
asparaginase. The pharmacological principles underlying asparaginase therapy in
the treatment of ALL are summarized in this article. A better understanding of
the many factors that influence asparaginase activity and subsequent asparagine
depletion may allow physicians to tailor treatment to the individual, maximizing
therapeutic effect and minimizing treatment-related toxicity. Therapeutic drug
monitoring provides a means of assessing a patient's current depletion status and
can be used to better evaluate the potential benefit of treatment adjustments.
PMID- 25586607
TI - Selective Janus associated kinase 1 inhibition as a therapeutic target in
myelofibrosis.
AB - Hyperactive Janus associated kinase-signal transducers and activators of
transcription (JAK-STAT) signaling has been shown to be integral to the
pathogenesis of myelofibrosis (MF) regardless of the driver mutational status
(JAK2V617F, JAK2 exon 12, MPL515L/K, CALR). Targeting of the JAK-STAT pathway has
been the intense focus of therapeutic development and led to the approval of the
JAK1/2 inhibitor, ruxolitinib. Despite the clear clinical success of ruxolitinib,
dose limiting thrombocytopenia, treatment associated anemia and failure to
effectively achieve bone marrow pathologic, cytogenetic and molecular remission
remain shortcomings. JAK1 inhibition leads to depression in inflammatory cytokine
expression associated with MF-related constitutional symptoms. The selective
targeting of JAK1 may provide an opportunity to alleviate MF-related symptoms
without anti-JAK2 therapy-related myelosuppression. Additionally, a JAK1
inhibitor may serve as an ideal candidate partner for combination therapeutic
approaches in the treatment of MF. Current evaluation of selective JAK1
inhibition in MF will further clarify the relative contribution of aberrant JAK1
signaling to the pathogenesis of MF.
PMID- 25586608
TI - Epigenetic regulation of microRNA expression in Hodgkin lymphoma.
AB - Epigenetic mechanisms are crucial for the inactivation of key genes related to
the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent
epigenetic mechanism of microRNA silencing. We have examined the methylation
induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed
our results in patient lymph nodes. In addition, we evaluated the in vitro
effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines. Ten microRNAs
containing CpG islands in their promoter region were re-expressed in both the L
428 and L-1236 cell lines. Interestingly, miR-34a and miR-203, both known tumor
suppressor microRNAs, were found to be methylated in cell lines and in patient
samples. 5-Aza-dC treatment resulted in a dose-dependent antiproliferative effect
at 72 h in all the HL cell lines. In summary, 5-Aza-dC treatment of HL cell lines
inhibits proliferation at high doses and produces re-expression of the tumor
suppressor microRNAs at low-intermediate doses.
PMID- 25586609
TI - "Heterogeneity within order" in metal-organic frameworks.
AB - Metal-organic frameworks (MOFs) are constructed by linking inorganic units with
organic linkers to make extended networks. Though more than 20 000 MOF structures
have been reported most of these are ordered and largely composed of a limited
number of different kinds building units, and very few have multiple different
building units (heterogeneous). Although heterogeneity and multiplicity is a
fundamental characteristic of biological systems, very few synthetic materials
incorporate heterogeneity without losing crystalline order. Thus, the question
arises: how do we introduce heterogeneity into MOFs without losing their ordered
structure? This Review outlines strategies for varying the building units within
both the backbone of the MOF and its pores to produce the heterogeneity that is
sought after. The impact this heterogeneity imparts on the properties of a MOF is
highlighted. We also provide an update on the MOF industry as part of this themed
issue for the 150th anniversary of BASF.
PMID- 25586610
TI - Changes in the contents of selected polycyclic aromatic hydrocarbons in soils of
various types.
AB - The aim of the paper was to determine the stability and the decomposition
intensity of selected polycyclic aromatic hydrocarbons (fluorene, anthracene,
pyrene, and chrysene) in soils that are under agricultural use. Soil was sampled
from the arable layer that is representative of the Kujawy and Pomorze Provinces,
which are located in the northwestern part of Poland. The soil samples were
polluted with selected PAHs at an amount corresponding to 10 mg PAHs/kg. PAH
polluted soil samples were incubated for 10, 30, 60, 120, 180, and 360 days at a
temperature of 20-25 degrees C and a fixed moisture of 50% field water capacity.
High-performance liquid chromatography (HPLC) was used to determine the content
of PAHs. It was found that the process of the degradation of PAHs was most
intensive during the first 30 days of the experiment; however, three-ring PAHs
(fluorene and anthracene) definitely decomposed faster than the four-ring ones
(pyrene and chrysene). The results also confirm the significant role of soil
organic matter in sorption and activation processes of PAHs.
PMID- 25586611
TI - Particulate matter concentration and chemical composition in the metro system of
Rome, Italy.
AB - Air quality at the main station of the metro system of Rome (Termini hub) has
been characterized by the point of view of particulate matter (PM) concentration
and chemical composition. Indoor air in different environments (underground train
platform and shopping center, metro carriages with and without air conditioning
system) has been studied and compared with outdoor air at a nearby urban site.
Air quality at the railway station, located outdoor at surface level, has been
also considered for comparison. PM chemical characterization included ions,
elemental carbon, organic carbon, macro-elements, and the bio-accessible and
residual fractions of micro- and trace elements. Train platform and carriages
without air conditioning resulted to be the most polluted environments, with
indoor/outdoor ratio up to two orders of magnitude for many components. PM mass
concentration was determined on filter membranes by the gravimetric procedure as
well as from the optical particle counter (OPC) number concentration
measurements. The OPC results, taken with the original calibration factor, were
below 40 % of the value obtained by the gravimetric measurements. Only a chemical
and morphological characterization of the collected dust could lead to a
reconciliation of the results yielded by the two methods. Macro-components were
used to estimate the strength of the main macro-sources. The most significant
contribution is confirmed to derive from wheels, rails, and brakes abrasion; from
soil re-suspension (over 50 % at the subway platform); and from organics (about
25 %). The increase in the concentration of elements was mostly due to the
residual fraction, but also the bio-accessible fraction showed a remarkable
enrichment, particularly in the case of Ba, Zn, Cd, and Ni.
PMID- 25586612
TI - Uptake and speciation of vanadium in the rhizosphere soils of rape (Brassica
juncea L.).
AB - The response of rape (Brassica juncea L.) to different vanadium (V) speciation in
rhizosphere soils was investigated in pot experiments using an agricultural soil
containing 147 mg V kg(-1) supplemented with 0-500 mg V kg(-1) of pentavalent V
[V(V)] and a mining soil containing 774 mg V kg(-1). Tetravalent V [V(IV)]
accounted for 76.1 and 85.9 % of total V in the untreated agricultural soil and
mining soil, respectively. The proportion of both V(V) and water-extractable V
increased with increasing concentrations of V(V) in the agricultural soil. The
growth of rape substantially reduced the concentrations of V(V) but not V(IV) in
the rhizosphere soil, suggesting that V(V) was actively involved in the soil-rape
interaction of V. Both soil V(V) and water-extractable V were negatively related
to the total rape biomass, but were positively correlated with the concentration
of root V. No such relationships were found for total V and soil V(IV). Together,
these results indicate that soil V(V) and water-extractable V might better
reflect the toxicity of V in soils than total V and soil V(IV). Rape accumulated
V in the sequence: roots > > stem > leaf > seed. As indicated by the remarkably
low root bioconcentration factor of V(V) (0.41-7.24 %), rape had a lower ability
to accumulate V than other plants reported in the literature (14.6-298 %). Only a
small fraction of V in rape roots was translocated to the aboveground organs (the
translocation factor was 3.57-46.9 %). No V was detectable in seeds in the soils
at 147 and 197 mg V kg(-1), and no seed was produced in the soils at higher V
concentrations. Thus, the risk of V intake by humans via the consumption of
rapeseed-based foods under normal conditions is considered to be lower than that
of other plants.
PMID- 25586613
TI - Cytotoxicity of zinc nanoparticles fabricated by Justicia adhatoda L. on root
tips of Allium cepa L.--a model approach.
AB - Zinc nanoparticles were synthesized using aqueous leaf extract of Justicia
adhatoda L. The characterization of nanoparticles was done by ultraviolet-visible
(UV-vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, atomic
force microscopy (AFM), and high-resolution transmission electron microscopy (HR
TEM). The characteristic absorption peak of the UV spectrum was recorded at 379
nm. The FTIR data revealed the possible biomolecules involved in bioreduction and
capping of zinc nanoparticles for efficient stabilization. AFM and HR-TEM images
have shown that the size of zinc nanoparticles ranges from 55 to 83 nm and they
are spherical in shape. The biogenic zinc nanoparticles were evaluated for their
toxic effect on mitotic chromosomes of Allium cepa as a model system. Experiments
were conducted in triplicate to assay the effect of 25, 50, 75, and 100 % of zinc
nanoparticles on mitotic chromosomes at an interval of 6 h duration for 24 h. The
investigation revealed that the mitotic index (MI) was decreased with increased
concentration of zinc nanoparticles and exposure duration. The results revealed
that zinc nanoparticles have induced abnormalities like anaphase bridge
formation, diagonal anaphase, C-metaphase, sticky metaphase, laggards, and sticky
anaphase at different percentages and times of exposure. It is evident from the
observation that mitotic cell division becomes abortive at 100 % treatment of
zinc nanoparticles.
PMID- 25586615
TI - Performance of a wall cascade constructed wetland treating surfactant-polluted
water.
AB - Carwashes are highly water-consuming processes that require wastewater treatment
before discharge into a sewer system due to the complex composition of leachate.
Anionic surfactants (AS) are the main constituents of this wastewater because of
their cleaning and solubilization properties; they can be potentially dangerous
for the environment if not adequately treated. Constructed wetlands (CWs) are low
cost systems increasingly used to treat different types of wastewater; however,
there are few studies on their use for the treatment of carwash wastewater. In
this study, an innovative constructed wetland arranged in a "cascade" to simulate
a wall system (WCCW) was experimented in 2010 and 2011 to treat AS. Three plant
species were tested at different AS inlet concentrations (10, 50, and 100 mg L(
1)) with two hydraulic retention times (HRTs; 3 and 6 days): ribbon grass
(Typhoides arundinacea (L.) Moench (syn. Phalaris arundinacea L.) var. picta;
Ta), water mint (Mentha aquatica L.; Ma), and divided sedge (Carex divisa Hudson;
Cd). All plant species grew constantly over the experimental period, showing a
capacity to tolerate even the highest AS concentration. Using the HRT of 6 days,
raising the inlet concentration increased the AS outlet concentration, with
similar values for the treatments (median values of 0.13-0.15, 0.47-0.78, and
1.19-1.46 mg L(-1) at inlet concentrations in the order 10, 50, and 100 mg L(
1)). The shorter HRT led to significant differences among treatments in the
reduction of outlet concentration, the best result being given by the tanks
vegetated with Ma (A = 97.7 % with outlet concentration 0.35 mg L(-1)). After
treatments of the WCCW, the AS content was reduced almost completely, with
removal in the ranges 0.07-10.2 g m(-2) day(-1) for tanks planted with Ta, 0.10
9.1 g m(-2) day(-1) for Ma tanks, and 0.11-9.5 g m(-2) day(-1) for Cd tanks
depending on the inlet concentration.
PMID- 25586616
TI - Using stable isotope analysis in stream mesocosms to study potential effects of
environmental chemicals on aquatic-terrestrial subsidies.
AB - While recent research has provided evidence that the emergence of merolimnic
insects (species with an aquatic larval stage) provides a considerable energy
subsidy to riparian food webs, it has also shown that merolimnic insects may
serve as a vector for contaminants. Therefore, riparian food webs may be at risk
from either an aquatic-terrestrial transfer of contaminants or from the
contaminant-driven reductions of emerging merolimnic insects. The objective of
the present study was to develop an integrated stream mesocosms test design
capable of identifying these inter-ecosystem boundary effects and to provide a
comprehensive approach as a basis for ecotoxicological testing. We chose the
widely distributed web-building spider Tetragnatha extensa as a representative
species for riparian predators. Trophic aspects of riparian food webs were
investigated by stable isotope analysis of carbon (delta(13)C) and nitrogen
(delta(15)N). Utilization of stable isotope ratios provided detailed information
on the riparian food web structure and the dietary composition of T. extensa.
Merolimnic invertebrates (mainly Cloeon spp. and Chironomidae) were found to
contribute up to 71 % of T. extensa's diet, demonstrating their importance in
riparian food webs in ecotoxicological mesocosm testing. This study provides a
conceptual and methodological basis for assessing aquatic insect emergence
related pollutant transfer or effect translation from aquatic to adjacent
terrestrial systems.
PMID- 25586614
TI - Exercise protects against PCB-induced inflammation and associated cardiovascular
risk factors.
AB - Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that
contribute to the initiation of cardiovascular disease. Exercise has been shown
to reduce the risk of cardiovascular disease; however, whether exercise can
modulate PCB-induced vascular endothelial dysfunction and associated
cardiovascular risk factors is unknown. We examined the effects of exercise on
coplanar PCB-induced cardiovascular risk factors including oxidative stress,
inflammation, impaired glucose tolerance, hypercholesteremia, and endothelium
dependent relaxation. Male ApoE(-/-) mice were divided into sedentary and
exercise groups (voluntary wheel running) over a 12-week period. Half of each
group was exposed to vehicle or PCB 77 at weeks 1, 2, 9, and 10. For ex vivo
studies, male C57BL/6 mice exercised via voluntary wheel training for 5 weeks and
then were administered with vehicle or PCB 77 24 h before vascular reactivity
studies were performed. Exposure to coplanar PCB increased risk factors
associated with cardiovascular disease, including oxidative stress and systemic
inflammation, glucose intolerance, and hypercholesteremia. The 12-week exercise
intervention significantly reduced these proatherogenic parameters. Exercise also
upregulated antioxidant enzymes including phase II detoxification enzymes.
Sedentary animals exposed to PCB 77 exhibited endothelial dysfunction as
demonstrated by significant impairment of endothelium-dependent relaxation, which
was prevented by exercise. Lifestyle modifications such as aerobic exercise could
be utilized as a therapeutic approach for the prevention of adverse
cardiovascular health effects induced by environmental pollutants such as PCBs.
PMID- 25586618
TI - Dynamics of dissolved organic matter during four storm events in two forest
streams: source, export, and implications for harmful disinfection byproduct
formation.
AB - Dynamics of river dissolved organic matter (DOM) during storm events have
profound influences on the downstream aquatic ecosystem and drinking water
safety. This study investigated temporal variations in DOM during four storm
events in two forest headwater streams (the EH and JH brooks, South Korea) and
the impacts on the disinfection byproducts (DBPs) formation potential. The within
event variations of most DOM quantity parameters were similar to the flow rate in
the EH but not in the larger JH brook. The dissolved organic carbon (DOC) showed
clockwise and counterclockwise hysteresis with the flow rate in the EH and JH
brooks, respectively, indicating the importance of both flow path and DOM source
pool size in determining the effects of storm events. The stream DOM became less
aromatic/humified from the first to the last event in both brooks, probably due
to the increasing fresh plant pool and the decreasing leaf litter pool during the
course of rainy season. The DOC export during each event increased 1.3-2.7- and
1.1-7.0-fold by stormflows in the EH and JH brooks, respectively. The leaf litter
and soil together was the major DOM source, particularly during early events. The
enhanced DOM export probably increases the risks of DBPs formation in
disinfection, as indicated by a strong correlation observed between DOC and
trihalomethanes formation potential (THMFP). High correlations between two humic
like fluorescent components and THMFP further suggested the potential of
assessing THMFP with in situ fluorescence sensors during storms.
PMID- 25586617
TI - Cadmium-induced rhizospheric pH dynamics modulated nutrient acquisition and
physiological attributes of maize (Zea mays L.).
AB - Cadmium (Cd) is a highly mobile toxic element in soil-plant systems that
interferes with plant growth and nutrient acquisition by modulations in the
rhizospheric environment. The current study investigated the influence of maize
roots on the medium pH, alterations in nutrient uptake, and impact on the plant's
physiological attributes under Cd stress. Among the nine maize cultivars,
subjected to Cd stress (9.15 mg/kg of sand), one was identified as Cd tolerant
(3062-Pioneer) and the second as Cd sensitive (31P41-Pioneer). The selected maize
cultivars were grown in nutrient solutions supplemented with 0, 10, 20, 30, 40,
or 50 MUM CdCl2 under controlled conditions and a starting pH of 6.0. The
rhizospheric pH dynamics were monitored each day up to 3 days. Both cultivars
caused medium basification; however, the response was different at low (10 and 20
MUM) Cd treatments (sensitive cultivar caused medium basification) and at higher
(50 MUM) Cd treatment (tolerant cultivar caused medium basification).
Furthermore, higher Cd was accumulated by the sensitive cultivar which was
predominantly found in the roots. Higher Cd levels in the medium resulted in
increased uptake and translocation of both Cd and K (in the tolerant cultivar) or
only Cd (in the sensitive cultivar). Uptake of other nutrients (Ca, Zn, and Fe)
was antagonistically affected by Cd stress in both cultivars. Moreover, Cd stress
significantly impaired chlorophyll content, catalase activity, and total protein
content; irrespective of the genotype. The malondialdehyde (MDA) content was
found to increase, in both cultivars, together with Cd level. However, the extent
to which Cd interfered with the studied attributes was more pronounced in the
sensitive cultivar as compared to the tolerant one. It is concluded that the
maize roots responded to Cd stress by initiating modulations of medium pH which
might be dependent on Cd tolerance levels. The study results may help to develop
strategies to reduce Cd accumulation in maize and decontamination of metal
polluted soil sediments.
PMID- 25586619
TI - Photolysis degradation of polyaromatic hydrocarbons (PAHs) on surface sandy soil.
AB - Polycyclic aromatic hydrocarbons (PAHs) are potent environmental pollutants, and
some of them have been identified as carcinogenic and mutagenic. To advance the
knowledge of the environmental fate of PAHs, we systematically investigated the
influence of different UV wavelengths irradiation on photolysis of PAHs on sandy
soil under tow wavelengths (254 and 306 nm) UV irradiation for six PAHs. In
addition, kinetic model and influence of several parameters on PAHs photolysis
have been studied. The results obtained indicated that UV radiation with a
wavelength of 306 nm was more efficient in the photolysis of the polycyclic
aromatic hydrocarbons. Our results showed that fluoranthene (Flt) was the fastest
in decomposition, has the greatest value for the coefficient of photolysis (7.4 *
10(-3) h(-1)), and has less half-life, reaching 94 h when using a wavelength of
254 nm. The results indicated that the pyrene (Pyr) was more resistant to
photolysis in comparison with indeno(1,2,3-cd) pyrene (IP) and fluoranthene
(Flt). The results indicate that photolysis is a successful way to remediate the
six studied PAHs compounds.
PMID- 25586620
TI - Influence of dietary zinc and copper on apparent mineral retention and serum
biochemical indicators in young male mink (Mustela vison).
AB - An experiment was conducted in a 3 * 3 (Cu * Zn) factorial experiment based on a
completely randomized design to evaluate the effects of dietary copper and zinc
on apparent mineral retention and serum biochemical indicators in young male mink
on a corn-fish meal based diet. Animals were fed basal diets supplemented with Cu
from copper sulfate (CuSO4) and Zn from zinc sulfate (ZnSO4). Supplemental Cu
levels were 0, 15, and 30 mg/kg copper, respectively, while supplemental Zn
levels were 0, 150, and 300 mg/kg, respectively. A metabolism trial of 4 days was
conducted during the last week of experimental feeding. Blood samples were
collected via the toe clip to determine blood hematology and blood metabolites.
Copper excretion, retention, and digestibility were influenced by dietary copper
(P < 0.05), however, there was also a zinc-copper interaction. Copper
digestibility and retention were substantially reduced when zinc was added to the
low copper diet but showed little change with zinc supplementation of the high
copper diet. Both plasma Cu and plasma Zn were influenced by dietary level of the
respective mineral (P < 0.05). There was no influence of dietary copper on plasma
zinc; however, high Zn in the diet reduced plasma Cu concentrations. There was a
zinc-copper interaction for plasma Cu (P = 0.053). Cu-Zn superoxide dismutase (Cu
Zn SOD) activity tended to be influenced by dietary zinc (P = 0.065) and dietary
copper (P = 0.035). Dietary copper had a significant effect on ceruloplasmin
(CER) and triglyceride (TG) concentrations (P < 0.05). Our results show that
moderately high Zn in the diet (Zn:Cu ratio of 40:1) significantly reduce the
apparent Cu digestibility. Our results also show that moderately high Cu in the
diet increases Cu retention, but not reduces Zn absorption, and moderately high
Zn in the diet reduced plasma Cu concentrations and CER activity.
PMID- 25586621
TI - Efficacy of selenium from hydroponically produced selenium-enriched kale sprout
(Brassica oleracea var. alboglabra L.) in broilers.
AB - An experiment was conducted to determine the efficacy of Se from hydroponically
produced Se-enriched kale sprout (HPSeKS) on performance, carcass
characteristics, tissue Se concentration, and physiological responses of broilers
in comparison to that of Se from Se-enriched yeast and sodium selenite. Three
hundred and sixty male broilers, 10 days of age, were assigned to 6 groups, 4
replicates of 15 broilers each, according to the completely randomized design.
The dietary treatments were the following: T1: control diet; T2: control diet
plus 0.3 mg Se/kg from sodium selenite; T3: control diet plus 0.3 mg Se/kg from
Se-enriched yeast; and T4, T5, and T6: control diet plus 0.3, 1.0, and 2.0 mg
Se/kg from HPSeKS, respectively. The results found that dietary Se
supplementation did not (p > 0.05) alter performance and carcass characteristics
of broilers. Se supplementation increased (p < 0.05) Se concentrations in the
liver and kidney of broilers. Heart tissue Se concentration of broilers fed Se
from sodium selenite was lower (p < 0.05) than that of broilers fed Se from
HPSeKS and Se-enriched yeast. Selenium from HPSeKS increased higher (p < 0.05)
GSH-Px activity when compared to Se from sodium selenite and Se-enriched yeast.
The results indicated that the efficacy of Se from HPSeKS was comparable in
increasing tissue Se concentration, but higher in improving GSH-Px activity in
Rbc when compared to those of Se from Se-enriched yeast.
PMID- 25586622
TI - Zinc might prevent heat-induced hepatic injury by activating the Nrf2-antioxidant
in mice.
AB - Zinc (Zn) is generally known to be an essential trace element with growth
promoting and antioxidant activities. The present study was performed to clarify
the role of Zn in the livers of heat-treated mice. Eight-week-old male mice were
divided into control (Con), heat treatment (HT) and heat treatment plus zinc
groups (HT + Zn) and were fed diets containing 60, 60, or 300 mg/kg Zn (zinc
sulfate), respectively. After 30 days of feeding on their respective diets, the
control group was maintained at a controlled temperature (25 degrees C), whereas
the HT and HT + Zn groups were exposed to an elevated ambient temperature (40-42
degrees C) for 2 h each day. After heat exposure for seven consecutive days, sera
and liver tissues were collected. The mice in the HT group exhibited reduced
liver weights and lower hepatosomatic indices. Histological findings revealed
that the hepatocytes of the HT group were subjected to serious damage and
exhibited irregular arrangements and nuclear pyknosis. Moreover, in the HT group,
the hepatic malondialdehyde levels were significantly increased, while the serum
alkaline phosphatase levels, hepatic copper/zinc-superoxide dismutase (CuZn-SOD)
and glutathione peroxidase activities were significantly reduced compared to
those of the control group. However, in the HT + Zn group, the histomorphology of
the liver was restored, the serum aspartate aminotransferase (AST) level was
significantly decreased, and the hepatic CuZn-SOD activity was significantly
increased compared to the HT group. Furthermore, expressions of the hepatic Nrf2
protein and Nrf2, Keap1, and NQO1 genes in the HT + Zn group were not only higher
than the HT group but also higher than the control group. Zn might alleviate heat
induced hepatic injury as revealed by restored histomorphology and AST level. Our
results further suggest that Zn might exert its protective effects via the
activation of the Nrf2-antioxidant pathway.
PMID- 25586623
TI - Evaluation of lactate detection using selective multiple quantum coherence in
phantoms and brain tumours.
AB - Lactate is a product of glucose metabolism. In tumour tissues, which exhibit
enhanced glycolytic metabolism, lactate signals may be elevated, making lactate a
potential useful tumour biomarker. Methods of lactate quantitation are
complicated because of overlap between the lactate methyl doublet CH3 resonance
and a lipid resonance at 1.3 ppm. This study presents the use of a selective
homonuclear multiple quantum coherence transfer sequence (SelMQC-CSI), at 1.5 T,
to better quantify lactate in the presence of lipids. Work performed on phantoms
showed good lactate detection (49%) and lipid suppression (98%) efficiencies. To
evaluate the method in the brain, the sequence was tested on a group of 23
patients with treated brain tumours, either glioma (N=20) or secondary metastases
in the brain (N=3). Here it was proved to be of use in determining lactate
concentrations in vivo. Lactate was clearly seen in SelMQC spectra of glioma,
even in the presence of lipids, with high grade glioma (7.3 +/- 1.9 mM, mean +/-
standard deviation) having higher concentrations than low grade glioma (1.9 +/-
1.5 mM, p=0.048). Lactate was not seen in secondary metastases in the brain.
SelMQC-CSI is shown to be a useful technique for measuring lactate in tumours
whose signals are otherwise contaminated by lipid.
PMID- 25586624
TI - Long-term symptomatic relief of bullous keratopathy with amniotic membrane
transplant.
AB - The purpose of this study was to assess the long-term outcome of patients with
symptomatic bullous keratopathy after amniotic membrane transplant. A
retrospective cohort study includes that 20 patients with symptomatic bullous
keratopathy, who have underwent amniotic membrane transplant at the Department of
Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Prince of
Wales Hospital & Alice Ho Miu Ling Hospital, Hong Kong between 04/1998 and
06/2011, were invited back. Clinical examination was performed, including, pain
score assessment (pain score out of 10), epithelial healing, and vision. A total
of 21 eyes of 20 patients returned for our study. The majority of eyes
experienced pain reduction (94 %), with a significant mean pain score difference
of 6.8 +/- 2.6, 2-tail p < 0.001 (99 % CI 4.9-8.7). The mean pre-operative and
post-operative pain scores were 7.3 +/- 2.9 and 0.5 +/- 1.0, respectively. 16
eyes (76 %) were completely pain free, and 10 eyes (47 %) remained symptom free
after a mean follow-up of 39.0 +/- 36.3 months (range 5-171 months). The median
epithelial healing time was 2 weeks (range 1-20 weeks). Amniotic membrane
transplant may be considered as a longer-term treatment for bullous keratopathy
patients, especially in patients with poorer visual prognosis, but it may also be
used as an interim measure for patients awaiting corneal transplant.
PMID- 25586625
TI - Relapsing acute lymphoblastic leukemia presenting with a rapidly enlarging and
vision-threatening orbital mass.
AB - This case report describes a patient with known acute lymphoblastic leukemia
(ALL) presenting with a rapidly enlarging and vision-threatening orbital mass.
Orbital disease is rare in patients with ALL, and to our knowledge only six cases
have been previously described, five of which are in children. We describe a 36
year-old Caucasian female with known acute lymphoblastic leukemia who developed
markedly decreased visual acuity, proptosis, and elevated intraocular pressure
over the course of 12 h. She was treated with emergent surgical intervention
followed by intrathecal chemotherapy and intravenous steroids. Following medical
and surgical intervention, the patient demonstrated rapid resolution of symptoms
and a return to baseline visual acuity. The initial presentation of acute onset
proptosis with optic nerve compromise can be suggestive of infectious etiologies,
however, this case suggests caution in evaluation of patients with known systemic
malignancy, particularly ALL, as early intervention with systemic steroids and
surgery may result in return of visual function.
PMID- 25586626
TI - Pulmonary function and blood gases after gastric bypass and lifestyle
intervention: a comparative study.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Impaired lung function associated with
obesity improves with weight loss. WHAT THIS STUDY ADDS: This is the first study
to compare the effects of obesity surgery and intensive lifestyle intervention on
pulmonary function and arterial blood gases. Arterial oxygenation and pulmonary
function improved to a greater extent after gastric bypass than after lifestyle
intervention. The superiority of surgical treatment might be mediated by greater
weight loss after gastric bypass. Impaired lung function associated with obesity
improves with weight loss. The effects of obesity surgery and intensive lifestyle
intervention on pulmonary function and arterial blood gases have not previously
been subjected to comparative examination. In this 1-year non-randomized
controlled clinical trial (ClinicalTrials.gov identifier NCT00273104), 139
morbidly obese subjects (19-66 years, mean [standard deviation] body mass index
[BMI] 45.1 kg m(-2) [5.6], 107 women) were treated with either Roux-en-Y gastric
bypass surgery (n = 76) or intensive lifestyle intervention (n = 63). Mean weight
reduction was 30 (8)% and 8 (9)%, respectively. Dynamic and static lung volumes,
gas diffusing capacity and arterial blood gases were measured. Compared with
lifestyle intervention, surgery resulted in a significantly greater increase in
forced vital capacity (mean [95% confidence interval] between-group difference, 7
[4-10]%), forced expiratory volume in 1 s (7 [5-9]%), total lung capacity (5 [1
8]%), vital capacity (7 [4-9]%), functional residual capacity (18 [12-24]%),
expiratory reserve volume (48 [30-66]%) and partial pressure of oxygen in
arterial blood (0.5 [0.0-1.0] kPa). These associations either disappeared or
diminished after adjusting for weight loss. Reduced central adiposity (waist
circumference and waist-to-hip ratio) and systemic inflammation (C-reactive
protein and adiponectin) had no effect on pulmonary function beyond the effect of
reduced general adiposity (BMI). In morbidly obese subjects, gastric bypass
surgery is more effective than lifestyle intervention at improving arterial
oxygenation and pulmonary function. The effect might be mediated by greater
weight loss after surgical treatment.
PMID- 25586627
TI - Self-reported symptoms of adult attention deficit hyperactivity disorder among
obese patients seeking bariatric surgery and its relation to alcohol consumption,
disordered eating and gender.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Symptoms of adult attention deficit
hyperactivity disorder (ADHD) are common among people with obesity. Symptoms of
ADHD are associated with other impulsive behaviours. Impulsivity can manifest
differently in women and men. WHAT THIS STUDY ADDS: The prevalence of ADHD
symptoms was equal in both sexes in this patient group. ADHD symptoms were
associated with hazardous alcohol consumption in men but not in women. It may be
important to investigate several comorbid conditions simultaneously instead of a
single diagnosis. Eating disorders and adult attention deficit hyperactivity
disorder (ADHD), both characterized by deficits in impulse control, are common
among bariatric surgery patients. Previous studies in other groups have found
gender differences in how symptoms of ADHD and eating disorders manifest as women
show more disordered eating and men show more risk consumption of alcohol. In the
present study, the association between symptoms of adult ADHD, eating disorders
and hazardous alcohol consumption was investigated, while considering gender
differences. Self-report questionnaires were obtained from 276 bariatric surgery
patients 3-6 months before surgery. The prevalence rates of adult ADHD and binge
eating disorder (BED) were 8.6% and 6.3%, respectively, with no evidence of
gender difference in the prevalence rates. Hazardous alcohol consumption was
reported by a significantly larger portion of men (16.9%) than women (8.6%).
There was an association between adult ADHD and both BED and hazardous alcohol
consumption. However, symptoms of adult ADHD were associated with hazardous
alcohol consumption in men but not in women. Our results suggest gender
differences in hazardous alcohol consumption and self-reported symptoms of
disordered eating despite similar prevalence rate of BED, but no gender
difference in symptoms of adult ADHD. Finally, as the associations between these
variables seem to be different in women and men, future studies need to
investigate potential gender-specific functional and temporal relations between
these variables.
PMID- 25586628
TI - Relationships between total and regional adiposity and epicardial fat in obese
women: how can dual-energy X-ray absorptiometry be associated with
echocardiographic epicardial fat measurements?
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity is an increasingly prevalent
metabolic disorder and it is associated with a large number of comorbidities,
including cardiovascular diseases. Adipose tissue is an active endocrine organ
and its ectopic depots and distribution have different metabolic meanings on
risks for health; as a matter of fact, epicardial fat seems to play a specific
role in cardiovascular diseases. The use of dual-energy X-ray absorptiometry
(DXA) to evaluate and follow-up patients affected by obesity is becoming a very
important point in the management of the disease. WHAT THIS STUDY ADDS: An
investigation of the association between epicardial fat and regional adiposity by
DXA in female obese patients. The total amount of central (trunk) fat mass is
more strongly correlated than android visceral fat mass to epicardial thickness
in obese women. In the interpretation of whole-body DXA data, physician should
consider trunk fat mass for good and independent predictivity on epicardial fat
depots. Our aim was to analyse in a population of obese women the relationship
between the amount of epicardial fat as measured by transthoracic
echocardiography (US) and the parameters of regional adiposity by dual-energy X
ray absorptiometry (DXA), with particular reference to a new software for
visceral fat assessment and to a new 'heart-suited' regions of interests (ROIs).
Sixty patients who satisfied technical inclusion criteria underwent whole-body
DXA scan and US on the same day. Total and android fat mass (FM) and FM
percentage (FM%) were considered as well as visceral fat (VAT) subcompartment in
the android region; moreover, six new ROIs were designed on whole-body DXA images
for the investigation of adiposity parameters at heart level. US provided
epicardial fat thickness (EPI-thickness) and area (EPI-area), as measured
following previously validated methods. Body mass index (BMI), gynoid and lower
limbs (FM and FM%) were found not statistically correlated with EPI-thickness.
The highest correlation was achieved by trunk FM (and FM%, with r = 0.544 and
0.480 respectively, P < 0.001), followed by ROI-1 FM (ROI-1 was drawn following
thoroughly the cardiac profile), and android FM. Multivariate analysis including
age, weight, BMI, trunk FM and the new ROIs (added one by one), retained in the
final model trunk FM. Correlations of DXA with EPI-area were superimposable. In
obese women, VAT or other new-designed ROIs are not better correlated than
traditional ROIs (i.e. trunk) with epicardial fat amount.
PMID- 25586629
TI - Behaviours associated with weight loss maintenance and regaining in a
Mediterranean population sample. A qualitative study.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In the US, the National Weight Control
Registry revealed lifestyle behaviours shared by weight loss maintainers. In the
US and the UK, qualitative studies compared the experiences of weight loss
maintainers and regainers. High rates of physical activity, a low-energy/low-fat
diet, weight self-monitoring, breakfast consumption and flexible control of
eating are well-established maintenance behaviours. WHAT THIS STUDY ADDS: The
Mediterranean lifestyle has not been studied relative to weight loss maintenance.
This study focused on a sample of Greek maintainers and regainers. Maintainers
emphasized home-cooked meals; their diet does not appear to be low-fat, as home
cooked Greek meals are rich in olive oil. Having a small dinner is a common
strategy among maintainers. Health motives were not mentioned by maintainers.
Maintainers, but not regainers, appeared to compensate for emotional eating.
Weight loss maintenance is imperative to successful obesity treatment. We
qualitatively explored lifestyle behaviours associated with weight regulation, in
a sample of Greek volunteers who had lost weight and either maintained or
regained it. A 10% intentional loss maintained for at least one year was
considered successful maintenance. Volunteers (n = 44, 41% men) formed eight
focus groups, four of maintainers and four of regainers. Questions regarded
weight loss, weight maintenance or regaining, and beliefs on weight maintenance
and regaining. All discussions were tape recorded. Maintainers lost weight on
their own, whereas regainers sought professional help. Maintainers exercised
during both the loss and maintenance phases, whereas regainers showed
inconsistent physical activity levels. Health motives for weight loss were
mentioned only by regainers. Emotional eating was a common barrier, but only
maintainers compensated for it. Maintainers continuously applied specific
strategies to maintain their weight: emphasizing home-cooked meals, high eating
frequency, a small dinner, portion size regulation, and sweets' intake
regulation. Regainers considered the behaviours leading to weight loss different
from their normal lifestyle, and resumed their old habits when the diet was over.
However, both groups believed that for long-term success, lifestyle changes need
to be permanent.
PMID- 25586630
TI - Weight loss for individuals with type 2 diabetes following a very-low-calorie
diet in a community-based setting with trained facilitators for 12 weeks.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Approximately 80% of people with type 2
diabetes mellitus (T2DM) are overweight or obese. Weight loss produces numerous
benefits in T2DM. People with T2DM have difficulty losing and maintaining weight.
WHAT THIS STUDY ADDS: Provision of a very-low-calorie diet (VLCD) with group
support and behaviour therapy for patients with T2DM is feasible within a
community-based setting with trained facilitators. VLCD approaches for weight
management in T2DM can achieve more than 90% of weight loss as compared with
obese individuals without T2DM. Identification of the need to investigate the
full impact of this approach in patients with T2DM by assessing changes in
glycaemia, liver function and medication. Approximately 80% of people with type 2
diabetes mellitus (T2DM) are overweight or obese, and obesity compounds the
cardiovascular risk of T2DM. The aim of this retrospective study was twofold:
first, to investigate whether a 12-week community-based very-low-calorie diet
(VLCD) programme can result in important weight loss; and second, to investigate
any potential difference in the weight loss achieved using this community-based
approach in individuals with and without T2DM. Three hundred and fifty-five
participants with T2DM were matched for age, body mass index (BMI) and gender to
participants without T2DM (total cohort comprised 204 males: 506 females (mean +/
standard deviation); age (years) 54.0 +/- 9.1; BMI (kg m(-2) ) 41.6 +/- 8.1;
weight (kg) 116.1 +/- 25.1). The programme included a daily intake of 550 kcal in
addition to group support and behaviour therapy provided by trained facilitators
within a community-based setting. After 12 weeks, there was significant weight
loss within each group when compared with baseline (T2DM: 115.0 +/- 24.4 kg vs.
96.7 +/- 21.4 kg, P < 0.0001; non-T2DM: 117.2 +/- 25.8 kg vs. 97.3 +/- 22.2 kg, P
< 0.0001). At 12 weeks, weight change (-18.3 +/- 7.3 kg vs. -19.9 +/- 7.0 kg, P =
0.012) and BMI change (-6.7 +/- 2.9 kg m(-2) vs. -7.1 +/- 2.1 kg m(-2) , P =
0.011) were significantly less in the T2DM group when compared with the non-T2DM
group. Our results suggest that the use of VLCD approaches for weight management
in T2DM can achieve more than 90% of the weight loss seen in obese individuals
without T2DM.
PMID- 25586631
TI - Connecting tube colonic erosion and gastrocolic fistula formation following late
gastric band erosion.
AB - Band erosion is a rare complication of laparoscopic adjustable gastric banding
(LAGB) with a reported prevalence varying from 0.3% to 14%. Intraluminal colonic
erosion of the connecting tube is very rare, as only isolated cases have been
described. Consequently, simultaneous gastric band erosion and connecting tube
colonic erosion is an extremely rare event. Herein, we present a case of a woman
with morbid obesity, who submitted to LABG 4 years ago. The patient presented
with symptoms and signs of right lower quadrant peritonitis. Computed tomography
(CT) demonstrated migration of the band into the gastric lumen, inflammation
around the intra-abdominal course of the connecting tube and an inflammatory mass
surrounding the tube at the right lower quadrant. Laparotomy revealed the eroded
band, the eroded transverse colon from the connecting tube, a gastrocolic fistula
along the course of the tube and a right lower quadrant phlegmon. The connecting
tube was mobilized from the surrounding adherent tissues, the gastric band
removed, the stomach and colon walls closed, and the gastrocolic fistula excised.
To our knowledge this is the second case of concurrent band erosion and
connecting tube colonic erosion along with gastrocolic fistula formation in a
patient with morbid obesity treated with LAGB.
PMID- 25586633
TI - Surgical cutdown versus percutaneous access in transfemoral transcatheter aortic
valve implantation: Insights from the Brazilian TAVI registry.
AB - OBJECTIVE: To compare the 1-year outcomes of complete percutaneous approach
versus surgical vascular approach for transfemoral transcatheter aortic valve
implantation (TAVI), among "real-world" patients from the multi-center Brazilian
TAVI registry. BACKGROUND: Vascular access still remains a major challenge for
TAVI via transfemoral approach. Vascular access through complete percutaneous
approaches or through open surgical vascular techniques seems to be acutely
similar. However, the long-term outcomes of both techniques remain poorly
described. METHODS: The study population comprised all patients treated via
transfemoral route in the Brazilian TAVI registry, a "real-world", nation-based,
multi-center study. Patients were divided according to the initial vascular
access approach (percutaneous vs. surgical) and clinically followed-up for 1
year. The primary endpoint was the incidence of combined adverse events all-cause
mortality, life-threatening bleeding, and/or major vascular complication at 1
year. RESULTS: A total of 402 patients from 18 centers comprised the study
population (percutaneous approach in 182 patients; surgical cutdown approach 220
patients). The incidence of combined adverse events was not different in the
percutaneous and the surgical groups at 30 days (17.6% vs. 16.3%; P = 0.8) and at
1 year (primary endpoint) (30.9% vs. 28.8%; P = 0.8). Also, the study groups
overall were comparable regarding the incidence of each individual safety adverse
events at 30 days and at 1 year. CONCLUSION: Total percutaneous techniques or
surgical cutdown and closure may provide similar safety and effectiveness during
the first year of follow-up in patients undergoing transfemoral TAVI.
PMID- 25586635
TI - Microarray technology to investigate genes associated with papillary thyroid
carcinoma.
AB - DNA microarray data on thyroid tissue from patients with papillary thyroid
carcinoma (PTC) and from healthy controls were compared in order to investigate
the regulatory genes and uncover the underlying regulatory network in PTC. The
DNA microarray data set, GSE3678, was downloaded from Gene Expression Omnibus
database. This included seven thyroid tissue samples from patients with PTC and
seven samples from healthy controls. Raw data were processed and differentially
expressed genes (DEGs) were identified using corresponding R packages. Gene
regulation analysis was conducted using TRANSFAC(r) and TRED. A total of 171 DEGs
were obtained. A regulatory network was then established, using 104 of the DEGs.
Subsequently, pathway enrichment analyses of the genes were conducted using
Database for Annotation, Visualization and Integrated Discovery (DAVID) online
tool. Three differentially expressed transcription factors were identified:
Trefoil factor 3, cut-like homeobox 2 and forkhead box protein A2. The most
significant pathways involving the 104 DEGs were pathways involved in cancer.
Biological process analysis using DAVID, suggested that these genes were
associated with the positive regulation of gene expression, gene transcription
and metabolic processes. The present study identified a range of genes associated
with the development of PTC. The results of the present study were beneficial for
understanding the regulatory mechanisms involved in PTC, and for developing
clinical diagnostic and therapeutic approaches for this disease.
PMID- 25586634
TI - Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala Induces
both Anxiety and Depressive-Like Symptoms.
AB - Depression has been associated with abnormalities in glutamatergic
neurotransmission and decreased astrocyte number in limbic areas. We previously
demonstrated that global and prefrontal cortical blockade of the astrocytic
glutamate transporter (GLT-1) induces anhedonia and c-Fos expression in areas
that regulate anxiety, including the central amygdala (CEA). Given the role of
the amygdala in anxiety and the high degree of comorbidity between anxiety and
depression, we hypothesized that GLT-1 blockade in the CEA would induce symptoms
of anhedonia and anxiety in rats. We microinjected the GLT-1 inhibitor,
dihydrokainic acid (DHK), into the CEA and examined effects on intracranial self
stimulation (ICSS) as an index of hedonic state, and on behavior in two anxiety
paradigms, elevated plus maze (EPM) and fear conditioning. At lower doses, intra
CEA DHK produced modest increases in ICSS responding (T0). Higher doses resulted
in complete cessation of responding for 15 min, suggesting an anhedonic or
depressive-like effect. Intra-CEA DHK also increased anxiety-like behavior such
that percent time in the open arms and total entries were decreased in the EPM
and acquisition of freezing behavior to the tone was increased in a fear
conditioning paradigm. These effects did not appear to be explained by non
specific changes in activity, because effects on fear conditioning were assessed
in a drug-free state, and a separate activity test showed no significant effects
of intra-CEA DHK on locomotion. Taken together, these studies suggest that
blockade of GLT-1 in the CEA is sufficient to induce both anhedonia and anxiety
and therefore that a lack of glutamate uptake resulting from glial deficits may
contribute to the comorbidity of depression and anxiety.
PMID- 25586636
TI - Dietary anthocyanins as a complementary medicinal approach for management of
inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD) is thought to result from a chronic or relapsing
activation of the immune system in the GI tract. A growing body of evidence
confirms the health benefits of dietary anthocyanins as plant-derived natural
agents. The aim of this review is to provide an overview of several natural
products rich in anthocyanins used worldwide for the treatment of IBD.
Anthocyanins possess both protective and therapeutic functions in the management
of IBD by alleviating oxidative stress processes, cytoprotective functions,
downregulation of inflammatory cytokines and suppressing cellular signaling
pathways of inflammatory processes. In conclusion, the consumption of anthocyanin
rich natural formulations must be promoted on the basis of their possible
function in the prevention and treatment of gastrointestinal inflammatory
disorders.
PMID- 25586637
TI - Heat stroke: typical MRI and (1)H-MRS features.
AB - Heat stroke (HS) is a life-threatening condition characterized by severe
hyperthermia associated with central nervous system abnormalities. We present two
interesting cases of HS with symmetric lesions in the dentate nuclei and
cerebellar peduncles. Typical MRI and (1)H-MRS features including follow-up
studies are illustrated.
PMID- 25586638
TI - Sex-sorted canine sperm cryopreservation: limits and procedural considerations.
AB - The aim of this study was to define a protocol to store dog sperm before and
after sorting to obtain an insemination dose sufficient to allow the conception
by artificial insemination. Experiment 1 and 2 were performed to evaluate the
more appropriate extender for preserving at room temperature dog sperm before and
after sorting. Four extenders were tested: (1) Tris-fructose-citrate (TFC), (2)
Tris-glucose-citrate (TGC), (3) modified Tyrode's albumin lactate pyruvate medium
(mTALP), and (4) third fraction of the ejaculate (after centrifugation at 5000* g
for 10 minutes; III FRAC). Experiment 3 and 4 were performed to evaluate the
ability of dog semen to withstand sex sorting and freezing/thawing. Modified
Tyrode's albumin lactate pyruvate medium was the best extender for canine sperm
storage at room temperature (20 degrees C-25 degrees C) before (total motility:
TFC, 8.3 +/- 1.7; TGC, 50.0 +/- 11.5; mTALP, 70.0 +/- 0.1; III FRAC, 25.0 +/- 1
0.4; P < 0.05) and after sorting (total motility: TFC, 7.3 +/- 1.5; TGC, 10.3 +/-
1.5; mTALP, 33.3 +/- 6.7; III FRAC, 8.7 +/- 5.8; P < 0.05), even if at 24-hour
sorted sperm quality was impaired in all extenders tested herein. Sperm quality
decreased after sorting (total motility: control, 92.5 +/- 0.9; sorted, 52.9 +/-
6.0; P < 0.05) and, especially, after freezing/thawing (total motility: frozen
control, 25.7 +/- 4.1; frozen sorted, 2.4 +/- 1.2; P < 0.05). In conclusion,
mTALP is an appropriate medium for canine sperm storage before and soon after
sorting (hours), but a long storage period of sexed sperm at room temperature is
not adequate. Cryopreservation greatly impaired sperm quality, and further
studies are needed to optimize the freezing protocol for sexed dog sperm.
PMID- 25586639
TI - Production of lion (Panthera leo) blastocysts after in vitro maturation of
oocytes and intracytoplasmic sperm injection.
AB - Assisted reproductive techniques are becoming widely applied to the breeding of
endangered species, but establishing reliable protocols for the production of
embryos in vitro is challenging because of the scarcity of sample material. In
our study, we applied an assisted reproductive technique protocol for IVM and
intracytoplasmic sperm injection (ICSI), developed in the domestic cat, to
oocytes retrieved from ovaries of four 2-year-old lionesses (Panthera leo) eight
hours postmortem. In total, 68 cumulus-oocyte complexes of good quality were
randomly distributed and cultured for 32 to 34 hours in two different maturation
culture media, consisting of Medium 199 with Earle's salts, 3 mg/mL BSA, 0.1
mg/mL cysteine, 1.4 mg/mL sodium pyruvate, 0.6 mg/mL sodium lactate, 0.15 mg/mL l
glutamine, and 0.055 mg/mL gentamicin. Hormonal supplementation of IVM_1 was 0.02
IU/mL FSH and 0.05 IU/mL LH; IVM_2 consisted of 1.64 IU/mL FSH, 1.06 IU/mL LH,
and 1 MUg/mL 17beta-estradiol. Differences in hormonal supplementation did not
produce significant differences in oocyte maturation rates, which were 39.4% in
IVM_1 and 34.3% in IVM_2. Matured oocytes were microinjected with homologous
frozen-thawed spermatozoa, and subsequent cleavage rates were 30.8% and 58.3%,
respectively. Half of the embryos derived from oocytes matured in IVM_1 developed
into blastocysts, whereas only 28.6% of embryos from oocytes matured in IVM_2
reached the blastocyst stage. Morula stages were present from Day 6 onward, and
blastocyst stages from Day 9 on, indicating a slower developmental speed in
comparison with domestic cats. This is the first report of in vitro-produced
blastocysts using ICSI in the lion, and the results report that IVM and ICSI can
be successfully performed with cumulus-oocyte complexes retrieved from ovaries
after eight hours of shipping, obtaining competent embryos in culture.
PMID- 25586640
TI - An in vitro investigation of the actions of reproductive hormones on the cervix
of the ewe in the follicular stage: the effects of 17beta-estradiol, oxytocin,
FSH, and arachidonic acid on the cervical pathway for the synthesis of
prostaglandin E2.
AB - During the periovulatory period, the cervix of the ewe relaxes and this mechanism
is thought to be mediated by oxytocin and prostaglandin E2 (PGE2) in response to
increased concentrations of 17beta-estradiol and perhaps FSH. The aim of the
study was to determine the in vitro effects of 17beta-estradiol, FSH, oxytocin,
and arachidonic acid (AA) on the synthesis of PGE2 and on the expression of
oxytocin receptor (OTR), cytoplasmic phospholipase A2 (cPLA2), and cyclooxygenase
2 (COX-2) in explants of cervical tissue collected from ewes in the periovulatory
phase of the estrous cycle. Cervical minces from ewes in the follicular phase of
the estrous cycle were cultured in supplemented Eagle's Minimum Essential Medium
for 48 hours with 17beta-estradiol, FSH, oxytocin, or AA. After incubation, the
tissue was stored at -80 degrees C and the media at -20 degrees C. Western
immunoblotting was used to determine relative levels of OTR, cPLA2, and COX-2 in
cervical tissue, and the media was analyzed by RIA, to determine the
concentration of PGE2. The addition of 17beta-estradiol increased the
concentration of PGE2 in the media (P = 0.001), the levels of COX-2 (P = 0.02)
and OTR (P = 0.006) but not those of cPLA2 (P = 0.15). The addition of FSH
increased the levels of COX-2 (P = 0.01) but, it had no effect on the
concentration of PGE2 (P = 0.08) or on the levels of OTR (P = 0.07) and cPLA2 (P
= 0.15). Oxytocin did not increase the levels of COX-2 (P = 0.38) but increased
those of OTR (P = 0.001) and cPLA2 (P = 0.01) but not on the concentration of
PGE2 in the media. Arachidonic acid increased the levels of cPLA2 (P = 0.01) and
those of COX-2 (P = 0.02) but not the concentration of PGE2 in the media. Our
findings suggest that the PGE2-mediated mechanisms of cervical relaxation in the
ewe during the follicular phase are stimulated by FSH, 17beta-estradiol,
oxytocin, and AA. They all appear to act by inducing receptors and enzymes along
the synthetic pathway for PGE2.
PMID- 25586642
TI - Fringing reefs exposed to different levels of eutrophication and sedimentation
can support similar benthic communities.
AB - Benthic communities are sensitive to anthropogenic disturbances which can result
in changes in species assemblages. A spatio-temporal survey of environmental
parameters was conducted over an 18-month period on four different fringing reefs
of Moorea, French Polynesia, with unusual vs. frequent human pressures. This
survey included assessment of biological, chemical, and physical parameters.
First, the results showed a surprising lack of a seasonal trend, which was likely
obscured by short-term variability in lagoons. More frequent sampling periods
would likely improve the evaluation of a seasonal effect on biological and
ecological processes. Second, the three reef habitats studied that were dominated
by corals were highly stable, despite displaying antagonistic environmental
conditions through eutrophication and sedimentation gradients, whereas the reef
dominated by macroalgae was relatively unstable. Altogether, our data challenge
the paradigm of labelling environmental parameters such as turbidity,
sedimentation, and nutrient-richness as stress indicators.
PMID- 25586641
TI - Optimizing cofactor availability for the production of recombinant heme
peroxidase in Pichia pastoris.
AB - BACKGROUND: Insufficient incorporation of heme is considered a central impeding
cause in the recombinant production of active heme proteins. Currently, two
approaches are commonly taken to overcome this bottleneck; metabolic engineering
of the heme biosynthesis pathway in the host organism to enhance intracellular
heme production, and supplementation of the growth medium with the desired
cofactor or precursors thereof to allow saturation of recombinantly produced apo
forms of the target protein. In this study, we investigated the effect of both,
pathway engineering and medium supplementation, to optimize the recombinant
production of the heme protein horseradish peroxidase in the yeast Pichia
pastoris. RESULTS: In contrast to studies with other hosts, co-overexpression of
genes of the endogenous heme biosynthesis pathway did not improve the recombinant
production of active heme protein. However, medium supplementation with hemin
proved to be an efficient strategy to increase the yield of active enzyme,
whereas supplementation with the commonly used precursor 5-aminolevulinic acid
did not affect target protein yield. CONCLUSIONS: The yield of active recombinant
heme peroxidase from P. pastoris can be easily enhanced by supplementation of the
cultivation medium with hemin. Thereby, secreted apo-species of the target
protein are effectively saturated with cofactor, maximizing the yield of target
enzyme activity.
PMID- 25586644
TI - Ozonated saline shows activity against planktonic and biofilm growing
Staphylococcus aureus in vitro: a potential irrigant for infected wounds.
AB - Infections associated with deep wounds require extensive surgical and medical
care. New adjunctive treatments are required to aid in the eradication of the
bacterial biofilms found on infected wounds and, in particular, any underlying
hardware. Ozone has been used as a safe and efficient disinfectant in water
treatment plants for many years. The purpose of this study is to investigate the
anti-biofilm potential of ozonated saline against biofilms of Staphylococcus
aureus, a microorganism commonly implicated in wound infections. A custom-made
bacterial biofilm bioreactor was used to grow S. aureus biofilms on discs of
medical grade titanium alloy. An ozone generator was connected in-line and
biofilms and planktonic bacteria were exposed to ozone in saline. Cytotoxicity
was assessed against primary ovine osteoblasts in the same system. In tests
against planktonic S. aureus, a 99% reduction in bacterial numbers was detected
within 15 minutes of exposure. S. aureus biofilms were significantly more
resistant to ozone, although complete eradication of the biofilm was eventually
achieved within 5 hours. Ozonated saline was not found to be cytotoxic to primary
ovine osteoblasts. Ozonated saline may be suitable as an adjuvant therapy to
treat patients as an instillation fluid for wound irrigation and sterilisation.
PMID- 25586643
TI - Signaling between two interacting sensor kinases promotes biofilms and
colonization by a bacterial symbiont.
AB - Cells acclimate to fluctuating environments by utilizing sensory circuits. One
common sensory pathway used by bacteria is two-component signaling (TCS),
composed of an environmental sensor [the sensor kinase (SK)] and a cognate,
intracellular effector [the response regulator (RR)]. The squid symbiont Vibrio
fischeri uses an elaborate TCS phosphorelay containing a hybrid SK, RscS, and two
RRs, SypE and SypG, to control biofilm formation and host colonization. Here, we
found that another hybrid SK, SypF, was essential for biofilms by functioning
downstream of RscS to directly control SypE and SypG. Surprisingly, although wild
type SypF functioned as an SK in vitro, this activity was dispensable for
colonization. In fact, only a single non-enzymatic domain within SypF, the HPt
domain, was critical in vivo. Remarkably, this domain within SypF interacted with
RscS to permit a bypass of RscS's own HPt domain and SypF's enzymatic function.
This represents the first in vivo example of a functional SK that exploits the
enzymatic activity of another SK, an adaptation that demonstrates the elegant
plasticity in the arrangement of TCS regulators.
PMID- 25586645
TI - Challenges in measuring the societal value of orphan drugs: insights from a
canadian stated preference survey.
AB - BACKGROUND: Expensive drugs for rare diseases (i.e. orphan drugs) often do not
meet traditional cost-effectiveness criteria and thus put further strain on
limited healthcare budgets. Failing to provide medically necessary care to
patients, however, violates one of the underlying tenets of most public health
insurance systems-equity. This has led payers to consider the value that society
places on the treatment of rare diseases, given the opportunity cost, when
deciding on whether to fund specific treatments. AIMS: In this article we aim to
illustrate two factors that make the measurement of societal value in this area
particularly difficult: the low level of public awareness of, and engagement
with, the orphan-drug issue, and the 'zero-sum' framing commonly used to describe
the policy challenge posed by orphan drugs. METHOD: We illustrate these
challenges using data from an original survey of 2,005 Canadian adults.
Respondents completed two tasks in which they were asked to choose between
funding the treatment of patients suffering from either rare or common diseases.
RESULTS: Respondents were more likely to display choice aversion and unstable
preferences if they had not completed a university degree and when a 'zero-sum'
frame was used to introduce the choice sets. CONCLUSIONS: The results suggest
that studies in which the stated opportunity costs of funding orphan drugs focus
exclusively on reductions in funding for other drugs or treatments may only
provide a limited understanding of citizens' policy preferences in the area of
rare diseases.
PMID- 25586646
TI - Measuring the Preferences of Homeless Women for Cervical Cancer Screening
Interventions: Development of a Best-Worst Scaling Survey.
AB - OBJECTIVE: Despite having multiple risk factors, women experiencing homelessness
are screened for cervical cancer at a lower rate than women in the general US
population. We report on the design of a stated preference study to assess
homeless women's preferences for cervical cancer screening interventions, to
inform efforts to overcome this disparity. METHODS: We conducted focus groups
with homeless women (n = 8) on cervical cancer screening decisions and analyzed
the data using thematic analysis. We applied inclusion criteria to select factors
for a stated preference survey: importance to women, relevance to providers,
feasibility, and consistency with clinical experience. We conducted pretests (n =
35) to assess survey procedures (functionality, recruitment, administration) and
content (understanding, comprehension, wording/language, length). RESULTS: We
chose best-worst scaling (BWS)-also known as object scaling-to identify decision
relevant screening intervention factors. We chose an experimental design with 11
"objects" (i.e., factors relevant to women's screening decision) presented in 11
subsets of five objects each. Of 25 objects initially identified, we selected 11
for the BWS instrument: provider-related factors: attitude, familiarity, and
gender; setting-related factors: acceptance and cost; procedure-related factors:
explanation during visit and timing/convenience of visit; personal fears and
barriers: concerns about hygiene, addiction, and delivery/fear of results; and a
general factor of feeling overwhelmed. CONCLUSION: Good practices for the
development of stated preference surveys include considered assessment of the
experimental design that is used and the preference factors that are included,
and pretesting of the presentation format. We demonstrate the development of a
BWS study of homeless women's cervical cancer screening intervention preferences.
Subsequent research will identify screening priorities to inform intervention
design.
PMID- 25586647
TI - The prevalence of Hymenolepis nana among preschool children of displacement
communities in Khartoum state, Sudan: a cross-sectional study.
AB - BACKGROUND: Hymenolepis nana is among the most common intestinal parasitic
infections causing a public health threat in poor communities in Sub-Saharan
Africa. The present study was conducted to determine the prevalence of H. nana
infections and associated risk factors among preschool children of displacement
communities in Khartoum state, Sudan. METHODS: A cross-sectional survey was
conducted in May 2013 in displacement camps, Khartoum state, Sudan. A simple
random sample of preschool children from the displacement camps, aged between 1
and 5 years, were included. Information was collected by presenting a
questionnaire and taking 500 fresh stool specimens which were examined
microscopically for the presence of eggs, using direct saline and formal-ether
concentration techniques. RESULTS: The prevalence of H. nana was determined to be
32.6% (163/500), 95% CI (28.5%-36.9%). Infections of H. nana were more prevalent
among males than females, and this association was statistically significant (P <
0.001, OR = 2.125, 95% CI = 1.452-3.108). H. nana infections were significantly
prevalent among the older age group (2.6-5.0 years) (P < 0.001, OR = 2.909, 95%
CI = 1.914-4.420). Approximately 76.7% of infected preschool children had
diarrhea and it was significantly associated with H. nana infection (P < 0.001,
OR = 9.45, 95% CI = 6.10-14.64). None of the preschool children had access to a
clean water supply. No significant association was found between use of latrines
and infections of H. nana (P = 0.56, OR = 0.880, 95% CI = 0.73-1.763).
CONCLUSIONS: There was a high prevalence rate of H. nana infection among
preschool children of displacement camps in Khartoum state, Sudan. Being male,
aged between 2.6 and 5.0 years, and having diarrhea were identified as important
risk factors for H. nana infection. Measures including health education,
environmental hygiene, water supply and treatment should be taken into account to
reduce the high prevalence of H. nana.
PMID- 25586649
TI - A LINE-1-encoded reverse transcriptase-dependent regulatory mechanism is active
in embryogenesis and tumorigenesis.
AB - LINE-1 (long interspersed nuclear elements) retrotransposons constitute a large
family of retrotransposable elements, accounting for 17% of the human genome.
They encode proteins required for their own mobilization, including a reverse
transcriptase (RT) enzyme highly expressed in mouse embryos and mouse and human
cancer cells and repressed in somatic differentiated healthy cells. We have found
that reverse transcription takes place in early murine embryos, yielding an
increase in LINE-1 copy number during preimplantation development, which also
occurs in tumor progression. RT inhibition irreversibly arrests embryo
development, reduces cancer cell proliferation, promotes differentiation,
antagonizes tumor growth, and causes a global reprogramming of transcription
profiles. These results strongly suggest that a previously unrecognized RT
dependent regulatory mechanism operates during preimplantation development, is
repressed during differentiation to normal tissues, and, when erroneously
reactivated in adult life, promotes cell transformation and cancer progression by
"resurrecting" embryonic transcriptional pathways. The RT-dependent mechanism
emerges as a major source of genetic and epigenetic changes with physiological,
pathological, and evolutionary implications.
PMID- 25586648
TI - A secondary dengue 4 infection in a traveler returning from Haiti confirmed by
virus isolation, complete genome sequencing and neutralisation assay: a brief
report.
AB - Here we report the clinical and laboratory findings of a dengue 4 virus (DENV)
secondary infection in a patient returning from Haiti to France. The diagnostic
of acute DEN-4 virus infection was demonstrated by (i) the presence of DEN-4 RNA
in two successive serum samples, (ii) the isolation of a DEN-4 virus in Vero
cells and subsequent identification of subtype IIb through complete genome
sequencing, (iii) the presence of dengue NS1 antigen, (iv) the seroconversion
with detection of dengue IgM in the second serum while negative in the first
serum. The diagnosis of secondary dengue episode was demonstrated by (i) the
presence of dengue IgG in the early serum, and (ii) the demonstration that
neutralising antibodies against DEN-3 were present at the acute stage of the
disease. Next-generation sequencing has a primary role to play in phylogeographic
studies including database sequences, sequences from imported cases, and
sequences from autochthonous cases.
PMID- 25586650
TI - Synergistic strengthening of polyelectrolyte complex membranes by functionalized
carbon nanotubes and metal ions.
AB - Hydrophilic polymers have garnered much attention due to their critical roles in
various applications such as molecular separation membranes, bio-interfaces, and
surface engineering. However, a long-standing problem is that their mechanical
properties usually deteriorate at high relative humidity (RH). Through the
simultaneous incorporation of functionalized carbon nanotubes and copper ions
(Cu(2+)), this study introduces a facile method to fabricate high strength
polyelectrolyte complex nanohybrid membranes resistant to high RH (90%). For
example, the tensile strength of the nanohybrid membranes is 55 MPa at 90% RH
(80% of the original value at 30% RH). These results are explained by copper ions
depressing the swelling degree of the membrane, and functionalized carbon
nanotubes promoting stress transfer between the polymer matrix and them. The
nanohybrid membranes are efficient in separating water/alcohol mixtures
containing relatively high water content (up to 30 wt%), whereas common
hydrophilic polymer membranes usually suffer from excessive swelling under this
condition.
PMID- 25586652
TI - Predictors of AA amyloidosis in familial Mediterranean fever.
AB - The aim of the study was to evaluate the clinical and genetic predictors of AA
amyloidosis in patients with familial Mediterranean fever (FMF). We
retrospectively studied 170 Armenian patients who were admitted to the two
tertiary centers in 2003-2014. The diagnosis of amyloidosis that was suspected
clinically (new proteinuria or nephrotic syndrome) was confirmed histologically.
Screening for MEFV gene mutations was performed in 70 patients. The most common
genotype was M694V/M694V (in 36 % of patients). Biopsy-proven AA amyloidosis was
found in 102 (60 %) of 170 patients. AA amyloidosis was diagnosed in 17 (68 %) of
25 patients with homozygous M694V mutation, 17 (53 %) of 32 patients with
heterozygous M694V allele and 4 (31 %) of 13 patients with other MEFV gene
mutations. The M694V homozygosity and heterozygosity were associated with
increased risk of AA amyloidosis, but this association did not reach statistical
significance (odds ratio 2.43; 95 % CI 0.87-6.76, and 3.33; 0.91-12.1,
respectively). Male gender, early onset of disease, severity of FMF, frequent
attacks, peritonitis, pleuritis and erysipelas-like erythema also did not predict
AA amyloidosis development. Recurrent arthritis was the only clinical finding
that was significantly associated with AA amyloidosis (odds ratio 2.28; 95 % CI
1.17-4.42). Involvement of the joint synovial membrane, that is capable of active
serum amyloid A production, is the main predictor of renal amyloidosis in FMF.
PMID- 25586651
TI - Evidence-based clinical practice guidelines for functional dyspepsia.
AB - General interest in functional gastrointestinal disorders is increasing among
Japanese doctors as well as patients. This increase can be attributed to a number
of factors, including recent increased interest in quality of life and advances
in our understanding of the pathophysiology of gastrointestinal disease. Japan
recently became the world's first country to list "functional dyspepsia" as a
disease name for national insurance billing purposes. However, recognition and
understanding of functional dyspepsia (FD) remain poor, and no standard treatment
strategy has yet been established. Accordingly, the Japanese Society of
Gastroenterology (JSGE) developed an evidence-based clinical practice guideline
for FD, consisting of five sections: concept, definition, and epidemiology;
pathophysiology; diagnosis; treatment; and prognosis and complications. This
article summarizes the Japanese guideline, with particular focus on the treatment
section. Once a patient is diagnosed with FD, the doctor should carefully explain
the pathophysiology and benign nature of this condition, establish a good doctor
patient relationship, and then provide advice for daily living (diet and
lifestyle modifications, explanations, and reassurance). The proposed
pharmacological treatment is divided into two steps: initial treatment including
an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation);
second-line treatment including anxiolytics, antidepressants, and Japanese
traditional medicine (weak recommendation). H. pylori eradication, strongly
recommended with a high evidence level, is positioned separately from other
treatment flows. Conditions that do not respond to these treatment regimens are
regarded as refractory FD. Patients will be further examined for other organic
disorders or will be referred to specialists using other approaches such as
psychosomatic treatment.
PMID- 25586653
TI - Dissecting the damage in Northern Greek patients with childhood-onset systemic
lupus erythematosus: a retrospective cohort study.
AB - The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has
resulted in longer patients' exposure to disease inflammation, medications and/or
comorbid diseases, which can all contribute to the development of organ damage.
The aim of this study was to assess the evolution of damage accrual in cSLE
patients overtime and investigate for predisposing factors. Disease
characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were
retrospectively reviewed. The Systemic Lupus International Collaboration
Clinics/American College of Rheumatology Damage Index (SDI) was used for damage
assessment and the European Consensus Lupus Activity Measurement (ECLAM) to
monitor cSLE activity. After a median disease duration of 7.4 years, 17/47
patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged
were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %)
one. Peripheral vascular and neuropsychiatric damage was seen more frequently
during the first 5 years of the disease. Longer exposure to azathioprine was
associated with higher SDI at the end of follow-up (beta = 0.008 for every
additional month of use, p = 0.041). The mean annual flare frequency was
associated with a shorter time interval until the development of the first damage
(hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while
hydroxychloroquine use was associated with longer time interval (HR 0.19, p =
0.007). The lower rates of damage accrual in this study compared to other cohorts
might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt
diagnosis and effective disease control. Damage was noticed early in the disease
course, and one-third of patients had an SDI > 0 at study completion. Disease
flares and a severe disease course leading to prolonged use of immunosuppressives
were significant risk factors, while hydroxychloroquine use was protective
against cSLE damage accrual.
PMID- 25586654
TI - The association between comorbidities and pain, physical function and quality of
life following hip and knee arthroplasty.
AB - The aim of the study was to examine the relationship between comorbidities and
pain, physical function and health-related quality of life (HRQoL) after total
hip arthroplasty (THA) and total knee arthroplasty (TKA). A cross-sectional
retrospective survey was conducted including 19 specific comorbidities,
administered in patients who underwent THA or TKA in the previous 7-22 months in
one of 4 hospitals. Outcome measures included pain, physical functioning, and
HRQoL. Of the 521 patients (281 THA and 240 TKA) included, 449 (86 %) had >=1
comorbidities. The most frequently reported comorbidities (>15 %) were severe
back pain; neck/shoulder pain; elbow, wrist or hand pain; hypertension;
incontinence of urine; hearing impairment; vision impairment; and cancer. Only
the prevalence of cancer was significantly different between THA (n = 38; 14 %)
and TKA (n = 52; 22 %) (p = 0.01). The associations between a higher number of
comorbidities and worse outcomes were stronger in THA than in TKA. In
multivariate analyses including all comorbidities with a prevalence of >5 %, in
THA dizziness in combination with falling and severe back pain, and in TKA
dizziness in combination with falling, vision impairments, and elbow, wrist or
hand pain was associated with worse outcomes in most of the analyses. A broad
range of specific comorbidities needs to be taken into account with the
interpretation of patients' health status after THA and TKA. More research
including the ascertainment of comorbidities preoperatively is needed, but it is
conceivable that in particular, the presence of dizziness with falling, pain in
other joints, and vision impairments should be assessed and treated in order to
decrease the chance of an unfavorable outcome.
PMID- 25586655
TI - Dimeric Cinchona alkaloids.
AB - Nature is full of dimeric alkaloids of various types from many plant families,
some of them with interesting biological properties. However, dimeric Cinchona
alkaloids were not isolated from any species but were products of designed
partial chemical synthesis. Although the Cinchona bark is amongst the sources of
oldest efficient medicines, the synthetic dimers found most use in the field of
asymmetric synthesis. Prominent examples include the Sharpless dihydroxylation
and aminohydroxylation ligands, and dimeric phase transfer catalysts. In this
article the syntheses of Cinchona alkaloid dimers and oligomers are reviewed, and
their structure and applications are outlined. Various synthetic routes exploit
reactivity of the alkaloids at the central 9-hydroxyl group, quinuclidine, and
quinoline rings, as well as 3-vinyl group. This availability of reactive sites,
in combination with a plethora of linker molecules, contributes to the diversity
of the products obtained.
PMID- 25586656
TI - Synthesis of C-glycosyl-bis-1,2,3-triazole derivatives from 3,4,6-tri-O-acetyl-D
glucal.
AB - We have developed an efficient, CuI-catalyzed, microwave-assisted method for the
synthesis of bis-1,2,3-triazole derivatives starting from a 3,4,6-tri-O-acetyl-D
glucal-derived mesylate. This mesylate was obtained from 3,4,6-tri-O-acetyl-D
glucal through C-glycosidation, deprotection of acetate groups to alcohols, and
selective mesylation of the primary alcohol. This mesylate moiety was then
converted to an azide through a microwave-assisted method with good yield. The
azide, once synthesized, was then treated with different terminal alkynes in the
presence of CuI to synthesize various bis-triazoles in high yields and short
reaction times.
PMID- 25586657
TI - Urticarial vasculitis and urticarial autoinflammatory syndromes.
AB - Urticaria is a frequent disorder classified as acute and chronic forms, which
presents with wheals that can be associated with angioedema. Several entities may
manifest with urticarial skin lesions, encompassing a heterogeneous group of
conditions that have to be differentiated from ordinary urticaria. This review is
focused on two of these urticarial syndromes: urticarial vasculitis (UV), which
represents the most important differential diagnosis with common urticaria, and
autoinflammatory diseases such as cryopyrin-associated periodic syndromes (CAPS)
and Schnitzler's Syndrome, both rare multisystem forms that may masquerade as
common urticaria. UV is a small-vessel vasculitis with predominant skin
involvement, characterized by wheals persisting for more than 24 hours, burning
rather than itching and resolving with hyperpigmentation as well as by other
cutaneous manifestations including purpura, papules, vesicles, bullae and
necrotic-ulcerative lesions. Histology shows a classic pattern of
leukocytoclastic vasculitis, with possible presence of upper dermal edema. CAPS
are classified as three distinct entities: familial cold autoinflammatory
syndrome, Muckle-Wells Syndrome and chronic infantile neurological cutaneous and
articular syndrome, which represent a spectrum of disorders caused by different
mutations in a single gene, NLRP3 (NOD-like receptor 3). This gene encodes for
cryopyrin, an inflammasome protein that activates interleukin-1beta, leading to
an overproduction of this pivotal proinflammatory cytokine. Histologically,
urticarial lesions are generally characterized by a perivascular neutrophilic
infiltrate. Unlike urticaria, neither UV nor urticarial autoinflammatory
syndromes do respond to antihistamines: thus, it is important not to misdiagnose
such conditions in order to give the patients specific treatments, potentially
preventing serious systemic complications.
PMID- 25586658
TI - Metastatic breast carcinoma of the jugular foramen: a rare case of Villaret
syndrome.
AB - BACKGROUND: The differential diagnosis of skull base masses is diverse and
includes benign and malignant neoplasms, vascular anomalies, congenital lesions,
as well as infectious and inflammatory processes. Metastatic masses of the skull
base are a rare manifestation of systemic malignancies. Breast cancer is the most
common cause of skull base metastases. Villaret syndrome refers to cranial nerves
IX, X, XI, and XII and sympathetic chain neuropathies. It is a clinical subtype
of jugular foramen syndromes. METHODS AND RESULTS: A 62-year-old woman with a
history of breast carcinoma presented with hoarseness dating to shortly after her
mastectomy years earlier. CT angiography showed enhancing tissue just outside the
right jugular foramen, and biopsy confirmed metastatic adenocarcinoma consistent
with breast cancer. CONCLUSION: Villaret syndrome caused by breast cancer
metastases has not been previously described. We present a case of Villaret
syndrome caused by metastasis of invasive breast adenocarcinoma and a review of
the literature of metastases of breast cancer to the skull base.
PMID- 25586659
TI - Selective lesions of the cholinergic neurons within the posterior
pedunculopontine do not alter operant learning or nicotine sensitization.
AB - Cholinergic neurons within the pedunculopontine tegmental nucleus have been
implicated in a range of functions, including behavioral state control,
attention, and modulation of midbrain and basal ganglia systems. Previous
experiments with excitotoxic lesions have found persistent learning impairment
and altered response to nicotine following lesion of the posterior component of
the PPTg (pPPTg). These effects have been attributed to disrupted input to
midbrain dopamine systems, particularly the ventral tegmental area. The pPPTg
contains a dense collection of cholinergic neurons and also large numbers of
glutamatergic and GABAergic neurons. Because these interdigitated populations of
neurons are all susceptible to excitotoxins, the effects of such lesions cannot
be attributed to one neuronal population. We wished to assess whether the
learning impairments and altered responses to nicotine in excitotoxic PPTg
lesioned rats were due to loss of cholinergic neurons within the pPPTg. Selective
depletion of cholinergic pPPTg neurons is achievable with the fusion toxin Dtx
UII, which targets UII receptors expressed only by cholinergic neurons in this
region. Rats bearing bilateral lesions of cholinergic pPPTg neurons (>90% ChAT+
neuronal loss) displayed no deficits in the learning or performance of fixed and
variable ratio schedules of reinforcement for pellet reward. Separate rats with
the same lesions had a normal locomotor response to nicotine and furthermore
sensitized to repeated administration of nicotine at the same rate as sham
controls. Previously seen changes in these behaviors following excitotoxic pPPTg
lesions cannot be attributed solely to loss of cholinergic neurons. These
findings indicate that non-cholinergic neurons within the pPPTg are responsible
for the learning deficits and altered responses to nicotine seen after
excitotoxic lesions. The functions of cholinergic neurons may be related to
behavioral state control and attention rather than learning.
PMID- 25586660
TI - Treatment patterns and clinical outcomes in patients with chronic immune
thrombocytopenia (ITP) switched to eltrombopag or romiplostim.
AB - This observational study aimed to assess real-world treatment patterns and
clinical outcomes for patients with chronic immune thrombocytopenia (ITP)
currently being treated with eltrombopag or romiplostim after switching from
corticosteroids, rituximab, or the alternate thrombopoietin receptor agonist (TPO
RA). The study examined the rationale for switching to TPO-RA therapy using aided
responses. Dosing patterns were also analyzed before and after switching.
Treatment outcomes were assessed through platelet counts at multiple time points
including treatment initiation and after switching at the last office visit. A
total of 280 patients were enrolled whose active therapy for ITP was replaced
with either eltrombopag (n = 130) or romiplostim (n = 150). Efficacy-related
issues (desired platelet count not achieved and/or lack of response to prior
therapy) were the main drivers for therapy switching among all patients (54 % for
eltrombopag vs. 57 % for romiplostim). Platelet counts at the last office visit
showed improvement compared with counts at the initiation of either eltrombopag
or romiplostim treatment. No significant differences were noted when comparing
clinical outcomes between the eltrombopag and romiplostim treatment cohorts. Our
results suggest that switching to the other TPO-RA may be beneficial if there is
inadequate response to treatment with the initial TPO-RA.
PMID- 25586661
TI - Anthocyanins as substrates for mitochondrial complex I - protective effect
against heart ischemic injury.
AB - Anthocyanins, a subclass of flavonoids, are known to protect against myocardial
ischemia; however, little is known about their direct, acute effects on
mitochondria injured by the ischemic insult. In this study, the effects of
delphinidin 3-O-glucoside (Dp3G), cyanidin 3-O-glucoside (Cy3G) and pelargonidin
3-O-glucoside (Pg3G) on the activity of complex I of the mitochondrial
respiratory chain were studied in mitochondria isolated from normal rat hearts
and rat hearts subjected to ischemia for 45 min. Cy3G and Dp3G increased the
activity of complex I, measured in the presence or absence of coenzyme Q1 (CoQ1
), in ischemia-damaged mitochondria, whereas in nonischemic mitochondria the
effect was observed only in the absence of CoQ1 . Dp3G and Cy3G but not Pg3G
increased state 3 respiration and ATP synthesis with NADH-dependent substrates in
mitochondria after ischemia. The results suggest that certain anthocyanins can
act as electron acceptors at complex I, and bypass ischemia-induced inhibition,
resulting in increased ATP production after ischemia. This study provides new
information on a possible role of certain anthocyanins in the regulation of
energy metabolism in mammalian cells.
PMID- 25586663
TI - Reversal by ranolazine of doxorubicin-induced prolongation in the inactivation of
late sodium current in rat dorsal root ganglion neurons.
PMID- 25586662
TI - Association of immunoexpression of the galectins-3 and -7 with histopathological
and clinical parameters in oral squamous cell carcinoma in young patients.
AB - An increasing incidence of oral squamous cell carcinoma (OSCC) in individuals
younger than 45 years has been observed in recent years. OSCC in younger patients
differs in terms of biological behavior and prognosis with the disease being more
aggressive than in older patients. The aim of this study was to analyze the
immunohistochemical expression of galectins-3 and -7 in 32 cases of OSCC in young
patients and to correlate this expression with clinical and morphological
parameters. All cases of OSCC of the sample were diagnosed at oncology referral
hospitals in Paraiba, Brazil, between 2002 and 2012. Clinical data were obtained
from the patient records. Histological malignancy grading systems proposed by
Bryne et al. (J Pathol 166:375-381, 1992) and the World Health Organization (In:
Pathology and genetics of head and neck tumours: Word Health Organization
classification of tumours, 2005) were used for morphological analysis.
Immunohistochemistry was performed by the streptavidin-biotin technique using
anti-galectin-3 and -7 antibodies. The results were analyzed statistically by the
Chi-squared and Fisher exact tests (p < 0.05). Immunoexpression of galectin-3 was
observed in 65.6 % of the cases analyzed, but showed no significant association
with any of the variables studied (clinical staging; histological malignancy
grading systems). Immunoexpression of galectin-7 was observed in 96.9 % of cases
and was significantly associated with histological malignancy grading systems (p
< 0.05). In conclusion, the results suggest the use of galectin-7 as marker of
biological behavior and tumor progression in OSCC in young patients.
PMID- 25586664
TI - Complex association between body weight and fracture risk in postmenopausal
women.
AB - Osteoporosis is a common disease, characterized by low bone mass with micro
architectural disruption and skeletal fragility, resulting in an increased risk
of fracture. A substantial number of studies has examined the possible
relationship between body weight, bone mineral density and fracture risk in post
menopausal women, with the majority of them concluding that low body weight
correlates with increased risk of fracture, especially hip fracture.
Controversies about the potential protective effect of obesity on osteoporosis
and consequent fracture risk still exist. Several recent studies question the
concept that obesity exerts a protective effect against fractures, suggesting
that it stands as a risk factor for fractures at specific skeletal sites, such as
upper arm. The association between body weight and fracture risk is complex,
differs across skeletal sites and body mass index, and is modified by the
interaction between body weight and bone mineral density. Some potential
explanations that link obesity with increased fracture risk may be the pattern of
falls and impaired mobility in obese individuals, comorbidities, such as asthma,
diabetes and early menopause, as well as, increased parathyroid hormone and
reduced 25-hydroxy-vitamin D concentrations.
PMID- 25586665
TI - Posterosuperior glenoid internal impingement of the shoulder in the overhead
athlete: pathogenesis, clinical features and MR imaging findings.
AB - Posterosuperior glenoid internal impingement (PGII) is an impingement syndrome of
the shoulder that is most commonly seen in the throwing or overhead athlete. The
supraspinatus can be normally compressed or impinged between the greater
tuberosity and the posterosuperior labrum in the abduction and external rotation
position. However, repetitive throwing and biomechanical abnormalities may lead
to the intensification of this contact and to the clinical and pathological
picture of PGII. The injured athlete usually complains of poor throwing
performance and pain located in the posterosuperior aspect of the shoulder. Two
main theories regarding the aetiology of PGII have been postulated with differing
initial mechanisms. The MRI features of PGII have been described and include
supraspinatus and anterior infraspinatus partial undersurface tears, bony changes
at the humeral head and labral pathology, including a variation of the type II
superior labrum from anterior to posterior lesion. This pictorial essay aims to
present cases illustrating the pathophysiology, clinical features and recently
described MRI findings, and discuss some of the MR protocol considerations.
PMID- 25586667
TI - Surface properties of heat-induced soluble soy protein aggregates of different
molecular masses.
AB - Suspensions (2% and 5%, w/v) of soy protein isolate (SPI) were heated at 80, 90,
or 100 degrees C for different time periods to produce soluble aggregates of
different molecular sizes to investigate the relationship between particle size
and surface properties (emulsions and foams). Soluble aggregates generated in
these model systems were characterized by gel permeation chromatography and
sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heat treatment
increased surface hydrophobicity, induced SPI aggregation via hydrophobic
interaction and disulfide bonds, and formed soluble aggregates of different
sizes. Heating of 5% SPI always promoted large-size aggregate (LA; >1000 kDa)
formation irrespective of temperature, whereas the aggregate size distribution in
2% SPI was temperature dependent: the LA fraction progressively rose with
temperature (80->90->100 degrees C), corresponding to the attenuation of medium
size aggregates (MA; 670 to 1000 kDa) initially abundant at 80 degrees C. Heated
SPI with abundant LA (>50%) promoted foam stability. LA also exhibited excellent
emulsifying activity and stabilized emulsions by promoting the formation of small
oil droplets covered with a thick interfacial protein layer. However, despite a
similar influence on emulsion stability, MA enhanced foaming capacity but were
less capable of stabilizing emulsions than LA. The functionality variation
between heated SPI samples is clearly related to the distribution of aggregates
that differ in molecular size and surface activity. The findings may encourage
further research to develop functional SPI aggregates for various commercial
applications.
PMID- 25586668
TI - The feasibility of coin motors for use in a vibrotactile display for the blind.
AB - We have tested the potential of three types of vibration motors for use in a
tactile vision substitution device for the blind. The motors were of the coin
type, which are available off-the-shelf, and are characterized by their
affordability, energy efficiency, and ease of implementation. The primary
limitation of coin motors is the lack of control they offer over stimulus
parameters. Specifically, adjusting the input voltage of a coin motor not only
changes the vibration intensity, but also the vibration frequency and duration.
This characteristic may result in unpredictable perceptions in psychophysical
tests. By using standard psychophysical procedures, we were able to show that the
tested coin motors evoked predictable magnitude perceptions across their dynamic
range, following Fechner's law as if vibration intensity alone were varied. The
best-performing motor was able to generate a median number of 15 available just
noticeable differences, meaning that it was potentially capable of conveying 16
gray levels in its dynamic range. We conclude that coin motors are potential
candidates for the construction of a tactile display to substitute for lost
vision.
PMID- 25586666
TI - Upregulation of miR-142-5p in atherosclerotic plaques and regulation of oxidized
low-density lipoprotein-induced apoptosis in macrophages.
AB - MicroRNA (miR)-142-5p is a member of the miR-142 family, which have been shown to
be associated with tumors, stem cells and disorders of the immune system.
However, the role of miR-142-5p in atherosclerosis has yet to be investigated. In
the present study, an atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse
model was constructed and fed a high-fat diet. The expression levels of miR-142
5p in the murine atherosclerotic plaques were detected by gene microarray
analysis. In addition, an in vitro assay was used to determine the expression
levels of miR-142-5p in human endothelial cells, smooth muscle cells and
macrophages, which were treated with oxidized low-density lipoprotein (ox-LDL).
Furthermore, a miR-142-5p inhibitor and mimic was transfected into cultured human
macrophages, in order to observe the effects on transforming growth factor-beta2
(TGF-beta2) expression. The effects of co-transfection of the miR-142-5p
inhibitor or mimic with TGF-beta2, in human macrophages, on the rate of apoptosis
was analyzed. The expression levels of miR-142-5p were 6.84-fold higher in mice
with stable atherosclerotic plaques, and 2.69-fold higher in mice with vulnerable
atherosclerotic plaques, as compared with the controls. Furthermore, the
expression levels of miR-142-5p were upregulated in the cultured human
macrophages. The percentage of apoptotic cells was lowest in the macrophages
transfected with both TGF-beta2 and miR-142-5p inhibitors and treated with ox
LDL. The expression levels of miR-142-5p were upregulated in the atherosclerotic
plaques of the apoE-/- mice. The findings of the present study have shown that
the upregulation of miR-142-5p expression may regulate apoptosis in human
macrophages by targeting TGF-beta2. This effect may have an important role in the
progression of atherosclerosis.
PMID- 25586670
TI - Brown adipose tissue triglyceride content is associated with decreased insulin
sensitivity, independently of age and obesity.
AB - The aim of the present study was to determine whether single-voxel proton
magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride
content in both supraclavicular fat depots and subcutaneous white adipose tissue
(WAT) to determine whether these measurements correlate to metabolic variables. A
total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose
positron emission tomography (PET) and (15)O-H2O PET perfusion during cold
exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were
collected from nine volunteers. The supraclavicular triglyceride content
determined by (1)H-MRS varied between 60 and 91% [mean +/- standard deviation
(s.d.) 77 +/- 10%]. It correlated positively with body mass index, waist
circumference, subcutaneous and visceral fat masses and 8-year diabetes risk
based on the Framingham risk score and inversely with HDL cholesterol and insulin
sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had
a significantly higher triglyceride content, 76-95% (mean +/- s.d. 87 +/- 5%; p =
0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits
measured by (1)H-MRS may be an independent marker of whole-body insulin
sensitivity, independent of brown adipose tissue metabolic activation.
PMID- 25586672
TI - Observation of dynamical heterogeneities and their time evolution on the surface
of an amorphous polymer.
AB - Although the formation of dynamic heterogeneities in glass-forming materials is
believed to play an essential role in determining their properties as the glass
transition is approached, direct imaging of these heterogeneities remains a
challenge. Here, we report on a direct observation of nanoscale dynamic
heterogeneities and their time evolution over ~10(3) s on the surface of a glassy
polymer, polystyrene (PS), using atomic force microscopy with a 1 nm radius tip.
The length scale of these heterogeneities was measured to be ~2.1 nm and the
lifetime was determined to be ~10(2) s, in agreement with the length and time
scales of heterogeneous dynamics reported for bulk polymers around the glass
transition. These results are consistent with the existence of a very thin liquid
like layer at the glassy polymer surface. The validity of the method is confirmed
by comparing the properties of surface dynamics of neat and plasticized films.
PMID- 25586669
TI - NQO1-induced activation of AMPK contributes to cancer cell death by oxygen
glucose deprivation.
AB - Oxygen and glucose deprivation (OGD) due to insufficient blood circulation can
decrease cancer cell survival and proliferation in solid tumors. OGD increases
the intracellular [AMP]/[ATP] ratio, thereby activating the AMPK. In this study,
we have investigated the involvement of NQO1 in OGD-mediated AMPK activation and
cancer cell death. We found that OGD activates AMPK in an NQO1-dependent manner,
suppressing the mTOR/S6K/4E-BP1 pathway, which is known to control cell survival.
Thus, the depletion of NQO1 prevents AMPK-induced cancer cell death in OGD. When
we blocked OGD-induced Ca(2+)/CaMKII signaling, the NQO1-induced activation of
AMPK was attenuated. In addition, when we blocked the RyR signaling, the
accumulation of intracellular Ca(2+) and subsequent activation of CaMKII/AMPK
signaling was decreased in NQO1-expressing cells under OGD. Finally, siRNA
mediated knockdown of CD38 abrogated the OGD-induced activation of
Ca(2+)/CaMKII/AMPK signaling. Taken together, we conclude that NQO1 plays a key
role in the AMPK-induced cancer cell death in OGD through the
CD38/cADPR/RyR/Ca(2+)/CaMKII signaling pathway.
PMID- 25586671
TI - Update on the role of angiotensin in the pathophysiology of coronary
atherothrombosis.
AB - BACKGROUND: Coronary atherothrombosis due to atherosclerotic plaque rupture or
erosion is frequently associated with acute coronary syndromes (ACS). Significant
efforts have been made to elucidate the pathophysiological mechanisms underlying
acute coronary events. MATERIALS AND METHODS: This narrative review is based on
the material searched for and obtained via PubMed up to August 2014. The search
terms we used were as follows: 'angiotensin, acute coronary syndromes, acute
myocardial infarction' in combination with 'atherosclerosis, vulnerability,
clinical trial, ACE inhibitors, inflammation'. RESULTS: Among several regulatory
components, the renin-angiotensin system (RAS) was shown as a key pathway
modulating coronary atherosclerotic plaque vulnerability. Indeed, these molecules
are involved in all stages of atherogenesis. Classically, the RAS is composed by
a series of enzymatic reactions leading to the angiotensin (Ang) II generation
and activity. However, the knowledge of RAS has expanded and become more complex.
The discovery of novel components and their functions has revealed additional
pathways that contribute to or counterbalance the actions of Ang II. In this
review, we discussed on recent findings concerning the role of different
angiotensin peptides in the pathophysiology of ACS and coronary atherothrombosis,
exploring the link between these molecules and atherosclerotic plaque
vulnerability. CONCLUSIONS: Treatments selectively targeting angiotensins
(including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and almandine in
oral formulations) have been tested in animal studies or in small human
subgroups, expanding the perspective in the ACS prevention. These novel
strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might
be promising to reduce plaque vulnerability and inflammation.
PMID- 25586673
TI - Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to
an LHX3 mutation.
AB - BACKGROUND: Canine pituitary dwarfism or combined pituitary hormone deficiency
(CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a
wide range of clinical manifestations. Some dogs with CPHD have neurological
signs that are localized to the cervical spine. In human CPHD, caused by an LHX3
mutation, anatomical abnormalities in the atlanto-axial (C1-C2) joint have been
described. OBJECTIVES: To evaluate the presence of atlanto-axial malformations in
dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate
the degree of similarity between the atlanto-axial anomalies found in canine and
human CPHD patients with an LHX3 mutation. ANIMALS: Three client-owned
Czechoslovakian wolfdogs and 1 client-owned German shepherd dog, previously
diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological
signs indicating a cervical spinal disorder. METHODS: Radiography, computed
tomography, and magnetic resonance imaging of the cranial neck and skull,
necropsy, and histology. RESULTS: Diagnostic imaging identified abnormal
positioning of the dens axis and incomplete ossification of the suture lines
between the ossification centers of the atlas with concurrent atlanto-axial
instability and dynamic compression of the spinal cord by the dens axis. The
malformations and aberrant motion at C1-C2 were confirmed at necropsy and
histology. CONCLUSIONS AND CLINICAL IMPORTANCE: The atlanto-axial abnormalities
of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3
mutation. These findings suggest an association between the LHX3 mutation in dogs
with CPHD and atlanto-axial malformations. Consequently, pituitary dwarfs should
be monitored closely for neurological signs.
PMID- 25586674
TI - Profile of plasma amino acids values as a predictor of sepsis in patients
following living donor liver transplantation: Special reference to sarcopenia and
postoperative early nutrition.
AB - AIM: Sarcopenia is an independent predictor of mortality and sepsis after living
donor liver transplantation (LDLT). However, the exact mechanisms by which
sarcopenia affects poor prognosis or worse immunity against postoperative sepsis
are unclear, particularly regarding muscular amino acid metabolism, and the
authors aimed to identify the role of plasma amino acids in sarcopenia by
retrospective study. METHODS: The area of the psoas muscle in 228 recipients of
LDLT was retrospectively measured by dynamic computed tomography. Additionally,
plasma amino acid levels were measured both pre- and postoperatively. The impact
of plasma amino acids for postoperative sepsis and the relationship between
sarcopenia and early nutrition after LDLT were analyzed. RESULTS: Among the
plasma amino acids, only leucine, isoleucine and glutamine in patients with
sarcopenia were significantly lower than those without sarcopenia (each, P <
0.05). Multivariate analysis identified the lower plasma glutamine levels as a
risk factor of postoperative sepsis after LDLT (odds ratio 5.371, P = 0.002). In
sarcopenia patients, plasma glutamine levels after LDLT were significantly
decreased compared with before LDLT in patients both with and without
postoperative early nutrition. However, in non-sarcopenia patients with early
nutrition, plasma glutamine levels after LDLT were comparable with those before
LDLT. CONCLUSION: This is the first report to study the profile of plasma amino
acid change before and after LDLT. Low preoperative glutamine values were an
independent risk factor for predicting postoperative sepsis. The efficacy of
postoperative early nutrition may prevent postoperative sepsis by improving
glutamine levels.
PMID- 25586675
TI - Surface-modified Epirubicin-HCl liposomes and its in vitro assessment in breast
cancer cell-line: MCF-7.
AB - BACKGROUND: Epirubicin-HCl is highly efficient for breast cancer management at a
concentration of 60-90 mg/m(2). However, its application is limited due to
cumulative dose-dependent cardio-toxicity. PURPOSE: The main aim of this study
was to formulate breast cancer-targeted liposomal carrier by surface conjugation
of transferrin to minimize cardio-toxicity of drug along with improved
pharmacokinetic profile. METHOD: Liposomes were formulated by ethanol injection
method using HSPC, cholesterol and DSPG and later loaded with drug by the
ammonium sulfate gradient method. The formulation was characterized for
physicochemical properties like size, zeta potential, entrapment efficiency, TEM;
in vitro tests like electro-flocculation, hemolysis and drug release; cell line
study (MCF-7 cells); in vivo studies including LD50 determination,
pharmacokinetic analysis, myocardial toxicity determination and stability.
RESULTS AND DISCUSSION: Optimized formulation had molar ratio of 60:30:8:2
(HSPC:Chol:DSPG:mPEG-DSPE) with entrapment efficiency ~83%, particle size below
200 nm and zeta potential about -20 mV. In vitro studies proved non-interfering
property and drug release character of formulation while cell line studies
demonstrated improvement in cell uptake and thereby increased cytotoxicity of
targeted formulation. The IC50 value obtained for epirubicin solution, non
targeted and targeted liposomes was 0.675, 0.532 and 0.192 ug/ml, respectively.
Furthermore, in vivo tests validated safety and distribution profile of prepared
formulations. CONCLUSION: Apt properties of prepared Epirubicin-HCl liposomal
formulation warrant its clinical application in breast cancer treatment after
further studies.
PMID- 25586676
TI - Structural characterization of MG and pre-MG states of proteins by MD
simulations, NMR, and other techniques.
AB - Almost all proteins fold via a number of partially structured intermediates such
as molten globule (MG) and pre-molten globule states. Understanding the structure
of these intermediates at atomic level is often a challenge, as these states are
observed under extreme conditions of pH, temperature, and chemical denaturants.
Furthermore, several other processes such as chemical modification, site-directed
mutagenesis (or point mutation), and cleavage of covalent bond of natural
proteins often lead to MG like partially unfolded conformation. However, the
dynamic nature of proteins in these states makes them unsuitable for most
structure determination at atomic level. Intermediate states studied so far have
been characterized mostly by circular dichroism, fluorescence, viscosity, dynamic
light scattering measurements, dye binding, infrared techniques, molecular
dynamics simulations, etc. There is a limited amount of structural data available
on these intermediate states by nuclear magnetic resonance (NMR) and hence there
is a need to characterize these states at the molecular level. In this review, we
present characterization of equilibrium intermediates by biophysical techniques
with special reference to NMR.
PMID- 25586677
TI - Postpartum consultations in Australian general practice.
AB - Many GPs undertake postpartum care for women and their infants. GP follow-up
enables early identification and management of problems, education and support
for parenting, and reconnection with general practice following the birth.
However, there is little information about GPs' understanding of their role in
postpartum care and how it is undertaken. This cross-sectional survey of GPs in
Southern Queensland, conducted between February and July 2013, describes the
involvement of GPs in postpartum care. GPs were posted a 52-item questionnaire
adapted from a previous Victorian GP study and were telephoned 2 weeks later. GPs
completed the survey on paper or online. The response rate was 17.4% (163 GPs).
Approximately 39% were uncertain whether women were happy with the GP-provided
postpartum care. GPs' recommendations for the timing of postpartum reviews were
inconsistent within and across birthing sectors and consultations took longer
than anticipated. Developing guidelines around the timing and appropriate length
of postpartum consultations could assist GPs in providing appropriate care for
mothers and infants.
PMID- 25586678
TI - Voxel-based dose calculation in radiocolloid therapy of cystic
craniopharyngiomas.
AB - Very high doses are administered in radiocolloid therapy of cystic
craniopharyngiomas. However individual dose planning is not common yet mainly due
to insufficient image resolution. Our aim was to investigate whether currently
available high-resolution image data can be used for voxel-based dose calculation
for short-ranged beta-emitters ((32)P,(90)Y,(186)Re) and to assess the achievable
accuracy. We developed a convolution algorithm based on voxelized dose activity
distributions and dose-spread kernels. Results for targets with 5-40 mm diameter
were compared with high-resolution Monte Carlo calculations in spherical
phantoms. Voxel size was 0.35 mm. Homogeneous volume and surface activity
distributions were used. Dose-volume histograms of targets and shell structures
were compared and gamma index (dose tolerance 5%, distance to agreement 0.35 mm)
was calculated for dose profiles along the principal axes. For volumetric
activity distributions 89.3% +/- 11.9% of all points passed the gamma test (mean
gamma 0.53 +/- 0.16). For surface distributions 33.6% +/- 14.8% of all points
passed the gamma test (mean gamma 2.01 +/- 0.60). The shift of curves in dose
volume histograms was -1.7 Gy +/- 7.6 Gy (-4.4 Gy +/- 24.1 Gy for (186)Re) in
volumetric distributions and 46.3% +/- 32.8% in surface distributions. The
results show that individual dose planning for radiocolloid therapy of cystic
craniopharyngiomas based on high-resolution voxelized image data is feasible and
yields highly accurate results for volumetric activity distributions and
reasonable dose estimates for surface distributions.
PMID- 25586679
TI - "Clinical significance of multifocal and multicentric breast cancers and choice
of surgical treatment: a retrospective study on a series of 1158 cases".
AB - BACKGROUND: The biological and clinical significance of multifocal and
multicentric (MF/MC) breast cancers and the choice of appropriate surgical
treatment for these tumors are still debated. METHODS: 1158 women operated on for
a stage I-III breast cancer were included in this retrospective study; clinical
and pathological data were obtained from the institutional database of the
Department of Oncology of the University of Siena, Italy. The impact of MF/MC
breast cancers on patterns of recurrence and breast cancer specific survival
(BCSS) was investigated in relation to the type of surgical treatment. RESULTS:
MF and MC cancers were present in 131 cases (11.3%) and 60 cases (5.2%)
respectively and were more frequently treated with mastectomy (55 MF and 60 MC
cancers, 81.2%) than with breast conserving surgery (36 MF cancers, 18.9%; p <
0.001). MF and MC breast cancers were associated with a worse prognosis with a
BCSS of 154 months compared to 204 months of unicentric cancers (p < 0.001). In
multivariate analysis, MF/MC cancers were independent prognostic factors for BCSS
together with higher number of metastatic axillary nodes, absence of estrogen
receptors and high proliferative activity. MF and MC cancers were related to a
significantly shorter BCSS in patients submitted to mastectomy as well as those
submitted to breast conserving surgery. Relapse at any site was higher in the
subgroup of MF and MC cancers but the incidence of loco-regional and distant
recurrences did not differ between patients treated with mastectomy or breast
conserving surgery. CONCLUSIONS: Our results indicate that MF/MC cancers have a
negative impact on prognosis and are related to higher loregional and distant
relapse independently from the type of surgery performed. Adjuvant therapies did
not modify the poorer outcome, but in patients receiving adjuvant anthacyclines,
the differences with unicentric tumors were reduced. Our data support the
hypothesis that MF/MC tumors may have a worse biological behavior and that the
presence of multiple foci should be considered in planning adjuvant treatments.
PMID- 25586680
TI - Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG
inactivating beta-oxygenation pathway in colorectal cancer.
AB - Bioinformatics and computational modeling offer innovative approaches to
investigate cancer metabolism and predict the secondary and tertiary cellular
responses. Dysregulation of metabolism has also been implicated in the
pathophysiology of cancer. A significant proportion of patients with glioblastoma
and hematological malignancies harbor the mutated forms of the oxidative
phosphorylation (OxPhos) enzymes, isocitrate dehydrogenase (IDH) 1 or 2. The
mutated forms of IDH1 and IDH2 produce an oncogenic metabolite, D-2
hydroxyglutarate (D2HG). A recent study of breast cancer patients showed that
D2HG can also be produced in the absence of mutated IDH, through an alternative
route involving over-activated MYC signaling. We developed a novel methodology to
computationally analyze gene expression in colorectal cancer (CRC), and
identified novel sets of genes that are associated with patient survival. The
study of OxPhos-related genes revealed that an imbalance between the expression
of IDH1 and IDH2, defined as overexpression of one isoform in relation to the
other, was associated with worse prognosis in CRC patients. This effect was
further accentuated by reduced expression of the beta-oxygenation enzyme, 3-D
hydroxyacyl-CoA dehydratase (HCDH) 4, which has been reported to contribute to
metabolism of intracellular D2HG. The present computational analysis revealed a
novel and potential mechanism of CRC development, through over-production of D2HG
when there is an imbalance between IDH1 and IDH2 expression, resulting in
decreased clearance of D2HG when the beta-oxidization pathway is diminished.
Additional validation analysis with another gene expression dataset resulted in
IDH1/2 imbalanced expression with a shorter DFS compared with balanced
expression. Altogether, these findings provide a strong rationale for studying
this mechanism further in order to discover novel therapeutic targets for the
treatment of CRC.
PMID- 25586681
TI - Carbapenem therapy is associated with improved survival compared with
piperacillin-tazobactam for patients with extended-spectrum beta-lactamase
bacteremia.
AB - BACKGROUND: The effectiveness of piperacillin-tazobactam (PTZ) for the treatment
of extended-spectrum beta-lactamase (ESBL) bacteremia is controversial. We
compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of
patients with ESBL bacteremia who all received definitive therapy with a
carbapenem. METHODS: Patients hospitalized between January 2007 and April 2014
with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling
dilutions in the minimum inhibitory concentration for third-generation
cephalosporins tested in combination with 4 ug/mL of clavulanic acid was used to
confirm ESBL status. The primary exposure was empiric therapy, defined as
antibiotic therapy administered to a patient before ESBL status was known.
Patients were excluded if they did not receive a carbapenem after ESBL production
was identified. The primary outcome was time to death from the first day of
bacteremia. Propensity scores using inverse probability of exposure weighting
(IPW) were used to estimate the probability that a patient would receive PTZ vs
carbapenems empirically. We calculated overall hazard ratios for mortality
censored at 14 days using Cox proportional hazards models on an IPW-adjusted
cohort. RESULTS: A total of 331 unique patients with ESBL bacteremia were
identified. One hundred three (48%) patients received PTZ empirically and 110
(52%) received carbapenems empirically. The adjusted risk of death was 1.92 times
higher for patients receiving empiric PTZ compared with empiric carbapenem
therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS: PTZ appears inferior
to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of
invasive ESBL infections, early carbapenem therapy should be considered. Our
findings should not be extended to beta-lactam/beta-lactamase inhibitor
combinations in development, as limited clinical data are available for these
agents.
PMID- 25586683
TI - Additional benefits of GeneXpert MTB/RIF assay for the evaluation of pulmonary
tuberculosis among inpatients.
PMID- 25586682
TI - Use of boosted protease inhibitors reduces Kaposi sarcoma incidence among male
veterans with HIV infection.
AB - BACKGROUND: Kaposi sarcoma (KS) incidence has decreased since combination
antiretroviral therapy (cART). However, effects of cART type and duration on KS
remain difficult to interpret secondary to KS-associated immune reconstitution
inflammatory syndrome (IRIS). METHODS: We performed a retrospective study of
Veterans Affairs Human Immunodeficiency Virus Clinical Case Registry data from
1985 to 2010. We analyzed the relationship between cART regimens and KS using
multivariable Poisson regression, stratified or adjusted for timing around cART
initiation. KS was identified by >= 1 inpatient or >= 2 outpatient International
Classification of Diseases, Ninth Revision codes (176.0-9). Percent of cART on
specific regimen and total duration on specific regimen were examined. RESULTS:
There were 341 KS cases among 25 529 HIV-infected male veterans (incidence rate =
2.02/1000 person-years). Stratified by years after starting cART, every
additional 10% time on boosted protease inhibitors (BPIs) was associated with
reduced KS incidence in the third year of cART (incidence rate ratio [IRR] =
0.79; 95% confidence interval [CI], .69-.90). Months on BPIs was associated with
lower KS incidence (P = .02). KS incidence was lower at 12-23 (IRR = 0.47; 95%
CI, .23-.95) and >= 36 (IRR = 0.14; 95% CI, .02-1.00) months on BPIs compared
with <6 months. Longer duration on other regimens was not associated with
decreased KS incidence. CONCLUSIONS: Lower KS incidence was observed with longer
BPI use, after accounting for potential IRIS and other factors. Future research
should evaluate newer cART regimens and long-term benefits of PI-based cART on KS
in other cohorts and prospective studies.
PMID- 25586684
TI - Editorial commentary: Bloodstream infection caused by extended-spectrum beta
lactamase-producing Gram-negative bacteria: how to define the best treatment
regimen?
PMID- 25586685
TI - Reply to Baker and Holtom.
PMID- 25586686
TI - T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood:
a clinical trial.
AB - BACKGROUND: Microbiologic cultures, the current gold standard diagnostic method
for invasive Candida infections, have low specificity and take up to 2-5 days to
grow. We present the results of the first extensive multicenter clinical trial of
a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of
candidemia. METHODS: Blood specimens were collected from 1801 hospitalized
patients who had a blood culture ordered for routine standard of care; 250 of
them were manually supplemented with concentrations from <1 to 100 colony-forming
units (CFUs)/mL for 5 different Candida species. RESULTS: T2MR demonstrated an
overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%
99.6%) with a mean time to negative result of 4.2 +/- 0.9 hours. Subanalysis
yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida
tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95%
CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity
was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 +/- 1.0 hours
for detection and species identification. The subgroup analysis showed a
sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2%
(95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C.
krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C.
krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C.
parapsilosis. The negative predictive value was estimated to range from 99.5% to
99.0% in a study population with 5% and 10% prevalence of candidemia,
respectively. CONCLUSIONS: T2MR is the first fully automated technology that
directly analyzes whole blood specimens to identify species without the need for
prior isolation of Candida species, and represents a breakthrough shift into a
new era of molecular diagnostics. CLINICAL TRIALS REGISTRATION: NCT01752166.
PMID- 25586687
TI - High capsid-genome correlation facilitates creation of AAV libraries for directed
evolution.
AB - Directed evolution of adeno-associated virus (AAV) through successive rounds of
phenotypic selection is a powerful method to isolate variants with improved
properties from large libraries of capsid mutants. Importantly, AAV libraries
used for directed evolution are based on the "natural" AAV genome organization
where the capsid proteins are encoded in cis from replicating genomes. This is
necessary to allow the recovery of the capsid DNA after each step of phenotypic
selection. For directed evolution to be used successfully, it is essential to
minimize the random mixing of capsomers and the encapsidation of nonmatching
viral genomes during the production of the viral libraries. Here, we demonstrate
that multiple AAV capsid variants expressed from Rep/Cap containing viral genomes
result in near-homogeneous capsids that display an unexpectedly high capsid-DNA
correlation. Next-generation sequencing of AAV progeny generated by bulk
transfection of a semi-random peptide library showed a strong counter-selection
of capsid variants encoding premature stop codons, which further supports a
strong capsid-genome identity correlation. Overall, our observations demonstrate
that production of "natural" AAVs results in low capsid mosaicism and high capsid
genome correlation. These unique properties allow the production of highly
diverse AAV libraries in a one-step procedure with a minimal loss in phenotype
genotype correlation.
PMID- 25586690
TI - Anaphylaxis attributed to exercise: considerations for sports medicine
specialists.
AB - Anaphylaxis is an unanticipated, acute, and sometimes life-threatening systemic
reaction with variable clinical presentations that is typically mediated by
immunoglobulin E and causes degranulation of mast cells and basophils. The onset
of symptoms can occur within minutes or hours after exposure to a known or
suspected trigger, and reactions sometimes progress very rapidly, which can lead
to death. One trigger of anaphylaxis in younger adults is moderately intense
physical exercise, which has been termed exercise-induced anaphylaxis (EIA).
Although rare, EIA should be recognized as a distinct and potentially life
threatening form of physical allergy, and is often undetected or inadequately
treated. The ingestion of specific foods, including seafood, tree nuts, and
wheat, or a nonspecific meal consisting of multiple food components shortly
before or after physical exertion, is sometimes, but not always, the principal
precipitant of EIA. This article briefly explores the current hypotheses on the
role of immunoglobulin E, response mediators, and physiologic changes that bring
on EIA, and discusses the current recommendations for diagnosis, including
allergen challenge and laboratory testing, emergency care, and long-term
prevention and patient follow-up. Accurate diagnosis of EIA is critical to
providing lifesaving therapy and care plans to patients at risk. With respect to
the medical management of EIA, mainstay therapy with epinephrine is described.
For those with a known history of EIA, a comprehensive anaphylaxis action plan is
central to successful patient management. Furthermore, patient education is
necessary to heighten awareness of the signs and symptoms of EIA and appropriate
strategies for allergen avoidance and self-management of anaphylactic episodes
with self-injectable epinephrine.
PMID- 25586688
TI - Intra-amniotic rAAV-mediated microdystrophin gene transfer improves canine X
linked muscular dystrophy and may induce immune tolerance.
AB - Duchenne muscular dystrophy (DMD) is a severe congenital disease due to mutations
in the dystrophin gene. Supplementation of dystrophin using recombinant
adenoassociated virus vector has promise as a treatment of DMD, although
therapeutic benefit of the truncated dystrophin still remains to be elucidated.
Besides, host immune responses against the vector as well as transgene products
have been denoted in the clinical gene therapy studies. Here, we transduced
dystrophic dogs fetuses to investigate the therapeutic effects of an AAV vector
expressing microdystrophin under conditions of immune tolerance. rAAV-CMV
microdystrophin and a rAAV-CAG-luciferase were injected into the amniotic fluid
surrounding fetuses. We also reinjected rAAV9-CMV-microdystrophin into the
jugular vein of an infant dystrophic dog to induce systemic expression of
microdystrophin. Gait and cardiac function significantly improved in the rAAV
microdystrophin-injected dystrophic dog, suggesting that an adequate treatment of
rAAV-microdystrophin with immune modulation induces successful long-term
transgene expression to analyze improved dystrophic phenotype.
PMID- 25586689
TI - First-in-man phase 1 clinical trial of gene therapy for advanced pancreatic
cancer: safety, biodistribution, and preliminary clinical findings.
AB - This phase 1 trial was aimed to determine the safety, pharmacokinetics, and
preliminary clinical activity of CYL-02, a nonviral gene therapy product that
sensitizes pancreatic cancer cells to chemotherapy. CYL-02 was administrated
using endoscopic ultrasound in 22 patients with pancreatic cancer that
concomitantly received chemotherapy (gemcitabine). The maximum-tolerated dose
(MTD) exceeded the maximal feasible dose of CYL-02 and was not identified.
Treatment-related toxicities were mild, without serious adverse events.
Pharmacokinetic analysis revealed a dose-dependent increase in CYL-02 DNA
exposure in blood and tumors, while therapeutic RNAs were detected in tumors. No
objective response was observed, but nine patients showed stable disease up to 6
months following treatment and two of these patients experienced long-term
survival. Panels of plasmatic microRNAs and proteins were identified as
predictive of gene therapy efficacy. We demonstrate that CYL-02 nonviral gene
therapy has a favorable safety profile and is well tolerated in patients. We
characterize CYL-02 biodistribution and demonstrate therapeutic gene expression
in tumors. Treated patients experienced stability of disease and predictive
biomarkers of response to treatment were identified. These promising results
warrant further evaluation in phase 2 clinical trial.
PMID- 25586692
TI - Atypical urothelial tissue fragments in noninstrumented voided urine specimens
are associated with low but significantly higher rates of urothelial neoplasia
than benign-appearing urothelial tissue fragments.
AB - BACKGROUND: The interpretation of urothelial tissue fragments (UTF) in voided
urine (VU) specimens is controversial. If UTF contain cytomorphologically
atypical cells, the diagnosis often becomes more challenging. The authors
previously analyzed the outcome of patients with benign-appearing UTF in 274
noninstrumented VU specimens. In this retrospective study, noninstrumented VU
specimens containing UTF with atypical cytomorphological features (AUTF) were
evaluated and compared with the previous results. METHODS: The Johns Hopkins
Hospital electronic pathology database was searched for VU cases containing UTF
over a 5-year period. RESULTS: A total of 170 noninstrumented VU specimens
containing AUTF were identified. Twenty-four specimens had subsequent or
coincidental surgical pathology specimens with the following overall rates of
neoplasia: high-grade urothelial carcinoma: 8.8% (15 specimens), low-grade
urothelial neoplasia: 1.2% (2 specimens), and prostate carcinoma invading the
bladder: 0.6% (1 specimen). A total of 49 specimens (28.8%) were diagnosed with
urolithiasis on follow-up. Twenty-five cases had follow-up cytology specimens,
all of which were negative for malignancy. Of 72 cases without histopathologic,
radiologic, or cytopathologic follow-up, 62 (86.1%) had a mean clinical follow-up
of 22.5 months and 10 cases did not have clinical follow-up. CONCLUSIONS: The
presence of AUTF in noninstrumented VU is associated with low rates of urothelial
neoplasia but a statistically higher risk of urothelial neoplasia than the
presence of BUTF (10.0% vs 4.4%; P<.05). In particular, the rate of high-grade
urothelial carcinoma is significantly higher in noninstrumented VU specimens
containing AUTF than those containing BUTF (8.8% vs 0.7%; P<.0001). In addition,
urolithiasis is associated with AUTF in a substantial percentage of
noninstrumented VU specimens.
PMID- 25586691
TI - Intrinsic cancer subtypes--next steps into personalized medicine.
AB - Recent technological advances have significantly improved our understanding of
tumor biology by means of high-throughput mutation and transcriptome analyses.
The application of genomics has revealed the mutational landscape and the
specific deregulated pathways in different tumor types. At a transcriptional
level, multiple gene expression signatures have been developed to identify
biologically distinct subgroups of tumors. By supervised analysis, several
prognostic signatures have been generated, some of them being commercially
available. However, an unsupervised approach is required to discover a priori
unknown molecular subtypes, the so-called intrinsic subtypes. Moreover, an
integrative analysis of the molecular events associated with tumor biology has
been translated into a better tumor classification. This molecular
characterization confers new opportunities for therapeutic strategies in the
management of cancer patients. However, the applicability of these new molecular
classifications is limited because of several issues such as technological
validation and cost. Further comparison with well-established clinical and
pathological features is expected to accelerate clinical translation. In this
review, we will focus on the data reported on molecular classification in the
most common tumor types such as breast, colorectal and lung carcinoma, with
special emphasis on recent data regarding tumor intrinsic subtypes. Likewise, we
will review the potential applicability of these new classifications in the
clinical routine.
PMID- 25586693
TI - Congenital absence of the left atrial appendage visualized by 3D echocardiography
in two adult patients.
AB - Congenital absence of left atrial appendage (LAA) is an extremely rare condition
and its physiological consequences are unknown. We present two cases of
incidental finding of a congenitally absent LAA in a 79-year-old male who
presented for routine transesophageal echocardiogram (TEE) to rule out
intracardiac thrombus prior to placement of biventricular implantable
cardioverter-defibrillator and a 54-year old female who presented for TEE prior
to radiofrequency ablation of atrial fibrillation. Characterization of patients
with such an absence is important because congenitally absent LAA may be confused
with flush thrombotic occlusion of the appendage. There are very few published
reports of congenital absence of LAA. To our knowledge, our report is the first
to demonstrate the congenital absence of LAA by 3D transesophageal
echocardiography.
PMID- 25586696
TI - A rare case of first motor branch of median nerve schwannoma.
PMID- 25586697
TI - BioMEMS and Lab-on-a-Chip Course Education at West Virginia University.
AB - With the rapid growth of Biological/Biomedical MicroElectroMechanical Systems
(BioMEMS) and microfluidic-based lab-on-a-chip (LOC) technology to biological and
biomedical research and applications, demands for educated and trained
researchers and technicians in these fields are rapidly expanding. Universities
are expected to develop educational plans to address these specialized needs in
BioMEMS, microfluidic and LOC science and technology. A course entitled BioMEMS
and Lab-on-a-Chip was taught recently at the senior undergraduate and graduate
levels in the Department of Computer Science and Electrical Engineering at West
Virginia University (WVU). The course focused on the basic principles and
applications of BioMEMS and LOC technology to the areas of biomedicine, biology,
and biotechnology. The course was well received and the enrolled students had
diverse backgrounds in electrical engineering, material science, biology,
mechanical engineering, and chemistry. Student feedback and a review of the
course evaluations indicated that the course was effective in achieving its
objectives. Student presentations at the end of the course were a highlight and a
valuable experience for all involved. The course proved successful and will
continue to be offered regularly. This paper provides an overview of the course
as well as some development and future improvements.
PMID- 25586695
TI - Hypomelanosis of Ito: a round on the frequency and type of epileptic
complications.
AB - There is an ample evidence that hypopigmentation of the skin along the Blaschko's
lines is frequently associated with neurological disorders. Nowadays, the term
"Hypomelanosis of Ito" (HI) is applied when, together with the cutaneous lesions,
various and multisystem organs are involved. Among these, the most frequent are
cerebral manifestations, such as cognitive delay and epileptic seizures. For this
reason, hypomelanosis of Ito has been included in the group of neurocutaneous
syndromes, neurologic manifestations being one of the most frequent. Epileptic
seizures have been reported in patients with this disorder, but in a very few
particular attention has been focused on the type and frequency of epilepsy and
on the response to the treatment. Herein, we report on five patients with HI who
showed episodes of epileptic seizures with onset in childhood, in absence of
malformative anomalies except for the skin lesions. A survey on the frequency and
types of epileptic seizures in HI children and in the literature is reported.
PMID- 25586698
TI - Nonlinear dielectric spectroscopy as an indirect probe of metabolic activity in
thylakoid membrane.
AB - Nonlinear dielectric spectroscopy (NDS) is a non-invasive probe of cellular
metabolic activity with potential application in the development of whole-cell
biosensors. However, the mechanism of NDS interaction with metabolic membrane
proteins is poorly understood, partly due to the inherent complexity of single
cell organisms. Here we use the light-activated electron transport chain of
spinach thylakoid membrane as a model system to study how NDS interacts with
metabolic activity. We find protein modification, as opposed to membrane pump
activity, to be the dominant source of NDS signal change in this system.
Potential mechanisms for such protein modifications include reactive oxygen
species generation and light-activated phosphorylation.
PMID- 25586699
TI - Dielectrophoresis Aligned Single-Walled Carbon Nanotubes as pH Sensors.
AB - Here we report the fabrication and characterization of pH sensors using aligned
single-walled carbon nanotubes (SWNTs). The SWNTs are dispersed in deionized (DI)
water after chemical functionalization and filtration. They are deposited and
organized on silicon substrates with the dielectrophoresis process. Electrodes
with "teeth"-like patterns-fabricated with photolithography and wet etching-are
used to generate concentrated electric fields and strong dielectrophoretic forces
for the SWNTs to deposit and align in desired locations. The device fabrication
is inexpensive, solution-based, and conducted at room temperature. The devices
are used as pH sensors with the electrodes as the testing pads and the
dielectrophoretically captured SWNTs as the sensing elements. When exposed to
aqueous solutions with various pH values, the SWNTs change their resistance
accordingly. The SWNT-based sensors demonstrate a linear relationship between the
sensor resistance and the pH values in the range of 5-9. The characterization of
multiple sensors proves that their pH sensitivity is highly repeatable. The real
time data acquisition shows that the sensor response time depends on the pH
value, ranging from 2.26 s for the pH-5 solution to 23.82 s for the pH-9
solution. The long-term stability tests illustrate that the sensors can maintain
their original sensitivity for a long period of time. The simple fabrication
process, high sensitivity, and fast response of the SWNT-based sensors facilitate
their applications in a wide range of areas.
PMID- 25586700
TI - Environmental osmolality influences sperm motility activation in an anuran
amphibian.
AB - Evolutionary theory predicts that selection will favour sperm traits that
maximize fertilization success in local fertilization environments. In externally
fertilizing species, osmolality of the fertilization medium is known to play a
critical role in activating sperm motility, but there remains limited evidence
for adaptive responses to local osmotic environments. In this study, we used a
split-sample experimental design and computer-assisted sperm analysis to (i)
determine the optimal medium osmolality for sperm activation (% sperm motility
and sperm velocity) in male common eastern froglets (Crinia signifera), (ii) test
for among-population variation in percentage sperm motility and sperm velocity at
various activation-medium osmolalities and (iii) test for among-population
covariation between sperm performance and environmental osmolality. Frogs were
obtained from nine populations that differed in environmental osmolality, and
sperm samples of males from different populations were subjected to a range of
activation-medium osmolalities. Percentage sperm motility was optimal between 10
and 50 mOsm kg(-1) , and sperm velocity was optimal between 10 and 100 mOsm kg(
1) , indicating that C. signifera has evolved sperm that can function across a
broad range of osmolalities. As predicted, there was significant among-population
variation in sperm performance. Furthermore, there was a significant interaction
between activation-medium osmolality and environmental osmolality, indicating
that frogs from populations with higher environmental osmolality produced sperm
that performed better at higher osmolalities in vitro. This finding may reflect
phenotypic plasticity in sperm functioning, or genetic divergence resulting from
spatial variation in the strength of directional selection. Both of these
explanations are consistent with evolutionary theory, providing some of the first
empirical evidence that local osmotic environments can favour adaptive sperm
motility responses in species that use an external mode of fertilization.
PMID- 25586701
TI - Two Multiple Sclerosis Quality-of-Life Measures: Comparison in a National Sample.
AB - BACKGROUND: Multiple sclerosis (MS) has a profound impact on patients' health
related quality of life (HRQoL). It is unclear how HRQoL can be best assessed for
different purposes. This study aimed to compare two HRQoL questionnaires of
differing lengths for feasibility of administration, patient perceptions and
psychometric properties. METHODS: This was an open-label, 24-month study in 334
patients with relapsing MS treated with subcutaneous interferon beta-1a. At
baseline and months 6, 12, 18 and 24, patients completed the Multiple Sclerosis
International Quality of Life (MusiQoL) and Multiple Sclerosis Quality of Life-54
(MSQOL-54) questionnaires and compared them using an evaluation questionnaire.
HRQoL scores over time and psychometric properties (correlations with clinical
disease measures, relative validity and responsiveness to change) of the
questionnaires were assessed. RESULTS: A minority of patients had missing items
on either HRQoL measure. Completion time was significantly shorter for MusiQoL
versus MSQOL-54 (p<0.0001). Patients felt that MusiQoL was easier to use than
MSQOL-54 but preferred MSQOL-54 in terms of thoroughness. Mean HRQoL scores
increased significantly from baseline to 24 months; correlations of both measures
were stronger with an anxiety and depression measure than with disability or
recent relapse occurrence. Relative validity and responsiveness to change were
similar for both instruments. CONCLUSION: The shorter MusiQoL is suitable for
evaluating HRQoL in patients with MS and may be more practical to administer than
the more thorough MSQOL-54.
PMID- 25586702
TI - Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and
Plasmodium falciparum.
AB - Intercellular adhesion molecules (ICAMs) belong to the immunoglobulin superfamily
and participate in diverse cellular processes including host-pathogen
interactions. ICAM-1 is expressed on various cell types including macrophages,
whereas ICAM-4 is restricted to red blood cells. Here we report the
identification of an 11-kDa synthetic protein, M5, that binds to human ICAM-1 and
ICAM-4, as shown by in vitro interaction studies, surface plasmon resonance and
immunolocalization. M5 greatly inhibits the invasion of macrophages and
erythrocytes by Mycobacterium tuberculosis and Plasmodium falciparum,
respectively. Pharmacological and siRNA-mediated inhibition of ICAM-1 expression
also results in reduced M. tuberculosis invasion of macrophages. ICAM-4 binds to
P. falciparum merozoites, and the addition of recombinant ICAM-4 to parasite
cultures blocks invasion of erythrocytes by newly released merozoites. Our
results indicate that ICAM-1 and ICAM-4 play roles in host cell invasion by M.
tuberculosis and P. falciparum, respectively, either as receptors or as crucial
accessory molecules.
PMID- 25586703
TI - An aqueous method for the controlled manganese (Mn(2+)) substitution in
superparamagnetic iron oxide nanoparticles for contrast enhancement in MRI.
AB - Despite the success in the use of superparamagnetic iron oxide nanoparticles
(SPION) for various scientific applications, its potential in biomedical fields
has not been exploited to its full potential. In this context, an in situ
substitution of Mn(2+) was performed in SPION and a series of ferrite particles,
MnxFe1-xFe2O4 with a varying molar ratio of Mn(2+) : Fe(2+) where 'x' varies from
0-0.75. The ferrite particles obtained were further studied in MRI contrast
applications and showed appreciable enhancement in their MRI contrast properties.
Manganese substituted ferrite nanocrystals (MnIOs) were synthesized using a
novel, one-step aqueous co-precipitation method based on the use of a combination
of sodium hydroxide and trisodium citrate (TSC). This approach yielded the
formation of highly crystalline, superparamagnetic MnIOs with good control over
their size and bivalent Mn ion crystal substitution. The presence of a TSC
hydrophilic layer on the surface facilitated easy dispersion of the materials in
an aqueous media. Primary characterizations such as structural, chemical and
magnetic properties demonstrated the successful formation of manganese
substituted ferrite. More significantly, the MRI relaxivity of the MnIOs improved
fourfold when compared to SPION crystals imparting high potential for use as an
MRI contrast agent. Further, the cytocompatibility and blood compatibility
evaluations demonstrated excellent cell morphological integrity even at high
concentrations of nanoparticles supporting the non-toxic nature of nanoparticles.
These results open new horizons for the design of biocompatible water dispersible
ferrite nanoparticles with good relaxivity properties via a versatile and easily
scalable co-precipitation route.
PMID- 25586704
TI - Dual-tip magnetic force microscopy with suppressed influence on magnetically soft
samples.
AB - Standard magnetic force microscopy (MFM) is considered as a powerful tool used
for magnetic field imaging at nanoscale. The method consists of two passes
realized by the magnetic tip. Within the first one, the topography pass, the
magnetic tip directly touches the magnetic sample. Such contact perturbs the
magnetization of the sample explored. To avoid the sample touching the magnetic
tip, we present a new approach to magnetic field scanning by segregating the
topological and magnetic scans with two different tips located on a cut
cantilever. The approach minimizes the disturbance of sample magnetization, which
could be a major problem in conventional MFM images of soft magnetic samples. By
cutting the cantilever in half using the focused ion beam technique, we create
one sensor with two different tips--one tip is magnetized, and the other one is
left non-magnetized. The non-magnetized tip is used for topography and the
magnetized one for the magnetic field imaging. The method developed we call dual
tip magnetic force microscopy (DT-MFM). We describe in detail the dual-tip
fabrication process. In the experiments, we show that the DT-MFM method reduces
significantly the perturbations of the magnetic tip as compared to the standard
MFM method. The present technique can be used to investigate microscopic magnetic
domain structures in a variety of magnetic samples and is relevant in a wide
range of applications, e.g., data storage and biomedicine.
PMID- 25586705
TI - In vitro comparison of biological and synthetic materials for skeletal chest wall
reconstruction.
AB - BACKGROUND: Various biological and synthetic materials have been proposed for use
in skeletal chest wall reconstruction (SCWR). Because of the lack of studies
allowing a direct comparison of SCWR materials, their clinical use often depends
on the surgeon's preference and experience. The aim of this study was to analyze
6 synthetic and 3 biological materials frequently used in SCWR with respect to
their cytotoxicity, bacterial adhesion, surface characteristics, and mechanical
properties to facilitate data-driven decisions. METHODS: The effect of the SCWR
materials and their extracts on the metabolism of human skeletal muscle cells
(SkMCs), dermal fibroblasts, adipose cells, and osteoblasts was analyzed in
vitro. Bacterial adhesion was quantified by incubating samples in bacterial
suspensions (Staphylococcus epidermidis, S aureus, and Escherichia coli),
followed by counting colony-forming units and performing scanning electron
microscopy. Moreover, the mechanical properties of the materials were analyzed
under uniaxial tensile loading to failure. RESULTS: The metabolism of all cell
types seeded on the SCWR materials was reduced compared with untreated cells.
With the exception of Vypro (Ethicon, Somerville, NJ), whose extracts
significantly reduced fibroblast viability, no cytotoxic leachable substances
were detected. Biological materials were less cytotoxic compared with synthetic
ones, but they demonstrated increased bacterial adhesion. Synthetic materials
demonstrated higher elongation to failure than did biological materials.
CONCLUSIONS: Biological and synthetic SCWR materials showed significant
differences in their cytotoxicity, bacterial adhesion, and biomechanical
properties, suggesting that they may be used for different indications in SCWR.
Further comparable in vivo studies are needed to analyze their performance in
different indications of clinical application.
PMID- 25586706
TI - Incidence and mechanisms of cerebral ischemia after transcatheter aortic valve
implantation compared with surgical aortic valve replacement.
AB - BACKGROUND: The most likely mechanisms of neurologic injury after transcatheter
aortic valve implantation (TAVI) and aortic valve replacement (AVR) are cerebral
embolization and hypoperfusion. We set out to determine potential mechanisms of
neurologic injury after TAVI compared with AVR. METHODS: One hundred twenty-seven
consecutive high-risk patients with severe aortic stenosis (AS) who underwent
TAVI (n = 85) or AVR (n = 42) were studied. Transcranial Doppler ultrasound
(TCD), cerebral oximetry, diffusion-weighted magnetic resonance imaging (DW-MRI)
(before, 6 days, and 3 months after procedure), and neurocognitive assessment
before and at 3 months were performed. RESULTS: Neurologic injury was not
significantly different between TAVI and AVR at 1 (1.1% vs 2.2%, p = 0.25) and 3
months (4.7% vs 2.2%, p = 1). At 3 months, overall cognitive score was higher in
AVR compared with TAVI when adjusted for baseline score; the estimated difference
between groups was 0.63 (95% confidence interval 0.87% to 1.17%; p = 0.02).
Cerebral embolic load was 212 (123 to 344) during AVR and 134 (76 to 244) during
TAVI (p = 0.07). Cerebral oxygen desaturation during AVR (7.56 +/- 2.16) was
higher compared with TAVI (5.93 +/- 2.47) (p < 0.01). Ischemic lesions measured
by DW-MRI occurred in 76% of TAVI and 71% of AVR patients at 6 days (p = 0.69)
and 63% and 39% at 3 months (p = 0.11). No significant association was found
between cerebral emboli, cerebral oxygen desaturation, brain ischemic lesions,
and general cognitive score. CONCLUSIONS: At 3 months follow-up, overall
cognitive score was higher in AVR compared with TAVI, adjusted for baseline
score. However, there was no difference in cerebral embolic load, ischemic
lesions, and oxygen desaturation.
PMID- 25586707
TI - Effect of macroscale formation of intraluminal thrombus on blood flow in
abdominal aortic aneurysms.
AB - A mathematical approach of blood flow within an abdominal aortic aneurysm (AAA)
with intraluminal thrombus (ILT) is presented. The macroscale formation of ILT is
modeled as a growing porous medium with variable porosity and permeability
according to values proposed in the literature. The model outlines the effect of
a porous ILT on blood flow in AAAs. The numerical solution is obtained by
employing a structured computational mesh of an idealized fusiform AAA geometry
and applying the Galerkin weighted residual method in generalized curvilinear
coordinates. Results on velocity and pressure fields of independent cases with
and without ILT are presented and discussed. The vortices that develop within the
aneurysmal cavity are studied and visualized as ILT becomes more condensed. From
a mechanistic point of view, the reduction of bulge pressure, as ILT is
thickening, supports the observation that ILT could protect the AAA from a
possible rupture. The model also predicts a relocation of the maximum pressure
region toward the zone proximal to the neck of the aneurysm. However, other
mechanisms, such as the gradual wall weakening that usually accompany AAA and ILT
formation, which are not included in this study, may offset this effect.
PMID- 25586708
TI - Real-time pretreatment review limits unacceptable deviations on a cooperative
group radiation therapy technique trial: quality assurance results of RTOG 0933.
AB - PURPOSE: RTOG 0933 was a phase II trial of hippocampal avoidance during whole
brain radiation therapy for patients with brain metastases. The results
demonstrated improvement in short-term memory decline, as compared with
historical control individuals, and preservation of quality of life. Integral to
the conduct of this trial were quality assurance processes inclusive of pre
enrollment credentialing and pretreatment centralized review of enrolled
patients. METHODS AND MATERIALS: Before enrolling patients, all treating
physicians and sites were required to successfully complete a "dry-run"
credentialing test. The treating physicians were credentialed based on accuracy
of magnetic resonance imaging-computed tomography image fusion and hippocampal
and normal tissue contouring, and the sites were credentialed based on protocol
specified dosimetric criteria. Using the same criteria, pretreatment centralized
review of enrolled patients was conducted. Physicians enrolling 3 consecutive
patients without unacceptable deviations were permitted to enroll further
patients without pretreatment review, although their cases were reviewed after
treatment. RESULTS: In all, 113 physicians and 84 sites were credentialed. Eight
physicians (6.8%) failed hippocampal contouring on the first attempt; 3 were
approved on the second attempt. Eight sites (9.5%) failed intensity modulated
radiation therapy planning on the first attempt; all were approved on the second
attempt. One hundred thirteen patients were enrolled in RTOG 0933; 100 were
analyzable. Eighty-seven cases were reviewed before treatment; 5 (5.7%) violated
the eligibility criteria, and 21 (24%) had unacceptable deviations. With
feedback, 18 cases were approved on the second attempt and 2 cases on the third
attempt. One patient was treated off protocol. Twenty-two cases were reviewed
after treatment; 1 (4.5%) violated the eligibility criteria, and 5 (23%) had
unacceptable deviations. CONCLUSIONS: Although >95% of the cases passed the pre
enrollment credentialing, the pretreatment centralized review disqualified 5.7%
of reviewed cases, prevented unacceptable deviations in 24% of reviewed cases,
and limited the final unacceptable deviation rate to 5%. Thus, pretreatment
review is deemed necessary in future hippocampal avoidance trials and is
potentially useful in other similarly challenging radiation therapy technique
trials.
PMID- 25586709
TI - Improved detection of bone metastases from lung cancer in the thoracic cage using
5- and 1-mm axial images versus a new CT software generating rib unfolding
images: comparison with standard 18F-FDG-PET/CT.
AB - RATIONALE AND OBJECTIVES: To evaluate the performance of a dedicated computed
tomography (CT) software called "bone reading" generating rib unfolded images for
improved detection of rib metastases in patients with lung cancer in comparison
to readings of 5- and 1-mm axial CT images and (18)F-Fluordeoxyglucose positron
emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS:
Ninety consecutive patients who underwent (18)F-FDG-PET/CT and chest CT scanning
between 2012 and 2014 at our institution were analyzed retrospectively. Chest CT
scans with 5- and 1-mm slice thickness were interpreted blindly and separately
focused on the detection of rib metastases (location, number, cortical vs.
medullary, and osteoblastic vs. sclerotic). Subsequent image analysis of unfolded
1 mm-based CT rib images was performed. For all three data sets the reading time
was registered. Finally, results were compared to those of FDG-PET. Validation
was based on FDG-PET positivity for osteolytic and mixed osteolytic/osteoblastic
focal rib lesions and follow-up for sclerotic PET-negative lesions. RESULTS: A
total of 47 metastatic rib lesions were found on FDG-PET/CT plus another 30
detected by CT bone reading and confirmed by follow-up CT. Twenty-nine lesions
were osteolytic, 14 were mixed osteolytic/osteoblastic, and 34 were sclerotic. On
a patient-based analysis, CT (5 mm), CT (1 mm), and CT (1-mm bone reading)
yielded a sensitivity, specificity, and accuracy of 76.5/97.3/93, 81.3/97.3/94,
and 88.2/95.9/92, respectively. On segment-based (unfolded rib) analysis, the
sensitivity, specificity, and accuracy of the three evaluations were
47.7/95.7/67, 59.5/95.8/77, and 94.8/88.2/92, respectively. Reading time for 5
mm/1 mm axial images and unfolded images was 40.5/50.7/21.56 seconds,
respectively. CONCLUSIONS: The use of unfolded rib images in patients with lung
cancer improves sensitivity and specificity of rib metastasis detection in
comparison to 5- and 1-mm CT slice reading. Moreover, it may reduce the reading
time.
PMID- 25586710
TI - Intraindividual comparison of two methods of volumetric breast composition
assessment.
AB - RATIONALE AND OBJECTIVES: To compare the results of two software-based methods,
Quantra and Volpara, for volumetric breast composition assessment. MATERIALS AND
METHODS: Four hundred forty-five normal, bilateral, two-view, digital mammograms
were included. Breast volume (BV), fibroglandular tissue volume (FTV), and
percent density (PD) were measured using both methods and compared. Deming
regression was performed to obtain linear equations for mapping the results of
one software on the other. RESULTS: The median and quartile ranges of both
methods agreed well for BV but were different for FTV and PD, with Quantra
showing much higher values of FTV and PD. The correlation of results obtained by
both methods for BV, FTV, and PD was 0.99, 0.91, and 0.94, respectively.
Intraclass correlation in the assignment of quartiles of BV, FTV, and PD was
0.96, 0.86, and 0.90, respectively. Both methods showed a similar association of
FTV and PD with patient age and similar left-to-right correlation. Mapping of
results onto each other using linear equations removed the systematic
differences. CONCLUSIONS: Although Quantra and Volpara use different models for
analysis of volumetric breast composition and produce different nominal results
of FTV and PD, both methods are highly correlated and show very good to excellent
agreement in quartile assignment of all parameters measured. Both methods show a
similar association with patient age and similar reproducibility. Both methods
can be mapped onto each other using the equations suggested.
PMID- 25586711
TI - The effectiveness of health animations in audiences with different health
literacy levels: an experimental study.
AB - BACKGROUND: Processing Web-based health information can be difficult, especially
for people with low health literacy. Presenting health information in an
audiovisual format, such as animation, is expected to improve understanding among
low health literate audiences. OBJECTIVE: The aim of this paper is to investigate
what features of spoken health animations improve information recall and
attitudes and whether there are differences between health literacy groups.
METHODS: We conducted an online experiment among 231 participants aged 55 years
or older with either low or high health literacy. A 2 (spoken vs written text) x
2 (illustration vs animation) design was used. Participants were randomly exposed
to one of the four experimental messages, all providing the same information on
colorectal cancer screening. RESULTS: The results showed that, among people with
low health literacy, spoken messages about colorectal cancer screening improved
recall (P=.03) and attitudes (P=.02) compared to written messages. Animations
alone did not improve recall, but when combined with spoken text, they
significantly improved recall in this group (P=.02). When exposed to spoken
animations, people with low health literacy recalled the same amount of
information as their high health literate counterparts (P=.12), whereas in all
other conditions people with high health literacy recalled more information
compared to low health literate individuals. For people with low health literacy,
positive attitudes mediated the relationship between spoken text and the
intention to have a colorectal cancer screening (b=.12; 95% CI 0.02-0.25).
CONCLUSIONS: We conclude that spoken animation is the best way to communicate
complex health information to people with low health literacy. This format can
even bridge the information processing gap between audiences with low and high
health literacy as the recall differences between the two groups are eliminated.
As animations do not negatively influence high health literate audiences, it is
concluded that information adapted to audiences with low health literacy suits
people with high health literacy as well.
PMID- 25586712
TI - Transfer of natalizumab into breast milk in a mother with multiple sclerosis.
AB - Natalizumab (Tysabri) is a recombinant humanized antibody to alpha4-integrin that
is approved by the Food and Drug Administration for the treatment of multiple
sclerosis (MS) and Crohn disease. This is a case report of a 28-year-old woman
with MS who was taking natalizumab (300 mg intravenously infused over 1 hour
every 4 weeks) while breastfeeding her 11.5-month-old daughter 3 times a day.
Breast milk samples were collected over a 50-day period after the patient's first
drug infusion. The average concentration of natalizumab was 0.93 ug/mL/d, and the
relative infant dose was 1.74% of the weight-adjusted maternal dose. Transfer of
natalizumab into human milk increased over time and with subsequent injections,
with the highest concentration of 2.83 ug/mL at day 50 with a relative infant
dose of 5.3%. Because these data suggest continued accumulation of natalizumab in
milk, and because we cannot provide an accurate assessment of levels of this drug
at 24 weeks (steady state), we are unable to determine safety at this time.
PMID- 25586714
TI - Early results of surgical management of conjunctival dermolipoma: partial
excision and free conjunctival autograft.
AB - BACKGROUND AND AIMS: There is a paucity of data in the literature on the surgical
management of conjunctival dermolipoma. In this study, we report outcomes of a
partial mass excision technique (excision of the portion visible when eyes open)
and free conjunctival autograft. METHODS: Medical records of 13 patients with
dermolipoma who had undergone partial mass excision at Seoul National University
Hospital from January 1999 to May 2014 were retrospectively reviewed. After
resection of the visible part of tumour, including the overlying thick surface
conjunctiva, the conjunctival defects were reconstructed with free conjunctival
autograft harvested from the contralateral superior bulbar area. RESULTS: The
median postoperative follow-up period was 5 months (range 1-84 months). The
cosmetic surgical results were satisfactory in all 13 patients. Three patients
showed thick texture on the grafted surgical area postoperatively, but there was
no significant scar formation resulting in restrictive symblepharon or eye
movement limitation. There were no other significant complications, such as
blepharoptosis, diplopia or keratoconjunctivitissicca during the follow-up
period. CONCLUSIONS: Partial mass (visible part only) excision, including that of
the overlying thick conjunctiva, and free conjunctival autograft from the
opposite eye, is a relatively simple and effective technique for the surgical
management of conjunctival dermolipoma.
PMID- 25586713
TI - Extending the diabetic retinopathy screening interval beyond 1 year: systematic
review.
AB - To determine whether the recommended screening interval for diabetic retinopathy
(DR) in the UK can safely be extended beyond 1 year. Systematic review of
clinical and cost-effectiveness studies. Nine databases were searched with no
date restrictions. Randomised controlled trials (RCTs), cohort studies,
prognostic or economic modelling studies which described the incidence and
progression of DR in populations with type 1 diabetes mellitus or type 2 diabetes
mellitus of either sex and of any age reporting incidence and progression of DR
in relation to screening interval (vs annual screening interval) and/or
prognostic factors were included. Narrative synthesis was undertaken. 14,013
papers were identified, of which 11 observational studies, 5 risk stratification
modelling studies and 9 economic studies were included. Data were available for
262,541 patients of whom at least 228,649 (87%) had type 2 diabetes. There were
no RCTs. Studies concluded that there is little difference between clinical
outcomes from screening 1 yearly or 2 yearly in low-risk patients. However there
was high loss to follow-up (13-31%), heterogeneity in definitions of low risk and
variation in screening and grading protocols for prior retinopathy results.
Observational and economic modelling studies in low-risk patients show little
difference in clinical outcomes between 1-year and 2-year screening intervals.
The lack of experimental research designs and heterogeneity in definition of low
risk considerably limits the reliability and validity of this conclusion. Cost
effectiveness findings were mixed. There is insufficient evidence to recommend a
move to extend the screening interval beyond 1 year.
PMID- 25586715
TI - MultiColor imaging in the evaluation of geographic atrophy due to age-related
macular degeneration.
AB - PURPOSE: To compare different imaging modalities and to investigate the ability
of MultiColor to evaluate geographic atrophy (GA) due to age-related macular
degeneration (AMD). METHODS: Twenty-two consecutive patients with GA underwent
MultiColor, colour fundus photography, blue fundus autofluorescence (FAF)
(excitation=488 nm; emission >500 nm), near-infrared FAF (NIR-FAF)
(excitation=787 nm; emission >800 nm) and spectral-domain optical coherence
tomography (SD-OCT) (Spectralis HRA+OCT; Heidelberg Engineering) imaging. Two
readers independently measured the size (area) and the width of GA (on horizontal
SD-OCT scan cutting the fovea), and evaluated the foveal sparing in each
examination. RESULTS: A total of 32 eyes (22 patients, mean age 79.2+/-8 years)
with GA were included. Intragrader and intergrader agreement considering the
evaluation of the size and width of GA was high for all the examinations.
MultiColor and FAF showed the greatest intergrader agreement for GA area
measurement (intraclass correlation (ICC)=0.990, 95% CI 0.980 to 0.995;
ICC=0.998, 95% CI 0.996 to 0.999, respectively). SD-OCT showed the highest
intergrader agreement of foveal involvement (k=1), followed by MultiColor and NIR
FAF (k=0.68). CONCLUSIONS: We demonstrated that several different imaging
modalities currently available in clinical practice are reliable for evaluating
GA due to AMD. MultiColor is an excellent tool for the measurement of GA area and
width, and for the detection of foveal sparing.
PMID- 25586716
TI - Mercury and other trace elements in Ohio River fish collected near coal-fired
power plants: Interspecific patterns and consideration of consumption risks.
AB - Many coal-fired electric generating facilities in the United States are
discharging higher loads of Hg, Se, and other chemicals to receiving streams due
to the installation of flue gas desulfurization (FGD) air pollution control
units. There are regulatory concerns about the potential increased uptake of
these bioaccumulative trace elements into food webs. We evaluated the
concentrations of As, total Hg (THg), methylmercury (MeHg), and Se in Ohio River
fish collected proximal to coal-fired power plants, of which 75% operate FGD
systems. Fillet samples (n = 50) from 6 fish species representing 3 trophic
levels were analyzed. Geometric mean fillet concentrations of THg (wet wt), MeHg
(wet wt), and Se (dry wt) in 3 species were 0.136, 0.1181, and 3.19 mg/kg
(sauger); 0.123, 0.1013, and 1.56 mg/kg (channel catfish); and 0.127, 0.0914, and
3.30 mg/kg (hybrid striped bass). For all species analyzed, only 3 fillet samples
(6% of total) had MeHg concentrations that exceeded the US Environmental
Protection Agency (USEPA) human health criterion (0.3 mg/kg wet wt); all of these
were freshwater drum aged >= 19 y. None of the samples analyzed exceeded the
USEPA proposed muscle and whole body Se thresholds for protection against
reproductive effects in freshwater fish. All but 8 fillet samples had a total As
concentration less than 1.0 mg/kg dry wt. Mean Se health benefit values (HBVSe )
for all species were >= 4, indicating that potential Hg-related health risks
associated with consumption of Ohio River fish are likely to be offset by
adequate Se concentrations. Overall, we observed no measurable evidence of
enhanced trace element bioaccumulation associated with proximity to power plant
FGD facilities, however, some enhanced bioaccumulation could have occurred in the
wastewater mixing zones. Furthermore, available evidence indicates that, due to
hydraulic and physical factors, the main stem Ohio River appears to have low net
Hg methylation potential.
PMID- 25586718
TI - A study on the encapsulation of an occludin lipophilic derivative in liposomal
carriers.
AB - Many peptides and proteins, although potentially useful for the treatment of
various diseases, are hindered in their clinical use by poor oral absorption and
rapid enzymatic degradation. One of the available solutions to these problems is
to increase the lipophilicity by conjugating the peptides to lipophilic moieties,
making them more able to cross the biomembranes by passive transport. Occludin is
a 65-kDa integral plasma-membrane protein located at the tight junctions. This
protein and the peptide derived from it have potential clinical application for
drug delivery. Peptide OP90-103 (1) is a fragment of occludin that shows a very
poor oral bioavailability and is highly susceptible to enzymatic degradation. The
conjugation of 1 with two lipoamino acid (LAA) moieties has been shown to enhance
its lipophilicity and bioavailability, as well as its enzymatic stability. The
purpose of this study was to evaluate the possibility of encapsulating
fluorescein modified lipidated OP90-103 (2), in unilamellar- (LUV) and
multilamellar liposomes (MLV), which have a different composition and surface
charge and are produced by different methods. The cell internalization of the
carrier systems was evaluated in vitro.
PMID- 25586719
TI - Cell Staining by Photo-activated Dye and Its Conjugate with Chitosan.
AB - Photo-activated or "Caged" rhodamine dyes are the most useful for microscopic
investigation of biological tissue by various fluorescent techniques. Novel
precursor of the fluorescent dye (PFD813) has been studied for photosensitive
staining of numerous animal cells. The functional rhodamine dye (Rho813) with
intensive fluorescence has been obtained after photoactivation of its precursor
PFD813 inside cells. The dye Rho813 has been successfully used for the optical
detection of particular features in biological objects (HaCaT cells, HBL-100,
MDCK, lymphocytes). Moreover, the chitosan conjugate with PFD molecules
("Chitosan-PFD813") has been obtained and studied for the first time. The
developed procedures and obtained data are important for further applications of
novel precursors of fluorescent dyes ("caged" dyes) for microscopic probing of
biological objects. As example, the synthesized "Chitosan-PFD813" has been
successfully applied in this study for intracellular transport visualization by
fluorescent microscopy.
PMID- 25586717
TI - Cocaine induces nuclear export and degradation of neuronal retinoid X receptor
gamma via a TNF-alpha/JNK- mediated mechanism.
AB - Cocaine abuse represents an immense societal health and economic burden for which
no effective treatment currently exists. Among the numerous intracellular
signaling cascades impacted by exposure to cocaine, increased and aberrant
production of pro-inflammatory cytokines in the CNS has been observed.
Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma
(RXR-gamma) in brains of mice chronically exposed to cocaine. Through obligate
heterodimerization with a number of nuclear receptors, RXRs serve as master
regulatory transcription factors, which can potentiate or suppress expression of
a wide spectrum of genes. Little is known about the regulation of RXR levels, but
previous studies indicate cellular stressors such as cytokines negatively
regulate levels of RXRs in vitro. To evaluate the mechanism underlying the
cocaine-induced decreases in RXR-gamma levels observed in vivo, we exposed
neurons to cocaine in vitro and examined pathways which may contribute to
disruption in RXR signaling, including activation of stress pathways by cytokine
induction. In these studies, we provide the first evidence that cocaine exposure
disrupts neuronal RXR-gamma signaling in vitro by promoting its nuclear export
and degradation. Furthermore, we demonstrate this effect may be mediated, at
least in part, by cocaine-induced production of TNF-alpha and its downstream
effector c-Jun-NH-terminal kinase (JNK). Findings from this study are therefore
applicable to both cocaine abuse and to pathological conditions characterized by
neuroinflammatory factors, such as neurodegenerative disease.
PMID- 25586720
TI - Comparison of Gene Expression Profile Between Tumor Tissue and Adjacent Non-tumor
Tissue in Patients with Gastric Gastrointestinal Stromal Tumor (GIST).
AB - Gastrointestinal stromal tumors (GISTs) are defined as spindle cell and/or
epithelioid tumors originated from interstitial Cajal cells or precursors in the
digestive tract. This study was conducted to identify genes differing in
expression between the gastric tumors and the adjacent non-cancerous mucosas in
patients with primary gastric GIST. The gene expression profile was determined by
using oligonucleotide-based DNA microarrays and further validated by quantitative
real-time PCR. The Kyoto encyclopedia of genes and genomes (KEGG) pathway
analysis was performed to predict signaling pathways involved in gastric GIST.
Our data showed that the expression levels of 957 genes (RAB39B, member RAS
oncogene family; VCAN, versican; etc.) were higher and that of 526 genes (CXCL14,
chemokine C-X-C motif ligand 14; MTUS1, microtubule-associated tumor suppressor
1; etc.) were lower in the gastric tumor tissues as compared with normal gastric
tissues. Results from KEGG pathway analysis revealed that the differentially
expressed genes were enriched into 16 signaling transduction pathways, including
Hedeghog and Wnt signaling pathways. Our study may provide basis for
identification of novel biomarkers associated with primary gastric GIST
pathogenesis and for exploration of underlying mechanisms involved in this
gastric sarcoma.
PMID- 25586722
TI - Gas-separation membranes loaded with porous aromatic frameworks that improve with
age.
AB - Porosity loss, also known as physical aging, in glassy polymers hampers their
long term use in gas separations. Unprecedented interactions of porous aromatic
frameworks (PAFs) with these polymers offer the potential to control and exploit
physical aging for drastically enhanced separation efficiency. PAF-1 is used in
the archetypal polymer of intrinsic microporosity (PIM), PIM-1, to achieve three
significant outcomes. 1) hydrogen permeability is drastically enhanced by 375% to
5500 Barrer. 2) Physical aging is controlled causing the selectivity for H2 over
N2 to increase from 4.5 to 13 over 400 days of aging. 3) The improvement with age
of the membrane is exploited to recover up to 98% of H2 from gas mixtures with N2
. This process is critical for the use of ammonia as a H2 storage medium. The
tethering of polymer side chains within PAF-1 pores is responsible for
maintaining H2 transport pathways, whilst the larger N2 pathways gradually
collapse.
PMID- 25586721
TI - Structural dynamics of native and V260E mutant C-terminal domain of HIV-1
integrase.
AB - The C-terminal domain (CTD) of HIV-1 integrase is a five stranded beta-barrel
resembling an SH3 fold. Mutational studies on isolated CTD and full-length IN
have reported V260E mutant as either homo-dimerization defective or affecting the
stability and folding of CTD. In this study, molecular dynamics simulation
techniques were used to unveil the effect of V260E mutation on isolated CTD
monomer and dimer. Both monomeric and dimeric forms of wild type and V260E mutant
are highly stable during the simulated period. However, the stabilizing pi
stacking interaction between Trp243 and Trp243' at the dimer interface is highly
disturbed in CTD-V260E (>6 A apart). The loss in entropy for dimerization is -30
and -25 kcal/mol for CTD-wt and CTD-V260E respectively signifying a weak
hydrophobic interaction and its perturbation in CTD-V260E. The mutant Glu260
exhibits strong attraction/repulsion with all the basic/acidic residues of CTD.
In addition to this, the dynamics of CTD-wild type and V260E monomers at 498 K
was analyzed to elucidate the effect of V260E mutation on CTD folding. Increase
in SASA and reduction in the number of contacts in CTD-V260E during simulation
highlights the instability caused by the mutation. In general, V260E mutation
affects both multimerization and protein folding with a pronounced effect on
protein folding rather than multimerization. This study emphasizes the importance
of the hydrophobic nature and SH3 fold of CTD in proper functioning of HIV
integrase and perturbing this nature would be a rational approach toward
designing more selective and potent allosteric anti-HIV inhibitors.
PMID- 25586723
TI - Cross-resistance and interactions between Bt toxins Cry1Ac and Cry2Ab against the
cotton bollworm.
AB - To delay evolution of pest resistance to transgenic crops producing insecticidal
proteins from Bacillus thuringiensis (Bt), the "pyramid" strategy uses plants
that produce two or more toxins that kill the same pest. We conducted laboratory
diet experiments with the cotton bollworm, Helicoverpa armigera, to evaluate
cross-resistance and interactions between two toxins in pyramided Bt cotton
(Cry1Ac and Cry2Ab). Selection with Cry1Ac for 125 generations produced 1000-fold
resistance to Cry1Ac and 6.8-fold cross-resistance to Cry2Ab. Selection with
Cry2Ab for 29 generations caused 5.6-fold resistance to Cry2Ab and 61-fold cross
resistance to Cry1Ac. Without exposure to Bt toxins, resistance to both toxins
decreased. For each of the four resistant strains examined, 67 to 100% of the
combinations of Cry1Ac and Cry2Ab tested yielded higher than expected mortality,
reflecting synergism between these two toxins. Results showing minor cross
resistance to Cry2Ab caused by selection with Cry1Ac and synergism between these
two toxins against resistant insects suggest that plants producing both toxins
could prolong the efficacy of Bt cotton against this pest in China. Including
toxins against which no cross-resistance occurs and integrating Bt cotton with
other control tactics could also increase the sustainability of management
strategies.
PMID- 25586724
TI - Postoperative impairment of motor function at train-of-four ratio >=0.9 cannot be
improved by sugammadex (1 mg kg-1).
AB - BACKGROUND: A train-of-four ratio (TOFR) >=0.9 measured by quantitative
neuromuscular monitoring is accepted as an indication of sufficient neuromuscular
recovery for extubation, even though many postsynaptic acetylcholine receptors
may still be inhibited. We investigated whether antagonism with sugammadex after
spontaneous recovery to TOFR>=0.9 further improves muscle function or subjective
well-being. METHODS: Following recovery to TOFR>=0.9 and emergence from
anaesthesia, 300 patients randomly received either sugammadex 1.0 mg kg(-1) or
placebo. Fine motor function (Purdue Pegboard Test) and maximal voluntary grip
strength were measured before and after surgery (before and after test drug
administration). At discharge from the postanaesthesia care unit, well-being was
assessed with numerical analogue scales and the Quality-of-Recovery Score 40 (QoR
40). RESULTS: Patients' fine motor function [6 (sd 4) vs 15 (3) pegs (30 s)(-1),
P<0.05] and maximal voluntary grip strength (284 (126) vs 386 (125) N, P<0.05)
were significantly lower after anaesthesia compared with the pre-anaesthesia
baseline. After sugammadex or placebo, motor function was significantly improved
in both groups but did not reach the preoperative level. There was no difference
between groups at any time. Global well-being was unaffected (QoR-40: placebo,
174 vs 185; sugammadex, 175 vs 186, P>0.05). CONCLUSIONS: Antagonizing rocuronium
at TOF>=0.9 with sugammadex 1.0 mg kg(-) (1) did not improve patients' motor
function or well-being when compared with placebo. Our data support the view that
TOFR>=0.9 measured by electromyography signifies sufficient recovery of
neuromuscular function. CLINICAL TRIAL REGISTRATION: The trial is registered at
ClinicalTrials.gov (NCT01101139).
PMID- 25586725
TI - Variability in practice and factors predictive of total crystalloid
administration during abdominal surgery: retrospective two-centre analysis.
AB - BACKGROUND: Variation in clinical practice in the perioperative environment and
intensive care unit is a major challenge facing modern medicine. The objective of
the present study was to analyse intraoperative crystalloid administration
practices at two academic medical centres in the USA. METHODS: We extracted
clinical data from patients undergoing intra-abdominal procedures performed at UC
Irvine (UCI) and Vanderbilt University (VU) Medical Centres. Limiting data to
uncomplicated elective surgery with minimal blood loss, we quantified variability
in fluid administration within individual providers, between providers, and
between types of procedures using a corrected coefficient of variation (cCOV).
Regression was performed using a general linear model to determine factors most
predictive of fluid administration. RESULTS: For provider analysis and model
building, 1327 UCI and 4585 VU patients were used. The average corrected
crystalloid infusion rate across all providers at both institutions was 7.1 (sd
4.9) ml kg(-1) h(-1), an overall cCOV of 70%. Individual providers ranged from
2.3 (sd 3.7) to 14 (sd 10) ml kg(-1) h(-1). The final regression model strongly
favoured personnel as predictors over other patient predictors. CONCLUSIONS: Wide
variability in crystalloid administration was observed both within and between
individual anaesthesia providers, which might contribute to variability in
surgical outcomes.
PMID- 25586726
TI - Population pharmacokinetics of epsilon-aminocaproic acid in adolescents
undergoing posterior spinal fusion surgery.
AB - BACKGROUND: Despite demonstrated efficacy of epsilon-aminocaproic acid (EACA) in
reducing blood loss in adolescents undergoing spinal fusion, there are no
population-specific pharmacokinetic data to guide dosing. The aim of this study
was to determine the pharmacokinetics of EACA in adolescents undergoing spinal
fusion surgery and make dosing recommendations. METHODS: Twenty children ages 12
17 years were enrolled, with 10 children in each of two groups based on diagnosis
(idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from
infants undergoing craniofacial surgery were included in the model to enable
dosing recommendations over a wide range of weights, ages, and diagnoses. A
population non-linear mixed effects modelling approach was used to characterize
EACA pharmacokinetics. RESULTS: Population pharmacokinetic parameters were
estimated using a two-compartment disposition model with allometrically scaled
weight and an age effect on clearance. Pharmacokinetic parameters for the typical
patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(
0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1)
kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre
kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23
litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect
on drug pharmacokinetics. CONCLUSIONS: The following dosing schemes are
recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading
dose and 40 mg kg(-1) h(-1) infusion; weight <=25 kg-<50 kg, 100 mg kg(-1)
loading dose and 35 mg kg(-1) h(-1) infusion; and weight >=50 kg, 100 mg kg(-1)
loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this
dosing strategy is warranted. CLINICAL TRIAL REGISTRATION: NCT01408823.
PMID- 25586728
TI - Point prevalence of surgical checklist use in Europe: relationship with hospital
mortality.
AB - BACKGROUND: The prevalence of use of the World Health Organization surgical
checklist is unknown. The clinical effectiveness of this intervention in
improving postoperative outcomes is debated. METHODS: We undertook a
retrospective analysis of data describing surgical checklist use from a 7 day
cohort study of surgical outcomes in 28 European nations (European Surgical
Outcomes Study, EuSOS). The analysis included hospitals recruiting >10 patients
and excluding outlier hospitals above the 95th centile for mortality.
Multivariate logistic regression and three-level hierarchical generalized mixed
models were constructed to explore the relationship between surgical checklist
use and hospital mortality. Findings are presented as crude and adjusted odds
ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 45 591
patients from 426 hospitals were included in the analysis. A surgical checklist
was used in 67.5% patients, with marked variation across countries (0-99.6% of
patients). Surgical checklist exposure was associated with lower crude hospital
mortality (OR 0.84, CI 0.75-0.94; P=0.002). This effect remained after adjustment
for baseline risk factors in a multivariate model (adjusted OR 0.81, CI 0.70
0.94; P<0.005) and strengthened after adjusting for variations within countries
and hospitals in a three-level generalized mixed model (adjusted OR 0.71, CI 0.58
0.85; P<0.001). CONCLUSIONS: The use of surgical checklists varies across
European nations. Reported use of a checklist was associated with lower
mortality. This observation may represent a protective effect of the surgical
checklist itself, or alternatively, may be an indirect indicator of the quality
of perioperative care. CLINICAL TRIAL REGISTRATION: The European Surgical
Outcomes Study is registered with ClinicalTrials.gov, number NCT01203605.
PMID- 25586727
TI - Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage:
randomized controlled trial.
AB - BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of
fibrinogen is associated with excessive subsequent bleeding and blood
transfusion. We hypothesized that pre-emptive treatment with fibrinogen
concentrate reduces the need for red blood cell (RBC) transfusion in patients
with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded,
parallel randomized controlled trial, we assigned subjects with severe PPH to a
single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or
equivalent was given to all subjects independent of body weight and the
fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up
to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of
blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC
transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe
PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at
least 4 units of RBCs, haemostatic intervention (angiographic embolization,
surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the
249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the
placebo group were included in the intention-to-treat analysis. At inclusion the
subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean
fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group
received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby
significantly increasing fibrinogen concentration compared with placebo by 0.40 g
litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood
transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the
placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88).
We found no difference in any predefined secondary outcomes, per-protocol
analyses, or adjusted analyses. No thromboembolic events were detected.
CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as
pre-emptive treatment for severe PPH in patients with normofibrinogenaemia.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov:
http://clinicaltrials.gov/show/NCT01359878. Published protocol:
http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
PMID- 25586729
TI - Aberrant right subclavian artery in fetuses with Down syndrome: a systematic
review and meta-analysis.
AB - OBJECTIVES: The primary objective was to estimate the prevalence of aberrant
right subclavian artery (ARSA) in fetuses with Down syndrome. Secondary
objectives were to assess the prevalence of ARSA in euploid fetuses, the
feasibility of ultrasound evaluation of the right subclavian artery (RSA) in the
first and second trimesters of pregnancy, the performance of ARSA in screening
for trisomy 21 and its association with other abnormalities. METHODS: Web-based
databases (PubMed, EMBASE and MEDLINE) were searched up to July 2014. The STROBE,
PRISMA and QUIPS instruments were used to assess all included studies and for
reporting of methodology, results and conclusions. Original studies that reported
prenatal ultrasound evaluation of ARSA, assessment of its prevalence in Down
syndrome and euploid fetuses, feasibility of ultrasound evaluation of the RSA in
the first and second trimesters of pregnancy and correlation of ARSA with other
abnormalities were included, excluding duplications and case reports. Collected
data were summarized to estimate prevalence and feasibility. A meta-analysis was
performed pooling the study-specific positive and negative likelihood ratios (LR+
and LR-), detection rates and false-positive rates for trisomy 21. RESULTS:
Prevalence of ARSA in Down-syndrome fetuses was 23.6% (95% CI, 19.4-27.9%),
whereas in euploid fetuses it was 1.02% (95% CI, 0.86-1.10%). Ultrasound
evaluation of the RSA course and origin in the first and second trimesters of
pregnancy was feasible in 85% and 98% of cases (first and second trimester,
respectively) and it was directly related to sonographic experience and fetal
crown-rump length and inversely related to maternal body mass index. In more than
20% of fetuses with ARSA there was an association with other abnormalities but
ARSA seemed to be an independent marker of trisomy 21. The meta-analysis showed
that ARSA is a significant risk factor for Down syndrome (pooled LR+ = 26.93, 95%
CI, 19.36-37.47, P for effect < 0.001, P for Q = 0.3, I(2) = 17.3%), whereas
normal RSA is a significant protective marker (pooled LR- = 0.71, 95% CI, 0.51
0.99, P for effect = 0.043, P for Q = 0.9, I(2) = 0%). CONCLUSIONS: ARSA appears
to be a clinically useful prenatal ultrasound marker of Down syndrome. Additional
testing when ARSA is diagnosed should involve evaluation of all risk factors by
applying a mathematical model. There is insufficient evidence to recommend fetal
karyotyping in cases with isolated ARSA. If the background risk is higher or
additional markers are present, full fetal karyotyping is advisable, including
analysis for 22q11 microdeletion.
PMID- 25586731
TI - Feasibility and safety of left ventricular endomyocardial biopsy via transradial
access: Technique and initial experience.
AB - BACKGROUND: Endomyocardial biopsy constitutes an essential part of the diagnostic
algorithm in patients with heart failure of unknown origin, but usually requires
transfemoral access. METHODS AND RESULTS: Here, we describe a novel method that
allows interventional cardiologists to obtain left ventricular biopsies via
transradial access with a 7.5F sheathless multipurpose (MP1.0) guiding catheter.
This approach was successfully conducted in 37 consecutive patients at our
institution with only one intraprocedural minor complication (ventricular
fibrillation during insertion of the guiding catheter). CONCLUSIONS: Transradial
access to obtain left ventricular endomyocardial biopsies is a feasible and safe
option for experienced radial operators.
PMID- 25586732
TI - The imperative to prevent and treat childhood obesity: why the world cannot
afford to wait.
AB - In the past 20 years, the prevalence of obesity in the United States increased
almost 50% among adults and by 300% in children. Today, 9.7% of all U.S. infants
up to 2 years old have abnormally high weight-for-recumbent length; 25% of
children under age 5 are either overweight or obese; and 17% of adolescents are
obese. Ethnic disparities in the rates of obesity are also large and apparent in
childhood. Further, 44% of obese adolescents have metabolic syndrome. Obese
children tend to become obese adults; thus, in a decade, young adults will likely
have much higher risks of chronic disease, which has tremendous implications for
the healthcare system. However, early childhood may be the best time to prevent
obesity. Teachers' healthy eating choices are positively associated with changes
in body mass index percentiles for children, for example. In addition, 8 million
children attend afterschool programs, which can successfully promote health and
wellness and successfully treat obesity. This childhood epidemic of obesity and
its health-related consequences in adolescents should be a clinical and public
health priority. However, this major public health problem cannot be managed
solely in clinical settings. Rather, public health strategies must be integrated
into home and family, school and community-based settings.
PMID- 25586730
TI - Virulence and the presence of aminoglycoside resistance genes of Staphylococcus
haemolyticus strains isolated from clinical specimens.
AB - We examined thirty methicillin-resistant Staphylococcus haemolyticus isolates
cultured from clinical specimens for antibiotic resistance, various important
interactions of the bacteria with epithelial cells and putative virulence
determinants. All strains were resistant to oxacillin and carried the mecA gene.
Aminocyclitol-3'-phosphotransferase (aph(3')-IIIa) gene encoding
nucleotidyltransferases was detected in 43 %, aminocyclitol-6'-acetyltransferase
aminocyclitol-2"-phosphotransferase (aac(6')/aph(2")) gene encoding bifunctional
acetyltransferases/phosphotransferases in 33 %, aminocyclitol-4'
adenylyltransferase (ant(4')-Ia) gene encoding phosphotransferases in 20 %. The
coexistence of resistance to methicillin and aminoglycosides was investigated in
multi-resistant strains. Coexisting (aac(6')/aph(2")) and (aph(3')-IIIa) genes
were detected in 33 % of isolates, whereas 63 % of isolates had at least one of
these genes. All strains revealed adherence ability and most of them (63 %) were
invasive to epithelial cells. Electron microscopy revealed that the bacteria were
found in vacuoles inside the cells. We observed that the contact of the bacteria
with host epithelial cells is a prerequisite to their cytotoxicity at 5 h
incubation. Culture supernatant of the strains induced a low effect of
cytotoxicity at the same time of incubation. Cell-free supernatant of all
isolates expressed cytotoxic activity which caused destruction of HEp-2 cells at
24 h. None of the strains was cytotonic towards CHO cells. Among thirty strains,
27 % revealed lipolytic activity, 43 % produced lecithinase and 20 % were
positive for proteinase activity. Analyses of cellular morphology and DNA
fragmentation exhibited typical characteristic features of those undergoing
apoptosis. The Pearson linear test revealed positive correlations between the
apoptotic index at 24 h and percentage of cytotoxicity. Our results provided new
insights into the mechanisms contributing to the development of S. haemolyticus
associated infections. The bacteria adhered and invaded to non-professional
phagocytes. The invasion of epithelial cells by S. haemolyticus could be similar
to phagocytosis that requires polymerization of the actin cytoskeleton. The
process is inhibited by cytochalasin D. Moreover, they survived within the cells
by residing in membrane bound compartments and induced apoptotic cell death.
PMID- 25586734
TI - The relationship of distance from the surgical centre on attendance and weight
loss after laparoscopic gastric bypass surgery in the United Kingdom.
AB - Obesity remains a significant worldwide health problem and is currently
increasing. Surgery remains the only proven long-term intervention and has been
shown to be cost-effective. Evidence suggests that regular follow-up following
laparoscopic adjustable gastric banding is related to improved outcome, such
evidence is lacking for laparoscopic gastric bypass surgery (laparoscopic Roux-en
Y gastric bypass [LRYGB]). This study examines the effect of distance on
attendance at post-operative clinics and subsequent weight loss following
surgery. A prospectively maintained database was interrogated to analyze patients
undergoing LRYGB before August 2010. Patient demographics, percentage excess
weight loss (%EWL), compliance with out-patient clinic attendances and the
distance the patients lived from the hospital were examined. Perfect clinic
attendees were compared with non-attendees and the distances patients lived from
the hospital evaluated. There was a significantly greater %EWL at 1 year post-op
observed in the perfect attendees group (65.5 vs. 59.5, P = 0.01). Increased %EWL
was also evident at 2 years post-op but did not reach statistical significance
(66.9 vs. 59.5, P = 0.06). There was a negative correlation observed between post
operative weight loss and distance from the bariatric centre (R = -0.21, P =
0.04). Close follow-up following LRYGB is essential to optimize outcomes.
Increased frequency of out-patient clinic visits was associated with improved
post-operative weight loss. Increasing distance between the patient's home and
the bariatric centre was associated with worse post-operative weight loss.
PMID- 25586733
TI - An intragastric balloon produces large weight losses in the absence of a change
in ghrelin or peptide YY.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: The development of obesity is a multi
factorial process that results in an alteration in the neuroendocrine hormones
that help regulate appetite and body weight. Weight loss has been shown to alter
this neuroendocrine balance so as to promote weight regain. An intragastric
balloon is an effective method to achieve significant weight loss in obese
patients and is well suited for those patients who are looking for an alternative
to lifestyle modification alone, and those who are not ready or suitable for
surgical intervention. Limited research has shown that the weight loss achieved
with an intragastric balloon is mediated by altered secretion of the hormones
that regulate appetite and weight. WHAT DOES THIS STUDY ADD?: There are currently
limited data on the effects of intragastric balloons on appetite and weight
related hormones. In the current study, we have investigated a broad range of gut
hormones and adipokines and their response to weight loss induced by differing
methods, and the subsequent effect this may have on weight regain. This is an
important research area as novel therapies and long-term strategies are needed to
counteract the unfavourable changes to the neuroendocrine control of appetite and
satiety associated with diet-induced weight loss. This study aims to determine
the effect of weight loss achieved with different methods on fasting levels of
appetite hormones. Sixty-six obese adults with metabolic syndrome were randomized
to intragastric balloon (IGB) for 6 months, with a 12-month behavioural
modification programme (IGB group, 'IGBG') or a 12-month behavioural modification
programme alone (control group, 'CG'). Anthropometric assessments and blood
samples were taken every 3 months and total ghrelin, peptide YY (PYY),
adiponectin and leptin were measured. Significant weight-loss differences
favouring the IGBG were evident between groups at all time points. Ghrelin
increased when the IGB was in situ (+39.3 pmol L(-1) vs. baseline) and returned
to baseline after its removal (-34.7 pmol L(-1) ). Adiponectin and PYY levels
remained stable in the IGBG, with transient increases noted in the CG. There were
no significant between-group differences for ghrelin, PYY or adiponectin. In the
IGBG, despite a decrease in leptin at 6 months (-11.7 ng mL(-1) ), levels
increased to baseline after IGB removal (-3.7 ng mL(-1) ). In summary, weight
loss associated with the IGB did not alter fasting levels of PYY or adiponectin.
There was a return of ghrelin and leptin levels to baseline values after IGB
removal. No compensatory rise in ghrelin was evident in either group 12 months
after initial weight reduction, suggesting that such treatment strategies may
lead to better long-term sustainable weight loss.
PMID- 25586735
TI - Patients' experiences after bariatric surgery: a qualitative study at 12-month
follow-up.
AB - This study used a qualitative approach to understand patients' experiences in
post-surgery adaptation related to bariatric surgery, 12 months after this
procedure. The study population included 30 obese adults, with a mean age of
40.17 years, who were interviewed 12 months after bariatric surgery. Individual
interviews, using open-ended questions, were audiotaped, transcribed and coded
according to the grounded theory methodology. The data showed that the subjects
described themselves as belonging to one of two opposite and separate groups:
success or failure. In both groups, two core categories emerged from the data:
outcomes and treatment. Previous expectations were reached by the patients who
described themselves as successful, with some remaining concerns related to
future weight maintenance and aesthetics issues. The failure group emphasized
their unmet expectations and the expectancy that surgery would change their lives
remained. Treatment in the successful cases integrated lifestyle changes and
bariatric surgery, highlighting the personal commitment required to achieve the
objectives. The failure group emphasized bariatric surgery without personal
commitment, and healthy eating behaviour was understood as a sacrifice. The post
surgical adaptation experiences were diverse: the cases that were described as a
success highlighted lifestyle changes, personal efforts and commitment with the
global treatment process. External understanding and the desire for a miracle
surgery characterized the cases described as a failure. According to these
results, it is necessary to promote adequate information about the whole process
and skills required to ensure commitment in all treatment dimensions.
PMID- 25586736
TI - Emergence of New Onset substance use disorders among post-weight loss surgery
patients.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Elevated rates of substance use
disorders (SUDs), particularly (but not only) alcohol use, are observed among
post-weight loss surgery (WLS) patients. The development of SUDs among post-WLS
patients typically occurs 1-2 years post-surgery. Post-WLS patients are
developing SUD at a much later time of life than is typical of SUDs in the
general population, suggesting they constitute a distinct SUD phenotype that is
directly related to having undergone WLS. WHAT THIS STUDY ADDS: Overall, findings
suggest that post-WLS patients are overrepresented in substance abuse treatment
programmes, and the majority of them report no history of SUD before WLS.
Relative to non-WLS patients in SUD treatment, post-WLS patients in substance
abuse treatment are disproportionally diagnosed with alcohol dependence,
including alcohol withdrawal. Post-WLS patients may be at elevated risk for
development of New Onset SUD in the absence of a prior SUD history; this group is
phenotypically different from those with a history of substance abuse prior to
surgery, and such patients may have unique treatment needs. A comprehensive
substance abuse treatment facility began observing increased admissions who
reported histories of weight loss surgery (WLS). Emerging evidence suggests that
roughly half of post-WLS patients in substance abuse treatment developed their
substance use disorder (SUD) after surgery. The present study examined
differences between SUD patients who developed New Onset SUD after surgery and
those with a reported SUD onset before WLS (SUD Hx+ group). Participants
completed a questionnaire and participated in a semi-structured interview. Data
were also obtained from participants' electronic medical records. Of the total
treatment sample (n = 4658), 2.8% reported a history of WLS. Post-WLS patients
were significantly more likely to be diagnosed with alcohol use disorders (AUDs).
Among post-WLS patients who were interviewed (n = 56), 60% were classified as New
Onset SUD, while only 40% were SUD Hx+. SUD Hx+ cases reported using
significantly more types of substances than New Onset cases and were more likely
to report pre-surgical binge eating disorder (BED). Post-WLS patients are
overrepresented in substance abuse treatment and are disproportionally diagnosed
AUDs. Post-WLS patients may be at elevated risk for development of New Onset SUD
at a time in life (middle age) when SUD onset is relatively uncommon.
PMID- 25586737
TI - Impact of physical activity and diet on lipoprotein particle concentrations in
severely obese women participating in a 1-year lifestyle intervention.
AB - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Physical activity and high aerobic
fitness protects against cardiovascular disease and early death, besides having a
very modest impact on lipoprotein-cholesterol in obese subjects. Physical
activity has been shown to favourably alter lipoprotein particle concentrations
and apolipoprotein B with minimal weight loss in overweight to moderately obese
subjects. WHAT THIS STUDY ADDS: We studied the impact of physical activity on
lipoprotein subclass particle concentrations in women with severe obesity.
Increased physical activity duration was associated with favourable changes,
whereas increased PA intensity was associated with adverse changes in some
lipoprotein particle subclasses in severely obese women. Severely obese women
that manage to increase their physical activity level can improve their
lipoprotein profile, whether or not they lose fat mass Physical activity (PA) and
high aerobic fitness protects against cardiovascular disease and early death
possibly among others because of an anti-atherogenic impact on lipoprotein
particle concentrations. The objective of this study was to determine the impact
of PA and diet on lipoprotein particle concentrations. Thirty-one severely obese
women (age 43.6 +/- 10.2 years; body mass index 43.0 +/- 6.3 kg m(-2) )
participated in a 1-year lifestyle intervention with repeated measurements of
lipoprotein particle subclass concentrations and size of very low density
lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein
(HDL), as well as fat mass, PA and diet. Multiple regression was used to
determine associations with change (Delta) in two principal components (PCs)
describing lipoprotein distributions: DeltaPC 1 LIPO (dominated by VLDL and LDL)
and DeltaPC 2 LIPO (dominated by large HDL and mean HDL particle size). DeltaPA
duration was the only variable that was significantly related to DeltaPC 1 LIPO
(partial r = -0.40, P = 0.008), while DeltaPA intensity was the only variable
that was significantly related to DeltaPC 2 LIPO (partial r = -0.43, P = 0.003)
in adjusted models. Increased PA duration was associated with favourable changes,
whereas increased PA intensity was associated with adverse changes in some
lipoprotein particle subclasses in severely obese women.
PMID- 25586738
TI - Toward a culturally sensitive conceptualization of resilience: Participatory
research with war-affected communities in northern Uganda.
AB - Resilience research with war-affected populations has long conceptualized
resilience as the absence of psychopathology and operationalized it by use of
standardized measures. However, literature on resilience increasingly highlights
the importance of also including indicators of positively valued functioning as
well as contextually sensitive indicators of resilience. This study used a
participatory approach to examine the contextual conceptualization of youth
resilience in the aftermath of war in northern Uganda, as defined by groups of
stakeholders (youths, parents, elders, leaders, teachers) in four communities.
The results identify 40 indicators covering a multiplicity of domains of
functioning. The rationales behind these indicators were clustered into the broad
themes: progress, self-reliance, social connectedness, morality, health, and
comfort. The findings suggest that positively and negatively valued aspects of
functioning are both key to conceptualizing resilience, and indicate the
importance of including contextually distinguished indicators. The findings
further point to the role of individual and collective processes in the
construction of resilience, and to the need to take into account the contexts
wherein resilience is conceptualized and observed. This study generated
contextually sensitive indicators of young people's resilience, which can be
used, complementary to existing measures of functioning, to provide a more
comprehensive and culturally sensitive view of youths' resilience in the wake of
war adversity.
PMID- 25586739
TI - Training international medical graduates in psychiatry: a cultural adventure.
PMID- 25586740
TI - MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human
lung cancer cell line via the transforming growth factor-beta/Smad2/STAT3/STAT5
pathway.
AB - Lung cancer is one of the primary causes of mortality worldwide and drug
resistance is the key contributing factor which results in the failure of lung
cancer chemotherapy. Previous studies have shown that microRNA (miR)-10a was
involved in the reversal of cisplatin (DDP) resistance in numerous types of
tumors; however, the underlying mechanism of action of this remains to be fully
elucidated. In the present study, miR-10a silencing in human DDP-resistant lung
cancer A549/DDP cells was demonstrated to improve DDP sensitivity, apoptosis,
intracellular rhodamine-123 content as well as the expression and activity of
caspase-3/8. In addition, miR-10a suppressed the cellular expression of P
glycoprotein, multi-drug resistance protein (MDR) 1, MDR-associated protein 1,
RhoE, B cell lymphoma-2 and survivin in A549/DDP cells. Furthermore, miR-10a
silencing inhibited the secretion of transforming growth factor (TGF)-beta,
phosphorylation of Sma- and Mad-related protein (Smad)2, signal transducer and
activator of transcription (STAT)3 and STAT5, the transcriptional activity of
hypoxia-inducible factor and eukaryotic translation initiation factor 4E in human
lung cancer A549/DDP cell line. These results therefore indicated that miR-10a
may be a potential target for improving the effectiveness of lung cancer
chemotherapy via regulation of the TGF-beta/Smad2/STAT3/STAT5 pathway.
PMID- 25586741
TI - Nitroprusside single-dose prevents the psychosis-like behavior induced by
ketamine in rats for up to one week.
AB - Recently, we found a rapid and long-lasting improvement of symptoms in
schizophrenic patients on antipsychotics after a single four-hour infusion of
sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life.
This improvement persisted for up to 4weeks. Because these patients remained on
antipsychotics after infusion of SNP was finished, the question arises about
whether this improvement was due to SNP itself. We have now investigated whether
SNP, alone, can produce preventive antipsychotic effects in rats treated with
ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4mg/kg,
KET 25mg/kg, or saline as follows: group1 - saline, group2 - SNP, group3 - KET,
group4 - KET 12h after SNP, group5 - KET 1day after SNP, group6 - KET 2days after
SNP, and group7 - KET 1week after SNP. The animals were filmed in an open field
arena for 30min and the videos were later analyzed by ANY-Maze software to
measure activity and stereotypy. SNP significantly prevented the emergence of
hyperactivity induced by KET when it was administered for up to 1week before KET,
and prevented the emergence of stereotypies when it was administered for up to
1day before KET. These findings in rats, which have an even faster metabolic rate
than humans, suggest that the long-lasting effects observed in our clinical trial
with SNP in humans could have been due to SNP itself, and indicate for the first
time that SNP may present preventive antipsychotic effects.
PMID- 25586742
TI - The defect of both angiogenesis and lymphangiogenesis is involved in
preeclampsia.
AB - INTRODUCTION: Pre-eclampsia (PE) is characterized by failed remodeling of
maternal vessels perfusing the placenta. Blood vessels and lymphatic system are
involved in vessel remodeling and flow homeostasis in the uterus during
pregnancy. This study aims to investigate the involvement of angiogenesis and
lymphangiogenesis in PE. METHODS: Placental and decidual tissues were obtained
from pregnancies with PE (n = 90), including PE cases with decidual vasculopathy
(DV) (n = 52) and without DV (n = 38), and healthy pregnancies (control, n = 20).
The clinical characteristics of these groups were analyzed. The expression levels
of VEGF1, CD34, PROX-1, VEGFR3, and CD31 in the placenta and decidua were
detected through immunohistochemistry, reverse-transcription polymerase chain
reaction, and Western blot. RESULTS: The lymphangiogenic markers PROX-1 and
VEGFR3 were negatively expressed in the placenta but positively expressed in the
decidua. The expression levels of the angiogenic markers VEGF1 and CD34 and the
panendothelial marker CD31 were significantly lower in the placenta and decidua
of the PE group than in those of the control group. The expression levels of
VEGF1, CD34, and CD31 were significantly lower in the placenta and decidua with
DV than in those without DV. Furthermore, the expression trends of PROX-1 and
VEGFR3 was similar to those of VEGF1, CD34, and CD31 among the groups.
CONCLUSIONS: Lymphangiogenesis occurred in the decidua but not in the placenta.
Impaired angiogenesis and lymphangiogenesis were associated with PE, particularly
in the presence of DV.
PMID- 25586743
TI - Chitosan-based scaffold modified with D-(+) raffinose for cartilage repair: an in
vivo study.
AB - BACKGROUND: Osteochondral defects significantly affect patients' quality of life
and represent challenging tissue lesions, because of the poor regenerative
capacity of cartilage. Tissue engineering has long sought to promote cartilage
repair, by employing artificial scaffolds to enhance cell capacity to deposit new
cartilage. An ideal biomaterial should closely mimic the natural environment of
the tissue, to promote scaffold colonization, cell differentiation and the
maintenance of a differentiated cellular phenotype. The present study evaluated
chitosan scaffolds enriched with D-(+) raffinose in osteochondral defects in
rabbits. Cartilage defects were created in distal femurs, both on the condyle and
on the trochlea, and were left untreated or received a chitosan scaffold. The
animals were sacrificed after 2 or 4 weeks, and samples were analysed
microscopically. RESULTS: The retrieved implants were surrounded by a fibrous
capsule and contained a noticeable inflammatory infiltrate. No hyaline cartilage
was formed in the defects. Although defect closure reached approximately 100% in
the control group after 4 weeks, defects did not completely heal when filled with
chitosan. In these samples, the lesion contained granulation tissue at 2 weeks,
which was then replaced by fibrous connective tissue by week 4. Noteworthy,
chitosan never appeared to be integrated in the surrounding cartilage.
CONCLUSIONS: In conclusion, the present study highlights the limits of D-(+)
raffinose-enriched chitosan for cartilage regeneration and offers useful
information for further development of this material for tissue repair.
PMID- 25586745
TI - Debunking myths and enhancing medical student learning within the emergency
department.
PMID- 25586744
TI - A BTP1 prophage gene present in invasive non-typhoidal Salmonella determines
composition and length of the O-antigen of the lipopolysaccharide.
AB - Salmonella Typhimurium isolate D23580 represents a recently identified ST313
lineage of invasive non-typhoidal Salmonellae (iNTS). One of the differences
between this lineage and other non-iNTS S. Typhimurium isolates is the presence
of prophage BTP1. This prophage encodes a gtrC gene, implicated in O-antigen
modification. GtrC(BTP) (1) is essential for maintaining O-antigen length in
isolate D23580, since a gtr(BTP) (1) mutant yields a short O-antigen. This
phenotype can be complemented by gtrC(BTP) (1) or very closely related gtrC
genes. The short O-antigen of the gtr(BTP) (1) mutant was also compensated by
deletion of the BTP1 phage tailspike gene in the D23580 chromosome. This
tailspike protein has a putative endorhamnosidase domain and thus may mediate O
antigen cleavage. Expression of the gtrC(BTP) (1) gene is, in contrast to
expression of many other gtr operons, not subject to phase variation and
transcriptional analysis suggests that gtrC is produced under a variety of
conditions. Additionally, GtrC(BTP) (1) expression is necessary and sufficient to
provide protection against BTP1 phage infection of an otherwise susceptible
strain. These data are consistent with a model in which GtrC(BTP) (1) mediates
modification of the BTP1 phage O-antigen receptor in lysogenic D23580, and
thereby prevents superinfection by itself and other phage that uses the same O
antigen co-receptor.
PMID- 25586746
TI - Mental health facility design: the case for person-centred care.
PMID- 25586747
TI - Fostering early and mid-career research in affective disorders.
PMID- 25586748
TI - Access to the internet in an acute child and adolescent mental health inpatient
unit.
PMID- 25586749
TI - Evolution of troponin, C-reactive protein and eosinophil count with the onset of
clozapine-induced myocarditis.
PMID- 25586750
TI - The role of anger and ongoing stressors in mental health following a natural
disaster.
AB - OBJECTIVE: Research has established the mental health sequelae following
disaster, with studies now focused on understanding factors that mediate these
outcomes. This study focused on anger, alcohol, subsequent life stressors and
traumatic events as mediators in the development of mental health disorders
following the 2009 Black Saturday Bushfires, Australia's worst natural disaster
in over 100 years. METHOD: This study examined data from 1017 (M = 404, F = 613)
adult residents across 25 communities differentially affected by the fires and
participating in the Beyond Bushfires research study. Data included measures of
fire exposure, posttraumatic stress disorder, depression, alcohol abuse, anger
and subsequent major life stressors and traumatic events. Structural equation
modeling assessed the influence of factors mediating the effects of fire exposure
on mental health outcomes. RESULTS: Three mediation models were tested. The final
model recorded excellent fit and observed a direct relationship between disaster
exposure and mental health outcomes (b = .192, p < .001) and mediating
relationships via Anger (b = .102, p < .001) and Major Life Stressors (b = .128,
p < .001). Each gender was compared with multiple group analyses and while the
mediation relationships were still significant for both genders, the direct
relationship between exposure and outcome was no longer significant for men (p =
.069), but remained significant (b = .234, p < .001) for women. CONCLUSIONS:
Importantly, anger and major life stressors mediate the relationship between
disaster exposure and development of mental health problems. The findings have
significant implications for the assessment of anger post disaster, the provision
of targeted anger-focused interventions and delivery of government and community
assistance and support in addressing ongoing stressors in the post-disaster
context to minimize subsequent mental health consequences.
PMID- 25586751
TI - Eating behavior and obesity in bipolar disorder.
AB - OBJECTIVES: Individuals with bipolar disorder are more frequently overweight or
obese than the general population, but the reasons for this association are
unknown. The aim of this study is to further understand the etiology of
overweight and obesity in bipolar disorder. METHODS: We invited patients in a
specialty outpatient bipolar clinic to complete the Eating Inventory. Patients
provided self-reported restraint, disinhibition, and perceived hunger as well as
general perceptions of dietary intake. RESULTS: Sixty-two individuals (37 female)
between the ages of 18 and 67 (M = 41.5, SD = 13.38) and with an average body
mass index (BMI) of 27.18 (SD = 5.71) completed the survey. Disinhibition and
perceived hunger were positively correlated with BMI and self-reported difficulty
eating healthy foods. Restraint was positively correlated with healthy eating (ps
< .05). Stepwise linear regressions revealed that hunger was the most significant
predictor of BMI (F(1) = 8.134, p = .006). Those participants with bipolar I or
II disorder reported greater hunger scores (p < .01) and difficulty eating
healthily (p < .05) than those without a full diagnosis. CONCLUSIONS: These
results suggest that disinhibition and perception of hunger may be linked to the
disproportionately high rate of obesity in bipolar disorder.
PMID- 25586752
TI - Cardiovascular risk factor associations in adults with psychosis and adults in a
national comparator sample.
AB - OBJECTIVE: Antipsychotic drug treatment alters status on key risk factors for
cardiovascular disease. The aim of this study was to test whether cardiovascular
risk factor associations differ in adults with psychosis and adults from the
general community. METHOD: Data were analysed for those aged 25-64 years from a
nationally representative psychosis sample (n = 1,457) and a national comparator
sample (n = 8,866). The Pearson correlation coefficient was used to estimate the
association among tobacco use, body mass index, waist circumference, diastolic
and systolic blood pressure and fasting total-, LDL- and HDL-cholesterol,
triglycerides and plasma glucose. The robust Levene test was used to test for
sample differences in variance. RESULTS: Correlations among cardiovascular risk
indicators and between cardiovascular risk indicators and age were often
significantly weaker in those with psychosis than in those from the national
comparator sample. This was not due to a reduction in variance within the
psychosis sample. CONCLUSIONS: Risk prediction that synthesizes multivariate risk
indicator data needs to be connected to verified cardiovascular morbidity and
mortality in those with psychosis to determine if standard risk calculators
adequately discriminate those at high, medium and low future risk of
cardiovascular morbidity and mortality. Until then the clinical implications of
low or absent correlations among cardiovascular risk indicators and their low or
absent association with increasing age is unclear but may indicate that risk
equations commonly used in the general population may not be applicable for those
with treated psychosis.
PMID- 25586753
TI - The association between use of antidepressants and bone quality using
quantitative heel ultrasound.
AB - OBJECTIVE: Osteoporosis and depression are major public health problems
worldwide. Studies have reported an association between antidepressant use,
mainly selective serotonin reuptake inhibitors (SSRIs), and bone mineral density
(BMD), but the issue remains unclear. METHODS: This study examined data collected
from 849 Australian men (aged 24-98 years) participating in the Geelong
Osteoporosis Study (GOS). Bone quality was determined using quantitative
ultrasound (QUS) and included the following parameters: Broadband Ultrasound
Attenuation (BUA), Speed of Sound (SOS) and Stiffness Index (SI). Anthropometry,
socio-economic status (SES), medication use and lifestyle factors were
determined. The cross-sectional associations between bone quality and use of
antidepressants were studied using multivariate linear regression adjusted for
potential confounders. RESULTS: At the time of assessment, 61 (7.2%) men were
using antidepressants, of which 44 (72.1%) used SSRIs. Antidepressant use was
associated with lower SI (p = .002), SOS (p = .010) and BUA (p = .053). However,
body weight was identified as an effect modifier; QUS values were lower for
antidepressant users with lower weight (< 90 kg) only. CONCLUSIONS: Use of
antidepressants was associated with lower QUS values for men with low body
weights. Thus, the risk of osteoporosis should be taken into account when
prescribing antidepressants, in particular among men who are in this weight
category.
PMID- 25586754
TI - Treatment of postnatal depression with cognitive behavioural therapy, sertraline
and combination therapy: a randomised controlled trial.
AB - OBJECTIVES: Both antidepressant medications and psychological therapy are common
treatments for depression in postpartum women. Antidepressant treatment may have
a number of practical disadvantages, including a preference by women to avoid
medication while breastfeeding. Consequently, more information about the relative
benefits of the two modalities in the perinatal period is helpful. In the
treatment of depressive disorders there is some evidence that combination
therapies (pharmacological plus psychological treatment) may be more efficacious
than either form of mono-therapy in isolation. However, in the treatment of
postnatal depression, such evidence is limited. METHOD: Forty five postpartum
women with a DSM-IV diagnosis of depression were randomised to receive either: 1)
cognitive behavioural therapy (CBT); 2) sertraline, or 3) a combination of both
treatment modalities. Psychometric measures were collected weekly for 12 weeks,
with a follow-up at 24 weeks. RESULTS: Symptoms of depression and anxiety were
reduced to a significant degree following all three treatments. CBT mono-therapy
was found to be superior to both sertraline mono-therapy and combination therapy
after 12 weeks. The CBT mono-therapy group appeared to display the most rapid
initial gains after treatment commencement. CONCLUSIONS: In this sample, a
specialised CBT program for postnatal depression was found to be superior as a
mono-therapy compared to sertraline, a commonly prescribed SSRI antidepressant.
This is in contrast to previous studies which have found no detectable difference
in the efficacies of drug and psychological treatment for postnatal depression.
Unlike some previous work, this study allowed a statistically independent
evaluation of CBT mono-therapy for postnatal depression compared to both
antidepressant and combination therapy. In line with previous studies in
postpartum women, there was no detectable advantage of combining pharmacological
and psychological treatments in the short term.
PMID- 25586755
TI - The impact of premorbid adjustment, neurocognition, and depression on social and
role functioning in patients in an early psychosis treatment program.
AB - OBJECTIVE: Functional impairments are debilitating concomitants of psychotic
disorders and are present early in the illness course and, commonly, prior to
psychosis onset. The factors affecting social and role functioning in early
psychosis (EP) following treatment are unclear. We evaluated whether six months
of participation in the PREP(R), Boston, EP treatment program, part of a public
academic community mental health center, was related to improvements in social
and role functioning and whether premorbid adjustment in adolescence, baseline
neurocognition, and depression symptoms predicted functional improvement. METHOD:
The Global Functioning Social and Role scales, MATRICS neurocognitive battery,
and Calgary Depression Scale were assessed at baseline and six months during
naturalistic treatment, while premorbid adjustment was measured at baseline. All
participants were psychotic disorder patients in PREP(R) (n = 46 with social
functioning and 47 with role functioning measures at both time points). RESULTS:
Large improvements were observed in role functioning (d = 0.84) and medium to
large improvements were observed in social functioning (d = 0.70). Models
consisting of adolescent premorbid adjustment and change in depression symptoms
predicted social and role functioning change, whereas neuropsychological
functioning did not. CONCLUSIONS: Substantial improvements in social and role
functioning were observed among this sample participating in a recovery-based EP
program. The impact of clinical factors on social and role functioning was
highlighted. Further studies of premorbid adjustment in adolescence and the
treatment of depression in EP programs in controlled treatment trials are needed
to confirm these findings.
PMID- 25586756
TI - What if nutrients could treat mental illness?
PMID- 25586757
TI - Could modafinil be a drug of dependence?
PMID- 25586758
TI - Is it time to update societal value sets for preference-based measures of health?
PMID- 25586760
TI - Vertebroplasty in a 10-year-old boy with Gorham-Stout syndrome.
AB - PURPOSE: To describe our experience using balloon vertebroplasty with
polymethylmethacrylate filler in a 10-year-old boy with Gorham-Stout syndrome.
Gorham-Stout syndrome is a rare disorder of unknown etiology characterized by
intraosseous proliferation of fibrovascular or lymphatic tissue that results in
progressive osteolysis and bone destruction. It can affect any part of the
skeleton and lead to pathological fractures and muscular weakness or atrophy. The
literature contains few reports on the surgical management of vertebral
osteolysis with risk of fracture in children. Spinal fusion is the treatment of
choice. METHODS: The patient was asymptomatic until age 10 years, when he began
to experience back pain. Annual magnetic resonance scans did not show progression
of bone disease. Medical treatment was unsuccessful, and the visual analog scale
(VAS) for lumbar back pain was 8-10. Balloon vertebroplasty with
polymethylmethacrylate filler was performed at L3 and L4, the vertebrae with an
increased risk of pathological fracture. RESULTS: The postoperative course was
uneventful. One month after surgery the VAS was 2-3. Four years later, the
patient remains free of procedure-related complications, his clinical situation
is stable, and no further low back pain has been reported. CONCLUSIONS: We report
the only application to date of vertebroplasty to treat vertebral osteolysis in a
pediatric patient. The outcome and possible complications of this technique
remain unknown in children. The patient in the present report underwent
vertebroplasty at two levels, and his progress remains satisfactory 4 years after
surgery. He has not developed technical complications or changes in spinal
growth. Therefore, we propose vertebroplasty for the treatment of vertebral
osteolysis in pediatric patients at risk of pathological fracture.
PMID- 25586759
TI - IPD without bony decompression versus conventional surgical decompression for
lumbar spinal stenosis: 2-year results of a double-blind randomized controlled
trial.
AB - PURPOSE: Interspinous process devices (IPDs) are implanted to treat patients with
intermittent neurogenic claudication (INC) based on lumbar spinal stenosis. It is
hypothesized that patients with lumbar spinal stenosis treated with IPD have a
faster short-term recovery, an equal outcome after 2 years and less back pain
compared with bony decompression. METHODS: A randomized design with variable
block sizes was used, with allocations stratified according to center.
Allocations were stored in prepared opaque, coded and sealed envelopes, and
patients and research nurses were blind throughout the follow-up. Five
neurosurgical centers (including one academic and four secondary level care
centers) included participants. 211 participants were referred to the Leiden-The
Hague Spine Prognostic Study Group. 159 participants with INC based on lumbar
spinal stenosis at one or two levels with an indication for surgery were
randomized into two groups. Patients and research nurses were blinded for the
allocated treatment throughout the study period. 80 participants received an IPD
and 79 participants underwent spinal bony decompression. The primary outcome at
long-term (2-year) follow-up was the score for the Zurich Claudication
Questionnaire. Repeated measurement analyses were applied to compare outcomes
over time. RESULTS: At two years, the success rate according to the Zurich
Claudication Questionnaire for the IPD group [69 % (95 % CI 57-78 %)] did not
show a significant difference compared with standard bony decompression [60 % (95
% CI 48-71 %) p value 0.2]. Reoperations, because of absence of recovery, were
indicated and performed in 23 cases (33 %) of the IPD group versus 6 (8 %)
patients of the bony decompression group (p < 0.01). Furthermore, long-term VAS
back pain was significantly higher [36 mm on a 100 mm scale (95 % CI 24-48)] in
the IPD group compared to the bony decompression group [28 mm (95 % CI 23-34) p
value 0.04]. CONCLUSIONS: This double-blinded study could not confirm the
advantage of IPD without bony decompression over conventional 'simple'
decompression, two years after surgery. Moreover, in the IPD treatment arm, the
reoperation rate was higher and back pain was even slightly more intense compared
to the decompression treatment arm.
PMID- 25586762
TI - Enhanced thermoelectric performance of In2O3-based ceramics via Nanostructuring
and Point Defect Engineering.
AB - The issue of how to improve the thermoelectric figure of merit (ZT) in oxide
semiconductors has been challenging for more than 20 years. In this work, we
report an effective path to substantial reduction in thermal conductivity and
increment in carrier concentration, and thus a remarkable enhancement in the ZT
value is achieved. The ZT value of In2O3 system was enhanced 4-fold by
nanostructuing (nano-grains and nano-inclusions) and point defect engineering.
The introduction of point defects in In2O3 results in a glass-like thermal
conductivity. The lattice thermal conductivity could be reduced by 60%, and
extraordinary low lattice thermal conductivity (1.2 W m(-1) K(-1) @ 973 K) below
the amorphous limit was achieved. Our work paves a path for enhancing the ZT in
oxides by both the nanosturcturing and the point defect engineering for better
phonon-glasses and electron-crystal (PGEC) materials.
PMID- 25586763
TI - Are benzodiazepines and opioids really safe in patients with severe COPD?
AB - Breathlessness is a key symptom in chronic obstructive pulmonary disease (COPD)
with prognostic implications on health status and survival. Since most conditions
underlying chronic refractory breathlessness in COPD are not modifiable, the use
of opioids and benzodiazepines has been proposed to relieve it. However,
respiratory depression is a known adverse event of these drugs, and concerns have
been raised on their use in patients with chronic respiratory failure. Despite
safety-related concerns, benzodiazepines are frequently prescribed for a variety
of reasons, including treatment of insomnia, depression and anxiety, as well as
to relieve refractory dyspnea in patients with COPD. The key role of opioids in
the end-of-life and in the management of dyspnea that is unresponsive to best
possible disease management is recognized. Moreover, the use of low dose opioids
to treat dyspnea, discomfort or refusal for patient undergoing non-invasive
ventilation is still debated. In the current review, we aim at discussing and
analyzing recently published findings on the use of benzodiazepines and opioids
in patients with COPD and at reviewing the literature on this topic. Recent
observations favor the use of lower doses of opioids (<=30 mg oral morphine
equivalents/day) for reduction of symptoms in those patients with severe COPD
receiving long-term oxygen therapy. Low dose opioids are not associated with an
increased risk of hospital admission or death in cohorts of COPD patients on long
term oxygen therapy. On the contrary, benzodiazepines and opioids at higher doses
might increase mortality.
PMID- 25586761
TI - Exercise training, creatine supplementation, and bone health in ovariectomized
rats.
AB - Evidence suggests that creatine may have some beneficial effects on bone. The
study aimed to investigate the effects of exercise alone or combined with
creatine on bone health in ovariectomized rats. Findings show that exercise, but
not creatine, has an important role in improving bone health. INTRODUCTION: The
aim of this study was to investigate the effects of exercise training alone or
combined with creatine supplementation on bone health parameters in
ovariectomized rats. METHODS: Wistar rats were randomly allocated into one of
five groups: (i) sham-operated, (ii) ovariectomized non-trained placebo
supplemented, (iii) ovariectomized non-trained creatine-supplemented, (iv)
ovariectomized exercise-trained placebo-supplemented, and (v) ovariectomized
exercise-trained creatine-supplemented. Downhill running training and/or creatine
supplementation (300 mg/kg body weight) were administered for 12 weeks. Bone
mineral content (BMC), bone mineral density (BMD), and biomechanical and
histomorphometric parameters were assessed. RESULTS: No interaction effects were
observed for BMC and BMD at whole body, femur, and lumbar spine (p > 0.05).
Importantly, a main effect of training was detected for whole body BMC and BMD (p
= 0.003 and p < 0.001, respectively), femoral BMC and BMD (p = 0.005 and p <
0.001, respectively), and lumbar spine BMC and BMD (p < 0.001 and p < 0.001,
respectively), suggesting that the trained animals had higher bone mass,
irrespective of creatine supplementation. Main effects of training were also
observed for maximal load (p < 0.001), stiffness (p < 0.001), and toughness (p =
0.046), indicating beneficial effects of exercise training on bone strength.
Neither a main effect of supplementation nor an interaction effect was detected
for biomechanical parameters (p > 0.05). No main or interaction effects were
observed for any of the histomorphometric parameters evaluated (p > 0.05).
CONCLUSIONS: Exercise training, but not creatine supplementation, attenuated
ovariectomy-induced bone loss in this rat model.
PMID- 25586764
TI - Multi-platform lung tumors profiling identifies actionable targets and unveils
series of uncommon/rare diseases.
AB - Lung cancer is characterized by a number of genetic alterations, of which a
proportion is still unknown. Nevertheless numerous pathogenetically important
driver changes have been already been detected in a substantial fraction of
patients and translated into a system to improve detection and outcome of the
disease. In this scenario, the Lung Cancer Mutation Consortium developed an
ambitious project aimed to perform on large scale the molecular profile of lung
adenocarcinoma in order to identify actionable targets. The review analyses the
paper - recently published showing study findings- taking into account if the car
and not the driver matters in lung cancer precision management.
PMID- 25586765
TI - Spirometric criteria to diagnose airway obstruction in the elderly: fixed ratio
vs lower limit of normal.
AB - COPD is the most common chronic lung disease. It becomes more prevalent with
increasing age but remains under-diagnosed in the elderly. A heated debate
concerns the most suitable way to diagnose airway obstruction in this age group.
Most COPD guidelines recommend to use a FEV1/FVC of 0.70 as threshold to define
an obstructive ventilatory defect. While the use of a 0.70 ratio may be simple,
it may result in under-diagnosis of airflow obstruction in young people and over
diagnosis in the elderly due to an age-related decline in pulmonary volumes,
especially in FEV1. This might lead to unnecessary use of medications and
increased risk of adverse effects. A proposed strategy for reducing the
misclassification of airway obstruction include the use of the statistically
derived lower limit of normal (LLN) for FEV1/FVC, calculated as the fifth
percentile of the normal distribution in a healthy population. Some authors
addressed the possibility to evaluate lung function through high-resolution CT.
In contrast to spirometry, CT imaging may allow for regional assessment of the
compartments involved (airways, parenchyma, vasculature), and may enable a
phenotype-driven characterization of COPD. Bhatt et al. recently observed that a
small proportion (7%) of subjects with CT-defined emphysema were identified by
the 0.70 threshold for FEV1/FVC but not by the LLN. However, there is no evidence
that CT-emphysema corresponds to a clinical entity that can benefit by inhaled
therapy. Further studies are needed to assess the classificatory and prognostic
value of the different proposed criteria to diagnose airway obstruction in the
elderly.
PMID- 25586766
TI - Erratum to: Single nucleotide polymorphism analysis of Korean native chickens
using next generation sequencing data.
PMID- 25586767
TI - Expression of genes related to mitochondrial function in Nellore cattle
divergently ranked on residual feed intake.
AB - Several measures have been proposed to investigate and improve feed efficiency in
cattle. One of the most commonly used measure of feed efficiency is residual feed
intake (RFI), which is estimated as the difference between actual feed intake and
expected feed intake based on the animal's average live weight. This measure
permits to identify and select the most efficient animals without selecting for
higher mature weight. Mitochondrial function has been indicated as a major factor
that influences RFI. The analysis of genes involved in mitochondrial function is
therefore an alternative to identify molecular markers associated with higher
feed efficiency. This study analyzed the expression of PGC1alpha, TFAM, UCP2 and
UCP3 genes by quantitative real-time PCR in liver and muscle tissues of two
groups of Nellore cattle divergently ranked on RFI values in order to evaluate
the relationship of these genes with RFI. In liver tissue, higher expression of
TFAM and UCP2 genes was observed in the negative RFI group. Expression of
PGC1alpha gene did not differ significantly between the two groups, whereas UCP3
gene was not expressed in liver tissue. In muscle tissue, higher expression of
TFAM gene was observed in the positive RFI group. Expression of PGC1alpha, UCP2
and UCP3 genes did not differ significantly between the two groups. These results
suggest the use of TFAM and UCP2 as possible candidate gene markers in breeding
programs designed to increase the feed efficiency of Nellore cattle.
PMID- 25586768
TI - Intrinsic binding of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides to
native and recombinant human carbonic anhydrase VI.
AB - Carbonic anhydrase (CA) VI is a potential drug target for cariogenesis and cancer
of the salivary gland. It is the only secreted human CA isozyme which is found in
saliva and milk. Here, CA VI was expressed in bacterial and mammalian cell
cultures and directly affinity-purified from human saliva. The binding of 4
substituted-2,3,5,6-tetrafluorobenezenesulfonamides to the native and recombinant
CA VI from these three sources was compared. Interaction between the enzyme and
inhibitors was determined by fluorescent thermal shift assay and isothermal
titration calorimetry. The observed dissociation constants were the same within
the error margin for all three CA VI preparations. The intrinsic binding
parameters for the compounds were obtained by determining and dissecting the
binding-linked protonation reactions. Intrinsic thermodynamic parameters of
binding arrange the compounds in a buffer- and pH-independent manner. Intrinsic
binding constants of nonfluorinated compounds were significantly stronger than
those of fluorinated benzenesulfonamides. An opposite result was determined for
the observed binding constants. The increase in observed affinity of the
fluorinated compounds was due to the fluorine effect on diminishing the pKa of
the compounds but not due to direct recognition of the protein. The temperature
stability profiles for recombinant and native CA VI were compared and showed that
CA VI is more stable in slightly acidic than neutral conditions.
PMID- 25586769
TI - Acupuncture provides short-term pain relief for patients in a total joint
replacement program.
AB - OBJECTIVE: Given the risks of opioid medications, nonpharmacological strategies
should be considered for total joint replacement patients. We investigated
acupuncture as an adjunct therapy for postsurgical pain management in a total
joint replacement program by examining which total hip and knee replacement
patients elected to receive acupuncture and the effect of acupuncture on short
term pain. DESIGN: A total joint replacement program using fast-track
physiotherapy offered elective postsurgical acupuncture to all patients, at no
additional cost, as an adjunct therapy to opioids for pain management. SETTING:
The Joint Replacement Center at Abbott Northwestern Hospital, a 630-bed teaching
and specialty hospital in Minneapolis, Minnesota from 2010 to 2012. SUBJECTS: Our
sample included 2,500 admissions of total hip (THR) and total knee replacement
(TKR) patients. METHODS: Self-reported pain was assessed before and after
acupuncture using a 0-10 scale and categorized as none/mild (0-4) and
moderate/severe pain (5-10). RESULTS: Seventy-five percent of admissions included
acupuncture. Women (Odds Ratio: 1.48, 95% Confidence Interval (CI): 1.22, 1.81)
had higher odds of receiving acupuncture compared to men, and nonwhite patients
(Odds Ratio: 0.55, 95% CI: 0.39, 0.78) had lower odds of receiving acupuncture
compared to white patients. Average short-term pain reduction was 1.91 points
(95% CI: 1.83, 1.99), a 45% reduction from the mean prepain score. Forty-one
percent of patients reported moderate/severe pain prior to receiving acupuncture,
while only 15% indicated moderate/severe pain after acupuncture. CONCLUSIONS:
Acupuncture may be a viable adjunct to pharmacological approaches for pain
management after THR or TKR.
PMID- 25586772
TI - Effects of ultraviolet light (UV-C) and heat treatment on the quality of fresh
cut Chokanan mango and Josephine pineapple.
AB - The effects of ultraviolet (UV-C) and medium heat (70 degrees C) treatments on
the quality of fresh-cut Chokanan mango and Josephine pineapple were
investigated. Quality attributes included physicochemical properties (pH,
titratable acidity, and total soluble solids), ascorbic acid content (vitamin C),
antioxidant activity, as well as microbial inactivation. Consumers' acceptance
was also investigated through sensory evaluation of the attributes (appearance,
texture, aroma and taste). Furthermore, shelf-life study of samples stored at 4
+/- 1 degrees C was conducted for 15 d. The fresh-cut fruits were exposed to UV
C for 0, 15, 30, and 60 min while heat treatments were carried out at 70 degrees
C for 0, 5, 10 and 20 min. Both UV-C and medium heat treatments resulted in no
significant changes to the physicochemical attributes of both fruits. The
ascorbic acid content of UV-C treated fruits was unaffected; however, medium heat
treatment resulted in deterioration of ascorbic acids in both fruits. The
antioxidants were enhanced with UV-C treatment which could prove invaluable to
consumers. Heat treatments on the other hand resulted in decreased antioxidant
activities. Microbial count in both fruits was significantly reduced by both
treatments. The shelf life of the fresh-cut fruits were also successfully
extended to a maximum of 15 d following treatments. As for consumers' acceptance,
UV-C treated fruits were the most accepted as compared to their heat-treated
counterparts. The results obtained through this study support the use of UV-C
treatment for better retention of quality, effective microbial inactivation and
enhancement of health promoting compounds for the benefit of consumers.
PMID- 25586770
TI - Magnetic resonance imaging and endorectal ultrasound for diagnosis of rectal
lesions.
AB - Endorectal ultrasonography (ERUS) and magnetic resonance imaging (MRI) allow
exploring the morphology of the rectum in detail. Use of such data, especially
assessment of the rectal wall, is an important tool for ascertaining the perianal
fistula localization as well as stage of the cancer and planning it appropriate
treatment, as stage T3 tumors are usually treated with neoadjuvant therapy,
whereas T2 tumors are initially managed surgically. The only advantage of ERUS
over MRI is the possibility of assessing T1 tumors that could be treated by
transanal endoscopic microsurgery. However, MRI is better for visualizing most
radiological prognostic features in rectal or anal cancer such as a
circumferential resection margin less than 1 mm, T stage at T1-T2 or T3 tumors
with extramural extension less than 5 mm, absence of extramural vascular
invasion, N stage at N0/N1, and tumors located in the middle or upper third of
the rectum. It can also evaluate the intersphincteric space or levator ani muscle
involvement. Increased signal on diffusion weighted imaging (DWI) and low
apparent diffusion coefficient (ADC) values as well as an irregular contour and
heterogeneous internal signal intensity seem to predict the involvement of pelvic
lymphatic nodes better than their size alone. Computed tomography as well as
other examination techniques, including digital rectal examination, contrast
edema, recto- and colonoscopy, are less useful in staging of rectal cancer but
still are very important screening tools.
PMID- 25586773
TI - In vitro hemodynamic evaluation of a novel pulsatile extracorporeal life support
system: impact of perfusion modes and circuit components on energy loss.
AB - The objective of this study is to investigate the impact of every component of
extracorporeal life support (ECLS) circuit on hemodynamic energy transmission in
terms of energy equivalent pressure (EEP), total hemodynamic energy (THE), and
surplus hemodynamic energy (SHE) under nonpulsatile and pulsatile modes in a
novel ECLS system. The ECLS circuit consisted of i-cor diagonal pump and console
(Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr
femoral arterial cannula, a 23/25 Fr femoral venous cannula, and 3/8-in ID
arterial and venous tubing. The circuit was primed with lactated Ringer's
solution and human whole blood (hematocrit 33%). All trials were conducted under
room temperature at the flow rates of 1-4 L/min (1 L/min increments). The
pulsatile flow settings were set at pulsatile frequency of 75 beats per minute
and differential speed values of 1000-4000 rpm (1000 rpm increments). Flow and
pressure data were collected using a custom-based data acquisition system. EEP
was significantly higher than mean arterial pressure in all experimental
conditions under pulsatile flow (P < 0.01). THE was also increased under
pulsatile flow compared with the nonpulsatile flow (P < 0.01). Under pulsatile
flow conditions, SHE was significantly higher and increased differential rpm
resulted in significantly higher SHE (P < 0.01). There was no SHE generated under
nonpulsatile flow. Energy loss depending on the circuit components was almost
similar in both perfusion modes at all different flow rates. The pressure drops
across the oxygenator were 3.8-24.9 mm Hg, and the pressure drops across the
arterial cannula were 19.3-172.6 mm Hg at the flow rates of 1-4 L/min. Depending
on the pulsatility setting, i-cor ECLS system generates physiological quality
pulsatile flow without increasing the mean circuit pressure. The iLA membrane
ventilator is a low-resistance oxygenator, and allows more hemodynamic energy to
be delivered to the patient under pulsatile mode. The 18 Fr femoral arterial
cannula has acceptable pressure drops under nonpulsatile and pulsatile modes.
Further in vivo studies are warranted to confirm these results.
PMID- 25586774
TI - Hookah Use Predicts Cigarette Smoking Progression Among College Smokers.
AB - INTRODUCTION: Hookah use is increasingly common among U.S. college students, but
little is known regarding the relationship between hookah and cigarette use. The
purpose of this study was to test the hypothesis that the added nicotine exposure
from hookah use may accelerate the uptake of cigarettes. METHODS: An ethnically
diverse sample of college students (n = 256; 43% female) who had smoked
cigarettes in the past month completed 2 in-person interviews over 6 months. This
study was a secondary analysis of data collected for a longitudinal study of
young adult cigarette smoking patterns. Analyses examined 6-month changes in past
30 day cigarettes smoked and number of days smoking, controlling for age,
nicotine dependence, marijuana use, and the respective baseline variable for each
outcome. RESULTS: Current hookah use (any use in past 30 days) was endorsed by
34% of participants at baseline, while 94% reported lifetime use. Change in past
30 day number of cigarettes (p = .043) and number of smoking days (p = .040)
differed significantly between those who did or did not report recent hookah use
at baseline. Hookah users reported a greater number of cigarettes smoked at the 6
month follow-up, while nonusers decreased their smoking quantity. For number of
smoking days in the past 30, hookah users reported a smaller decrease than
nonusers. CONCLUSIONS: Recent hookah use predicted increased cigarette smoking
over 6 months in a college sample. These are the first prospective data
demonstrating this relationship, indicating the value of developing strategies to
prevent hookah use among college students.
PMID- 25586771
TI - Special AT-rich sequence-binding protein-1 participates in the maintenance of
breast cancer stem cells through regulation of the Notch signaling pathway and
expression of Snail1 and Twist1.
AB - The stem cell populations in cancerous tissues and cell lines vary widely and are
often associated with aggressive cases of breast cancer. Despite research on the
topic, the mechanism underlying the regulation of the breast cancer stem cell
(BCSC) population within tumors remains to be fully elucidated. To investigate
the function of special AT-rich sequence-binding protein-1 (SATB1) in the
maintenance of the BCSC population, SATB1 was overexpressed with lentivirus in
MCF-7 cells or knocked down with shRNA-lentivirus in BT-549 cells. The effects of
SATB1 overexpression or knockdown on mammosphere formation, the size of the of
BCSC population, cell invasion and tumorigenesis were investigated. Activation of
the Notch signaling pathway and expression of Snail1 and Twist1 were also
examined in the cells. Overexpression of SATB1 in MCF-7 cells was observed to
increase mammosphere formation, the size of the BCSC population, cell invasion
and tumorigenesis, accompanied by an increase in the activation of Notch
signaling and expression levels of Snail1 and Twist1. Conversely, knockdown of
SATB1 in BT-549 cells produced the opposite effects. The results indicated that
expression of SATB1 may increase the size of the BCSC population via the
activation of the Notch signaling pathway and by increasing expression levels of
Snail1 and Twist1.
PMID- 25586775
TI - Economic Impact of Smoke-Free Legislation: Did the Spanish Tobacco Control Law
Affect the Economic Activity of Bars and Restaurants?
AB - INTRODUCTION: The potential of smoke-free bans to negatively impact the
hospitality business has been an argument of the hospitality and tobacco industry
against such legislation. A partial smoke-free legislation was introduced in
Spain in 2006 allowing smoking in most bars and restaurants due to the pressure
of the hospitality sector. However, this partial ban was later amended in 2011 to
include all the hospitality premises without exceptions. The stepped Spanish
process permits to evaluate whether the entry into force of the smoke-free
legislation had any effect on the economic activity of the hospitality sector.
METHODS: We employed a pooled time series cross-sectional design, with national
data over 6 years (2006-2011). The dependent variable used was the total number
of bars and restaurants per 100,000 inhabitants. The explanatory variables used
were the average amount of spending per household in bars and restaurants, and
the total unemployment rate in Spain by regions. RESULTS: For every 1% increase
in the unemployment rate there was a 0.05% decrease in the number of bars and
restaurants. In 2007, the number of bars and restaurants was significantly
reduced by 13.06% (all others factors being held constant), 4.87% in 2008, and
10.42% in 2009. No statistically significant effect of the smoke-free legislation
emerged from 2010 (6.76%) to 2011 (7.69%). CONCLUSION: The new Spanish smoke-free
legislation had no effect on the number of bars and restaurants.
PMID- 25586776
TI - The Association Between Tobacco Control Policy and Educational Inequalities in
Smoking Cessation in the Netherlands from 1988 Through 2011.
AB - INTRODUCTION: Tobacco control policies seemed to have failed to reduce
socioeconomic inequalities in smoking in the past. It has been argued that a
comprehensive mix of policies is needed. Our aim was to assess whether tobacco
control policy development in the Netherlands between 1988 and 2011 was
associated with educational inequalities in smoking cessation and cigarette
consumption. METHODS: Data were derived from the cross-sectional Dutch Continuous
Survey of Smoking Habits, with a study sample of 259,140 respondents from 1988
through 2011. Outcomes were the quit ratio and mean number of cigarettes smoked
per day. The determinant was the Tobacco Control Scale (TCS). We used multilevel
logistic regression modeling, with years, quarters, and individuals as levels,
and controlled for sex, age, and time. RESULTS: A significant association between
the TCS and smoking cessation was found in 2001-2011, but not in 1988-2000.
Associations for low- and high-education groups were similar (OR = 1.23; 95% CI =
1.12-1.34 and OR = 1.17; 95% CI = 1.03-1.32 respectively). The TCS was not
significantly associated with the number of cigarettes smoked per day for either
the low- or high-education groups (B = -0.09; 95% CI = -0.46-0.27 and B = -0.59;
95% CI = -1.24-0.06 respectively). CONCLUSIONS: Strong tobacco control policies
introduced in the Netherlands after 2000 were positively associated with national
trends in smoking cessation, whereas weaker policies introduced gradually before
2000 were not. However, these measures do not seem to have either widened or
narrowed educational inequalities in smoking cessation rates-both groups
benefitted about equally.
PMID- 25586777
TI - Comment on Farsalinos et al., "Evaluation of Electronic Cigarette Liquids and
Aerosol for the Presence of Selected Inhalation Toxins".
PMID- 25586778
TI - Why We Consider the NIOSH-Proposed Safety Limits for Diacetyl and Acetyl
Propionyl Appropriate in the Risk Assessment of Electronic Cigarette Liquid Use:
A Response to Hubbs et al.
PMID- 25586779
TI - Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2
diabetes: the GUARD study.
AB - The present GUARD study was a prospective, non-interventional study evaluating
the clinical effectiveness, safety and tolerability of vildagliptin with or
without metformin in adult patients with type 2 diabetes mellitus (T2DM) studied
in routine clinical practice. Patients were enrolled from countries across four
geographical regions. The primary endpoint was change in glycated haemoglobin
(HbA1c) concentration from baseline after 24 weeks of treatment with vildagliptin
with or without metformin. Of 19 331 patients analysed, 3511 received
vildagliptin and 15 820 received vildagliptin plus metformin. At week 24, the
mean HbA1c was reduced significantly from baseline by -1.27% (vildagliptin:
1.17%; vildagliptin plus metformin: -1.29%; p < 0.0001). Significant reductions
in HbA1c from baseline were consistently reported regardless of patient age, body
mass index (BMI) or baseline HbA1c. Weight and BMI were also significantly
reduced from baseline. Vildagliptin treatment with or without metformin was
generally well tolerated. It provided clinically relevant glycaemic and weight
control, and was well tolerated in a large multi-ethnic population of patients
with T2DM studied in routine clinical practice.
PMID- 25586781
TI - Low serum tryptophan predicts higher mortality in cardiovascular disease.
AB - BACKGROUND: The essential amino acid tryptophan is required for protein synthesis
and formation of the neurotransmitter serotonin and may exert immunoregulatory
functions. An accelerated tryptophan breakdown rate is associated with
inflammation and immune activation. MATERIALS AND METHODS: Serum concentrations
of free tryptophan, neopterin and high-sensitivity C-reactive protein (hsCRP)
were measured in 1196 patients with coronary artery disease (CAD) derived from
the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. RESULTS:
Tryptophan concentrations did not differ between patients with (mean +/- SD: 40.1
+/- 9.8 MUM) or without (42.3 +/- 23.9 MUM; not significant, Welch's test)
angiographic CAD, but patients with CAD had higher neopterin (9.1 +/- 8.2 nM) and
hsCRP (9.3 +/- 18.5 mg/L) concentrations compared to patients without (neopterin:
7.6 +/- 4.7 nM, hsCRP: 5.8 +/- 7.6 mg/L; both P < 0.0001). There existed an
inverse correlation between serum tryptophan and neopterin (Spearman's rank
correlation: rs = -0.273) and hsCRP (rs = -0.163; both P < 0.0001)
concentrations. Median observation time was 10.5 years, and 385 patients had
died, including 244 patients due to cardiovascular and 132 due to
noncardiovascular causes. After adjustments for cardiovascular risk factors and
other possible confounders, the hazard ratio (with 95% CI) in the first
tryptophan quartile of the study population was 1.51 (1.19-1.90; P = 0.0006) for
total mortality, 1.41 (1.05-1.89; P = 0.0224) for cardiovascular and 1.79 (1.20
2.67; P = 0.0042) for noncardiovascular mortalities, respectively, thus
indicating a significantly higher risk of death in patients with tryptophan
concentrations < 34 MUM. CONCLUSIONS: Low serum tryptophan in patients with CAD
is associated with immune activation and indicates reduced life expectancy.
PMID- 25586780
TI - Co-immunization with DNA and protein mixture: a safe and efficacious
immunotherapeutic strategy for Alzheimer's disease in PDAPP mice.
AB - Active immunotherapy targeting beta-amyloid (Abeta) is the most promising
strategy to prevent or treat Alzheimer's disease (AD). Based on pre-clinical
studies and clinical trials, a safe and effective AD vaccine requires a delicate
balance between providing therapeutically adequate anti-Abeta antibodies and
eliminating or suppressing unwanted adverse T cell-mediated inflammatory
reactions. We describe here the immunological characterization and protective
efficacy of co-immunization with a 6Abeta15-T DNA and protein mixture without
adjuvant as an AD immunotherapeutic strategy. Impressively, this co-immunization
induced robust Th2-polarized Abeta-specific antibodies while simultaneously
suppressed unwanted inflammatory T cell reactions and avoiding Abeta42-specific T
cell-mediated autoimmune responses in immunized mice. Co-immunization with the
DNA + protein vaccine could overcome Abeta42-associated hypo-responsiveness and
elicit long-term Abeta-specific antibody responses, which helped to maintain
antibody-mediated clearance of amyloid and accordingly alleviated AD symptoms in
co-immunized PDAPP mice. Our DNA and protein combined vaccine, which could induce
an anti-inflammatory Th2 immune response with high level Abeta-specific
antibodies and low level IFN-gamma production, also demonstrated the capacity to
inhibit amyloid accumulation and prevent cognitive dysfunction. Hence, co
immunization with antigen-matched DNA and protein may represent a novel and
efficacious strategy for AD immunotherapy to eliminate T cell inflammatory
reactions while retaining high level antibody responses.
PMID- 25586782
TI - Evolutionary forward genomics reveals novel insights into the genes and pathways
dysregulated in recurrent early pregnancy loss.
AB - STUDY QUESTION: Are the genes that gained novel expression in the endometria of
Eutherian (placental) mammals more likely to be dysregulated in patients with
endometrial-associated recurrent early pregnancy loss (REPL)? SUMMARY ANSWER:
There was a significant enrichment of genes dysregulated in REPL patients among
the Eutherian-specific endometrial genes. WHAT IS KNOWN ALREADY: Pregnancy loss
is the most common complication of human pregnancy. REPL has multiple etiologies,
including dysregulation of endometrial function, leading to 'suboptimal'
implantation. Although the implantation process is tightly regulated in Eutherian
(placental) mammals, the molecular factors contributing to dysregulated
endometrial gene expression patterns in women with REPL are largely unknown.
STUDY DESIGN, SIZE, DURATION: Endometrial biopsies were obtained from 32 REPL
patients during the mid-luteal phase, and evaluated for glandular development
arrest based on elevated nuclear cyclin E levels in gland cells, and for out-of
phase endometrial development based on histology. Gene expression levels were
measured using Illumina Human HT-12v4 BeadChip arrays. PARTICIPANTS/MATERIALS,
SETTING, METHODS: Differentially expressed genes were identified between patients
with (i) out-of-phase (n = 10) versus normal (n = 22) histological dating and
(ii) abnormally elevated (n = 9) versus normal (n = 23) cyclin E levels in the
nuclei of endometrial glands, using a likelihood ratio test. Enrichment of
dysregulated genes in REPL endometria among Eutherian-specific genes was tested
by permutation. Gene ontology and pathway enrichment analyses were carried out
for the dysregulated genes. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-eight and
eighty-one genes were identified as differentially expressed at P < 0.001 in
women with out-of-phase histological dating and abnormally elevated glandular
cyclin E levels, respectively. Genes that were recruited into endometrial
expression during the evolution of pregnancy in Eutherian mammals were
significantly enriched for dysregulated genes (P = 0.002 for histology, P = 0.021
for cyclin E), as well as for genes involved in immune response and signaling
pathways with essential roles in implantation and endometrial biology.
LIMITATIONS, REASONS FOR CAUTION: Small sample size limits the statistical power
to detect dysregulated genes, and the lack of non-REPL control women does not
allow us to test for the contribution of these genes to overall risk of REPL.
WIDER IMPLICATIONS OF THE FINDINGS: Enrichment of functional gene categories, as
well as genes gained expression in the Eutherian endometria, help to identify
molecular etiologies that contribute to normal functioning of the endometrium.
These pathways are also strong candidates for successful pregnancy outcomes.
Using the evolutionary history of mammalian gene expression in the endometrial
tissue may be a promising approach to discover genes involved in female
reproductive disorders. STUDY FUNDING/COMPETING INTERESTS: This work is supported
by National Institutes of Health (NIH) grant R01 HD21244 to C.O. Authors declare
no competing interests.
PMID- 25586783
TI - Follicle pool, ovarian surgery and the risk for a subsequent trisomic pregnancy.
AB - STUDY QUESTION: Is there an association between trisomic pregnancy, a marker for
decreased oocyte quality, and the reduced oocyte quantity that follows ovarian
surgery? SUMMARY ANSWER: Previous ovarian surgery is not associated with an
increased risk for a subsequent trisomic pregnancy. WHAT IS KNOWN ALREADY:
Ovarian surgery diminishes the number of oocytes. The risk for a trisomic
pregnancy is suggested to be higher in women with fewer oocytes, independent of
their chronological age. STUDY DESIGN, SIZE, DURATION: This is a matched case
control study. Cases are women with a confirmed trisomic pregnancy occurring
between 1 January 2000 and 31 December 2010 regardless of pregnancy outcome and
controls are women that had a live born child without a trisomy. In total, there
were 8573 participants in the study; 1723 cases and 6850 controls.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from Danish medical
registries. Matching criteria were maternal age and year of conception. Number of
controls matched per case ranged from one to four. Among cases and controls with
a trisomic pregnancy, 2.7% (46/1723) versus 2.5% (172/6850) had undergone ovarian
surgery before pregnancy. MAIN RESULTS AND ROLE OF CHANCE: History of ovarian
surgery is not associated with a higher risk for a subsequent trisomic pregnancy
(odds ratio = 1.00, 95% confidence interval 0.99-1.01). Subgroup analyses by
indication of surgery and interval between ovarian surgery and pregnancy do not
show an effect on trisomic pregnancy risk. LIMITATIONS, REASONS FOR CAUTION: The
medical registries used to select cases and controls did not contain information
on surgical technique nor volume of ovarian tissue resected, previous trisomic
pregnancy prior to the ovarian surgery or long-term use of oral contraceptives.
Therefore, correction for these factors was not performed. WIDER IMPLICATIONS OF
THE FINDINGS: We did not confirm the hypothesis that ovarian surgery, a marker
for decreased oocyte quantity, is related to trisomic pregnancy, a marker for
decreased oocyte quality. This suggests that ovarian surgery, which has a direct
reductive effect on the size of the follicle pool, may affect oocyte quality
differently when compared with the reduction in follicle pool size due to ageing.
STUDY FUNDING/COMPETING INTERESTS: The study was supported by grants from the
Gratama Stichting, University of Groningen and the University Medical Center
Groningen, The Netherlands. O.L. has within the last 3 years received honoraria
for speeches in pharmacoepidemiological issues, not related to this study. The
Department of Obstetrics and Gynaecology receives unrestricted educational grants
from Ferring Pharmaceuticals. A.H. received a grant from ZonMW (i.e. National
Dutch Scientific funding) for a RCT not related to this publication. Dr A.H.
received speakers fee from MSD for an educational presentation. All other authors
have no conflict of interest.
PMID- 25586784
TI - Polycystic ovary syndrome susceptibility single nucleotide polymorphisms in women
with a single PCOS clinical feature.
AB - STUDY QUESTION: What is the direct genetic contribution of the polycystic ovary
syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNPs), identified
by previous genome-wide association studies (GWAS) to the definitive clinical
features of the syndrome? SUMMARY ANSWER: Each single PCOS clinical feature had a
specific genetic association, and rs4385527 in the chromosome 9 open reading
frame 3 (C9orf3) conferred a particular risk to the three defined PCOS clinical
features in this study, which suggested its fundamental role in the etiology of
PCOS. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder characterized by
anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCOM).
Two previous GWAS in China have identified 15 independent susceptibility SNPs
related to PCOS (PCOS-SNPs). However, little is known about the candidate gene of
each clinical feature. STUDY DESIGN, SIZE, DURATION: Case-control study. Three
independent groups of women were recruited from 2010 to 2012: 746 subjects with
OA only, 278 subjects with HA only and 536 subjects with PCOM only. A total of
1790 healthy women with none of the above pathological characteristics were also
enrolled as control subjects during the same time period. PARTICIPANTS/MATERIALS,
SETTING, METHODS: All participants were women of reproductive age. Genotype and
allelic frequencies of 15 PCOS-SNPs were determined in all subjects using direct
sequencing and Sequenom Arrays. The allelic frequencies of each case group were
compared with the controls. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment
for age and BMI, variants in luteinizing hormone/choriogonadotropin receptor
(LHCGR) (rs13405728), C9orf3 (rs4385527) and insulin receptor gene (INSR)
(rs2059807) were strongly associated with OA (Padjust < 0.01, <0.001 and <0.05,
respectively); rs4385527 in C9orf3 was strongly associated with HA (Padjust<
0.001); variants in the thyroid adenoma associated gene (THADA) (rs13429458 and
rs12478601), DENN/MADD domain containing 1A (DENND1A)(rs10818854), and C9orf3
(rs4385527) were significantly associated with PCOM (Padjust < 0.01, <0.001,
<0.05 and <0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: The sample
size of some case groups was relatively small, which therefore limited the
statistical power of the analysis to a certain extent. WIDER IMPLICATIONS OF THE
FINDINGS: The present study indicates a potential common genetic basis of three
PCOS clinical features. Other specific associated genes may play a synergistic
role, leading to heterogeneous pathophysiological changes. Additionally, the
increased frequency of PCOS-risk alleles in women with single PCOS clinical
features suggests that these subjects have an elevated risk of developing the
syndrome, although they cannot be currently diagnosed. STUDY FUNDING/COMPETING
INTERESTS: This research was supported by the National Basic Research Program of
China (973 Program) (2012CB944700, 2011CB944502), the National Key Technology
Research and Development Program(2011BAI17B00), the National Natural Science
Foundation of China (81430029, 81201441, 81490743, 31371453), the Scientific
Research Foundation of Shandong Province of Outstanding Young Scientist
(2012BSE27089) and the Fundamental Research Funds of Shandong
University(2014GN025). There were no competing interests.
PMID- 25586785
TI - Histological evaluation of ureteral involvement in women with deep infiltrating
endometriosis: analysis of a large series.
AB - STUDY QUESTION: In women with deeply infiltrating endometriosis (DIE) what is the
prevalence of involvement of endometriotic tissue and fibrosis in ureteral
endometriosis (UE), as assessed by histological staining? SUMMARY ANSWER: In
women with DIE, ureteral involvement is more often due to endometriotic tissue
rather than fibrosis. WHAT IS KNOWN ALREADY: In the current literature,
histological evaluation of ureteral endometriosis is mainly based on the degree
of wall infiltration by endometriosis instead of the tissue composition. A few
studies reported ill-defined and contradictory histological data on the tissue
composition of UE. STUDY DESIGN, SIZE, DURATION: Retrospective observational
study based on clinical records of women affected by DIE, laparoscopically
treated for UE at a tertiary referral center, between January 2010 and March
2013. All cases of ureteral nodule excision or ureterectomy with histological
examination of the specimens were included. Exclusion criteria were other
identified causes of hydroureteronephrosis, medical therapy for a period of at
least 3 months before surgery and previous surgery for DIE.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 77 patients were included in
the study and among them seven (9%) presented with bilateral ureteral
involvement, giving a total of 84 cases of UE available for analysis. All
patients had stage IV endometriosis. According, respectively, to the presence of
endometrial glands and/or stroma cells or of fibrotic tissue only, the
endometriotic UE and fibrotic UE groups were compared with regard to
hydroureteronephrosis at pre-operative urinary tract computerized tomography
scan, type of surgical procedure performed to treat UE (nodule removal or
ureterectomy), association with other locations of the disease and post-operative
complications (ureteral fistula or stenosis). MAIN RESULTS AND THE ROLE OF
CHANCE: For the 84 cases of UE, 65 (77%) and 19 (23%), respectively, showed
endometriotic tissue and fibrotic tissue only. Presence of hydroureteronephrosis
and endometriotic pattern of UE showed a significant association [endometriotic
UE 44/65 (68%) versus fibrotic UE 8/19 (42%); P = 0.04]. Fibrotic pattern of UE
and presence of concomitant recto-vaginal endometriosis showed a significant
association [endometriotic group: 29/65 (45%) versus fibrotic group 18/19 (95%);
P < 0.001]. LIMITATIONS, REASONS FOR CAUTION: The retrospective and monocentric
(tertiary referral center) study design. WIDER IMPLICATIONS OF THE FINDINGS:
Besides the distinction between extrinsic and intrinsic UE based on the degree of
wall infiltration by endometriosis, a new classification according to the
histological pattern of UE could be useful for clinicians, both in the diagnostic
and therapeutic fields. STUDY FUNDING/COMPETING INTERESTS: None.
PMID- 25586787
TI - Estimating the net effect of progesterone elevation on the day of hCG on live
birth rates after IVF: a cohort analysis of 3296 IVF cycles.
AB - STUDY QUESTION: What is the proper way of assessing the effect of progesterone
elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo
transfer after in vitro fertilization (IVF) using GnRH analogues and
gonadotrophins? SUMMARY ANSWER: This study indicates that a multivariable
approach, where the effect of the most important confounders is controlled for,
can lead to markedly different results regarding the association between PE on
the day of hCG and live birth rates after IVF when compared with the bivariate
analysis that has been typically used in the relevant literature up to date. WHAT
IS KNOWN ALREADY: PE on the day of hCG is associated with decreased pregnancy
rates in fresh IVF cycles. Evidence for this comes from observational studies
that mostly failed to control for potential confounders. STUDY DESIGN, SIZE,
DURATION: This is a retrospective analysis of a cohort of fresh
IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF
centre during the period 2001-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS:
Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH
analogues. Natural cycles and cycles where stimulation involved the
administration of clomiphene were excluded. In order to reflect routine clinical
practice, no other exclusion criteria were imposed on this dataset. The primary
outcome measure for this study was live birth defined as the delivery of a live
infant after 24 weeks of gestation. We compared the association between PE on the
day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple
bivariate analyses with that derived from multivariable logistic regression. The
multivariable analysis controlled for female age, number of oocytes retrieved,
number of embryos transferred, developmental stage of embryos at transfer
(cleavage versus blastocyst), whether at least one good-quality embryo was
transferred, the woman's body mass index, the total dose of FSH administered
during ovarian stimulation and the type of GnRH analogues used (agonists versus
antagonists) during ovarian stimulation. In addition, an interaction analysis was
performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes)
has a moderating effect on the association of PE on the day of hCG with live
birth rates after IVF. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates were
not significantly different between cycles with and those without PE when a
bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval
(CI): 0.56-1.09]. However, when a multivariable analysis was performed,
controlling for the effect of the aforementioned confounders, live birth rates
(OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE
on the day of hCG. The number of oocytes retrieved was the most potent
confounder, causing a 29.4% reduction in the OR for live birth between the two
groups compared. Furthermore, a moderating effect of ovarian response on the
association between PE and live birth rates was not supported in the present
analysis since no interaction was detected between PE and the type of ovarian
response (<6, 6-18, >18 oocytes). LIMITATIONS, REASONS FOR CAUTION: This is a
retrospective analysis of data collected during a 12-year period, and although
the effect of the most important confounders was controlled for in the
multivariable analysis, the presence of residual bias cannot be excluded. WIDER
IMPLICATIONS OF THE FINDINGS: This analysis highlights the need for a
multivariable approach when researchers or clinicians aim to evaluate the impact
of PE on pregnancy rates in their own clinical setting. Failure to do so might
explain why many past studies have failed to identify the detrimental effect of
PE in fresh IVF cycles. STUDY FUNDING/COMPETING INTERESTS: None.
PMID- 25586786
TI - Differentiation of primordial germ cells from induced pluripotent stem cells of
primary ovarian insufficiency.
AB - STUDY QUESTION: Can the induced pluripotent stem cells (iPSCs) derived from women
with primary ovarian insufficiency (POI) differentiate into germ cells for
potential disease modeling in vitro? SUMMARY ANSWER: The iPSC lines derived from
POI patients with 46, X, del(X)(q26) or 46, X, del(X)(q26)9qh+ could
differentiate into germ cells and expressed lower levels of genes in the deletion
region of the X chromosome. WHAT IS KNOWN ALREADY: iPSC technology has been
envisioned as an approach for generating patient-specific stem cells for disease
modeling and for developing novel therapies. It has also been confirmed that
iPSCs differentiate into germ cells. STUDY DESIGN, SIZE, DURATION: We compared
the differentiation ability of germ cells and the gene expression level of germ
cell-related genes in the X chromosome deletion region of iPSC lines derived from
POI patients (n = 2) with an iPSC line derived from normal fibroblasts (n = 1).
PARTICIPANTS/MATERIALS, SETTING, METHODS: We established three iPSC lines from
two patients with partial Xq deletion-induced POI and normal fibroblasts by
overexpressing four factors: octamer-binding transcription factor 4 (OCT4), sex
determining region Y-box 2 (SOX2), Nanog homeobox (NANOG), and lin-28 homolog
(LIN28), using lentiviral vectors. We then generated stable-transfected
fluorescent reporter cell lines under the control of the Asp-Glu-Ala-Asp box
polypeptide 4 (DDX4, also called VASA) promoter, and selected clonal derived
sublines. We induced subline differentiation into germ cells by adding Wnt3a (30
ng/ml) and bone morphogenetic protein 4 (100 ng/ml). After 12 days of
differentiation, green fluorescent protein (GFP)-positive and GFP-negative cells
were isolated via fluorescence-activated cell sorting and analyzed for endogenous
VASA protein (immunostaining) and for germ cell markers and genes expressed in
the deleted region of the X chromosome (quantitative RT-PCR). MAIN RESULTS AND
THE ROLE OF CHANCE: The POI- and normal fibroblast-derived iPSCs had typical self
renewal and pluripotency characteristics. After stable transfection with the VASA
GFP construct, the sublines POI1-iPS-V.1, POI2-iPS-V.1 and hEF-iPS-V.1 produced
green fluorescent cells in the differentiated cultures, and the percentage of GFP
positive cells increased over the 12 days of differentiation to a maximum of 6.9
+/- 0.33%, 5.3 +/- 0.57% and 8.5 +/- 0.29%, respectively, of the total cell
population. Immunohistochemical analysis confirmed that endogenous VASA was
enriched in the GFP-positive cells. Quantitative reverse transcription-PCR
revealed significantly higher expression of germ cell markers [PR domain
containing 1, with ZNF domain (PRDM1, BLIMP1), developmental pluripotency
associated 3 (DPPA3, STELLA), deleted in azoospermia-like (DAZL), and VASA
(DDX4)] in GFP-positive cells than in GFP-negative cells. Moreover, the GFP
positive cells from POI-iPSCs had reduced expression of the family with sequence
similarity 122C (FAM122C), inhibitor of kappa light polypeptide gene enhancer in
B-cells, kinase gamma (IKBKG), and RNA binding motif protein, X-linked (RBMX),
genes located in the deleted region of the X chromosome and that are highly
expressed in differentiated germ cells, compared with cells from normal iPSCs.
LIMITATIONS, REASONS FOR CAUTION: Gene expression profiling indicated that the
germ cells differentiated from POI-iPSCs were pre-meiotic. Therefore, how the
differentiated primordial germ cells could progress further to meiosis and form
follicles remains to be determined in the study of POI. WIDER IMPLICATIONS OF THE
FINDINGS: Our results might provide an in vitro model for studying germ cell
development in patients with POI. STUDY FUNDING/COMPETING INTERESTS: This work
was supported by grants from the Major State Basic Research Development Program
of China (No. 2012CB944901), the National Science Foundation of China (No.
81222007 and 81471432), the Program for New Century Excellent Talents in
University and the Fundamental Research Funds for Central Universities (No.
721500003). The authors have no competing interests to declare. TRIAL
REGISTRATION NUMBER: Not applicable.
PMID- 25586788
TI - EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a
Canadian Pediatric Brain Tumor Consortium study.
AB - BACKGROUND: The cure rate for childhood intracranial ependymoma is approximately
70% in the setting of a gross total resection followed by radiation, but
management remains challenging in patients with residual disease. Therefore,
robust biomarkers are needed to guide the development of new targeted therapy.
The authors evaluated the expression of several biomarkers in pediatric
intracranial ependymoma and observed that the expression of enhancer of zeste
homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of
gene expression, was independently associated with poor survival. METHODS: Tissue
microarray immunostaining was performed on 180 ependymoma samples from 12 of 16
Canadian pediatric centers. Expression levels of EZH2, Ki-67, B lymphoma Moloney
murine leukemia virus insertion region 1 homolog, tumor protein 16 (P16), Y-box
binding protein 1, phosphorylated protein kinase B (pAKT), and epidermal growth
factor receptor were evaluated. Cox regression analyses were performed, and the
Kaplan-Meier method was used to construct survival curves. RESULTS: EZH2
expressed in 16% of tumors was associated with inferior 5-year overall survival.
Ki-67 and pAKT levels were associated with a poor outcome in patients with
posterior fossa ependymoma, and the absence of P16 was associated with a poor
outcome in patients with supratentorial ependymoma. Multivariate analysis
revealed that younger age and EZH2 expression (95% confidence interval, 1.1-36.0)
were independent markers of a poor prognosis. CONCLUSIONS: EZH2 is a novel,
independent marker of a poor prognosis in patients with ependymoma, especially in
those who have tumors located in the posterior fossa. EZH2, pAKT, and P16 are
potential therapeutic targets, particularly for patients who have tumors in which
standard gross total resection plus fractionated radiotherapy is not feasible.
PMID- 25586789
TI - Potential cell-specific functions of CXCR4 in atherosclerosis.
AB - The chemokine CXCL12 and its receptor CXCR4 form an important axis contributing
to cellular functions in homeostasis and disease. In addition, the atypical
CXCL12 receptor CXCR7 may shape the availability and function of CXCL12. Further
to their role through progenitor cell mobilization, CXCL12 and CXCR4 may affect
native atherogenesis by modifying atherosclerosis-relevant cellular functions.
This short review intends to provide a concise summary of current knowledge with
regards to cell-specific functions of CXCL12 and its receptors CXCR4 and CXCR7
with potential implications for the initiation and progression of
atherosclerosis.
PMID- 25586790
TI - Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis
isolates (1996-2012).
AB - BACKGROUND: Few studies report the minimum inhibitory concentrations for
antimicrobials against equine Corynebacterium pseudotuberculosis isolates.
HYPOTHESIS/OBJECTIVES: To evaluate trends in the in vitro activities of 20
antimicrobials against equine Corynebacterium pseudotuberculosis isolates from
1996 to 2012 and to determine if a relationship exists between the minimum
inhibitory concentration (MIC) and location of the abscess. ANIMALS:
Corynebacterium pseudotuberculosis isolates from 196 horses with naturally
occurring disease. METHODS: Retrospective and cross-sectional design. Medical
records were reviewed to obtain clinical and MIC data. Minimum inhibitory
concentrations were determined by the microdilution technique. The MIC results
over 3 periods were compared (1996-2001, 2002-2006, 2007-2012). RESULTS: The
MIC90 values for clinically relevant antimicrobials were as follows:
chloramphenicol <= 4 MUg/mL, enrofloxacin <= 0.25 MUg/mL, gentamicin <= 1 MUg/mL,
penicillin =0.25 MUg/mL, rifampin <= 1 MUg/mL, tetracycline <= 2 MUg/mL,
trimethoprim-sulfamethoxazole (TMS) <= 0.5 MUg/mL, ceftiofur =2 MUg/mL, and
doxycycline <= 2 MUg/mL. There were no significant changes in MIC results over
the study period. There was no relationship between MIC patterns and abscess
location. CONCLUSIONS AND CLINICAL IMPORTANCE: The MIC50 and MIC90 values of
antimicrobials evaluated in this study for equine isolates of C.
pseudotuberculosis did not vary over time. Abscess location was not associated
with different MIC patterns in cultured isolates. Several commonly used
antimicrobials are active in vitro against C. pseudotuberculosis in vitro.
PMID- 25586791
TI - Transmission of infection to liver transplant recipients from donors with
infective endocarditis: lessons learned.
AB - Donors not meeting standard criteria, such as those with bacteremia, are now
being used in response to the increasing need for organs for transplantation.
Recommended strategies to prevent the occurrence of donor-derived bacteremia
include the use of directed antibiotic prophylaxis. However, this approach does
not eliminate the risk of infection transmission. Similarly, the management of
organ recipients from donors with infective endocarditis (IE) remains
uncharacterized. We report 2 cases of donor-derived bacterial infections in liver
transplant recipients despite pathogen-specific antibiotic prophylaxis. In both
instances, the donors had documented IE treated with appropriate antimicrobial
therapy and clearance of bacteremia. Recipients had very distinctive clinical
outcomes likely related to pathogen virulence and the extent of donor infection.
Persistent infection in the transplanted liver should be suspected in organ
recipients of a liver from donors with IE, despite the absence of bacteremia at
the time of death and organ procurement. For eradication, recipients may require
prolonged pathogen-directed antimicrobial therapy, such as is used for
endovascular infections. Prompt recognition of donors with IE, appropriate
notification, and prolonged antibiotic prophylaxis are key to reducing the risk
of such donor-derived infections.
PMID- 25586793
TI - Interprofessional collaboration in mental health crisis response systems: a
scoping review.
AB - Post deinstitutionalization saw the rise of mental health crisis (MHC) response
in Canada. First points of contact for individuals in a MHC are often police
services or emergency departments. Professionals in these areas may report
feeling unprepared, ill equipped, and a lack of confidence to work with clients
in crisis. Police indicate that this work is time consuming, demanding, and "not
their job". Entry points can exacerbate the crisis given the chaotic, over
stimulating and frightening environment of emergency departments and the
perceived threat of police officers. Despite the outcry of support for working
more collaboratively, little is known about the impact Interprofessional
collaboration (IPC) has in mental health crisis response systems (MHCRS).
PURPOSE: Given this challenge, the aim of this scoping review is to contribute to
understanding the current state of knowledge related to IPC in MHCRS. METHODS: A
scoping reviews was conducted to address the research topic. RESULTS: Review of
the literature identified 18 articles for inclusion, 5 experimental or
exploratory papers, 7 models of care, and 6 discussion papers. Analysis
identified the following themes: Support for interprofessional collaboration,
quest for improved care delivery system, merging distinct visions of care, and
challenges to interprofessional collaboration. Implications for practice, policy,
and research are discussed, as well as issues in the literature related to: Lack
of conceptual clarity, absent client perspectives, unequal representation across
sectors, and a young and emergent body of literature. CONCLUSION: Key concepts
need better conceptualization, and further empirical research is needed.
IMPLICATIONS FOR REHABILITATION: Conceptualizing mental health crisis (MHC)
response as occurring within a system of services, rather than independent
sectors, is critical to meeting the needs of clients. Purposefully built in
mechanisms to sustain collaboration across care teams and services are required.
Merging the distinct, and at times conflicting, visions of care espoused by the
diverse sectors involved in MHC response requires deliberate effort.
PMID- 25586792
TI - Amino acid composition analysis of secondary transport proteins from Escherichia
coli with relation to functional classification, ligand specificity and
structure.
AB - We have performed an amino acid composition (AAC) analysis of the complete
sequences for 235 secondary transport proteins from Escherichia coli, which have
functions in the uptake and export of organic and inorganic metabolites, efflux
of drugs and in controlling membrane potential. This revealed the trends in
content for specific amino acid types and for combinations of amino acids with
similar physicochemical properties. In certain proteins or groups of proteins,
the so-called spikes of high content for a specific amino acid type or
combination of amino acids were identified and confirmed statistically, which in
some cases could be directly related to function and ligand specificity. This was
prevalent in proteins with a function of multidrug or metal ion efflux. Any tool
that can help in identifying bacterial multidrug efflux proteins is important for
a better understanding of this mechanism of antibiotic resistance. Phylogenetic
analysis based on sequence alignments and comparison of sequences at the N- and C
terminal ends confirmed transporter Family classification. Locations of specific
amino acid types in some of the proteins that have crystal structures (EmrE,
LacY, AcrB) were also considered to help link amino acid content with protein
function. Though there are limitations, this work has demonstrated that a basic
analysis of AAC is a useful tool to use in combination with other computational
and experimental methods for classifying and investigating function and ligand
specificity in a large group of transport or other membrane proteins, including
those that are molecular targets for development of new drugs.
PMID- 25586794
TI - Effectiveness of commercial video gaming on fine motor control in chronic stroke
within community-level rehabilitation.
AB - PURPOSE: The purpose of this study was to investigate the effectiveness of
commercial gaming as an intervention for fine motor recovery in chronic stroke.
METHODS: Ten chronic phase post-stroke participants (mean time since CVA = 39
mos; mean age = 72 yrs) completed a 16-session program using the Nintendo Wii for
15 min two times per week with their more affected hand (10 right handed).
Functional recovery (Jebsen Hand Function Test (JHFT), Box and Block Test (BBT),
Nine Hole Peg Test (NHPT)), and quality of life (QOL; Stroke Impact Scale (SIS))
were measured at baseline (pre-testing), after 8 sessions (mid-testing) and after
16 sessions (post-testing). RESULTS: Significant improvements were found with the
JHFT, BBT and NHPT from pre-testing to post-testing (p = 0.03, p = 0.03, p =
0.01, respectively). As well, there was an increase in perceived QOL from pre
testing to post-testing, as determined by the SIS (p = 0.009). CONCLUSION:
Commercial gaming may be a viable resource for those with chronic stroke. Future
research should examine the feasibility of this as a rehabilitation tool for this
population. IMPLICATIONS FOR REHABILITATION: Stroke survivors often live with
lasting effects from their injury, however, those with chronic stroke generally
receive little to no rehabilitation due to a perceived motor recovery plateau.
Virtual reality in the form of commercial gaming is a novel and motivating way
for clients to complete rehabilitation. The Nintendo Wii may be a feasible device
to improve both functional ability and perceived quality of life in chronic
stroke survivors.
PMID- 25586795
TI - Reliability and validity of the Falls Efficacy Scale-International after hip
fracture in patients aged >= 65 years.
AB - PURPOSE: To assess the measurement properties of the Falls Efficacy Scale
International (FES-I) in patients after a hip fracture aged >= 65 years. METHODS:
In a sample of 100 patients, we examined the structural validity, internal
consistency and construct validity. For the structural validity a confirmatory
factor analysis was carried out. For construct validity predetermined hypotheses
were tested. In a second sample of 21 older patients the inter-rater reliability
was evaluated. RESULTS: The factor analysis yielded strong evidence that the FES
I is uni-dimensional in patients with a hip fracture; the Cronbach's alpha was
0.94. When testing the reliability, the intra-class correlation coefficient was
0.72, while the Standard Error of Measurement was 6.4 and the Smallest Detectable
Change was 17.7 (on a scale from 16 to 64). The Spearman correlation of the FES-I
with the one-item fear of falling instrument was high (r = 0.68). The correlation
was moderate with instruments measuring functional performance constructs and low
with instruments measuring psychological constructs. CONCLUSIONS: Reliability and
structural validity of the FES-I in patients after a hip fracture are good. The
construct validity appears more closely related to functional performance
constructs than to psychological constructs, suggesting that the concept measured
by the FES-I may not capture all aspects of fear of falling. IMPLICATIONS FOR
REHABILITATION: The Falls Efficacy Scale-International (FES-I), which is commonly
used to measure fear of falling in community-dwelling older persons, can also be
used to assess fear of falling in patients after a hip fracture. The reliability
and the structural validity of the FES-I for these hip patients are good, whereas
the construct validity of the FES-I is not optimal. The FES-I may not capture all
aspects of fear of falling and may be more closely related to functional
performance than to psychological concepts such as anxiety.
PMID- 25586797
TI - Involving family members in physiotherapy for older people transitioning from
hospital to the community: a qualitative analysis.
AB - PURPOSE: To generate an understanding of the opinions of key people associated
with a program for older people transitioning from hospital back to the community
and explore their thoughts around training family members to help provide
physiotherapy. METHOD: A qualitative study using focus groups and semi-structured
interviews was conducted. Participants included patients admitted to a
transitional care program, their family members, physiotherapists working in
transitional care and members of a consumer group from the health service where
the transitional care program was based. Data were transcribed verbatim and a
thematic analysis was conducted. RESULTS: Four patients, four family members,
four consumer group members and eight physiotherapists participated in this
study. Three themes emerged: family members providing physiotherapy may improve
outcomes for patients; training family members to provide physiotherapy should
include key elements and be individualised; and involving family members in
physiotherapy may impact positively and negatively on people and relationships.
CONCLUSIONS: Older people transitioning from hospital to the community are at
risk of functional decline and may receive very little physiotherapy. Training
family members to assist with physiotherapy was perceived as a way to improve
patient outcomes and relationships between patients and their family, although
there were concerns raised about caregiver stress. Evaluation of the feasibility
and effectiveness of this approach is warranted. IMPLICATIONS FOR REHABILITATION:
Older people transitioning from hospital to the community are at risk of
functional decline and often receive very little physiotherapy. Training family
members to assist with simple physiotherapy programs may increase the amount of
physiotherapy patients transitioning from hospital to the community can receive
and improve functional outcomes for patients. Stakeholders perceive that
individualising a program to patient and family member needs is important.
Involving family members in physiotherapy may not increase caregiver stress and
may improve relationship dynamics between patients and family members.
PMID- 25586798
TI - Understanding factors that influence participation in physical activity among
people with a neuromusculoskeletal condition: a review of qualitative studies.
AB - PURPOSE: This review aims to describe the factors that influence participation in
physical activity (PA) in people with neuromusculoskeletal (NMS) conditions.
METHODS: A systematic search of six databases was conducted. Articles were
included if the study qualitatively explored factors that influence participation
in PA by individuals with a NMS condition. Fifteen peer-reviewed articles
published between 2003 and 2013 were analysed for common themes and critically
appraised. RESULTS: Results were categorised using the International
Classification of Functioning, Disability and Health framework. The most common
demotivators reported for the three areas of functioning, body function and
structures, activities and participation were lack of walking balance, muscle
weakness, pain, stiffness, bladder and blower problems, depression,
thermoregulation and fear of injury. Fluctuating symptoms and fatigue were
mentioned as demotivators in all of the progressive conditions. Maintaining
independence, function and weight, and the prevention of secondary conditions
were the leading motivators reported in this domain. Most common environmental
barriers include accessibility, costs, transport and insufficient information and
knowledge from health professionals. Social support is a consistent determinate
of PA and is reported as a facilitator in every study. The most common personal
demotivators include lack of motivation, feelings of self-consciousness and
embarrassment in public, anxiety, frustration and anger. Personal motivators
include goal setting and achieving, enjoyment, feeling good, feeling "normal",
motivation and optimism, redefining self and escapism from everyday boundaries.
CONCLUSIONS: Individuals with NMS conditions report complex common barriers,
facilitators, demotivators and motivators to participation in PA. The way these
factors influence participation in PA is unique to the individual; therefore, it
is necessary to adopt an individually tailored approach when designing
interventions. IMPLICATIONS FOR REHABILITATION: Individuals with
neuromusculoskeletal conditions report common factors that influence
participation in physical activity. It is the characteristics, attitude and
beliefs of an individual that determine the way in which these factors influence
participation in physical activity. Health professionals should be guided by the
International Classification of Functioning, Disability and Health framework when
assessing individuals, as the model will ensure all major factors of interest
with regard to disability and physical activity behaviour are considered.
Interventions to promote participation in physical activity in people with
neuromusculoskeletal conditions require an individual approach that facilitates
the assessment and management of an individual's barriers to physical activity. A
multi-disciplinary approach may be required to address factors that influence
participation in physical activity. Health professionals must be informed about
other areas of expertise and draw on this when necessary.
PMID- 25586796
TI - Activities and participation of children with cerebral palsy: parent
perspectives.
AB - PURPOSE: To explore parents' views of the activities and participation of
children with cerebral palsy (CP) with a range of communicative abilities and the
factors (personal and environmental) that influenced these. METHODS: Thirteen
parents of children with CP aged 4-9 years participated in semi-structured
individual interviews. Interviews were recorded, transcribed and analysed
thematically. Identified codes and themes were mapped to the domains of the
International Classification of Functioning, Disability and Health - Children and
Youth Version (ICF-CY). RESULTS: Parents' responses reflected all ICF-CY domains
comprising activity, participation and environmental factors. Codes were
primarily mapped to the domains learning and applying knowledge, communication,
mobility and interpersonal interactions and relationships. Key barriers
identified included aspects of parents' own interactions with their child (e.g.
not offering choices), unfamiliar people and settings, negative attitudes of
others and children's frustration. Facilitators included support received from
the child's family and school, being amongst children, having a familiar routine
and the child's positive disposition. CONCLUSIONS: Despite the barriers
experienced, children participated in a range of activities. Parents placed
importance on communication and its influence on children's independence,
behaviour and relationships. Barriers and facilitators identified highlight
aspects of the environment that could be modified through intervention to enhance
communication and participation. IMPLICATIONS FOR REHABILITATION: Children's
activities and participation were largely related to early learning tasks (e.g.
literacy), communication, mobility and interactions. Intervention aimed at
improving activities and participation may address the various child, impairment,
social and environment factors identified here as impacting on activities and
participation (e.g. the child's personal characteristics, communication and
physical impairments, the support and attitudes of others and the familiarity of
the environment). Therapists will need to consider (and manage) the potential
negative impact communication deficits may have on children's behaviour,
independence and social skills which may in turn detrimentally impact on activity
and participation.
PMID- 25586799
TI - Ten years of hospitalisation for oral health-related conditions in Western
Australia: an unjust dichotomy.
AB - The objective of this study was: (1) to examine the demographics of in-patient
oral health care by Aboriginal status; (2) to identify the mix of oral conditions
by Aboriginal status; and (3) to describe trends over a 10-year period, comparing
Aboriginal and non-Aboriginal groups. Hospitalisation data were obtained from the
Western Australian Morbidity Data System (HMDS). The principal diagnosis, as
classified by the International Classification of Disease (ICD-10AM), was
obtained for every episode for adult patients who were discharged from all
hospitals in Western Australia (WA) for the financial years 1999-2000 to 2008-09.
Results indicated that more than 130000 persons were admitted to hospitals in WA
over 10 years, for oral health-related conditions, at a direct cost of more than
$400million. Most of those admitted were younger than 30 years, and 2.8% of all
those admitted were Aboriginal people. Aboriginal people were admitted at
significantly higher rates, for a very different mix of conditions, they were
mostly from younger age groups, were mostly from very remote and the most
disadvantaged areas and were almost all uninsured, compared with non-Aboriginal
people. Hospital admissions for oral health-related conditions, as well as the
mix of conditions that drive these hospitalisations, are strongly divided across
social, racial and geographic variables, and remain a burden to the health-care
system.
PMID- 25586800
TI - Validation of the SimSET simulation package for modeling the Siemens Biograph mCT
PET scanner.
AB - Monte Carlo simulation provides a valuable tool in performance assessment and
optimization of system design parameters for PET scanners. SimSET is a popular
Monte Carlo simulation toolkit that features fast simulation time, as well as
variance reduction tools to further enhance computational efficiency. However,
SimSET has lacked the ability to simulate block detectors until its most recent
release. Our goal is to validate new features of SimSET by developing a
simulation model of the Siemens Biograph mCT PET scanner and comparing the
results to a simulation model developed in the GATE simulation suite and to
experimental results. We used the NEMA NU-2 2007 scatter fraction, count rates,
and spatial resolution protocols to validate the SimSET simulation model and its
new features. The SimSET model overestimated the experimental results of the
count rate tests by 11-23% and the spatial resolution test by 13-28%, which is
comparable to previous validation studies of other PET scanners in the
literature. The difference between the SimSET and GATE simulation was
approximately 4-8% for the count rate test and approximately 3-11% for the
spatial resolution test. In terms of computational time, SimSET performed
simulations approximately 11 times faster than GATE simulations. The new block
detector model in SimSET offers a fast and reasonably accurate simulation toolkit
for PET imaging applications.
PMID- 25586802
TI - Pancreatitis in dogs and cats: definitions and pathophysiology.
AB - Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats
and presents a spectrum of disease severities from acute to chronic and mild to
severe. It is usually sterile, but the causes and pathophysiology remain poorly
understood. The acute end of the disease spectrum is associated with a high
mortality but the potential for complete recovery of organ structure and function
if the animal survives. At the other end of the spectrum, chronic pancreatitis in
either species can cause refractory pain and reduce quality of life. It may also
result in progressive exocrine and endocrine functional impairment. There is
confusion in the veterinary literature about definitions of acute and chronic
pancreatitis and there are very few studies on the pathophysiology of naturally
occurring pancreatitis in dogs and cats. This article reviews histological and
clinical definitions and current understanding of the pathophysiology and causes
in small animals by comparison with the much more extensive literature in humans,
and suggests many areas that need further study in dogs and cats.
PMID- 25586803
TI - Diagnosis of pancreatitis in dogs and cats.
AB - Pancreatitis is the most common disorder of the exocrine pancreas in both dogs
and cats. Ante-mortem diagnosis of canine and feline pancreatitis can be
challenging. The clinical picture of dogs and cats with pancreatitis varies
greatly (from very mild to severe or even fatal) and is characterised by non
specific findings. Complete blood count, serum biochemistry profile and
urinalysis should always be performed in dogs and cats suspected of having
pancreatitis, although findings are not-specific for pancreatitis. Serum amylase
and lipase activities and trypsin-like immunoreactivity (TLI) concentrations have
no or only limited clinical value for the diagnosis of pancreatitis in either
dogs or cats. Conversely, serum pancreatic lipase immunoreactivity (PLI)
concentration is currently considered to be the clinicopathological test of
choice for the diagnosis of canine and feline pancreatitis. Abdominal radiography
is a useful diagnostic tool for the exclusion of other diseases that may cause
similar clinical signs to those of pancreatitis. Abdominal ultrasonography can be
very useful for the diagnosis of pancreatitis, but this depends largely on the
clinician's experience. Histopathological examination of the pancreas is
considered the gold standard for the diagnosis and classification of
pancreatitis, but it is not without limitations. In clinical practice, a
combination of careful evaluation of the animal's history, serum PLI
concentration and abdominal ultrasonography, together with pancreatic cytology or
histopathology when indicated or possible, is considered to be the most practical
and reliable means for an accurate diagnosis or exclusion of pancreatitis
compared with other diagnostic modalities.
PMID- 25586801
TI - Canine and feline pancreatitis: a challenging and enigmatic disease.
PMID- 25586804
TI - Management of acute pancreatitis in dogs: a critical appraisal with focus on
feeding and analgesia.
AB - Knowledge about acute pancreatitis has increased recently in both the medical and
veterinary fields. Despite this expansion of knowledge, there are very few
studies on treatment interventions in naturally occurring disease in dogs. As a
result, treatment recommendations are largely extrapolated from experimental
rodent models or general critical care principles. General treatment principles
involve replacing fluid losses, maintaining hydrostatic pressure, controlling
nausea and providing pain relief. Specific interventions recently advocated in
human medicine include the use of neurokinin-1 antagonists for analgesia and
early interventional feeding. The premise for early feeding is to improve the
health of the intestinal tract, as unhealthy enterocytes are thought to
perpetuate systemic inflammation. The evidence for early interventional feeding
is not supported by robust clinical trials to date, but in humans there is
evidence that it reduces hospitalisation time and in dogs it is well tolerated.
This article summarises the major areas of management of acute pancreatitis in
dogs and examines the level of evidence for each recommendation.
PMID- 25586805
TI - Pancreatitis and triaditis in cats: causes and treatment.
AB - Pancreatitis in cats is frequently accompanied by concurrent disease in other
organ systems. Co-morbidities include hepatic lipidosis, inflammatory liver
disease, bile duct obstruction, diabetes mellitus, inflammatory bowel disease,
vitamin deficiency (B12/cobalamin, folate or K), intestinal lymphoma, nephritis,
pulmonary thromboembolism and pleural and peritoneal effusions. "Triaditis" is
the term used to describe concurrent inflammation of the pancreas, liver and
small intestines. Triaditis has been reported in 50 to 56% of cats diagnosed with
pancreatitis and 32 to 50% of those with cholangitis/inflammatory liver disease.
A definitive diagnosis of triaditis is based on the histopathological evaluation
of each organ. However, the specific conditions of each organ that constitute a
diagnosis of triaditis remains to be defined. While the aetiopathogenesis of
pancreatitis and its relationship to inflammation in other organ systems is
unclear, preliminary studies point to a heterogeneous group of conditions with
differential involvement of host inflammatory and immune responses and enteric
bacteria. Comprehensive, prospective studies that simultaneously evaluate the
presence of predefined clinical, clinicopathological and histopathological
abnormalities, coupled with high-resolution evaluation of pancreaticobiliary
morphology, immunological profiling and screening for bacterial colonisation are
required to advance diagnosis and therapy.
PMID- 25586807
TI - A cross-sectional study of the quality of telephone triage in a primary care out
of-hours service.
AB - We evaluated the quality of telephone triage and the appropriateness of the
decisions resulting from it at a primary care out-of-hours service. Four
simulated clinical cases were used in the Incognito Standardized Patient method:
an adult with nosebleed, an adult with fever, a child with fever and a child with
vomiting. There was a set of obligatory questions for each case, translated from
those used in a previous study. Quality was assessed by the proportion of
questions asked by the call-handlers during telephone triage versus those that
should have been asked. A total of 22 out-of-hours doctors were involved in the
study, working in two different locations in the Verona city area. Over a 4-month
period each of the four simulated clinical cases was used five times in calls to
the two centres involved. The proportion of obligatory questions asked compared
to those expected to be asked was 27-36%. On three occasions out of the 40
simulations, all of which were considered to be manageable by telephone, the
patient was advised to go to an outpatient clinic for a face-to-face evaluation.
The average duration of the calls was 3 min 47 s. The quality of telephone triage
in the regions studied was low and provided considerable room for improvement.
This is relevant to patient safety and risk management of the service.
PMID- 25586806
TI - Diabetes mellitus and pancreatitis--cause or effect?
AB - Diabetes mellitus and pancreatitis are two distinct diseases encountered commonly
in small animal practice. Whilst the clinical signs of diabetes mellitus are
usually unmistakeable, a firm diagnosis of pancreatitis can prove more elusive,
as clinical signs are often variable. Over the past 10 to 15 years, despite the
fact that the clinical signs of diabetes mellitus are remarkably consistent, it
has become more apparent that the underlying pathology of diabetes mellitus in
dogs and cats is heterogeneous, with exocrine pancreatic inflammation
accompanying diabetes mellitus in a number of cases. However, the question
remains as to whether the diabetes mellitus causes the pancreatitis or whether,
conversely, the pancreatitis leads to diabetes mellitus--as there is evidence to
support both scenarios. The concurrence of diabetes mellitus and pancreatitis has
clinical implications for case management as such cases may follow a more
difficult clinical course, with their glycaemic control being "brittle" as a
result of variation in the degree of pancreatic inflammation. Problems may also
arise if abdominal pain or vomiting lead to anorexia. In addition, diabetic cases
with pancreatitis are at risk of developing exocrine pancreatic insufficiency in
the following months to years, which can complicate their management further.
PMID- 25586808
TI - High mobile phone ownership, but low Internet and email usage among pregnant, HIV
infected women attending antenatal care in Johannesburg.
AB - We investigated mobile phone usage amongst HIV-positive pregnant women attending
antenatal services in a primary care clinic in Johannesburg (n = 50). We
conducted a semi-structured interview and asked them about their mobile phone,
Internet and email use. The median age of the women was 28 years, 36% had moved
one or more times in the past year, and most were employed or recently employed,
albeit earning low wages. Nearly all women (94%) reported that they did not share
their phone and 76% of the SIM cards were registered to the woman herself. The
median time with the current phone was one year (range 1 month-6 years) and the
median time with the current phone number was three years (range 1 month-13
years). Even though 42% of the participants were from outside South Africa, they
all had mobile phone numbers local to South Africa. About one-third of
respondents reported Internet use (30%) and about one-fifth reported using email
(18%). Overall, 20% accessed the Internet and 10% accessed email on their mobile
phone. Mobile phone interventions are feasible amongst HIV-positive pregnant
women and may be useful in prevention of mother-to-child transmission of HIV
(PMTCT). Email and Internet-based interventions may not yet be appropriate.
PMID- 25586809
TI - A pilot study of a mobile phone application to improve lifestyle and adherence of
patients with kidney disease.
PMID- 25586810
TI - Telemonitoring for chronic obstructive pulmonary disease: a cost and cost-utility
analysis of a randomised controlled trial.
AB - We compared the costs and cost-effectiveness of telemonitoring vs usual care for
patients with chronic obstructive pulmonary disease (COPD). A total of 256
patients were randomised to either telemonitoring or usual care. In the
telemonitoring arm, the touch-screen telemonitoring equipment transmitted data to
clinical teams monitoring the patients. Total healthcare costs were estimated
over a 12-month period from a National Health Service perspective and quality
adjusted life year (QALYs) were estimated by the EQ-5D tool. Telemonitoring was
not significantly more costly than usual care (mean difference per patient
L2065.90 (P < 0.18). The increased costs were predominantly due to telemonitoring
service costs and non-significantly higher secondary care costs. Telemonitoring
for COPD was not cost-effective at a base case of L137,277 per QALY with only 15%
probability of being cost-effective at the usual threshold of L30,000 per QALY.
Although there was some statistical and methodological uncertainty in the
measures used, telemonitoring was not cost-effective in the sensitivity analyses
performed. It seems unlikely that a telemonitoring service of the kind that was
trialled would be cost-effective in providing care for people with COPD.
PMID- 25586811
TI - Client satisfaction with telehealth services in home health care agencies.
AB - We assessed client satisfaction with the home telemonitoring service provided by
14 home health care agencies in five US states. Clients were randomised to two
groups. Telehealth services (health monitoring and patient safety) were provided
to 450 experimental subjects. Control subjects (n = 409) received usual care.
Clients were asked to rate their satisfaction with their service providers on 25
items, at baseline, 6 months post-discharge (to home) and 12 months post
discharge. The mean age of the clients was 78 years. Out of the initial 859
subjects, 490 had dropped out of the study by the 12-month follow-up, an overall
attrition rate of 57%. There were similar proportions of clients reporting high
satisfaction with external systems at baseline and at 6 months; at 12 months,
there were significantly more clients in the experimental group who reported high
satisfaction (P = 0.049). There were similar proportions of clients reporting
high satisfaction with internal systems at baseline and at 12 months; at 6
months, there were significantly more clients in the experimental group who
reported high satisfaction (P = 0.031). Clients with home monitoring were more
satisfied with health-related and medical services post-discharge than those
receiving usual care over a 6-12 month period.
PMID- 25586812
TI - A randomised clinical trial of the effectiveness of home-based health care with
telemonitoring in patients with COPD.
AB - We studied the effect of telemonitoring in addition to usual care compared to
usual care alone in patients with chronic obstructive pulmonary disease (COPD). A
total of 110 patients with moderate to severe COPD were recruited from a
specialist respiratory service in Northern Ireland. Patients had at least two of:
emergency department admissions, hospital admissions or emergency general
practitioner (GP) contacts in the 12 months before the study. Exclusion criteria
were patients who had any respiratory disorder other than COPD, or were
cognitively unable to learn the process of monitoring. Patients were randomised
to receive six months of home telemonitoring with usual care, or six months of
usual care. The primary outcome measure was disease-specific quality of life, as
measured by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C).
Of 100 patients completing the study, 48 patients were randomised to
telemonitoring and 52 patients were randomised to the control group. The SGRQ-C
scores improved significantly in the intervention group compared to usual care (P
= 0.001). The HADS anxiety score was significantly higher in the telehealth group
compared to the usual care group (P = 0.01). There were significantly more
contacts with the Community Respiratory Team in the telemonitoring group compared
to the control group (P = 0.029). There were no significant between group
differences in EQ-5D scores, HADS depression scores, GP activity, emergency
department visits, hospital admissions or exacerbations. The total cost to the
health service of the intervention over the 6-month study period was L2039,
giving an estimated ICER of L203,900. In selected patients with COPD,
telemonitoring was effective in improving health-related quality of life and
anxiety, but was not a cost-effective intervention.
PMID- 25586813
TI - The effect of telemedicine on the duration of treatment in dementia patients.
AB - We studied 442 patients who met the DSM-IV-TR criteria for dementia and whose
treatment was initiated at the Kangwon National University Hospital (KNUH) in
Chuncheon. Over a five-year period, there were 259 patients who regularly visited
the KNUH dementia clinic in person, and 168 patients who received medical
services from the dementia clinic via telemedicine. The telemedicine patients
attended a public health centre in Hongcheon, a facility located in a rural area
about 50 km south east of the KNUH. The mean treatment duration was significantly
longer for the telemedicine group than for the clinical visit group (P < 0.001),
with durations of 26.6 and 14.6 months, respectively. Low Clinical Dementia
Rating scores (hazard ratio = 1.47, 95% confidence interval = 1.26-1.71) and use
of telemedicine (hazard ratio = 0.55, 95% confidence interval = 0.42-0.72) were
found to be independent predictive factors of increased treatment duration. These
findings suggest that telemedicine may be useful in slowing disease progression
in dementia patients in rural areas.
PMID- 25586814
TI - Feasibility and accuracy of using mobile phone images of electrocardiograms to
initiate the cardiac catheterization process.
AB - We assessed the feasibility of interpreting the presence of ST-segment elevation
myocardial infarction (STEMI) using ECGs captured and transmitted by mobile
phones. Transmitted ECGs were interpreted by four independent and blinded
physicians, who classified them as STEMI, non-STEMI or indeterminate. After 2-4
weeks the same physicians were given the original paper ECGs for interpretation.
In total, 87 ECGs were randomly selected for review. The overall agreement
between the digital image readings and the printed copy readings was 94%. Of the
87 patients, 65 (75%) had cardiac catheterization following a STEMI ECG and 22
(25%) did not receive cardiac catheterization. The accuracy of digital ECGs and
printed ECGs when compared to the findings from cardiac catheterization was
similar. Agreement in ECG interpretations between printed images and mobile phone
images was excellent, and both had similar accuracy in activating the cardiac
catheterization laboratory. Mobile phone transmission is an inexpensive method of
evaluating ECG images sent from pre-hospital settings to the emergency
department.
PMID- 25586815
TI - Can clans protect adolescent players of massively multiplayer online games from
violent behaviors?
AB - OBJECTIVES: To examine whether clan membership mediates observed associations
between violent game content and externalizing behaviors among youth who play
massively multiplayer online games (MMOGs). METHODS: Responses from 486 11- to 18
year-olds who: live in the United States, read English, have been online at least
once in the past 6 months, and have played MMOGs in the past year were examined.
Generalized estimating equations were used to estimate the population-averaged
incident rate ratio of aggressive, delinquent, and seriously violent behaviors
among MMOG players given one's self-reported exposure to in-game content
depicting violence. RESULTS: Twenty-nine percent of all youth respondents played
MMOGs in the past year. Rates of aggressive, IRR: 1.59, 95% CI [1.11, 2.26], and
delinquent, IRR: 1.44, 95% CI [0.99, 2.08], behaviors were significantly higher
for MMOG players who were in clans versus not in clans. For females, clan
membership attenuated but did not eliminate the observed relation between
exposure to in-game violent content and both aggressive and seriously violent
behavior (16% and 10% reductions in IRR, respectively); whereas for males, clan
membership was largely uninfluential (i.e., less than 2% change). CONCLUSIONS:
Clan membership is neither associated with lower rates of externalizing behaviors
for youth, nor does it affect the likelihood of reporting externalizing behaviors
among male players. There is some suggestion that clan membership may attenuate
the concurrent association between in-game violent content and some externalizing
behaviors for females.
PMID- 25586817
TI - Bond cleavage, fragment modification and reassembly in enantioselective three
component reactions.
AB - Chemical bond cleavage and reconstruction are common processes in traditional
rearrangement reactions. In contrast, the process that involves bond cleavage,
fragment modification and then reconstruction of the modified fragment provides
an efficient way to build structurally diversified molecules. Here, we report a
palladium(II)/chiral phosphoric acid catalysed three-component reaction of
aryldiazoacetates, enamines and imines to afford alpha-amino-delta-oxo pentanoic
acid derivatives in good yields with excellent diastereoselectivities and high
enantioselectivities. The stereoselective reaction went through a unique process
that involves cleavage of a C-N bond, modification of the resulting amino
fragment and selective reassembly of the modified fragment. This innovative multi
component process represents a highly efficient way to build structurally
diversified polyfunctional molecules in an atom and step economic fashion. A keto
iminium is proposed as a key intermediate and a chiral palladium/phosphate
complex is proposed as an active catalyst.
PMID- 25586816
TI - Media use and depression: exposure, household rules, and symptoms among young
adolescents in the USA.
AB - OBJECTIVES: To determine the longitudinal and cross-sectional associations
between different types of electronic media use (mobile phones, TV, computers,
video games, and music) and young adolescents' depressive symptoms, and to
explore the potential for household media rules to reduce young people's
depression. METHODS: 126 young adolescents were recruited from the Northeastern
USA. Each type of media use was assessed using survey questions, time use
diaries, and ecological momentary assessment. The Beck Depression Index for
Primary Care was administered at baseline and 1 year later as part of a
questionnaire that also included items assessing the presence of household rules
about TV and video games. RESULTS: Baseline use of mobile phones and TV viewing
were associated with higher levels of depression 1 year later controlling for
demographic information and baseline depression score. Having household rules
about TV at baseline predicted lower levels of depression at follow-up.
CONCLUSIONS: Both TV viewing and mobile phone use may contribute to the
development of depressive symptoms. Implementing household rules about the
duration and content of TV could help reduce depression in young adolescents.
PMID- 25586818
TI - Exercise-associated hyponatremic encephalopathy and exertional heatstroke in a
soldier: High rates of fluid intake during exercise caused rather than prevented
a fatal outcome.
AB - Athletes are often advised to drink in order to "fully replace bodyweight losses"
in order to prevent exertional heatstroke (EHS) during exercise in the heat.
There is little evidence that "dehydration" in the range experienced by athletes
adversely affects thermoregulation or is the exclusive cause of EHS. In contrast
it is established that excess fluid intake can cause exercise-associated
hyponatremia (EAH) sometimes associated with encephalopathy (EAHE). As part of a
series of experiments to determine optimal fluid replacement during exercise in
the heat, we studied a group of exceptionally well-conditioned and heat-adapted
members of the South African National Defence Force. A 20 year old male started a
time restricted 50 km route-march in a dry bulb temperature that reached 37.5
degrees C (WBGT of 33.6 degrees C, relative humidity of 85%). Pre-march plasma
osmolality, serum [Na(+)] and total body water measures indicated euhydration.
Fluid was available ad libitum and isotonic sports drinks at 5 km intervals.
Fluid intake and core body temperature (Tc) were recorded throughout while he was
tracked by a global positioning system measuring distance travelled, position and
speed. Comparing the total fluid intake of the soldier (12930 mL) to the rest of
the participants (mean intake of 9 038 mL) up to 40 km, it is evident that his
intake was 3892 mL (approximately 300 mL h(-1)) more than the mean for group. At
approximately 17h14 the soldier was found lying by himself at the side of the
route, 2.24 km from the finish point. He passed away the next day in a medical
care facility. This tragic event provides the valuable opportunity to present
data on the pacing, temperature regulation and fluid consumption of an
exceptional athlete during the development of a fatal case of combined EAHE and
EHS. Pacing, fluid intake, Tc and environmental condition data are presented for
5 km intervals throughout the march. We propose a novel hypothesis on the
possible contribution of EAHE to the development of EHS.
PMID- 25586819
TI - Continued effects of context reinstatement in recognition.
AB - The context reinstatement effect refers to the enhanced memory performance found
when the context information paired with a target item at study is re-presented
at test. Here we investigated the consequences of the way that context
information is processed in such a setting that gives rise to its beneficial
effect on item recognition memory. Specifically, we assessed whether reinstating
context in a recognition test facilitates subsequent memory for this context,
beyond the facilitation conferred by presentation of the same context with a
different study item. Reinstating the study context at test led to better
accuracy in two-alternative forced choice recognition for target faces than did
re-pairing those faces with another context encountered during the study phase.
The advantage for reinstated over re-paired conditions occurred for both within
subjects (Exp. 1) and between-subjects (Exp. 2) manipulations. Critically, in a
subsequent recognition test for the contexts themselves, contexts that had
previously served in the reinstated condition were recognized better than
contexts that had previously served in the re-paired context condition. This
constitutes the first demonstration of continuous effects of context
reinstatement on memory for context.
PMID- 25586821
TI - Radiofrequency ablation of drug-resistant cancer cells using molecularly targeted
carboxyl-functionalized biodegradable graphene.
AB - Under ultralow radiofrequency (RF) power, transferrin-conjugated graphene
nanoparticles can thermally ablate drug- or radiation-resistant cancer cells very
effectively. The results suggest that graphene-based RF hyperthermia can be an
efficient method to manage drug-/radiation-resistant cancers.
PMID- 25586822
TI - Sustained ventricular tachycardia as the first manifestation of hydatid cyst
located in the interventricular septum.
AB - Echinococcus granulosus infection may manifest with cardiac involvement causing
various symptoms. Here, we discuss a case of a young patient who presented with
sustained ventricular tachycardia (VT) causing hemodynamic compromise. Diagnosis
of cardiac hydatid cyst was established with echocardiography, computed
tomography imaging, and serological examination. After surgical removal of the
cyst VT did not recur.
PMID- 25586823
TI - Shoulder surgery.
PMID- 25586824
TI - Erratum to: Prediction of osteonecrosis collapse of the femoral head based on the
proportion of the proximal sclerotic rim.
PMID- 25586826
TI - Monitoring the Effect of Metal Ions on the Mobility of Artemia salina Nauplii.
AB - This study aims to measure the effect of toxic aqueous solutions of metals on the
mobility of Artemia salina nauplii by using digital image processing. The
instrument consists of a camera with a macro lens, a dark chamber, a light source
and a laptop computer. Four nauplii were inserted into a macro cuvette, which
contained copper, cadmium, iron and zinc ions at various concentrations. The
nauplii were then filmed inside the dark chamber for two minutes and the video
sequence was processed by a motion tracking algorithm that estimated their
mobility. The results obtained by this system were compared to the mortality
assay of the Artemia salina nauplii. Despite the small number of tested
organisms, this system demonstrates great sensitivity in quantifying the mobility
of the nauplii, which leads to significantly lower EC50 values than those of the
mortality assay. Furthermore, concentrations of parts per trillion of toxic
compounds could be detected for some of the metals. The main novelty of this
instrument relies in the sub-pixel accuracy of the tracking algorithm that
enables robust measurement of the deterioration of the mobility of Artemia salina
even at very low concentrations of toxic metals.
PMID- 25586825
TI - The MAST(r) D68C test: an interesting tool for detecting extended-spectrum beta
lactamase (ESBL)-producing Enterobacteriaceae.
AB - The Mast(r) D68C test is a phenotypical test that allows the detection of
extended-spectrum beta-lactamase (ESBL) production, even in AmpC-producing
Enterobacteriaceae. We assessed its detection accuracy against a large collection
of 106 Enterobacteriaceae isolates producing a wide diversity of well
characterized beta-lactamases (53 ESBL producers, 25 Amp. producers, seven AmpC
and ESBL producers, five carbapenemase producers, three carbapenemase and ESBL
producers, one AmpC, carbapenemase, and ESBL producer, three TEM-1 producers,
three SHV-1 producers, three OXA-1 producers, and one hyperOXY producer, ATCC
35218, ATCC 25922 [a beta-lactamase-negative control strain]). The results were
compared with those of the double disk test and the Clinical and Laboratory
Standards Institute (CLSI) confirmatory test for the detection of ESBL. The
sensitivity was 90.6 % for the synergy test, 87.5 % for the CLSI method, and only
73.1 % for D68C, which, however, reached 92.1 % if the strains for which
supplementary investigations were recommended and the complex mutant TEM (CMT)
producing strains were excluded versus 94.1 % and 88.2 % for the other methods.
The specificity was 90.2 % for the synergy test and 100 % for the CLSI method and
D68C. D68C was also efficient in detecting AmpC-overproducing strains
(sensitivity = 97 %, specificity = 95.9 %): among the 74 strains belonging to
natural AmpC-producing species, the sensitivity and specificity were 100 and 94.8
%, respectively. The Mast(r) D68C-test is a promising method that is easy to
perform for the detection of current ESBLs and could also be useful for the
detection of plasmid-encoded AmpC enzymes (sensitivity = 100 %).
PMID- 25586827
TI - Nonlinear impedance of whole cells near an electrode as a probe of mitochondrial
activity.
AB - By simultaneously measuring the bulk media and electrode interface voltages of a
yeast (Saccharomyces cerevisiae) suspension subjected to an AC voltage, a yeast
dependent nonlinear response was found only near the current injection
electrodes. Computer simulation of yeast near a current injection electrode found
an enhanced voltage drop across the yeast near the electrode due to slowed
charging of the electrode interfacial capacitance. This voltage drop is
sufficient to induce conformation change in membrane proteins. Disruption of the
mitochondrial electron transport chain is found to significantly change the
measured nonlinear current response, suggesting nonlinear impedance can be used
as a non-invasive probe of cellular metabolic activity.
PMID- 25586828
TI - Kinetic ELISA in microfluidic channels.
AB - In this article, we describe the kinetic ELISA of Blue Tongue and Epizootic
Hemorrhagic Disease viral antibodies in microfluidic channels by monitoring the
rate of generation of the enzyme reaction product under static conditions. It has
been shown that this format of the immunoassay allows very reliable quantitation
of the target species using inexpensive glass microchips and a standard
epifluorescence microscope system coupled to a CCD camera. For the viral
antibodies assayed here, the limit of detection (LOD) for the analyte
concentration in our microchips was established to be 3-5 times lower than that
obtained on commercial microwell plates using a fiftieth of the sample volume and
less than a third of the incubation time. Our analyses further show that when
compared to the end-point ELISA format, the kinetic mode of this assay yields an
improvement in the LOD by over an order of magnitude in microfluidic devices.
This benefit is primarily realized as the observed variation in the background
fluorescence (signal at the start of the enzyme reaction period) was
significantly larger than that in the rate of signal generation upon repeating
these assays in different microchannels/microchips. Because the kinetic ELISA
results depend only on the latter quantity, the noise level in them was
substantially lower compared to that in its end-point counterpart in which the
absolute fluorescence measurements are of greater significance. While a similar
benefit was also recorded through implementation of kinetic ELISAs on the
microwell platform, the improvement in LOD registered in that system was not as
significant as was observed in the case of microfluidic assays.
PMID- 25586829
TI - Hypothermic neuroprotection is associated with recovery of spectral edge
frequency after asphyxia in preterm fetal sheep.
AB - BACKGROUND AND PURPOSE: Electroencephalographic recovery is predictive of outcome
after perinatal hypoxia-ischemia, but it is unknown whether early changes in
electroencephalographic can predict the response to therapeutic hypothermia in
the preterm brain. METHODS: 0.7 gestation fetal sheep received umbilical cord
occlusion or sham occlusion for 25 minutes, followed by sham hypothermia or whole
body cooling started either 30 minutes or 5 hours after occlusion and continued
for 72 hours. RESULTS: Early but not delayed hypothermia reduced neuronal loss
and microglial induction in the striatum, with faster recovery of spectral edge
frequency, reduced seizure burden, and less suppression of
electroencephalographic amplitude (P<0.05). CONCLUSIONS: Recovery of higher
electroencephalographic frequencies may be a biomarker of effective hypothermic
neuroprotection in the preterm-equivalent brain.
PMID- 25586831
TI - Brief history of patent foramen ovale and stroke.
PMID- 25586832
TI - Response to letter regarding article, "amplification of regulatory T cells using
a CD28 superagonist reduces brain damage after ischemic stroke in mice".
PMID- 25586833
TI - Influence of intracerebral hemorrhage location on incidence, characteristics, and
outcome: population-based study.
AB - BACKGROUND AND PURPOSE: The characteristics of intracerebral hemorrhage (ICH) may
vary by ICH location because of differences in the distribution of underlying
cerebral small vessel diseases. Therefore, we investigated the incidence,
characteristics, and outcome of lobar and nonlobar ICH. METHODS: In a population
based, prospective inception cohort study of ICH, we used multiple overlapping
sources of case ascertainment and follow-up to identify and validate ICH
diagnoses in 2010 to 2011 in an adult population of 695 335. RESULTS: There were
128 participants with first-ever primary ICH. The overall incidence of lobar ICH
was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7-12.4] versus 8.6
[95% confidence interval, 6.7-11.1] per 100 000 adults/y). At baseline, adults
with lobar ICH were more likely to have preceding dementia (21% versus 5%;
P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger
ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%;
P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar
ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH
(adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95%
confidence interval, 0.07-0.63; P=0.006, after adjustment for known predictors of
outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of
lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence
interval, 4.6%-28.5% versus 0% after nonlobar ICH; log-rank P=0.04). CONCLUSIONS:
The baseline characteristics and outcome of lobar ICH differ from other
locations.
PMID- 25586834
TI - Letter by Gauberti and Vivien regarding article, "amplification of regulatory T
cells using a CD28 superagonist reduces brain damage after ischemic stroke in
mice".
PMID- 25586836
TI - The Journal of Paediatrics and Child Health is celebrating its 50th anniversary.
PMID- 25586837
TI - It is desirable that our neighbours have a clear image of all aspects of
Australian life and culture.
PMID- 25586838
TI - An explosion, a tsunami, a runaway train: half a century of genetics.
AB - Let's face it. There is no way of writing about the last half century of genetics
without getting a little bit excitable. All of the terms in the title of this
piece have been used by otherwise level-headed geneticists to describe the pace
of change in genetics over the past few years. The thing is--they are right.
Genetics is moving faster and faster. Five years ago, few people would have
predicted that we would be where we are today. Five years from now, presumably,
it will seem like 2015 was some kind of Dark Age when nothing much was happening.
So it would be easy to lose perspective on the achievements of the past, or to
assume that nothing much was happening in genetics until recently. However,
everything that is happening in genetics now rests on the foundations built up
over the past century, and particularly the past half century. And through that
time, this journal has been a part of that story.
PMID- 25586839
TI - Fifty years of paediatric ethics.
AB - In 1965, when the first issue of Journal of Paediatrics and Child Health
appeared, medical ethics was just becoming established as a discipline. The sub
speciality of paediatric ethics did not make an appearance until the late 1980s,
with the first key texts appearing in the 1990s. Professional concern to practice
ethically in paediatrics obviously goes much further back than that, even if not
named as such. In clinical areas of paediatrics, the story of the last 50 years
is essentially a story of progress - better understanding of disease, better
diagnosis, more effective treatment, better outcomes. In paediatric ethics, the
story of the last 50 years is a bit more complicated. In ethics, the idea of
progress, rather than just change, is not so straightforward and is sometimes
hotly contested. There has certainly been change, including some quite radical
shifts in attitudes and practices, but on some issues, the ethical debate now
looks remarkably similar to that of 40-50 years ago. This is the story of some
things that have changed in paediatric ethics, some things that have stayed the
same and the key ethical ideas lying beneath the surface.
PMID- 25586835
TI - Genes from a translational analysis support a multifactorial nature of white
matter hyperintensities.
AB - BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) of presumed vascular
origin increase the risk of stroke and dementia. Despite strong WMH heritability,
few gene associations have been identified. Relevant experimental models may be
informative. METHODS: We tested the associations between genes that were
differentially expressed in brains of young spontaneously hypertensive stroke
prone rats and human WMH (using volume and visual score) in 621 subjects from the
Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361
subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology
(CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH
associations found in subjects from CHARGE. RESULTS: Of 126 spontaneously
hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume
or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and
MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10
(XPNPEP1, P=6.7*10(-5); FARP1, P=0.024) plus another spontaneously hypertensive
stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10
respectively, were associated with WMH in subjects from CHARGE. Gene set
enrichment showed significant associations for downregulated spontaneously
hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936,
we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and
TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS: Despite not passing
multiple testing thresholds individually, these genes collectively are relevant
to known WMH associations, proposed WMH mechanisms, or dementia: associations
with Alzheimer's disease, late-life depression, ATP production, osmotic
regulation, neurodevelopmental abnormalities, and cognitive impairment. If
replicated further, they suggest a multifactorial nature for WMH and argue for
more consideration of vascular contributions to dementia.
PMID- 25586840
TI - Fifty years of immunisation in Australia (1964-2014): the increasing opportunity
to prevent diseases.
AB - Medicine has seen dramatic changes in the last 50 years, and vaccinology is no
different. Australia has made a significant contribution to world knowledge on
vaccine-preventable diseases. Certain deadly diseases have disappeared or become
rare in Australia following successful introduction of vaccines. As diseases
become rarer, public knowledge about the diseases and their serious consequences
has decreased, and concerns about potential vaccine side effects have increased.
To maintain confidence in immunisations, sharing of detailed information about
the vaccines and the diseases we are trying to prevent is integral to the
continued success of our public health programme. Modern quality immunisation
programmes need to communicate complex information to immunisation providers and
also to the general community. Improving immunisation coverage rates and
eliminating the gap in coverage and timeliness between Aboriginal and Torres
Strait Islander peoples and non-Indigenous people has become a high priority.
PMID- 25586841
TI - Historical aspects of rheumatic fever.
AB - Few diseases have experienced such a remarkable change in their epidemiology over
the past century, without the influence of a vaccine, than rheumatic fever.
Rheumatic fever has all but disappeared from industrialised countries after being
a frequent problem in the 1940s and 1950s. That the disease still occurs at high
incidence in resource limited settings and in Indigenous populations in
industrialised countries, particularly in Australia and New Zealand, is an
indication of the profound effect of socio-economic factors on the disease.
Although there have been major changes in the epidemiology of rheumatic fever,
diagnosis remains reliant on careful clinical judgement and management is
remarkably similar to that 50 years ago. Over the past decade, increasing
attention has been given to rheumatic fever and rheumatic heart disease as public
health issues, including in Australia and particularly in New Zealand, as well as
in selected low and middle income countries. Perhaps the greatest hope for public
health control of rheumatic fever is the development of a vaccine against
Streptococcus pyogenes, and there are encouraging initiatives in this area.
However, an effective vaccine is some time away and in the meantime public health
efforts need to focus on effective translation of the known evidence around
primary and secondary prophylaxis into policy and practice.
PMID- 25586842
TI - Paediatric cardiology: the last 50 years.
AB - In the last half-century, the outlook for children with heart disease has changed
dramatically. Morphologists have transformed our understanding of heart defects.
Improved imaging methods, such as echocardiography, computed tomography and
magnetic resonance imaging, have made diagnostic cardiac catheterisation almost
redundant. However, interventional catheterisation has flourished as
transcatheter procedures have replaced surgery for many lesions. The ability to
pharmacologically manipulate the duct has revolutionised the management of the
sick neonate with major heart disease. Better surgical techniques, such as deep
hypothermia and circulatory arrest, allow repair of lesions in early infancy
before irreversible complications develop. Advances in anaesthesia and intensive
care have been integral. New sub-disciplines, such as fetal cardiology and
electrophysiology, have emerged. The sum of these numerous developments is
enormous. Lesions that were previously considered lethal are now routinely
treated. Consequently, the great majority of children with major heart disease
now reach adulthood in good health.
PMID- 25586843
TI - Conquering rotavirus: from discovery to global vaccine implementation.
AB - Rotavirus, the commonest cause of severe dehydrating gastroenteritis world-wide,
was discovered less than 50 years ago. It causes about 450,000 deaths per year in
children <5 years of age and hospitalises millions more. Rotavirus vaccines have
been shown to have a major impact on hospital admissions due to rotavirus
gastroenteritis and all-cause gastroenteritis and reduce mortality in developing
countries. In Australia, there has been a 71% decrease in rotavirus
hospitalisations in children 0-5 years of age. From the discovery of rotavirus as
the major causative agent for severe gastroenteritis, through vaccine development
and vaccine post-marketing surveillance activities, Australian scientists and
clinicians have played a significant role in the global effort to reduce the
burden of rotavirus infection.
PMID- 25586844
TI - In the beginning, there was general paediatrics ....
AB - In this article, we address how general paediatrics has evolved and adapted to
change over the past 50 years and speculate on its future directions. We compare
the state of general paediatrics with that of general adult medicine. We argue
that general paediatrics must continue to have a strong role both in paediatric
teaching hospitals and the community.
PMID- 25586845
TI - Closing the gaps in child health in the Pacific: an achievable goal in the next
20 years.
AB - It is not inconceivable that by 2035 the substantial gaps in child health across
the Pacific can close significantly. Currently, Australia and New Zealand have
child mortality rates of 5 and 6 per 1000 live births, respectively, while
Pacific island developing nations have under 5 mortality rates ranging from 13 to
16 (Vanuatu, Fiji and Tonga) to 47 and 58 per 1000 live births (Kiribati and
Papua New Guinea, respectively). However, these Pacific child mortality rates are
falling, by an average of 1.4% per year since 1990, and more rapidly (1.9% per
year) since 2000. Based on progress elsewhere, there is a need to (i) define the
specific things needed to close the gaps in child health; (ii) be far more
ambitious and hopeful than ever before; and (iii) form a new regional compact
based on solidarity and interdependence.
PMID- 25586846
TI - Regression in autism spectrum disorders.
AB - Since the Journal of Paediatrics and Child Health was first published, there has
been substantial change in the field of autism spectrum disorders (ASDs) with an
exponential increase in the amount of funded and published research. In this
paper, we focus on regression in children with ASD, a phenomenon that remains
poorly understood. We discuss the implications of what we know about regression
in ASD for the way we think about ASD more broadly and for paediatric practice.
PMID- 25586847
TI - Attention-deficit/hyperactivity disorder: the past 50 years.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental
disorder and one of the main diagnoses seen by general paediatricians today.
Despite the impression often portrayed in the media, it is not a new condition;
in fact it has been described for over 200 years. The past 50 years has seen a
progressive increase in our understanding of the underlying neurocognitive
deficits in ADHD, and over the past 20 years behavioural genetics and
neuroimaging studies have shed light on the complex causal factors and
neurobiological processes operating. The plethora of ADHD research has advanced
our knowledge of the condition, but so far has had little impact on improving
clinical practice. Stimulant medication has been the mainstay of symptomatic
treatment for over 30 years; however, it is still unclear how developmental
trajectories can be modified to achieve best outcomes. It is hoped that novel
therapies and more individualised management will evolve over the coming decades.
PMID- 25586848
TI - Lessons from 50 years of curing childhood leukaemia.
AB - One of the great success stories of modern medicine is undoubtedly the remarkable
improvement in outcome for childhood cancer, achieved through the work of the co
operative groups enrolling patients in randomised controlled trials. In 1965,
survival was almost zero; now 5-year survival rates exceed 80% in high-income
countries. The lessons learned in the care of patients with the most common
malignancy in childhood--acute lymphoblastic leukaemia--have been used in all
other cancers of childhood and more recently in the management of adults. These
lessons can be broadly applied in medical practice, because elements of
laboratory science in all branches of pathology, as well as a deep understanding
of biochemistry, physiology, pharmacology, genetics and molecular science, run
through this story. Far from being a sad area of practice, paediatric haematology
and oncology remains the champion of embedded clinical and translational
research, diagnosis from bench to bedside and lifelong multidisciplinary
management of the child and their family.
PMID- 25586849
TI - Viewpoint article: Childhood obesity--looking back over 50 years to begin to look
forward.
AB - The last 50 years have seen the emergence of childhood obesity as a major public
health concern and a condition now regularly encountered in routine general
paediatric practice. Causes are extremely complex, bringing together
multifactorial environmental factors and individual genetics, and we still do not
have a clear understanding of why some children appear predisposed to exaggerated
and sometimes extreme weight gain. Overweight and obese children of today face an
uncertain future. They are likely to experience higher rates of type 2 diabetes
and heart disease, as well as many other health problems. However, while the
prevalence of childhood obesity has progressively increased over the last few
decades, so has research into its underlying causes. This has led to large-scale
trials aimed at improving prevention or treatment. As data have emerged from such
studies, we have begun to accept that the heterogeneity of obesity means that
broad 'common sense' strategies to address diet and activity will not lead to
success on their own. Now is the time to begin to build on this information,
dispelling myths and beliefs, in order to focus research efforts and take first
steps towards more sophisticated strategies that go beyond the surface behaviours
that simply potentiate obesity. Through carefully designed studies, aimed at
tackling fundamental questions missed in the hasty development of 'common sense'
approaches, will come answers that can lead to the development of more effective
community- and health-care-orientated prevention and treatment programmes.
PMID- 25586850
TI - Fifty years of allergy: 1965-2015.
AB - The last 50 years in allergy could almost be considered the first 50 years. Over
this time period, we have witnessed the emergence of allergy as a subspecialty,
have seen and continue to observe a tremendous change in prevalence of allergic
disease and have gained insight into the mechanisms that underlie allergic
predisposition and disease manifestation. We have improved the care of children
with many forms of allergic disease and now sit poised to be able to alter the
natural history of allergic disease with the use of specific immunotherapy. There
is much left to do in the next 50 years including understanding what underlies
both the predisposition to atopic disease and its natural resolution and
identifying the environmental cofactors involved in the 'allergic epidemic' and
therefore targets for effective primary prevention.
PMID- 25586851
TI - Theatre of paediatric surgery.
AB - In the 50 years since the first edition of this journal, operative paediatric
surgery has undergone radical change. Many of the most common instruments are
unchanged, both as a testament to their utility and in recognition of past
surgeons remembered eponymously. Surrounding that basic core of instruments,
theatre has changed radically as new tools and techniques have arisen. Surgeons
have come down from their pedestals, recognising surgery as a team sport rather
than a solo performance. More than half of the current paediatric surgical
trainees are women, a higher proportion than in any other craft group of the
Royal Australasian College of Surgeons. The appearance, and rapid development, of
laparoscopy is to many observers the most notable change in surgery over the last
50 years. Placed in its context though, it is simply the most prominent example
of a frameshift in surgical thinking. The patient as a whole is now the focus,
rather than just the disease. Recent developments are as much about minimising
harm to normal tissues as they are about extirpating pathology. As a surgical
maxim, 'Primum non nocere' is even more in evidence in 2015 than it was in 1965.
PMID- 25586852
TI - Fifty years of newborn screening.
AB - Newborn screening has evolved fast following recent advances in diagnosis and
treatment of disease, particularly the development of multiplex testing and
applications of molecular testing. Formal evidence of benefit from newborn
screening has been largely lacking, due to the rarity of individual disorders.
There are wide international differences in the choice of disorders screened, and
ethical issues in both screening and not screening are apparent. More evidence is
needed about benefit and harm of screening for specific disorders and renewed
discussion about the basic aims of newborn screening must be undertaken.
PMID- 25586853
TI - Sudden unexpected death in infancy: a historical perspective.
AB - Epidemiological, developmental and pathological research over the last 40 years
has done much to unravel the enigma of sudden unexpected death in infancy (SUDI)
and sudden infant death syndrome (SIDS) that has afflicted the human condition
for millennia. Modifications in infant care practices based on the avoidance of
risk factors identified from a consistent epidemiological profile across time and
multiple locations have resulted in dramatic reductions in the incidence of SUDI
and SIDS in particular. The definition of SIDS (or unexplained SUDI) has been
continually refined allowing enhanced multidisciplinary research, results of
which can be more reliably compared between investigators. These latter expanded
definitions mandating death scene investigations, evaluation of the circumstances
of death and more comprehensive autopsies including additional ancillary testing
have illuminated the importance of life-threatening sleep environments. The
triple-risk hypothesis for SIDS has been increasingly validated and formulates an
inextricable relationship between an infant's state of development, underlying
pathological vulnerability and an unsafe sleep environment for sudden infant
death to occur. Today, the major risk factors for SUDI are maternal smoking and
bed sharing, and the challenge is to implement effective strategies that will
reduce the exposure to such risks as was done with prone sleeping position. The
challenges ahead include development of clinical methods and/or laboratory
testing that will accurately identify which infants are at particularly high risk
of SIDS but also means by which their deaths can be prevented.
PMID- 25586854
TI - Neurodevelopmental and behavioural paediatrics.
AB - One of the notable shifts in Paediatrics across the last 50 years has been
towards disorders that are chronic and qualitative in nature. In addition to
physical health, these impact on childhood development, behaviour and wellbeing.
Understanding and management of these problems extends the traditional biological
toolkit of paediatrics into the complexities of uncertainties of psychological
and social context. In Australasia, the profession has responded with the
development of Community Paediatrics as a recognised sub-specialty, of which
Neurodevelopmental and Behavioural Paediatrics is an important component. These
developments are reviewed along with consideration of future challenges for this
field of health care.
PMID- 25586855
TI - Serpiginous lesion on the foot.
PMID- 25586856
TI - What is the diagnosis?
PMID- 25586859
TI - Hitchhiker's guide to the literature: journal: Nature.
PMID- 25586860
TI - The role of temperature in reported chickenpox cases from 2000 to 2011 in Japan.
AB - Annual periodicities of reported chickenpox cases have been observed in several
countries. Of these, Japan has reported a two-peaked, bimodal annual cycle of
reported chickenpox cases. This study investigated the possible underlying
association of the bimodal cycle observed in the surveillance data of reported
chickenpox cases with the meteorological factors of temperature, relative
humidity and rainfall. A time-series analysis consisting of the maximum entropy
method spectral analysis and the least squares method was applied to the
chickenpox data and meteorological data of 47 prefectures in Japan. In all of the
power spectral densities for the 47 prefectures, the spectral lines were observed
at the frequency positions corresponding to the 1-year and 6-month cycles. The
optimum least squares fitting (LSF) curves calculated with the 1-year and 6-month
cycles explained the underlying variation of the chickenpox data. The LSF curves
reproduced the bimodal and unimodal cycles that were clearly observed in northern
and southern Japan, respectively. The data suggest that the second peaks in the
bimodal cycles in the reported chickenpox cases in Japan occurred at a
temperature of approximately 8.5 degrees C.
PMID- 25586862
TI - Classification of solar cells according to mechanisms of charge separation and
charge collection.
AB - In the last decade, photovoltaics (PV) has experienced an important
transformation. Traditional solar cells formed by compact semiconductor layers
have been joined by new kinds of cells that are constituted by a complex mixture
of organic, inorganic and solid or liquid electrolyte materials, and rely on
charge separation at the nanoscale. Recently, metal organic halide perovskites
have appeared in the photovoltaic landscape showing large conversion
efficiencies, and they may share characteristics of the two former types. In this
paper we provide a general description of the photovoltaic mechanisms of the
single absorber solar cell types, combining all-inorganic, hybrid and organic
cells into a single framework. The operation of the solar cell relies on a number
of internal processes that exploit internal charge separation and overall charge
collection minimizing recombination. There are two main effects to achieve the
required efficiency, first to exploit kinetics at interfaces, favouring the
required forward process, and second to take advantage of internal electrical
fields caused by a built-in voltage and by the distribution of photogenerated
charges. These principles represented by selective contacts, interfaces and the
main energy diagram, form a solid base for the discussion of the operation of
future types of solar cells. Additional effects based on ferroelectric
polarization and ionic drift provide interesting prospects for investigating new
PV effects mainly in the perovskite materials.
PMID- 25586863
TI - Templated fabrication of periodic arrays of metallic and silicon nanorings with
complex nanostructures.
AB - Here we report a scalable colloidal templating approach for fabricating periodic
arrays of metallic and silicon nanorings with complex nanostructures. Non-close
packed monolayer silica colloidal crystal prepared by a simple spin-coating
technology is first used as template for making periodic arrays of mushroom-like
composite nanostructures consisting of silica spherical caps and polymer stems.
Subsequent metal sputtering and reactive ion etching lead to the formation of
ordered asymmetric nickel nanorings which can be further utilized as etching
masks for patterning periodic arrays of symmetric silicon nanorings. Moreover,
periodic arrays of metallic and silicon concentric double nanorings can be
fabricated by using the asymmetric nickel nanorings as templates. We have also
demonstrated that gold concentric double nanorings show strong surface-enhanced
Raman scattering (SERS) with a SERS enhancement factor of ~9.5 * 10(7) from
adsorbed benzenethiol molecules. The SERS enhancement and the electric field
amplitude distribution surrounding gold concentric double nanorings have been
calculated by using finite element electromagnetic modeling. This new colloidal
templating technique is compatible with standard microfabrication and enables
wafer-scale production of a variety of periodic nanorings with hierarchical
structures that could find important technological applications in plasmonic and
magnetic devices.
PMID- 25586861
TI - Chirality-selected phase behaviour in ionic polypeptide complexes.
AB - Polyelectrolyte complexes present new opportunities for self-assembled soft
matter. Factors determining whether the phase of the complex is solid or liquid
remain unclear. Ionic polypeptides enable examination of the effects of
stereochemistry on complex formation. Here we demonstrate that chirality
determines the state of polyelectrolyte complexes, formed from mixing dilute
solutions of oppositely charged polypeptides, via a combination of electrostatic
and hydrogen-bonding interactions. Fluid complexes occur when at least one of the
polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding
networks. Pairs of purely chiral polypeptides, of any sense, form compact,
fibrillar solids with a beta-sheet structure. Analogous behaviour occurs in
micelles formed from polypeptide block copolymers with polyethylene oxide, where
assembly into aggregates with either solid or fluid cores, and eventually into
ordered phases at high concentrations, is possible. Chirality is an exploitable
tool for manipulating material properties in polyelectrolyte complexation.
PMID- 25586864
TI - New contraceptive patch wearability assessed by investigators and participants in
a randomized phase 3 study.
AB - OBJECTIVE: To evaluate skin irritation and patch adhesiveness of a new weekly low
dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (LNG/EE
patch). STUDY DESIGN: This analysis was part of an open-label, parallel-group,
multicenter, phase 3 study that randomized healthy women to the LNG/EE patch (one
patch weekly for three consecutive weeks, followed by a patch-free week for 13
cycles) or to an oral contraceptive for six cycles followed by seven LNG/EE patch
cycles. Participants selected patch application sites of abdomen, buttock or
upper torso. Investigators rated patch adhesiveness and skin irritation using
standardized scales. Participants rated skin irritation and itching daily using
standardized scales and recorded patch fall-off on daily diary cards. RESULTS: A
total of 32,508 patches were applied (n=1273). At the five clinic visits in which
investigators rated the patches, they rated adhesiveness=0 (no lift) for >=84% of
participants and skin irritation=absent/mild for 97% of patches. Participants
reported that 2-3.7% of patches fell off and rated skin irritation as absent or
mild for 92- 95% of patches, according to site. CONCLUSION: Investigator- and
participant-rated assessments of LNG/EE patch adhesiveness and irritation
demonstrated a low incidence of patch detachment, skin irritation and pruritus.
IMPLICATIONS STATEMENT: This secondary analysis of a phase 3 clinical trial of a
new weekly low-dose LNG and EE contraceptive patch, which used assessment by both
investigators and participants, observed a low incidence of skin irritation,
pruritus and patch detachment.
PMID- 25586866
TI - Development of a novel multiplexed assay for quantification of transforming
growth factor-beta (TGF-beta).
AB - Changes in activity or levels of transforming growth factor-beta (TGF-beta) are
associated with a variety of diseases; however, measurement of TGF-beta in
biological fluids is highly variable. TGF-beta is biologically inert when
associated with its latency-associated peptide (LAP). Most available immunoassays
require exogenous activation by acid/heat to release TGF-beta from the latent
complex. We developed a novel electrochemiluminescence-based multiplexed assay on
the MesoScale Discovery(r) platform that eliminates artificial activation,
simultaneously measures both active TGF-beta1 and LAP1 and includes an internal
control for platelet-derived TGF-beta contamination in blood specimens. We
optimized this assay to evaluate plasma levels as a function of activation type
and clinical specimen preparation. We determined that breast cancer patients'
plasma have higher levels of circulating latent TGF-beta (LTGF-beta) as measured
by LAP1 than healthy volunteers (p < 0.0001). This assay provides a robust tool
for correlative studies of LTGF-beta levels with disease, treatment outcomes and
toxicity with a broad clinical applicability.
PMID- 25586867
TI - Medicine of the thousand poems.
PMID- 25586865
TI - Patient perspectives on online health information and communication with doctors:
a qualitative study of patients 50 years old and over.
AB - BACKGROUND: As health care systems around the world shift toward models that
emphasize self-care management, there is increasing pressure for patients to
obtain health information online. It is critical that patients are able to
identify potential problems with using the Internet to diagnose and treat a
health issue and that they feel comfortable communicating with their doctor about
the health information they acquire from the Internet. OBJECTIVE: Our aim was to
examine patient-identified (1) problems with using the Internet to identify and
treat a health issue, (2) barriers to communication with a doctor about online
health information seeking, and (3) facilitators of communication with a doctor
about patient searches for health information on the Internet. METHODS: For this
qualitative exploratory study, semistructured interviews were conducted with a
sample of 56 adults age 50 years old and over. General concerns regarding use of
the Internet to diagnose and treat a health issue were examined separately for
participants based on whether they had ever discussed health information obtained
through the Internet with a doctor. Discussions about barriers to and
facilitators of communication about patient searches for health information on
the Internet with a doctor were analyzed using thematic analysis. RESULTS: Six
higher-level general concerns emerged: (1) limitations in own ability, (2)
credibility/limitations of online information, (3) anxiety, (4) time consumption,
(5) conflict, and (6) non-physical harm. The most prevalent concern raised by
participants who communicated with a doctor about their online health information
seeking related to the credibility or limitations in online information.
Participants who had never communicated with a doctor about their online health
information seeking most commonly reported concerns about non-physical harm. Four
barriers to communication emerged: (1) concerns about embarrassment, (2) concerns
that the doctor doesn't want to hear about it, (3) belief that there is no need
to bring it up, and (4) forgetting to bring it up. Facilitators of communication
included: (1) having a family member present at doctor visits, (2) doctor
initiated inquiries, and (3) encountering an advertisement that suggested talking
with a doctor. CONCLUSIONS: Overall, participants displayed awareness of
potential problems related to online health information seeking. Findings from
this study point to a set of barriers as well as facilitators of communication
about online health information seeking between patients and doctors. This study
highlights the need for enhanced patient communication skills, eHealth literacy
assessments that are accompanied by targeted resources pointing individuals to
high-quality credible online health information, and the need to remind patients
of the importance of consulting a medical professional when they use online
health resources to diagnose and treat a health issue.
PMID- 25586868
TI - Unveiling SEER-CAHPS(r): a new data resource for quality of care research.
AB - BACKGROUND: Since 1990, the National Cancer Institute (NCI) and Centers for
Medicare and Medicaid Services (CMS) have collaborated to create linked data
resources to improve our understanding of patterns of care, health care costs,
and trends in utilization. However, existing data linkages have not included
measures of patient experiences with care. OBJECTIVE: To describe a new resource
for quality of care research based on a linkage between the Medicare Consumer
Assessment of Healthcare Providers and Systems (CAHPS(r)) patient surveys and the
NCI's Surveillance, Epidemiology and End Results (SEER) data. DESIGN: This is an
observational study of CAHPS respondents and includes both fee-for-service and
Medicare Advantage beneficiaries with and without cancer. The data linkage
includes: CAHPS survey data collected between 1998 and 2010 to assess patient
reports on multiple aspects of their care, such as access to needed and timely
care, doctor communication, as well as patients' global ratings of their personal
doctor, specialists, overall health care, and their health plan; SEER registry
data (1973-2007) on cancer site, stage, treatment, death information, and patient
demographics; and longitudinal Medicare claims data (2002-2011) for fee-for
service beneficiaries on utilization and costs of care. PARTICIPANTS: In total,
150,750 respondents were in the cancer cohort and 571,318 were in the non-cancer
cohort. MAIN MEASURES: The data linkage includes SEER data on cancer site, stage,
treatment, death information, and patient demographics, in addition to
longitudinal data from Medicare claims and information on patient experiences
from CAHPS surveys. KEY RESULTS: Sizable proportions of cases from common cancers
(e.g., breast, colorectal, prostate) and short-term survival cancers (e.g.,
pancreas) by time since diagnosis enable comparisons across the cancer care
trajectory by MA vs. FFS coverage. CONCLUSIONS: SEER-CAHPS is a valuable resource
for information about Medicare beneficiaries' experiences of care across
different diagnoses and treatment modalities, and enables comparisons by type of
insurance.
PMID- 25586870
TI - "Targeted" consent for pragmatic clinical trials.
AB - Research on interventions within the standard of care has enormous potential, yet
it also raises several ethical and regulatory challenges. Perhaps the most
important is determining what consent process is needed for these "pragmatic"
clinical trials. Some argue that pragmatic clinical trials need to obtain in
depth research consent. This approach ensures that patients are informed, but may
introduce substantial selection bias and disruption of clinical care. Others
argue that trials limited to interventions within the standard of care do not
need to obtain research consent at all. While this approach avoids the problems
with in-depth consent, it results in patients not knowing whether they are in
research. The present manuscript proposes a way to avoid both sets of concerns.
It argues that consent for research needs to supplement appropriate consent for
standard care only to the extent that the research differs from standard care.
Hence, pragmatic trials designed to mirror clinical care can obtain consent with
only minimal additions to consent for standard care. This conclusion suggests
that it may be possible for many pragmatic trials to obtain consent that is
ethically appropriate, satisfies research regulations, and does not introduce
substantial selection bias or clinical disruption.
PMID- 25586869
TI - Predicting Non-Adherence with Outpatient Colonoscopy Using a Novel Electronic
Tool that Measures Prior Non-Adherence.
AB - BACKGROUND: Accurately predicting the risk of no-show for a scheduled colonoscopy
can help target interventions to improve compliance with colonoscopy, and thereby
reduce the disease burden of colorectal cancer and enhance the utilization of
resources within endoscopy units. OBJECTIVES: We aimed to utilize information
available in an electronic medical record (EMR) and endoscopy scheduling system
to create a predictive model for no-show risk, and to simultaneously evaluate the
role for natural language processing (NLP) in developing such a model. DESIGN:
This was a retrospective observational study using discovery and validation
phases to design a colonoscopy non-adherence prediction model. An NLP-derived
variable called the Non-Adherence Ratio ("NAR") was developed, validated, and
included in the model. PARTICIPANTS: Patients scheduled for outpatient
colonoscopy at an Academic Medical Center (AMC) that is part of a multi-hospital
health system, 2009 to 2011, were included in the study. MAIN MEASURES: Odds
ratios for non-adherence were calculated for all variables in the discovery
cohort, and an Area Under the Receiver Operating Curve (AUC) was calculated for
the final non-adherence prediction model. KEY RESULTS: The non-adherence model
included six variables: 1) gender; 2) history of psychiatric illness, 3) NAR; 4)
wait time in months; 5) number of prior missed endoscopies; and 6) education
level. The model achieved discrimination in the validation cohort (AUC= =70.2 %).
At a threshold non-adherence score of 0.46, the model's sensitivity and
specificity were 33 % and 92 %, respectively. Removing the NAR from the model
significantly reduced its predictive power (AUC = 64.3 %, difference = 5.9 %, p <
0.001). CONCLUSIONS: A six-variable model using readily available clinical and
demographic information demonstrated accuracy for predicting colonoscopy non
adherence. The NAR, a novel variable developed using NLP technology,
significantly strengthened this model's predictive power.
PMID- 25586871
TI - Whole arm deletions of 18p: medical and developmental effects.
AB - Deletions of the short arm of chromosome 18 have been well-described in case
reports. However, the utility of these descriptions in clinical practice is
limited by varied and imprecise breakpoints. As we work to establish genotype
phenotype correlations for 18p-, it is critical to have accurate and complete
clinical descriptions of individuals with differing breakpoints. In addition, the
developmental profile of 18p- has not been well-delineated. We undertook a
thorough review of the medical histories of 31 individuals with 18p- and a
breakpoint in the centromeric region. We collected developmental data using
mailed surveys and questionnaires. The most common findings included neonatal
complications; cardiac anomalies; hypotonia; MRI abnormalities; endocrine
dysfunction; strabismus; ptosis; and refractive errors. Less common features
included holoprosencephaly and its microforms; hearing loss; and orthopedic
anomalies. The developmental effects of the deletion appear to be less severe
than reported in the literature, as average IQ scores were in the range of
borderline intellectual functioning. Based on responses to standardized
questionnaires, it appears this population has marked difficulty with activities
of daily living, though several young adults were able to live independent of
their parents. This manuscript represents the most comprehensive description of a
cohort of 18p- individuals with identical breakpoints. Despite identical
breakpoints, a great deal of phenotype variability remained among this
population, suggesting that many of the genes on 18p- cause low-penetrance
phenotypes when present in a hemizygous state. Future efforts will focus on the
clinical description of individuals with more distal breakpoints and the
identification of critical regions and candidate genes.
PMID- 25586872
TI - Discreet and distinct clustering of five model membrane proteins revealed by
single molecule localization microscopy.
AB - Compartmentalization is a functionally important property of the plasma membrane,
yet the underlying principles that organize membrane proteins into distinct
domains are not well understood. Using single molecule localization microscopy,
we assessed the clustering of five model membrane proteins in the plasma membrane
of HeLa cells. All five proteins formed discrete and distinct nano-scaled
clusters. The extent of clustering of the five proteins, independent of their
membrane anchors, increased significantly when the fluorescent protein mEOS2 was
employed, suggesting that protein-protein interactions are a key driver for
clustering. Further, actin depolymerization or reduction of membrane order had a
greater, and in some instances opposing effects on the clustering of membrane
proteins fused to mEOS2 compared to PS-CFP2-fusion proteins. The data propose
that protein interactions can override the lateral organization imposed by
membrane anchors to provide an exquisite regulation of the mosaic-like
compartmentalization of the plasma membrane.
PMID- 25586873
TI - Designing elastic organic crystals: highly flexible polyhalogenated N
benzylideneanilines.
AB - The intermolecular interactions and structural features in crystals of seven
halogenated N-benzylideneanilines (Schiff bases), all of which exhibit remarkable
flexibility, were examined to identify the common packing features that are the
raison d'etre for the observed elasticity. The following two features, in part
related, were identified as essential to obtain elastic organic crystals: 1) A
multitude of weak and dispersive interactions, including halogen bonds, which may
act as structural buffers for deformation through easy rupture and reformation
during bending; and 2) corrugated packing patterns that would get interlocked
and, in the process, prevent long-range sliding of molecular planes.
PMID- 25586874
TI - Ovulation requires the activation on proestrus of M1 muscarinic receptors in the
left ovary.
AB - We analyzed the effects of chemically blocking type 1 muscarinic receptors (M1R)
on either the left or right ovary on ovulation rate, number of ova shed and
steroid hormones levels. M1R were unilaterally blocked in ovary with the M1R
selective antagonist pirenzepine (PZP). PZP was delivered into the bursa ovarica
of the left or right ovary of adult rats at 13:00 h on proestrus day. PZP
treatment in the left but not in the right ovary blocked ovulation. PZP did not
modify the number of ova shed, nor progesterone or 17beta-estradiol serum levels.
The surge of luteinizing hormone levels was diminished while that of follicle
stimulating hormone did not change in animals treated with PZP in the left ovary.
Interestingly, treatment with either synthetic luteinizing hormone-releasing
hormone or human chorionic gonadotropin 1 h after PZP administration in the left
ovary restored ovulation in both ovaries. The presence of M1R protein in the
theca cells of the ovarian follicles as well as in cells of the corpus luteum was
detected on proestrus day. These results suggest that M1R activation in the left
ovary is required for pre-ovulatory gonadotropin-releasing hormone (GnRH)
secretion and ovulation. Furthermore, these results also suggest that M1R in the
left ovary might be regulating ovulation asymmetrically through a stimulatory
neural signal relayed to the hypothalamus via the vagus nerve to induce the GnRH
secretion which then triggers ovulation.
PMID- 25586876
TI - Asymmetric interaction paired with a super-rational strategy might resolve the
tragedy of the commons without requiring recognition or negotiation.
AB - Avoiding the tragedy of the commons requires that one or more individuals in a
group or partnership "volunteer", benefiting the group at a cost to themselves.
Recognition and negotiation with social partners can maintain cooperation, but
are often not possible. If recognition and negotiation are not always the
mechanism by which cooperative partnerships avoid collective tragedies, what
might explain the diverse social cooperation observed in nature? Assuming that
individuals interact asymmetrically and that both "weak" and "strong" players
employ a super-rational strategy, we find that tragedy of the commons can be
avoided without requiring either recognition or negotiation. Whereas in the
volunteer's dilemma game a rational "strong" player is less likely to volunteer
to provide a common good in larger groups, we show that under a wide range of
conditions a super-rational "strong" player is more likely to provide a common
good. These results imply that the integration of super-rationality and
asymmetric interaction might have the potential to resolve the tragedy of the
commons. By illuminating the conditions under which players are likely to
volunteer, we shed light on the patterns of volunteerism observed in variety of
well-studied cooperative social systems, and explore how societies might avert
social tragedies.
PMID- 25586875
TI - Subthreshold amplitude and phase resonance in models of quadratic type: nonlinear
effects generated by the interplay of resonant and amplifying currents.
AB - We investigate the biophysical and dynamic mechanisms of generation of
subthreshold amplitude and phase resonance in response to sinusoidal input
currents in two-dimensional models of quadratic type. These models feature a
parabolic voltage nullcline and a linear nullcline for the recovery gating
variable, capturing the interplay of the so-called resonant currents (e.g.,
hyperpolarization-activated mixed-cation inward and slow potassium) and
amplifying currents (e.g., persistent sodium) in biophysically realistic
parameter regimes. These currents underlie the generation of resonance in medial
entorhinal cortex layer II stellate cells and CA1 pyramidal cells. We show that
quadratic models exhibit nonlinear amplifications of the voltage response to
sinusoidal inputs in the resonant frequency band. These are expressed as an
increase in the impedance profile as the input amplitude increases. They are
stronger for values positive than negative to resting potential and are
accompanied by a shift in the phase profile, a decrease in the resonant and phase
resonant frequencies, and an increase in the sharpness of the voltage response.
These effects are more prominent for smaller values of ? (larger levels of the
time scale separation between the voltage and the resonant gating variable) and
for values of the resting potential closer to threshold for spike generation. All
other parameter fixed, as ? increases the voltage response becomes "more linear";
i.e., the nonlinearities are present, but "ignored". In addition, the nonlinear
effects are strongly modulated by the curvature of the parabolic voltage
nullcline (partially reflecting the effects of the amplifying current) and the
slope of the resonant current activation curve. Following the effects of changes
in the biophysical conductances of realistic conductance-based models through the
parameters of the quadratic model, we characterize the qualitatively different
effects that resonant and amplifying currents have on the nonlinear properties of
the voltage response. We identify different classes of resonant currents,
represented by h- and slow potassium, according to whether they enhance (h-) or
attenuate (slow potassium) the nonlinear effects. Finally, we use dynamical
systems tools to investigate the dynamic mechanisms of generation of resonance
and phase-resonance. We show that the nonlinear effects on the voltage response
(e.g., amplification of the voltage response in the resonant frequency band and
shifts in the resonant and phase-resonant frequencies) result from the ability of
limit cycle trajectories to follow the unstable (right) branch of the voltage
nullcline for a significant amount of time. This is a canard-related mechanism
that has been shown to underlie the generation of intrinsic subthreshold
oscillations in quadratic type models such as medial entorhinal cortex stellate
cells. Overall, our results highlight the complexity of the voltage response to
oscillatory inputs in nonlinear models and the roles that resonant and amplifying
currents have in shaping these responses.
PMID- 25586877
TI - Natural history of early first-trimester pregnancies implanted in Cesarean scars.
AB - OBJECTIVE: To describe the ultrasound findings and natural history of pregnancies
implanted within or on Cesarean section scars in the first trimester of
pregnancy. METHODS: This was a prospective observational study of 10 women
diagnosed with a pregnancy implanted in or on a Cesarean section scar in the
first trimester, who declined medical intervention because of their desire to
continue the pregnancy. The study population comprised women at < 12 weeks'
gestation who were seen in our early pregnancy unit between January 2011 and
September 2013. Nine women were followed up by serial ultrasound examinations and
had detailed care plans for delivery at King's College Hospital (KCH). One woman
was followed up and delivered at another teaching hospital. The first-trimester
ultrasound findings were compared with the clinical outcome of the pregnancy.
RESULTS: The nine patients who were followed up at KCH developed ultrasound
findings of morbidly adherent placenta (MAP) in the second and third trimesters.
All 10 patients were diagnosed with MAP at the time of delivery by Cesarean
section. The gestational age at delivery ranged from 26 to 38 weeks. The uterus
was conserved in five patients, and Cesarean hysterectomy was performed in the
remaining five. All three women with complete implantation of the gestational sac
within the scar and two of three cases with placental lakes in the first
trimester had hysterectomies. The two cases with bulging of the gestational sac
out of the uterine contour had a preterm emergency hysterectomy due to placenta
percreta. Histology confirmed placenta accreta in the five hysterectomy
specimens. There were no fetal or neonatal complications. CONCLUSIONS:
Implantation of a pregnancy on or in a Cesarean section scar is a precursor of
MAP; however, the degree of morbidity associated with this implantation is
variable and difficult to predict based on first-trimester ultrasound findings
only. The assessment of ongoing pregnancies implanted in Cesarean scars is most
beneficial when performed between 7 and 9 weeks' gestation. Complete implantation
within the myometrial defect, bulging of the trophoblast from the uterine contour
and large placental lakes in the first trimester are ultrasound findings that may
predict severe placenta accreta or percreta and consequently a poor outcome.
PMID- 25586879
TI - Asymmetrically fused polyoxometalate-silver alkynide composite cluster.
AB - We demonstrate that an asymmetric composite cluster,
[Ag25{C=CC(CH3)3}16(CH3CN)4(P2W15Nb3O62)] (1), consisting of directly fused
polyoxometalate and silver alkynide moieties can be facilely synthesized by a one
pot reaction between a Nb-substituted Dawson-type polyoxometalate, H4[alpha
P2W15Nb3O62](5-), and the mixture of (CH3)3CC=CAg and CF3SO3Ag. Single-crystal X
ray diffraction revealed the structure of 1, where Ag atoms are selectively
attached to the Nb-substituted hemisphere of the pedestal Dawson anion. Its
structural integrity in the solution was demonstrated by (31)P NMR spectroscopy
and analytical ultracentrifugation. The latter method also unveiled the stepwise
formation mechanism of 1.
PMID- 25586878
TI - EBT Fidelity Trajectories Across Training Cohorts Using the Interagency
Collaborative Team Strategy.
AB - The Interdisciplinary Collaborative Team (ICT) strategy uses front-line providers
as adaptation, training and quality control agents for multi-agency EBT
implementation. This study tests whether an ICT transmits fidelity to subsequent
provider cohorts. SafeCare was implemented by home visitors from multiple
community-based agencies contracting with child welfare. Client-reported fidelity
trajectories for 5,769 visits, 957 clients and 45 providers were compared using
three-level growth models. Provider cohorts trained and live-coached by the ICT
attained benchmark fidelity after 12 weeks, and this was sustained. Hispanic
clients reported high cultural competency, supporting a cultural adaptation
crafted by the ICT.
PMID- 25586880
TI - A deadly cause of syncope.
PMID- 25586881
TI - Bridging the gender gap in atrial fibrillation.
AB - Women have a similar lifetime prevalence of non-valvular atrial fibrillation
(NVAF) compared with that of men. Given the significant morbidity and potential
mortality associated with NVAF, it is crucial to understand gender differences
with NVAF. Women can be more symptomatic than men. Despite a higher baseline
stroke risk, they are less likely to be on anticoagulation. Women have a greater
risk of thromboembolism and a similar rate of bleeding risk compared with men on
anticoagulation. Initial experience suggests that novel oral anticoagulants have
similar safety and efficacy profile in men and women. Although women can have
more adverse reactions from antiarrhythmic therapies, they are often referred
later than men for ablation. As a group, a mitigating factor in ablation referral
is that women also have a higher incidence of procedural complications from
catheter ablation. This review summarizes the available literature highlighting
significant gender-based differences and also highlights areas for research to
improve NVAF outcomes in women.
PMID- 25586883
TI - Dereplication-guided isolation of depsides thielavins S-T and lecanorins D-F from
the endophytic fungus Setophoma sp.
AB - Dereplication methodology using UHPLC-DAD-QTOFMS was applied during the metabolic
profiling investigation of the endophyte Setophoma sp., a fungus isolated from
symptomless guava fruits. The approach performed allowed a fast analysis of the
microbial secondary metabolites. From this fungus, seven highly C-alkylated
depsides were isolated and identified as polyketides thielavins S, T, U and V and
lecanorins D, E and F. Their structures were elucidated through spectroscopic
methods including NMR, HRMS and especially with assistance of HRMS/MS
experiments. The compounds were tested for quorum sensing regulation activity in
the virulence gene expression of Staphylococcus aureus, but no inhibitory effect
was detected. Nevertheless, moderate antibacterial activity was encountered in
three of tested depsides, particularly with thielavin T, whose MIC was 6.25
MUg/mL against S. aureus.
PMID- 25586882
TI - Neuromelanin activates proinflammatory microglia through a caspase-8-dependent
mechanism.
AB - BACKGROUND: We have uncovered a caspase-dependent (caspase-8/caspase-3/7)
signaling governing microglia activation and associated neurotoxicity.
Importantly, a profuse non-nuclear activation of cleaved caspases 8 and 3 was
found in reactive microglia in the ventral mesencephalon from subjects with
Parkinson's disease, thus supporting the existence of endogenous factors
activating microglia through a caspase-dependent mechanism. One obvious candidate
is neuromelanin, which is an efficient proinflammogen in vivo and in vitro and
has been shown to have a role in the pathogenesis of Parkinson's disease.
Consequently, the goal of this study is to test whether synthetic neuromelanin
activates microglia in a caspase-dependent manner. RESULTS: We found an in-vivo
upregulation of CD16/32 (M1 marker) in Iba1-immunolabeled microglia in the
ventral mesencephalon after neuromelanin injection. In vitro experiments using
BV2 cells, a microglia-derived cell line, demonstrated that synthetic
neuromelanin induced a significant chemotactic response to BV2 microglial cells,
along with typical morphological features of microglia activation, increased
oxidative stress and induction of pattern-recognition receptors including Toll
like receptor 2, NOD2, and CD14. Analysis of IETDase (caspase-8) and DEVDase
(caspase-3/7) activities in BV2 cells demonstrated a modest but significant
increase of both activities in response to neuromelanin treatment, in the absence
of cell death. CONCLUSIONS: Caspase-8 inhibition prevented typical features of
microglia activation, including morphological changes, a high rate of oxidative
stress and expression of key proinflammatory cytokines and iNOS.
PMID- 25586884
TI - The small regulatory RNA FasX enhances group A Streptococcus virulence and
inhibits pilus expression via serotype-specific targets.
AB - Bacterial pathogens commonly show intra-species variation in virulence factor
expression and often this correlates with pathogenic potential. The group A
Streptococcus (GAS) produces a small regulatory RNA (sRNA), FasX, which regulates
the expression of pili and the thrombolytic agent streptokinase. As GAS serotypes
are polymorphic regarding (a) FasX abundance, (b) the fibronectin, collagen, T
antigen (FCT) region of the genome, which contains the pilus genes (nine
different FCT-types), and (c) the streptokinase-encoding gene (ska) sequence (two
different alleles), we sought to test whether FasX regulates pilus and
streptokinase expression in a serotype-specific manner. Parental, fasX mutant and
complemented derivatives of serotype M1 (ska-2, FCT-2), M2 (ska-1, FCT-6), M6
(ska-2, FCT-1) and M28 (ska-1, FCT-4) isolates were compared. While FasX reduced
pilus expression in each serotype, the molecular basis differed, as FasX bound,
and inhibited the translation of, different FCT-region mRNAs. FasX enhanced
streptokinase expression in each serotype, although the degree of regulation
varied. Finally, we established that the regulation afforded by FasX enhances GAS
virulence, assessed by a model of bacteremia using human plasminogen-expressing
mice. Our data are the first to identify and characterize serotype-specific
regulation by an sRNA in GAS, and to show an sRNA directly contributes to GAS
virulence.
PMID- 25586886
TI - Redox signaling and stress tolerance in plants: a focus on vitamin E.
AB - Plants are subject to specific redox processes, in which photosynthesis plays a
prominent role. Chloroplasts function in light at high oxygen tensions and are
enormous generators of reactive oxygen species, mainly singlet oxygen. This side
product of photosynthesis inflicts damage to thylakoid membranes at high
concentrations, but at the same time it is an essential component of cellular
signaling. Detoxification of singlet oxygen is achieved by different means,
including quenching and scavenging by tocopherols, responsible for controlling
singlet oxygen levels, and the extent of lipid peroxidation in chloroplasts.
Here, environmental conditions leading to excess light in chloroplasts will be
used to show the importance of singlet oxygen, tocopherols, and lipid
peroxidation in cell signaling. Defects in antioxidant protection (e.g.,
tocopherol deficiency) can lead to increased photo-oxidative damage, but also to
the activation of defense pathways, illustrating the phenotypic plasticity
evolved by plants to withstand stress. Most importantly, these studies show how
redox signaling processes are integrated within the cell and illustrate the great
capacity of plants to adapt to their environment.
PMID- 25586885
TI - Barriers and facilitators of medication reconciliation processes for recently
discharged patients from community pharmacists' perspectives.
AB - BACKGROUND: Community pharmacists play a vital part in reconciling medications
for patients transitioning from hospital to community care, yet their roles have
not been fully examined in the extant literature. OBJECTIVES: The objectives of
this study were to: 1) examine the barriers and facilitators community
pharmacists face when reconciling medications for recently discharged patients;
and 2) identify pharmacists' preferred content and modes of information transfer
regarding updated medication information for recently discharged patients.
METHODS: Community pharmacists were purposively and conveniently sampled from the
Wisconsin (U.S. state) pharmacist-based research network, Pharmacy Practice
Enhancement and Action Research Link (PEARL Rx). Community pharmacists were
interviewed face-to-face, and transcriptions from audio recordings were analyzed
using directed content analysis. The Theory of Planned Behavior (TPB) guided the
development of questions for the semi-structured interviews. RESULTS: Interviewed
community pharmacists (N = 10) described the medication reconciliation process to
be difficult and time-consuming for recently discharged patients. In the context
of the TPB, more barriers than facilitators of reconciling medications were
revealed. Themes were categorized as organizational and individual-level themes.
Major organizational-level factors affecting the medication reconciliation
process included: pharmacy resources, discharge communication, and hospital
resources. Major individual-level factors affecting the medication reconciliation
process included: pharmacists' perceived responsibility, relationships, patient
perception of pharmacist, and patient characteristics. Interviewed pharmacists
consistently responded that several pieces of information items would be helpful
when reconciling medications for recently discharged patients, including the
hospital medication discharge list and stop-orders for discontinued medications.
CONCLUSIONS: The TPB was useful for identifying barriers and facilitators of
medication reconciliation for recently discharged patients from community
pharmacists' perspectives. The elucidation of these specific facilitators and
barriers suggest promising avenues for future research interventions to improve
exchange of medication information between the community pharmacy, hospitals, and
patients.
PMID- 25586887
TI - The role of microRNAs in toxicology.
AB - A number of environmental toxicants affect our health through physical,
biological or chemical mechanisms. There is growing evidence indicating that
microRNA (miRNA) plays an important role in toxicogenomics, disease aetiology and
the effect of toxicants. This article summarises recent findings on miRNAs
associated with various toxicants and those targeted in the development of
therapeutics. Environmental epigenetic studies have revealed the role of miRNAs
in the regulation of gene activities induced by environmental changes after
exposure to toxic substances. Toxicant-induced changes in miRNA expression have a
potential to be informative markers in the evaluation of toxicant risks. miRNAs
are now considered to be predictive biomarkers or indicators of tissue injury due
to toxicant exposure; thus, miRNAs can also be utilised as therapeutic targets.
PMID- 25586888
TI - Reply to the letter of Anderson J entitled "Comment on Schindler, BK; Weiss, T;
Schutze, A; et al. Occupational exposure of air crews to tricresyl phosphate
isomers and organophosphate flame retardants after fume events, Arch Toxicol
(2013) 87:645-648".
PMID- 25586889
TI - Novel image encryption based on quantum walks.
AB - Quantum computation has achieved a tremendous success during the last decades. In
this paper, we investigate the potential application of a famous quantum
computation model, i.e., quantum walks (QW) in image encryption. It is found that
QW can serve as an excellent key generator thanks to its inherent nonlinear
chaotic dynamic behavior. Furthermore, we construct a novel QW-based image
encryption algorithm. Simulations and performance comparisons show that the
proposal is secure enough for image encryption and outperforms prior works. It
also opens the door towards introducing quantum computation into image encryption
and promotes the convergence between quantum computation and image processing.
PMID- 25586890
TI - Chemotherapy intensification in patients with advanced seminoma and adverse
prognostic factors.
AB - PURPOSE: The aim of our study was to identify factors which influence survival in
patients with disseminated seminoma in the good prognostic group according to
IGCCCG, as well as to evaluate the impact of treatment intensification in
patients with negative prognostic factors. METHODS: We analyzed the database of
the patients with metastatic seminoma who had received treatment at our
department from 1986 to 2005. Inclusion criteria were as follows: morphologically
verified seminoma; favorable prognosis according to IGCCCG; modern chemotherapy
regimen (EP +/- bleomycin); AFP level <15 IU/ml; and HCG level <300 mIU/ml. The
primary endpoint was overall survival (OS). RESULTS: With median follow-up 83
months, 5-year OS rate was 91% in 206 patients. Only three negative prognostic
factors were associated with OS: retroperitoneal lymph nodes >5 cm (p < 0.01),
pulmonary metastases (p < 0.01) and LDH level >= 2.25 * ULN (p = 0.01). In view
of the obtained data, we have changed our treatment approach since 2005. In case
of any negative prognostic factors, we administered an intensified CT regimen-
4BEP or 3BEP + 1EP. Prospective phase of the study included 34 patients with
unfavorable prognosis. We observed an increase of 5-year OS rate in the
intensified CT group in comparison with the standard CT group in patients with
unfavorable prognostic from 85 to 100%. CONCLUSION: Administration of 4 cycles of
induction CT (4BEP or 3BEP + 1EP) in patients with metastatic seminoma who have
LDH level >= 2.25 ULN, and/or retroperitoneal lymph nodes >5 cm and/or pulmonary
metastases results in decreased disease progression rate and significant gain in
OS.
PMID- 25586891
TI - Changes in fibrillin-1 expression, elastin expression and skin surface texture at
sites of cultured epithelial autograft transplantation onto wounds from burn scar
excision.
AB - This study investigated the recovery process during which grafted cultured
epithelium generated skin elasticity and skin surface microarchitecture. The
subjects were 18 patients whose burn scars were excised at a depth not exposing
the fat layer and who subsequently received cultured epithelial autografts. A
total of 24 samples were obtained from the grafted sites: 6 samples within 6
weeks (stage 1), 5 samples after 6 weeks and within 6 months (stage 2), 6 samples
after 6 months and within 18 months (stage 3) and 7 samples beyond 18 months
(stage 4) of transplantation. These samples were evaluated by taking replicas of
skin surface, and histological changes of fibrillin-1 and elastin. The expression
patterns were classified using a grading scale. The grade of skin surface texture
was significantly higher at stage 3 and marginally significantly higher at stage
4 compared with stage 1. The grade of fibrillin-1 was marginally significantly
higher at stage 3 and significantly higher at stage 4 compared with stage 1. The
grade of elastin was marginally significantly higher at stage 4 compared with
stage 1. These results showed that it is important for patients to have skin care
and avoid external forces for at least 18 months after transplantation.
PMID- 25586892
TI - Progestogen safety in multiple gestations: application of the Bradford Hill
criteria.
PMID- 25586894
TI - The pain--suffering association, a review.
AB - OBJECTIVE: This review wished to determine the reported prevalence of suffering
in various patient diagnostic groups and examine the evidence for the association
of pain and suffering. DESIGN/SETTING: Twenty-four studies fulfilled inclusion
exclusion criteria. They were divided into the following groups: advanced
cancer/terminal illness/hospice patients (AC/TI/H) (7 studies); hastened
death/assisted suicide/euthanasia patients (HD/AS/E) (14 studies); noncancer (NC)
patients (3 studies). No chronic nonmalignant pain (CNMP) suffering studies
fulfilled inclusion-exclusion criteria of this review. The reported prevalence of
suffering for each study was abstracted and the overall percentage of sufferers
in each grouping calculated. For those studies that provided a statistical
relationship between pain and suffering information was abstracted for whether
these studies supported/did not support the association of pain and suffering. A
vote counting method was utilized to determine the overall percentage of studies
supporting/not supporting this association. The consistency of this data for
supporting this association was then rated by Agency for Health Care Research and
Quality guidelines. RESULTS: The prevalence of suffering in each grouping was as
follows: AC/IT/H 45.7%; HD/AS/E 81.9%; NC 19.2%; and all groupings combined
59.9%. AC/TI/H and all groupings combined received an A rating (consistent
evidence multiple studies for a statistical relationship between suffering and
pain). HD/AS/E received a C (evidence which is inconsistent). For NC there were
not enough studies for a consistency rating. CONCLUSIONS: The above results
indicate a consistent association between suffering and pain in some patient
groups. Studies addressing suffering are needed in CNPM patients.
PMID- 25586893
TI - Efficacy of positive airway pressure on brain natriuretic peptide in patients
with heart failure and sleep-disorder breathing: a meta-analysis of randomized
controlled trials.
AB - OBJECTIVE: Positive airway pressure (PAP) has been recognized as an effective
therapeutic option for sleep-disordered breathing (SDB) in patients with heart
failure (HF), and it can improve left ventricular function. Whether PAP can
ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is
controversial. The purpose of the present study was to quantitatively assess the
efficacy of PAP on BNP in patients with HF and SDB. METHODS: A systematic search
of PubMed, Embase, Web of Science and Cochrane library identified six randomized
controlled trials (RCTs), in which PAP was compared with medical therapy,
subtherapeutic PAP or different types of PAP. The data of BNP were extracted and
pooled into meta-analysis using STATA 12.0. RESULTS: Totally 6 RCT studies (7
cohorts) with 222 patients were enrolled into analysis. The quality of each study
was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A
significant reduction of BNP was observed after PAP treatment in patients with HF
and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000). CONCLUSION:
Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of
BNP in patients with HF and SDB.
PMID- 25586895
TI - Association between the sense of coherence 13-item version scale score of
pregnant women in the second trimester of pregnancy and threatened premature
birth.
AB - OBJECTIVES: The purpose of this study is to determine whether the score of the
sense of coherence 13-item version (SOC-13) scale in the second trimester of
pregnancy is associated with threatened premature birth. METHODS: All the
subjects gave their informed written consent before their participation in the
study. A self-reported questionnaire survey was conducted on the pregnant women
at approximately 18 weeks of pregnancy. The questionnaire consisted of items on
demographic characteristics, perinatal abnormalities, stress perception scale
(SPS), and SOC-13 scale. Approximately 30 weeks of pregnancy after the first
survey, we surveyed whether any treatment had been provided for threatened
premature birth during the course of the current pregnancy. The study period was
from December 2007 to February 2010. One hundred and seventy-seven pregnant women
participated in the study, but only the data from 151 pregnant women were
analyzed. RESULTS: Forty-three (28.5%) pregnant women had threatened premature
birth and received some treatment. Logistic regression analysis was carried out
with threatened premature birth as the dependent variable and age, childbirth
history, smoking habit, history of miscarriage or premature birth in previous
pregnancies, SPS score, and SOC-13 scale score as the independent variables. It
was shown that SOC-13 scale score affected threatened premature birth (p < 0.001)
and that a low SOC-13 scale score was associated with threatened premature birth.
CONCLUSIONS: This study suggests that the SOC-13 scale score in the second
trimester of pregnancy could be of great value in clinical health care of
pregnant women with a risk of threatened premature birth in the subsequent course
of pregnancy.
PMID- 25586896
TI - Effect of short ageing on lees on the mannoprotein content, aromatic profile, and
sensorial character of white wines.
AB - In Albarino white wines, aging of wines on lees is a technique not used or only
used empirically by some producers to obtain a distinctive character in the final
wine. This study analyzes the influence of a short aging on lees on the chemical
and sensorial parameters of this young white wine. Albarino grape must was
inoculated with a locally selected yeast (Saccharomyces cerevisiae 1) and the
effect of a short aging on lees was studied during different times (10, 20, 30,
40, and 50 d). Mannoprotein content and the aromatic profile were determined and
a sensorial analysis of the wines was conducted. Results showed that aging time
was correlated with the concentration of some key aroma compounds and
mannoproteins in Albarino wines. The best sensorial character was obtained in
wines aged 20 d on lees. Further aging times decreased the sensorial quality of
Albarino wine and modified its volatile profile and mannoprotein concentration.
PMID- 25586897
TI - Stories of the Accused: A Phenomenological Inquiry of MFTs and Accusations of
Unprofessional Conduct.
AB - Interviews were conducted with 10 MFTs (six females and four males) who had
received a formal accusation of unprofessional conduct and went before state
licensure boards in three different states. Accusations included dual
relationships, financial fraud/errors, receiving DUIs, sexual misconduct, and
emotionally harming a client. Utilizing Moustakas' (1994, Phenomenological
research methods, Thousand Oaks, CA: Sage) transcendental phenomenology, five
essential themes emerged: (a) The experience of being formally accused of
unprofessional conduct is life-changing, (b) state MFT licensing boards are more
punitive than rehabilitative, (c) obtaining support is vital, (d) making
accusations creates stigma, (e) therapists were unprepared to handle accusations
of unprofessional conduct. Clinical implications include the importance of
supervision, personal therapy, and strategies for prevention and rehabilitation
with this population.
PMID- 25586898
TI - Understanding the role of nitrogen in plasma-assisted surface modification of
magnetic recording media with and without ultrathin carbon overcoats.
AB - A novel scheme of pre-surface modification of media using mixed argon-nitrogen
plasma is proposed to improve the protection performance of 1.5 nm carbon
overcoats (COC) on media produced by a facile pulsed DC sputtering technique. We
observe stable and lower friction, higher wear resistance, higher oxidation
resistance, and lower surface polarity for the media sample modified in 70%Ar +
30%N2 plasma and possessing 1.5 nm COC as compared to samples prepared using
gaseous compositions of 100%Ar and 50%Ar + 50%N2 with 1.5 nm COC. Raman and X-ray
photoelectron spectroscopy results suggest that the surface modification process
does not affect the microstructure of the grown COC. Instead, the improved
tribological, corrosion-resistant and oxidation-resistant characteristics after
70%Ar + 30%N2 plasma-assisted modification can be attributed to, firstly, the
enrichment in surface and interfacial bonding, leading to interfacial strength,
and secondly, more effective removal of ambient oxygen from the media surface,
leading to stronger adhesion of the COC with media, reduction of media corrosion
and oxidation, and surface polarity. Moreover, the tribological, corrosion and
surface properties of mixed Ar + N2 plasma treated media with 1.5 nm COCs are
found to be comparable or better than ~2.7 nm thick conventional COC in
commercial media.
PMID- 25586900
TI - Factors associated with good adherence to self-care behaviours amongst
adolescents with food allergy.
AB - BACKGROUND: Our understanding of factors which affect adherence to health
sustaining self-care behaviours in adolescents with food allergy is limited. This
study used the Health Belief Model to explore the relationship between food
allergic adolescents' health beliefs, demographic, structural and social
psychological factors with adherence to self-care behaviours, including allergen
avoidance and carrying emergency medication. METHODS: A cross-sectional study of
188 13- to 19- olds identified from hospital prescribed auto-injectable
epinephrine for food allergy. Data were collected on demographics, structural
factors, social psychological factors, health beliefs and current adherence
behaviour using a postal questionnaire. RESULTS: Full adherence was reported by
16% of participants. Multivariate analysis indicated that adherence was more
likely to be reported if the adolescents belonged to a support group (OR = 2.54,
(1.04, 6.20) 95% CI), had an anaphylaxis management plan (OR = 3.22, (1.18, 8.81)
95% CI), perceived their food allergy to be more severe (OR = 1.24, (1.01, 1.52)
95% CI) and perceived fewer barriers to disease management (OR = 0.87, (0.79,
0.96) 95% CI). CONCLUSIONS: Membership of a patient support group and having an
anaphylaxis management plan were associated with good adherence to self-care
behaviours in adolescents with food allergy. Our results suggest that
interventions to improve provision and utilisation of management plans, address
adolescents' perceptions of the severity of anaphylaxis and reduce barriers to
disease management may facilitate good adherence behaviours than focussing on
knowledge-based interventions.
PMID- 25586899
TI - HIV viraemia during hepatitis B vaccination shortens the duration of protective
antibody levels.
AB - OBJECTIVES: Individuals with HIV infection often have early waning of protective
antibody following hepatitis B virus (HBV) vaccination. HIV viraemia at the time
of vaccination may limit the durability of serum anti-HBV surface antibody
(HBsAb) levels. We investigated the relationship of HIV plasma viral load (VL)
and duration of HBsAb among vaccinees enrolled in the US Military HIV Natural
History Study. METHODS: We included in the study participants who had no history
of prior HBV infection, who had received all HBV vaccine doses after HIV
diagnosis, and who had demonstrated an initial vaccine response, defined as HBsAb
>= 10 IU/L. Responders were retrospectively followed with serial HBV serology
from the time of the last vaccine dose until the development of waning (HBsAb <
10 IU/L) or the last HBsAb measurement. Time to and risk for waning were
evaluated with Kaplan-Meier survival methods and Cox proportional hazards models,
respectively. RESULTS: A total of 186 initial vaccine responders were identified.
During 570 person-years of observation, HBsAb waned in 52 of 186 participants
(28%). The cumulative proportion maintaining HBsAb >= 10 IU/L was 83% at 2 years
and 56% at 5 years. Participants with an undetectable VL [hazard ratio (HR) 0.37;
95% confidence interval (CI) 0.18-0.76] or with detectable VL of <= 10 000
copies/mL (HR 0.46; 95% CI 0.21-1.00) had reduced risk of waning. Other factors
including age, number of vaccine doses, CD4 count, and receipt of highly active
antiretroviral therapy (HAART) were not significantly associated with risk of
waning HBsAb. CONCLUSIONS: Undetectable or low HIV VL at the time of HBV
vaccination is associated with greater durability of vaccine response in patients
with HIV infection.
PMID- 25586901
TI - Combination of ultrasound guided percutaneous microwave ablation and radioiodine
therapy in benign thyroid diseases. A suitable method to reduce the 131I activity
and hospitalization time?
AB - AIM: Goiters and thyroid nodules are an ongoing problem in healthcare. There has
not been any treatment of goiters and thyroid nodules based on the combined
therapy of microwave ablation (MWA) and radioiodine therapy (RIT) until now. In
this study the potential benefit of a combined therapy versus single RIT is
evaluated in order to achieve improvements concerning 131I-dose and
hospitalization time. PATIENTS, MATERIAL, METHODS: Ten patients with goiter and
benign thyroid nodules or Graves' disease were included. Pre-ablation assessments
included sonographical imaging, functional imaging with 99mTc and FNAB to collect
data of nodules and total thyroid volume and to exclude malignancy. Prior to
treatment, radioiodine uptake test was performed. MWA was operated under local
anesthesia with a system working in a wavelength field 902-928 MHz. Post-MWA,
thyroid volume was recalculated ultrasonically. Due to reduced vital volume,
changes of 131I-dose and hospitalization time could be monitored. RESULTS: Mean
absolute thyroid volume reduction by MWA before applying RIT was 22 +/- 11 ml,
meaning a relative reduction of 24 +/- 6% (p < 0.05). Thereby, administered
activity could be reduced by 393 +/- 188 MBq using the combined therapy,
reflecting a relative reduction of 24 +/- 6% (p < 0.05). Additionally, mean
hospitalization time was decreased by 2.1 +/- 0.8 days using MWA prior to RIT,
implying a relative reduction of 28 +/- 6% (p < 0.05). CONCLUSION: Depending on
ablated volume by MWA, RIT-monotherapy requires on average 31.2% more 131I
activity than the combined therapy. The combined therapy remarkably decreases
131I-dose and hospitalization time. The combined MWA and RIT therapy is a
considerable, effective and safer alternative to surgery for the treatment of
very large benign nodular goiters.
PMID- 25586902
TI - Garlic and onions: their cancer prevention properties.
AB - The Allium genus includes garlic, onions, shallots, leeks, and chives. These
vegetables are popular in cuisines worldwide and are valued for their potential
medicinal properties. Epidemiologic studies, while limited in their abilities to
assess Allium consumption, indicate some associations of Allium vegetable
consumption with decreased risk of cancer, particularly cancers of the
gastrointestinal tract. Limited intervention studies have been conducted to
support these associations. The majority of supportive evidence on Allium
vegetables cancer-preventive effects comes from mechanistic studies. These
studies highlight potential mechanisms of individual sulfur-containing compounds
and of various preparations and extracts of these vegetables, including decreased
bioactivation of carcinogens, antimicrobial activities, and redox modification.
Allium vegetables and their components have effects at each stage of
carcinogenesis and affect many biologic processes that modify cancer risk. This
review discusses the cancer-preventive effects of Allium vegetables, particularly
garlic and onions, and their bioactive sulfur compounds and highlights research
gaps.
PMID- 25586905
TI - Feasibility of lateral dose profile measurements in a small field using TLDs.
AB - The purpose of this work was to study the feasibility of lateral dose profile
measurements in a small field using thermoluminescent dosimeters (TLDs) and to
evaluate the impact of the field size on the absorbed dose ratio factor fmd of
LiF and Al2O3 TLDs. The Monte Carlo package BEAM/EGSNRC was used to simulate the
lateral dose profile in solid water phantoms (RW3 slab phantom) with various
field sizes beyond the build-up region for 6 MV x-rays, and a LiF : Mg, Cu, P (GR
200) dosimeter with dimensions of 0.1 * 0.1 * 0.1 cm(3) was used to measure
the lateral dose profile under the same conditions as the Monte Carlo
simulations. To enable comparisons between dosimeters, Gafchromic EBT3 films were
used. The results indicate that (1) the measured results are in agreement with
the simulated results within the uncertainty of the simulation; (2) the values of
fmd for Al2O3 and LiF in a 1 * 1 cm(2) field are 2.8% and 1.6% less,
respectively, than those in a 10 * 10 cm(2) field; and (3) within the 80%
profile region, the dose differences between TLDs and solid water are less than
1%. In the 80-10% profile region, the TLD results are in agreement with the
absorbed doses in the solid water within 1 mm. It is generally acceptable to
ignore the impact of field size on the absorbed dose ratio factor fmd when the
field sizes are larger than 1 * 1 cm(2) for LiF and 2 * 2 cm(2) for Al2O3.
For 6 MV x-rays, the small GR-200 chip can be used to measure the relative
lateral dose profiles of small fields.
PMID- 25586903
TI - Salpingectomy as a means to reduce ovarian cancer risk.
AB - Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk
reduction in women at hereditary risk of ovarian cancer. Although this procedure
significantly decreases both the incidence of and mortality from ovarian cancer,
it affects quality of life, and the premature cessation of ovarian function may
have long-term health hazards. Recent advances in our understanding of the
molecular pathways of ovarian cancer point to the fallopian tube epithelium as
the origin of most high-grade serous cancers (HGSC). This evolving appreciation
of the role of the fallopian tube in HGSC has led to the consideration of
salpingectomy alone as an option for risk management, especially in premenopausal
women. In addition, it is postulated that bilateral salpingectomy with ovarian
retention (BSOR), may have a public health benefit for women undergoing benign
gynecologic surgery. In this review, we provide the rationale for salpingectomy
as an ovarian cancer risk reduction strategy.
PMID- 25586906
TI - Inhibitory effects of deferasirox on the structure and function of bovine liver
catalase: a spectroscopic and theoretical study.
AB - Deferasirox (DFX), as an oral chelator, is used for treatment of transfusional
iron overload. In this study, we have investigated the effects of DFX as an iron
chelator, on the function and structure of bovine liver catalase (BLC) by
different spectroscopic methods of UV-visible, fluorescence, and circular
dichroism (CD) at two temperatures of 25 and 37 degrees C. In vitro kinetic
studies showed that DFX can inhibit the enzymatic activity in a competitive
manner. KI value was calculated 39 nM according to the Lineweaver-Burk plot
indicating a high rate of inhibition of the enzyme. Intrinsic fluorescence data
showed that increasing the drug concentrations leads to a significant decrease in
the intrinsic emission of the enzyme indicating a significant change in the three
dimensional environment around the chromophores of the enzyme structure. By
analyzing the fluorescence quenching data, it was found that the BLC has two
binding sites for DFX and the values of binding constant at 25 and 37 degrees C
were calculated 1.7 * 10(7) and 3 * 10(7) M(-1), respectively. The static type of
quenching mechanism is involved in the quenching of intrinsic emission of enzyme.
The thermodynamic data suggest that hydrophobic interactions play a major role in
the binding reaction. UV-vis spectroscopy results represented the changes in
tryptophan (Trp) absorption and Soret band spectra, which indicated changes in
Trp and heme group position caused by the drug binding. Also, CD data represented
that high concentrations of DFX lead to a significant decreasing in the content
of beta-sheet and random coil accompanied an increasing in alpha-helical content
of the protein. The molecular docking results indicate that docking may be an
appropriate method for prediction and confirmation of experimental results and
also useful for determining the binding mechanism of proteins and drugs.
According to above results, it can be concluded that the DFX can chelate the
Fe(III) on the enzyme active site leading to changes in the function and
structure of catalase which can be considered as a side effect of this drug and
consequently has an important role in hepatic complications and fibrosis.
PMID- 25586907
TI - Special issue commemorating the 65th birthday of Craig A. Elmets. Introduction.
PMID- 25586908
TI - Child obesity service provision: a cross-sectional survey of physiotherapy
practice trends and professional needs.
AB - This study explored current physiotherapy practice trends for management of
children who are overweight or obese. The professional needs of physiotherapists
working with this population were also assessed, including the perceived need for
physiotherapy clinical guidelines for prevention and management of children with
obesity. A cross-sectional survey design was used, with questionnaires
purposefully distributed through 13 key physiotherapy services throughout
Australia. Snowball sampling resulted in completed questionnaires from 64
physiotherapists who provided services to children. Half (n=33, 52%) of
respondents provided services specifically to overweight or obese children. Of
those providing services, one-quarter had prior training specific to working with
this population. Most used multi-disciplinary models (n=16, 76%) and provided
under 5h of obesity-related services each week (n=29, 88%). Half (n=16, 49%) used
body mass index as an outcome measure but more (n=25, 76%) used bodyweight. Only
14 (42%) assessed motor skills. The majority of respondents (n=57, 89%) indicated
a need for physiotherapy guidelines to best manage overweight and obese children.
Professional development priorities included: 'Educating children and families',
'Assessment methods' and 'Exercise prescription' for overweight and obese
children. This data provides workforce intelligence to guide future professional
training and inform development of clinical guidelines for physiotherapists in
prevention and management of children with obesity and related chronic disease.
PMID- 25586909
TI - Cascaded optical transparency in multimode-cavity optomechanical systems.
AB - Electromagnetically induced transparency has great theoretical and experimental
importance in many areas of physics, such as atomic physics, quantum optics and,
more recent, cavity optomechanics. Optical delay is the most prominent feature of
electromagnetically induced transparency, and in cavity optomechanics, the
optical delay is limited by the mechanical dissipation rate of sideband-resolved
mechanical modes. Here we demonstrate a cascaded optical transparency scheme by
leveraging the parametric phonon-phonon coupling in a multimode optomechanical
system, where a low damping mechanical mode in the unresolved-sideband regime is
made to couple to an intermediate, high-frequency mechanical mode in the resolved
sideband regime of an optical cavity. Extended optical delay and higher
transmission as well as optical advancing are demonstrated. These results provide
a route to realize ultra-long optical delay, indicating a significant step
towards integrated classical and quantum information storage devices.
PMID- 25586904
TI - Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic
transformation and their potential clinical use.
AB - Exposure to toxicants leads to cumulative molecular changes that overtime
increase a subject's risk of developing urothelial carcinoma. To assess the
impact of arsenic exposure at a time progressive manner, we developed and
characterized a cell culture model and tested a panel of miRNAs in urine samples
from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To
prepare an in vitro model, we chronically exposed an immortalized normal human
bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a
time-dependent manner after arsenic treatment and cellular morphology was
changed. In a soft agar assay, colonies were observed only in arsenic-treated
cells, and the number of colonies gradually increased with longer periods of
treatment. Similarly, invaded cells in an invasion assay were observed only in
arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not
reverse the tumorigenic properties of arsenic-treated cells. Western blot
analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic
treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated
in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human
urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P =
0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases
from controls with high sensitivity and specificity (AUC = 0.845). Our study
suggests that exposure to arsenic rapidly induces a multifaceted
dedifferentiation program and miR-205 has potential to be used as a marker of
arsenic exposure as well as a maker of early urothelial carcinoma detection.
PMID- 25586910
TI - Achilles tendons in people with type 2 diabetes show mildly compromised
structure: an ultrasound tissue characterisation study.
AB - BACKGROUND: Musculotendinous overuse injuries are prevalent in people with type 2
diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening
may play a role. In this case-control study we determined whether patients with
diabetes had poorer ultrasonographic structure in their Achilles tendons compared
to age-matched controls. METHODS: People with type 1 diabetes or type 2 diabetes,
and age-matched controls, had computerised ultrasound tissue characterisation of
both Achilles tendons. In contiguous ultrasonographic images of the tendon,
echopatterns were quantified and categorised into four echo-types. Tendon
abnormality was quantified as sum of echo-types III+IV. Furthermore, skin
autofluorescence (AF) of the forearm (AF-value) was gathered. RESULTS: Twenty
four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20
controls were included. AF-value was higher in type 1 diabetes (1.55+/-0.17) than
in their controls (1.39+/-0.18, p<0.001) and in type 2 diabetes (2.28+/-0.38)
compared to their controls (1.84+/-0.32, p<0.001) Achilles tendons of type 2
diabetes patients contained more echo-types III+IV (14.1+/-7.9%) than matched
controls (8.0+/-5.4%, p<0.001). There was a trend towards a difference in echo
types III+IV between type 1 diabetes patients (9.5+/-5.3%) and their controls
(6.5+/-3.7%, p=0.055). In a stepwise linear regression analysis, body mass index
(BMI) was moderately associated with tendon abnormality in patients with diabetes
and controls (beta=0.393, p<0.001). CONCLUSIONS: Type 2, and possibly type 1,
diabetes patients showed poorer ultrasonographic Achilles tendon structure that
may be a risk factor for tendinopathy. Although markers for accumulation of
advanced glycation end products were elevated in both diabetes populations, only
BMI was associated with these abnormalities. TRIAL REGISTRATION NUMBER: NTR2209.
PMID- 25586911
TI - Older people's perspectives on participation in physical activity: a systematic
review and thematic synthesis of qualitative literature.
AB - BACKGROUND: Physical inactivity accounts for 9% of all deaths worldwide and is
among the top 10 risk factors for global disease burden. Nearly half of people
aged over 60 years are inactive. Efforts to identify which factors influence
physical activity behaviour are needed. OBJECTIVE: To identify and synthesise the
range of barriers and facilitators to physical activity participation. METHODS:
Systematic review of qualitative studies on the perspectives of physical activity
among people aged 60 years and over. MEDLINE, EMBASE, CINAHL, PsychINFO and AMED
were searched. Independent raters assessed comprehensiveness of reporting of
included studies. Thematic synthesis was used to analyse the data. RESULTS: From
132 studies involving 5987 participants, we identified six major themes: social
influences (valuing interaction with peers, social awkwardness, encouragement
from others, dependence on professional instruction); physical limitations (pain
or discomfort, concerns about falling, comorbidities); competing priorities;
access difficulties (environmental barriers, affordability); personal benefits of
physical activity (strength, balance and flexibility, self-confidence,
independence, improved health and mental well-being); and motivation and beliefs
(apathy, irrelevance and inefficacy, maintaining habits). CONCLUSIONS: Some older
people still believe that physical activity is unnecessary or even potentially
harmful. Others recognise the benefits of physical activity, but report a range
of barriers to physical activity participation. Strategies to enhance physical
activity participation among older people should include (1) raising awareness of
the benefits and minimise the perceived risks of physical activity and (2)
improving the environmental and financial access to physical activity
opportunities.
PMID- 25586912
TI - Concussion in youth rugby union and rugby league: a systematic review.
AB - BACKGROUND: Children and adolescents who play rugby are at increased risk of
concussion and its effects. Competitive rugby union and rugby league feature as
major sports in the school sport curriculum in the UK. There is a need for a
thorough understanding of the epidemiology of concussion in youth rugby, the
mechanisms involved in injuries and predisposing risk factors. DATA SOURCES: The
publication databases Pubmed, Embase and SportDISCUS were searched in April 2014
for primary research studies of child and adolescent rugby union and rugby league
(under 20 years) in English language with data on concussion injuries. The review
was conducted within a larger all injury systematic review on rugby union and
rugby league where key words used in the search included rugby, injury and
concussion with child, adolescent, paediatric and youth. RESULTS: There were 25
studies retrieved with data on child or adolescent rugby and concussion, 20 were
on rugby union, three on rugby league and in two the code of rugby was
unspecified. There was significant heterogeneity in the definitions of injuries
and of concussion. The incidence of child and adolescent match concussion ranged
from 0.2 to 6.9 concussions per 1000 player-hours for rugby union and was 4.6 and
14.7 concussions per 1000 player-hours for rugby league, equivalent to a
probability of between 0.3% and 11.4% for rugby union and of 7.7% and 22.7% for
rugby league. CONCLUSIONS: There is a significant risk of concussion in children
and adolescents playing rugby union and rugby league evident from the studies
included in this systematic review. There is a need for reliable data through
routine monitoring and reporting in schools and clubs and in hospital emergency
departments in order to inform prevention. Concussion protocols should be
implemented and tested.
PMID- 25586913
TI - Patient-Reported Outcome (PRO) questionnaires for young to middle-aged adults
with hip and groin disability: a systematic review of the clinimetric evidence.
AB - BACKGROUND/AIM: To recommend Patient-Reported Outcome (PRO) questionnaires to
measure hip and groin disability in young-aged to middle-aged adults. METHODS: A
systematic review was performed in June 2014. The methodological quality of the
studies included was determined using the COnsensus-based Standards for the
selection of health Measurement INstruments list (COSMIN) together with
standardised evaluations of measurement properties of each PRO. RESULTS: Twenty
studies were included. Nine different questionnaires for patients with hip
disability, and one for hip and groin disability, were identified. Hip And Groin
Outcome Score (HAGOS), Hip Outcome Score (HOS), International Hip Outcome Tool-12
(IHOT-12) and IHOT-33 were the most thoroughly investigated PROs and studies
including these PROs reported key aspects of the COSMIN checklist. HAGOS and IHOT
12 were based on studies with the least ratings of poor study methodology (23%
and 31%, respectively), whereas IHOT-33 and HOS had a somewhat larger
distribution (46%). These PROs all contain adequate measurement qualities for
content validity (except HOS), test-retest reliability, construct validity,
responsiveness and interpretability. No information or poor quality rating on
methodological aspects made it impossible to fully evaluate the remaining PROs at
present. CONCLUSIONS: HAGOS, HOS, IHOT-12 and IHOT-33 can be recommended for
assessment of young-aged to middle-aged adults with pain related to the hip
joint, undergoing non-surgical treatment or hip arthroscopy. At present, HAGOS is
the only PRO also aimed for young-aged to middle-aged adults presenting with
groin pain and is recommended for use in this population. TRIAL REGISTRATION
NUMBER: CRD42014009995.
PMID- 25586915
TI - Child Maltreatment and Social Connectedness Among Formerly Institutionalized
Females: Links With Depression.
AB - This study aimed to examine the effects of child maltreatment subtypes (physical
abuse, sexual abuse, neglect, and exposure to domestic violence) and cumulative
child maltreatment on depressive symptoms in adulthood, and examine the
protective effects of social connectedness in a sample of formerly
institutionalized females. The sample consisted of 124 females who were
institutionalized in a Dutch juvenile justice institution during adolescence and
were followed-up when they were on average 32 years old. Information about child
maltreatment was extracted from treatment files. Retrospective data on social
connectedness in young adulthood were established during interviews using a Life
History Calendar. Relationship quality at follow-up was assessed with items
derived from the Rochester Youth Development Study. The Center for
Epidemiological Studies Scale for Depression (CES-D) was used to measure
depressive symptoms in adulthood. Results showed that 85.5% of the females
experienced child maltreatment, and co-occurrence of subtypes was high.
Cumulative child maltreatment increased the risk of depression in adulthood.
Furthermore, social connectedness, that is, more employment over time and the
quality of the romantic relationship at follow-up, protected against the
development of depression. However, social connectedness did not buffer the
effect of maltreatment on depression. Our findings indicate that treatment of
these girls should focus on improving the social-emotional development to promote
positive interpersonal relationships and include educational and vocational
components to guide these girls toward increased opportunities on the labor
market.
PMID- 25586916
TI - Subjective Sleep Quality in Women With Divorce Histories: The Role of Intimate
Partner Victimization.
AB - A marital status of divorced or separated, as opposed to married, predicts
increased risk of health problems, but not for all persons. Focusing on one
established health risk that has been linked with divorce--poor subjective sleep
quality--the present cross-sectional study examined whether a history of physical
intimate partner victimization (IPV) helps identify divorced women at potentially
greater risk of health problems. Community midlife women with divorce histories,
all of whom were free of current IPV, reported on their past month sleep quality
and lifetime IPV. The predicted odds of poor sleep quality were significantly
greater for women with, versus without, IPV histories. This held after adjusting
for socioemotional, medical, or sociodemographic risks. A dose-response
relationship between IPV chronicity and poor quality sleep was observed. IPV
history may help identify divorced women at increased risk of poor quality sleep
and, more broadly, poor health.
PMID- 25586917
TI - Bringing Research Into Practice: An Evaluation of Michigan's Sexual Assault Kit.
AB - The importance of research-informed practice for the field of sexual assault has
been stressed by academics and practitioners alike. However, there are few
examples of researcher-practitioner partnerships in the literature, therefore
providing minimal guidance for this process. This article describes a researcher
practitioner partnership that was successful in using evaluation data to guide
practice and policy decisions regarding the development and implementation of a
new sexual assault kit for the state of Michigan. Cousins's practical
participatory evaluation theory was used as the guiding framework for the
evaluation. Data collection methods included focus groups with practitioners from
five, regionally dispersed health care settings in Michigan, and surveys with
forensic scientists throughout the state's regional laboratory system. This case
study highlights how researchers and practitioners worked together for data
collection, analysis, and dissemination to support research-informed practice in
this state. Lessons learned and future recommendations for forming researcher
practitioner partnerships to improve the response to sexual assault are
discussed.
PMID- 25586914
TI - Prospective Study of the Mental Health Consequences of Sexual Violence Among
Women Living With HIV in Rural Uganda.
AB - The association between sexual violence and depression is well known, but the
temporal aspects of the association have not been well established. We analyzed
data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed
every 3 months for a median of 1.8 years of follow-up. The method of generalized
estimating equations (GEE) was used to model the marginal expectation of
depression symptom severity (Hopkins Symptom Checklist for Depression), mental
health-related quality of life (MOS-HIV Mental Health Summary), and heavy
drinking (Alcohol Use Disorders Identification Test) as a function of self
reported forced-sex victimization in the 3 months prior to interview. Estimates
were adjusted for variables known to confound the association between
victimization and mental health status. To assess any potential reciprocal
relationships, we reversed the temporal ordering of the exposures and outcomes
and refitted similar GEE models. In multivariable analyses, victimization was
associated with greater depression symptom severity (b = 0.17; 95% CI = [0.02,
0.33]) and lower mental health-related quality of life (b = -5.65; 95% CI = [
9.34, -1.96]), as well as increased risks for probable depression (adjusted
relative risk [ARR] = 1.58; 95% CI = [1.01, 2.49) and heavy drinking (ARR = 3.99;
95% CI = [1.84, 8.63]). We did not find strong evidence of a reciprocal
relationship. Our findings suggest that forced sex is associated with adverse
mental health outcomes among HIV-positive women in rural Uganda. Given the
substantial mental health-related impacts of victimization, effective health
sector responses are needed.
PMID- 25586918
TI - Effect of adding nano-titanium dioxide on the microstructure, mechanical
properties and in vitro bioactivity of a freeze cast merwinite scaffold.
AB - In the present research, merwinite (M) scaffolds with and without nano-titanium
dioxide (titania) were synthesized by water-based freeze casting method. Two
different amounts (7.5 and 10 wt%) of n-TiO2 were added to M scaffolds. They were
sintered at temperature of 1573.15 degrees K and at cooling rate of 4 degrees
K/min. The changes in physical and mechanical properties were investigated. The
results showed that although M and M containing 7.5 wt% n-TiO2 (MT7.5) scaffolds
had approximately the same microstructures in terms of pore size and wall
thickness, these factors were different for sample MT10. In overall, the
porosity, volume and linear shrinkage were decreased by adding different weight
ratios of n-TiO2 into the M structure. According to the obtained mechanical
results, the optimum mechanical performance was related to the sample MT7.5 (E =
51 MPa and sigma = 2 MPa) with respect to the other samples, i.e.: M (E = 47 MPa
and sigma = 1.8 MPa) and MT10 (E = 32 MPa and sigma = 1.4 MPa). The acellular in
vitro bioactivity experiment confirmed apatite formation on the surfaces of all
samples for various periods of soaking time. Based on cell study, the sample
which possessed favorable mechanical behavior (MT7.5) supported attachment and
proliferation of osteoblastic cells. These results revealed that the MT7.5
scaffold with improved mechanical and biological properties could have a
potential to be used in bone substitute.
PMID- 25586919
TI - Performance potential and limit of MoS2 transistors.
AB - High-performance MoS2 transistors scaled down to 100 nm are studied at various
temperatures down to 20 K, where a highest drive current of 800 MUA MUm(-1) can
be achieved. Extremely low electrical noise of 2.8 * 10(-10) MUm(2) Hz(-1) at 10
Hz is also achieved at room temperature. Furthermore, a negative differential
resistance behavior is experimentally observed and its origin of self-heating is
identified using pulsed-current-voltage measurements.
PMID- 25586920
TI - Effects of Hemodialysis on Tei Index: Comparison between Flow Doppler and Tissue
Doppler Imaging.
AB - OBJECTIVE: Myocardial performance index (MPI, Tei index) has been described as a
noninvasive measurement of left ventricle (LV) function. Our aim was to
investigate the influence of preload on the LV MPI obtained by pulsed-wave tissue
Doppler imaging (PWTDI) and determined by flow Doppler waveforms in patients with
end-stage chronic renal failure (CRF). The second aim of this study was to
investigate the relationship between the Tei indices obtained by both methods.
METHODS: Eighty-four patients on regular hemodialysis (HD) treatment were
included (mean age of 45.3 +/- 14.5 years). Standard echocardiographic
measurements, the Tei indices obtained by conventional flow Doppler and PWTDI
methods, mitral inflow velocities, and mitral lateral annulus tissue Doppler
velocities were measured immediately before and after hemodialysis. RESULTS:
After HD, weight loss in patients was significantly revealed (predialysis 63.6 +/
13.3 kg; postdialysis 60.9 +/- 13.0 kg; P < 0.001). Left ventricle and left
atrium diameters were significantly decreased after HD. Transmitral E and A
velocities decreased after HD. Although Tei index measuring by conventional flow
Doppler method significantly increased, Tei index measuring by PWTDI did not
change after HD. CONCLUSIONS: The conventional flow Doppler-derived LV Tei index
is influenced by hemodialysis. However, PWTDI-derived LV Tei index is not
influenced by hemodialysis. The loading status of a patient should be taken into
account during the application of the Tei index to the evaluation of myocardial
performance.
PMID- 25586922
TI - A Novel Immunoreagent for the Specific and Sensitive Detection of the Explosive
Triacetone Triperoxide (TATP).
AB - Triacetone triperoxide (TATP) is a primary explosive, which was used in various
terrorist attacks in the past. For the development of biosensors, immunochemical
u-TAS, electronic noses, immunological test kits, or test strips, the
availability of antibodies of high quality is crucial. Recently, we presented the
successful immunization of mice, based on the design, synthesis, and conjugation
of a novel TATP derivative. Here, the long-term immunization of rabbits is shown,
which resulted in antibodies of extreme selectivity and more than 1,000 times
better affinity in relation to the antibodies from mice. Detection limits below
10 ng L-1 (water) were achieved. The working range covers more than four decades,
calculated from a precision profile. The cross-reactivity tests revealed an
extraordinary selectivity of the antibodies-not a single compound could be
identified as a relevant cross-reactant. The presented immunoreagent might be a
major step for the development of highly sensitive and selective TATP detectors
particularly for security applications.
PMID- 25586921
TI - Review of transducer principles for label-free biomolecular interaction analysis.
AB - Label-free biomolecular interaction analysis is an important technique to study
the chemical binding between e.g., protein and protein or protein and small
molecule in real-time. The parameters obtained with this technique, such as the
affinity, are important for drug development. While the surface plasmon resonance
(SPR) instruments are most widely used, new types of sensors are emerging. These
developments are generally driven by the need for higher throughput, lower sample
consumption or by the need of complimentary information to the SPR data. This
review aims to give an overview about a wide range of sensor transducers, the
working principles and the peculiarities of each technology, e.g., concerning the
set-up, sensitivity, sensor size or required sample volume. Starting from optical
technologies like the SPR and waveguide based sensors, acoustic sensors like the
quartz crystal microbalance (QCM) and the film bulk acoustic resonator (FBAR),
calorimetric and electrochemical sensors are covered. Technologies long
established in the market are presented together with those newly commercially
available and with technologies in the early development stage. Finally, the
commercially available instruments are summarized together with their sensitivity
and the number of sensors usable in parallel and an outlook for potential future
developments is given.
PMID- 25586923
TI - Determination of alanine aminotransferase with an electrochemical nano ir-C
biosensor for the screening of liver diseases.
AB - Alanine aminotransaminase (ALT), is an enzyme that normally resides in serum and
body tissues, especially in the liver. It is released into the serum as a result
of tissue injury; hence the concentration of ALT in the serum may be increased
with acute damage to hepatic cells. A single use, disposable biosensor,
comprising iridium nano-particle as catalyst dispersed on carbon paste, has been
developed for the determination of ALT concentration. The biosensor is based on
quantifying H2O2 concentration produced by a serial of ALT enzymatic reactions.
It operates well at room temperature in different physiological fluids: phosphate
buffer, calf serum and human serum for ALT concentration of 0-544 ng/mL.
Experimental results in human serum are compared to those obtained by
spectrophotometric assays with excellent agreement. Therefore, the Ir/C biosensor
shows good relationship on the dilution of concentrated ALT clinical
applications.
PMID- 25586924
TI - Polycrystalline-Diamond MEMS Biosensors Including Neural Microelectrode-Arrays.
AB - Diamond is a material of interest due to its unique combination of properties,
including its chemical inertness and biocompatibility. Polycrystalline diamond
(poly-C) has been used in experimental biosensors that utilize electrochemical
methods and antigen-antibody binding for the detection of biological molecules.
Boron-doped poly-C electrodes have been found to be very advantageous for
electrochemical applications due to their large potential window, low background
current and noise, and low detection limits (as low as 500 fM). The
biocompatibility of poly-C is found to be comparable, or superior to, other
materials commonly used for implants, such as titanium and 316 stainless steel.
We have developed a diamond-based, neural microelectrode-array (MEA), due to the
desirability of poly-C as a biosensor. These diamond probes have been used for in
vivo electrical recording and in vitro electrochemical detection. Poly-C
electrodes have been used for electrical recording of neural activity. In vitro
studies indicate that the diamond probe can detect norepinephrine at a 5 nM
level. We propose a combination of diamond micro-machining and surface
functionalization for manufacturing diamond pathogen-microsensors.
PMID- 25586925
TI - Invited Commentary of "Concepts in Navel Aesthetic: A Comprehensive Surface
Anatomy Analysis".
PMID- 25586926
TI - Role of the Cytosolic Heat Shock Protein 70 Ssa5 in the Ciliate Protozoan
Tetrahymena thermophila.
AB - Heat shock protein 70 (Hsp70) is a member of a family of conserved chaperone
proteins whose function is well investigated in many model organisms. Here we
focus on an Hsp70 called Ssa5 in the ciliate protozoan Tetrahymena thermophila,
and reveal that its translation is heat inducible as for general Hsps. Moreover,
the protein is abundantly expressed in the cytoplasm during sexual reproduction
(conjugation) as well as in response to heat-stress. Knocking out of SSA5
(DeltaSSA5) does not affect the survival of the cell under heat-stress, likely
due to other Hsp70 paralogs compensating for the defect. During conjugation,
DeltaSSA5 leads to a fertilization defect in which the two pronuclei are in close
proximity but never fuse. The unfertilized pronuclei differentiate, resulting in
a heterokaryon with developed haploid germline and somatic nuclei. In addition,
degeneration of the parental somatic nucleus is not affected. These results
suggest a specific involvement of Ssa5 in pronuclear fusion and fertilization.
PMID- 25586928
TI - Brain area-related neurological soft signs in depressive patients with different
types of childhood maltreatment.
AB - INTRODUCTION: This study aims to investigate the effects of childhood
maltreatment on neurological soft signs (NSS) associated with certain brain area
in depressive patients. METHODS: One hundred three depressive patients were
enrolled into this study, and evaluated by Childhood Trauma Questionnaire (CTQ),
brain area-related neurological examination scale, 24-item Hamilton Rating scale
(HAMD24), the scale for suicidal ideation (SSI) and Beck Hopelessness Scale
(BHS). RESULTS: Patients undergoing childhood maltreatment exhibited higher
frontal area-related NSS scores than patients without childhood maltreatment
experience. Patients experiencing childhood emotional or physical neglect
displayed more frontal area-related NSS compared to their respective non
maltreatment group. Moreover, physical neglect maltreatment caused more temporal
area-related NSS. Patients suffering from childhood sexual abuse had more
frontal, temporal and occipital area-related NSS than patients lacking experience
of childhood sexual abuse. Further correlation analysis revealed that the total
score of maltreatment positively correlated with frontal and temporal area
related NSS score. There was a positive correlation between emotional abuse,
emotional neglect or physical abuse and frontal area-related NSS. Physical
neglect and sexual abuse were positively associated with the temporal area
related NSS score. HAMD24 score was positively correlated with all brain area
related NSS score; The SSI score correlated with three area (excluded occipital
area)-related NSS score. The BHS score only positively correlated with frontal
area score of NSS. Finally, no significant association was found between suicidal
frequencies and brain area-related NSS score. DISCUSSION: Childhood maltreatment
adversely affects the brain of depressive patients; the different maltreatment
may impair different brain areas, especially frontal and temporal areas.
PMID- 25586927
TI - Dysfunctional inhibitory mechanisms in locus coeruleus neurons of the wistar
kyoto rat.
AB - BACKGROUND: The noradrenergic nucleus locus coeruleus (LC) has functional
relevance in several psychopathologies such as stress, anxiety, and depression.
In addition to glutamatergic and GABAergic synaptic inputs, the activation of
somatodendritic alpha2-adrenoceptors is the main responsible for LC activity
regulation. The Wistar Kyoto (WKY) rat exhibits depressive- and anxiety-like
behaviors and hyperresponse to stressors. Thus, the goal of the present study was
to investigate in vitro the sensitivity of alpha2-adrenoceptors, as well as the
glutamatergic and GABAergic synaptic activity on LC neurons of the WKY strain.
METHODS: For that purpose patch-clamp whole-cell recordings were done in LC
slices. RESULTS: The alpha2-adrenoceptors of LC neurons from WKY rats were less
sensitive to the effect induced by the agonist UK 14 304 as compared to that
recorded in the Wistar (Wis) control strain. In addition, the GABAergic input to
LC neurons of WKY rats was significantly modified compared to that in Wis rats,
since the amplitude of spontaneous GABAergic postsynaptic currents was reduced
and the half-width increased. On the contrary, no significant alterations were
detected regarding glutamatergic input to LC neurons between rat strains.
CONCLUSIONS: These results point out that in WKY rats the inhibitory control
exerted by alpha2-adrenoceptors and GABAergic input onto LC neurons is
dysregulated. Overall, this study supports in this animal model the hypothesis
that claims an imbalance between the glutamatergic-GABAergic systems as a key
factor in the pathophysiology of depression.
PMID- 25586930
TI - Tailoring plasmonic properties of gold nanohole arrays for surface-enhanced Raman
scattering.
AB - The wide plasmonic tuning range of nanotriangle and nanohole array patterns
fabricated by nanosphere lithography makes them promising in surface-enhanced
Raman scattering (SERS) sensors. Unfortunately, it is challenging to optimize
these patterns for SERS sensing because their optical response is a complex
mixture of localized surface plasmon resonance (SPR) and propagating surface
plasmon polariton (SPP). In this paper, transmission and reflection measurements
are combined with finite difference time domain simulations to identify and
separate each plasmonic mode, discerning which resonance leads to the
electromagnetic field enhancement. The SERS enhancement is found to be dominated
by the absorption, which is shifted from the transmission and reflection dips
usually used as tuning points, and by the 'gap' defects formed within the
pattern. These effects have different spectral and geometric dependences, forming
two optimization curves which can be used to predict the best performance for a
given excitation wavelength. The developed model is verified with experimental
SERS measurements for several nanohole sizes and periodicities, and then used to
give optimal fabrication parameters for a range of measurement conditions. The
results will promote the application of two-dimensional plasmonic nanoarrays in
SERS sensors.
PMID- 25586931
TI - Treating periprosthetic joint infections as biofilms: key diagnosis and
management strategies.
AB - Considerable evidence suggests that microbial biofilms play an important role in
periprosthetic joint infection (PJI) pathogenesis. Compared to free-floating
planktonic bacteria, biofilm bacteria are more difficult to culture and possess
additional immune-evasive and antibiotic resistance mechanisms, making infections
harder to detect and eradicate. This article reviews cutting-edge advances in
biofilm-associated infection diagnosis and treatment in the context of current
PJI guidelines and highlights emerging technologies that may improve the efficacy
and reduce costs associated with PJI. Promising PJI diagnostic tools include
culture-independent methods based on sequence comparisons of the bacterial 16S
ribosomal RNA gene, which offer higher throughput and greater sensitivity than
culture-based methods. For therapy, novel methods based on disrupting biofilm
specific properties include quorum quenchers, bacteriophages, and
ultrasound/electrotherapy. Since biofilm infections are not easily detected or
treated by conventional approaches, molecular diagnostic techniques and next
generation antibiofilm treatments should be integrated into PJI clinical practice
guidelines in the near future.
PMID- 25586929
TI - Distribution and antimicrobial resistance of enteric pathogens in Chinese
paediatric diarrhoea: a multicentre retrospective study, 2008-2013.
AB - The enteric pathogens causing diarrhoea impair children's health severely. This
study retrospectively analysed 1577 pathogens isolated from inpatients and
outpatients in six hospitals located in Northern (Inner Mongolia), Northeastern
(Hebei), Eastern (Shanghai and Jiangsu), Southern (Hainan) and Central (Hubei)
China between 2008 and 2013. Of the 1577 enteric pathogens, Salmonella presented
with the highest frequency (36.0%), followed by diarrhoeagenic Escherichia coli
(23.7%), Staphylococcus aureus (15.0%), Shigella (13.1%), and Aeromonas (4.6%).
The predominant pathogens varied in different regions of China, with Salmonella
most prevalent in Shanghai and Hainan, diarrhoeagenic E. coli most prevalent in
Inner Mongolia, Jiangsu and Hubei, and Shigella most prevalent in Hebei. Enteric
pathogens were more frequently isolated in males (56.9%) than in females (43.1%).
The highest proportion of all enteric pathogens was found in infants (67.6%) with
a peak in summer and autumn (68.5%). Antimicrobial susceptibility assay
demonstrated that Shigella was more resistant to ampicillin, ceftriaxone and
sulfamethoxazole than Salmonella. Of the top two serotypes in Salmonella,
Typhimurium was more resistant to ciprofloxacin, sulfamethoxazole and
chloramphenicol than Enteritidis (P < 0.001). Meanwhile, the resistance rates of
Shigella flexneri against ampicillin/sulbactam, ciprofloxacin, and
chloramphenicol were significantly higher than those of Shigella sonnei (P <
0.001). Multidrug resistance was apparent in 58.2% of Shigella and 45.9% of
Salmonella, and this phenomenon was more pronounced in S. flexneri.
PMID- 25586932
TI - Clostridium difficile infection, a descriptive analysis of solid organ transplant
recipients at a single center.
AB - Clostridium difficile is a bacterial enteric pathogen, which causes clinical
disease among solid organ transplant (SOT) recipients. This large, single-center,
retrospective study describes incidence, demographics, and impact of C. difficile
infection (CDI) among adult SOT recipients, cardiac (n=5), lung (n=14), liver
(n=9), renal (n=26), and multiorgan (n=9) patients transplanted and diagnosed
with CDI (geneB PCR) between 9/2009 and 12/2012. The overall incidence of CDI in
our population during the 40-month period of study was 4%. CDI incidence among
cardiac, lung, liver, and renal transplant recipients was 1.9%, 7%, 2.7%, and
3.2%, respectively (P=0.03 between organ-types). Median time from transplant to
CDI for all was 51 (14-249) days, with liver recipients having the shortest time
to infection, median 36 (15-101) days, and lung recipients having a longer time
to infection, median 136 (29-611) days. Antibiotic exposure within 3 months of
CDI was evident in 45 of the 63 (71%) patients in this study, 80%, 79%, 100%,
58%, and 67% of cardiac, lung, liver, renal, and multiorgan transplant
recipients, respectively. Most patients (83%) were hospitalized within the 3
months preceding CDI. Recipients were followed for a median time of 23 (16-31)
months; at the time of last follow-up, 83% of allografts were functioning, and
86% of patients were alive. One death and 1 graft failure were causally related
to CDI. CDI had an overall incidence of 4%; clinicians should have heightened
awareness for CDI, especially among patients receiving antibiotics, with
increased monitoring and aggressive management of CDI.
PMID- 25586933
TI - Assessment and clinical validation of margins for adaptive simultaneous
integrated boost in neo-adjuvant radiochemotherapy for rectal cancer.
AB - PURPOSE: An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of
rectal cancer was clinically implemented. In this study population margins
M(90,90) considering rectal deformation were derived for 10 consecutive patients
treated at 18 * 2.3Gy with Helical Tomotherapy (HT) and prospectively validated
on 20 additional patients treated with HT, delivering ACB in the last 6
fractions. METHODS: Sectorial margins M(90,90) of the whole and second treatment
parts were assessed for 90% population through a method combining the 90%
coverage probability maps of rectal positions (CPC90%) with 3D local distance
measurements between the CPC90% and a reference rectal contour. M(90,90) were
compared with the margins M(90,90)(95%/99%), ensuring CPC90% coverage with
95%/99% confidence level. M(90,90) of the treatment second part were chosen as
ACB margins which were clinically validated for each patient by means of %volume
missing of CPC5/6 excluded by the ACB margins. RESULTS: The whole treatment
M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior
sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior
direction and <5 mm elsewhere. M(90,90)(95%/99%) did not significantly differ
from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5%
for 9/10 female patients. The dosimetry impact on R_adapt for the patients with
the largest residual error was negligible. CONCLUSIONS: Local deformation
measurements confirm an anisotropic motion of rectum once set-up error is rigidly
corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB.
Female patients show a slightly larger residual error.
PMID- 25586934
TI - Dynamic consent: a possible solution to improve patient confidence and trust in
how electronic patient records are used in medical research.
AB - With one million people treated every 36 hours, routinely collected UK National
Health Service (NHS) health data has huge potential for medical research.
Advances in data acquisition from electronic patient records (EPRs) means such
data are increasingly digital and can be anonymised for research purposes. NHS
England's care.data initiative recently sought to increase the amount and
availability of such data. However, controversy and uncertainty following the
care.data public awareness campaign led to a delay in rollout, indicating that
the success of EPR data for medical research may be threatened by a loss of
patient and public trust. The sharing of sensitive health care data can only be
done through maintaining such trust in a constantly evolving ethicolegal and
political landscape. We propose that a dynamic consent model, whereby patients
can electronically control consent through time and receive information about the
uses of their data, provides a transparent, flexible, and user-friendly means to
maintain public trust. This could leverage the huge potential of the EPR for
medical research and, ultimately, patient and societal benefit.
PMID- 25586935
TI - The role of age in association analyses of ADHD and related neurocognitive
functioning: A proof of concept for dopaminergic and serotonergic genes.
AB - Elucidating genetic mechanisms involved in Attention-Deficit/Hyperactivity
Disorder (ADHD) has been challenging. Relatively unexplored is the fact that
genetic mechanisms can differ with age. The current study explored the
association between dopaminergic and serotonergic genes, ADHD symptoms, and
neurocognitive functioning in relation to age. Associations of three genetic ADHD
risk factors, DAT1, DRD4, and 5-HTT with symptoms and six neurocognitive measures
were explored in two samples of the NeuroIMAGE study: 756 children, adolescents,
and young adults with ADHD, their siblings, and controls (M age 17 years, SD
3.2), and 393 parents with and without ADHD (M age 48 years, SD 4.8). Association
analyses were performed in both samples, and effects were compared to address
dichotomous age effects. Gene*age interactions were examined to address
continuous age effects. Moderating effects of age were found for DRD4-7R
carriership and ADHD symptoms in the adult group only; in the adolescents the 5
HTT LL genotype was differentially associated with inhibition and with motor
timing at different ages, and to inhibition in adults; DAT1 10-6 haplotype
carriership showed differential working memory performance depending on age. None
of our effects survived correction for multiple comparisons. Our results are
preliminary, but may point to differential genotype-phenotype associations at
different ages. This can be seen as a proof of concept for the importance of age
in dopaminergic and serotonergic genetic association analyses. Our findings are
consistent with the idea that genetic and neurocognitive mechanisms underlying
ADHD may change throughout life. (c) 2015 Wiley Periodicals, Inc.
PMID- 25586936
TI - Comparison of experimentally-induced wounds in rabbits treated with different
sources of platelet-rich plasma.
AB - Over the years, autologous platelet-rich plasma (PRP) has been used to great
advantage in the healing of acute and chronic wounds. However, it is impossible
to use in some situations so alternative PRPs need to be considered, such as
homologous or heterologous PRPs. In order to evaluate the effects of PRP in the
form of autologous, heterologous and homologous gels on in vivo cutaneous wound
healing, 18 animals divided into three groups of six, were used for the study,
with another six animals used as PRP donors. For the heterologous group an adult,
mixed breed dog was used to obtain the PRP. The wounds were induced using an 8 mm
punch. The left side was treated with NaCl 0.9%(r) (A) and a PRP gel was applied
(GA = autologous; GHE = heterologous and GHO = homologous) on the right side (B).
The wounds were evaluated for a period of 17 days. On the 17th day biopsies were
taken for histopathological assessment of the wounds. The percentage of
contraction was evident in side B (treated), which was confirmed in the
microscopic analysis of the histological sections. Thus, it was concluded that
PRP, regardless of the source, improves and accelerates the healing process,
demonstrating its therapeutic potential on cutaneous lesions and its use in
patients with impaired wound healing.
PMID- 25586937
TI - Comparison of haematopoietic stem cell engraftment through the retro-orbital
venous sinus and the lateral vein: alternative routes for bone marrow
transplantation in mice.
AB - Bone marrow transplantation in mice is performed by intravenous administration of
haematopoietic repopulating cells, usually via the lateral tail vein. This
technique can be technically challenging to carry out and may cause distress to
the mice. The retro-orbital sinus is a large area where there is a confluence of
several vessels that provides an alternative route for intravenous access. Retro
orbital injection, although aesthetically unpleasant, can be performed rapidly
without requiring mechanical restriction or heat-induced vasodilation. In
addition, this technique can be easily learned by novice manipulators. This route
of administration has been reported for use in bone marrow transplantation but
there is no comparison of retro-orbital and tail vein injections reported for
this specific purpose, although both routes have been compared for many other
applications. Here, we provide for the first time a comprehensive comparison
between tail vein and retro-orbital injections for two different bone marrow
transplant scenarios in P3B and B6D2F1 mice. In both cases, no significant
differences regarding donor engraftment were observed between mice transplanted
using each of the techniques. Haematological counts and leukocyte subpopulation
distribution were practically identical between both animal groups. Moreover,
donor engraftment levels were less homogenous when cells were transplanted by
tail vein injection, probably due to a higher risk of failure associated with
this technique. All these data suggest that retro-orbital injection is a
compelling alternative to conventional tail vein injection for bone marrow
transplant in mice, providing similar and more homogenous haematopoietic
reconstitution.
PMID- 25586939
TI - Bacterial infections following non-ablative fractional laser treatment: a case
series and discussion.
AB - Non-ablative fractional laser procedures have become increasingly popular since
their introduction in 2004. The fractional 1,927 nm thulium laser is a non
ablative device that penetrates up to 300 MUm in the skin and the 1,550 nm
erbium:glass laser penetrates up to 1,400 MUm. These procedures are considered
minimally invasive with a high safety profile; therefore, infectious
complications are exceedingly rare. However, we report five recent cases of
bacterial infection with both gram-positive and gram-negative organisms following
treatment with the fractional 1550/1927 nm laser approximately 1 day to 1 week
post-procedure. One patient had a rapidly progressing pustular eruption with
symptoms of sepsis. These patients were seen immediately, cultures were obtained
and empiric antibiotic therapy was initiated. They recovered without long-term
complications. Rapid-onset bacterial infections following non-ablative laser
resurfacing with the 1550/1927 nm laser have not been previously reported in the
literature. The infections can progress quickly and lead to serious sequelae,
including systemic illness and severe scarring, if not identified and
appropriately treated. We present these cases to highlight the importance of
close surveillance and when appropriate, rapid intervention, following non
ablative fractional procedures, especially when patients present with atypical
symptoms and signs.
PMID- 25586938
TI - Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic
PEEP in COPD?
AB - INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during
exercise, a strategy that, by increasing intrinsic positive end-expiratory
pressure, may optimise lung mechanics and exercise tolerance. A similar role for
laryngeal narrowing in modulating exercise airways resistance and the respiratory
cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of
this study was to assess the characteristics of laryngeal narrowing and its role
in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied
19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched
controls (n=11). Baseline physiological characteristics and clinical status were
assessed prior to an incremental maximal cardiopulmonary exercise test with
continuous laryngoscopy. Laryngeal narrowing measures were calculated at the
glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest,
expiratory laryngeal narrowing was pronounced at the glottic level in patients
and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=
0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak
ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001)
and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076,
respectively). Exercise glottic narrowing was also inversely related to peak
oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients
considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related
to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients
(r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is
prevalent in patients with COPD and is related to disease severity, respiratory
duty cycle and exercise capacity.
PMID- 25586940
TI - Organic synthesis: march of the machines.
AB - Organic synthesis is changing; in a world where budgets are constrained and the
environmental impacts of practice are scrutinized, it is increasingly recognized
that the efficient use of human resource is just as important as material use.
New technologies and machines have found use as methods for transforming the way
we work, addressing these issues encountered in research laboratories by enabling
chemists to adopt a more holistic systems approach in their work. Modern
developments in this area promote a multi-disciplinary approach and work is more
efficient as a result. This Review focuses on the concepts, procedures and
methods that have far-reaching implications in the chemistry world. Technologies
have been grouped as topics of opportunity and their recent applications in
innovative research laboratories are described.
PMID- 25586941
TI - Relationship of Troponin T and Age- and Sex-Adjusted BNP Elevation Following
Subarachnoid Hemorrhage with 30-Day Mortality.
AB - BACKGROUND: Troponin and brain natriuretic peptide (BNP) levels are predictors of
mortality following subarachnoid hemorrhage (SAH). Prior studies used strict
cutoffs for BNP elevation; however, normal levels of BNP are increased in older
persons and women. We explored the association of troponin elevation and BNP
elevation adjusted for sex and age with 30-day mortality. METHODS: In this
retrospective cohort study of patients with SAH, collected data included peak
troponin T and BNP levels. Mortality data were obtained from inpatient mortality
data and available records. Troponin T elevation was defined as more than 0.10
ng/mL; BNP elevation was defined as greater than the 95th percentile reference
limit by age and sex for patients without cardiovascular disease. Associations of
elevated troponin T and BNP were estimated from a log-binomial regression model
reporting relative risks (RRs), 95 % CIs, and P values; missing data were imputed
with the sample median or most frequent category. RESULTS: This study included
175 SAH patients. In single-variable analysis, peak troponin T level greater than
0.10 ng/mL was associated with increased risk in 30-day mortality (RR 4.38; 95 %
CI 2.43-7.89; P < .001); there was no association with elevated peak BNP adjusted
for age and sex (RR 1.13; 95 % CI 0.55-2.35; P = .74). There was no evidence
suggesting that the combination of elevated peak BNP and elevated peak troponin
increased the risk of 30-day mortality. CONCLUSIONS: Elevated troponin was an
independent predictor of 30-day mortality following SAH; however, when adjusted
for age and sex, elevations in BNP did not have this association.
PMID- 25586942
TI - Abnormal shape of the cavum septi pellucidi: an indirect sign of partial agenesis
of the corpus callosum.
AB - OBJECTIVE: To describe and assess the presence of a new indirect sign of partial
agenesis of the corpus callosum (pACC): an abnormally shaped cavum septi
pellucidi (CSP). METHODS: We analyzed retrospectively images from all 71 cases of
pACC seen at two referral centers between September 2006 and April 2014.
Abnormally shaped CSP was diagnosed when its lateral dimension was greater than
its anteroposterior dimension in the axial transthalamic plane, and the incidence
of this sign was assessed. We also examined the following variables: gestational
age at referral, indication for referral, which (if any) of the four corpus
callosal segments were abnormal, presence of other, previously established,
indirect signs of callosal agenesis (ACC) and presence of additional cerebral or
extracerebral anomalies. RESULTS: In 56 of the 71 (79%) cases, the CSP was
measurable; it was abnormally shaped in 19 (34%) of these cases, 15 (79%) of
which had no other indirect signs of pACC. Of 23 cases with isolated pACC and no
other indirect signs, 12 (52%) had an abnormally shaped CSP. CONCLUSIONS: In a
significant proportion of cases of pACC detected prenatally, the shape of the CSP
is abnormal. This should be considered an additional indirect sign of pACC, and
is frequently the only clue to the diagnosis. When observing this sign in a
screening context, pACC should be considered, and an attempt to visualize the
corpus callosum directly in the midsagittal plane is suggested.
PMID- 25586944
TI - MicroRNA and targeted mRNA expression profiling analysis in human colorectal
adenomas and adenocarcinomas.
AB - BACKGROUND: Colorectal cancer (CRC) mainly develops from colorectal adenomas
(CRAs). MicroRNAs (miRs) are short non-coding transcripts that regulate gene
expression by binding to target mRNAs, preventing their expression. It was
suggested that miRs were involved in cancer as tumour suppressors or oncogenes,
thereby being also potential cancer biomarkers. We conducted an expression
analysis of miRNAs and several of their target mRNAs, by using microarrays and
quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) (RT-qPCR),
in CRA and CRC, as compared to normal mucosa (NOR), in order to identify
candidate miRNAs involved in CRC progression. RESULTS: Microarray, together with
confirmatory RT-qPCR analyses, showed 17 significantly deregulated miRNAs in
colorectal lesions. While, as expected, some miRNAs have been previously reported
to be associated with CRC, including miR-21 and miR-145, others were new (miR
125a-5p and miR-320 family). Some miRNAs were specific for the CRC versus NOR
comparison (miR-320b), or for the CRA versus NOR comparison (miR-15b or miR-16),
but several of them (miR-21, miR-24, miR-145, mir-150, miR-378) were deregulated
in both CRAs and CRCs, as compared to NOR. The impact of these changes in miR
expression on target genes is suggested by the associated deregulation of these
genes in CRA and CRC. CONCLUSIONS: We confirmed that several miRNAs were
abnormally expressed in colorectal lesions, identified new deregulated miRs, and
showed that several miRNAs could mark the transition from NOR to CRA, thereby
marking progression from the early steps of cancer.
PMID- 25586945
TI - The association between alcohol use and engagement in casual sexual relationships
and experiences: a meta-analytic review of non-experimental studies.
AB - The present study provides a meta-analytic review of the association between
alcohol use and engagement in casual sexual relationships and experiences
(CSREs). Specifically, the meta-analysis focused on non-experimental studies of
community and college samples. Results from the meta-analysis, which included 29
relevant studies (34 effect sizes), indicated that alcohol use was significantly
associated with engaging in CSREs, r = .34, 95 % CI [.29-.38], but that this link
showed considerable variability. Subsequent analyses examined moderators that may
explain this heterogeneity. Results revealed that age and method of assessment
significantly moderated the effect of alcohol use on CSRE engagement such that
the association was greater for emerging adults (18-24 year olds) than older
adults and online assessments produced greater effect sizes than paper-and-pencil
assessments. These results have implications for future research and intervention
development. In particular, this meta-analysis emphasizes the need for studies
that utilize consistent measurements of CSRE engagement, include diverse
methodology, and expand upon sampling.
PMID- 25586943
TI - Ion and molecular recognition using aryl-ethynyl scaffolding.
AB - The aryl-ethynyl linkage has been extensively employed in the construction of
hosts for a variety of guests. Uses range from ion detection (e.g., of metal
cations in the environment or industrial waste and of anions prevalent in
nature), to molecular mimics for biological systems, and to applications
targeting future safety issues (such as CO2 capture and indicators for the
manufacture of chemical weapons). This Focus Review examines the utilization of
the aryl-ethynyl linkage in engineering host molecules for a variety of different
guests, and how the alkyne unit plays an integral part as both a rigid
scaffolding section in host geometry design as well as a linker to allow
conjugative communication between discrete pi-electron systems.
PMID- 25586946
TI - Pediatric cochlear implantation in residual hearing candidates.
AB - OBJECTIVES: To propose categories for the various types of residual hearing in
children and to review the outcomes of cochlear implantation (CI) in children
with these different hearing conditions. METHODS: We identified 53 children with
residual hearing who had received a cochlear implant. Five groups were
arbitrarily defined based on auditory features: G1, characterized by low
frequency residual hearing (n=5); G2, characterized by severe sensorineural
hearing loss (SNHL) and low speech discrimination (n=12); G3, characterized by
asymmetric SNHL (n=9); G4, characterized by progressive SNHL (n=15); and G5,
characterized by fluctuating SNHL (n=12). The main audiometric features and
outcomes of the groups were analyzed. RESULTS: The mean age at implantation was
10.15 years (range, 2.5-21 years). The mean preoperative score for the
discrimination of open-set words was 48%; this score increased to 74% at 12
months and 81% at 24 months after the CI procedure (G1 to G5, respectively:
79/62/77%, 50/81/88%, 59/75/86%, 35/74/67%, and 39/69/80%). Children who were
implanted after 10 years of age did not improve as much as those who were
implanted at a younger age (open-set word list speech perception [OSW] score at
12 months: 62% vs 83%; P=.0009). Shorter delays before surgery were predictive of
better performance (P=.003). Inner ear malformation and SLC26A4 mutations were
not predictive of the outcome. CONCLUSIONS: CIs provide better results compared
with hearing aids in children with residual hearing. Factors that may impact the
benefits of CIs in patients with residual hearing are age, delay in performing
the CI procedure, which ear is implanted, and initial underestimation of the
patient's hearing difficulties.
PMID- 25586947
TI - Reliability of the penetration aspiration scale with flexible endoscopic
evaluation of swallowing.
AB - OBJECTIVES: The Penetration Aspiration Scale (PAS), although designed for
videofluoroscopy, has been utilized with flexible endoscopic evaluation of
swallowing (FEES) in both research and clinical practice. The purpose of this
investigation was to determine inter- and intrarater reliability of the PAS with
FEES as a function of clinician FEES experience and retest interval. METHODS:
Three groups of 3 clinicians (N=9) with varying FEES experience (beginning,
intermediate, and advanced) assigned PAS scores to 35 swallows. Initial ratings
were repeated following short-term (ie, 1 day) and long-term (ie, 1 week) retest
intervals. RESULTS: Intraclass correlation coefficients were calculated to assess
interrater reliability on the first rating for each group. The coefficients were
.91, .82, and .89 for the beginning, intermediate, and advanced clinicians,
respectively. Overall interrater reliability across all 9 clinicians,
irrespective of experience, was .85. Intraclass correlation coefficients were
also calculated to assess intrarater reliability. The intrarater reliability for
short- and long-term ratings was .90, .94, and .96 and .96, .97, and .94 for the
beginning, intermediate, and advanced clinicians, respectively. Overall
intrarater reliability across all 9 clinicians and all 3 ratings was .94.
CONCLUSIONS: Excellent inter- and intrarater reliability was evidenced with the
application of the PAS for FEES regardless of clinician experience and retest
interval.
PMID- 25586948
TI - Hearing in static unilateral vestibular schwannoma declines more than in the
contralateral ear.
AB - OBJECTIVE: To determine the effect of static vestibular schwannomas on hearing.
STUDY DESIGN: Retrospective review of audiometric measures in 15 patients with
documented nongrowth of internal auditory canal and cerebellopontine angle
enhancing masses. METHODS: Data from patients seen in an ambulatory tertiary care
setting between the years of 2002 and 2012 with a diagnosis of acoustic neuroma
or vestibular schwannoma were reviewed. Exclusion criteria included preexisting
otologic disease, prior therapy for the schwannoma, and tumor growth. Radiology
reports were reviewed to ensure nongrowth and were confirmed by taking magnetic
resonance imaging (MRI) measurements ourselves. Audiologic measurements included
pure tone average, enhanced pure tone average (average of .5, 1, 2, and 4 KHz
thresholds), 4 KHz threshold, 8 KHz threshold, and speech discrimination. The
data were analyzed using mixed effect model with unstructured variance-covariance
structure. RESULTS: Difference in audiometric measures between ears significantly
(P<.05) increased for all measures except 8 KHz. CONCLUSION: Spontaneous decline
in hearing relative to time is exaggerated in the affected ear despite no
vestibular schwannoma growth. This finding can be useful for patient counseling
and treatment decision making.
PMID- 25586953
TI - This year and this issue.
PMID- 25586951
TI - Stereotactic body radiotherapy and treatment at a high volume facility is
associated with improved survival in patients with inoperable stage I non-small
cell lung cancer.
AB - BACKGROUND: This study examined the comparative effectiveness of no treatment
(NoTx), conventional fractionated radiotherapy (ConvRT), and stereotactic body
radiotherapy (SBRT) in patients with inoperable stage I non-small cell lung
cancer. This population based cohort also allowed us to examine what facility
level characteristics contributed to improved outcomes. METHODS: We included
patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0
inoperable lung cancer (n=13,036). Overall survival (OS) was estimated using
Kaplan-Meier methods and Cox proportional hazard regression. RESULTS: The median
follow up was 68months (interquartile range: 35-83months) in surviving patients.
Among the cohort, 52% received NoTx, 41% received ConvRT and 6% received SBRT.
The 3-year OS was 28% for NoTx, 36% for ConvRT radiotherapy, and 48% for the SBRT
cohort (p<0.0001). On multivariate analysis, the hazard ratio for SBRT and ConvRT
were 0.67 and 0.77, respectively, as compared to NoTx (1.0 ref) (p<0.0001).
Patients treated at a high volume facility vs. low volume facility had a hazard
ratio of 0.94 vs. 1.0 (p=0.01). CONCLUSIONS: Patients with early stage inoperable
lung cancer treated with SBRT and at a high volume facility had a survival
benefit compared to patients treated with ConvRT or NoTx or to those treated at a
low volume facility.
PMID- 25586954
TI - What's new about NATA?
PMID- 25586952
TI - Safety of dose escalation by simultaneous integrated boosting radiation dose
within the primary tumor guided by (18)FDG-PET/CT for esophageal cancer.
AB - PURPOSE: To observe the safety of selective dose boost to the pre-treatment high
(18)F-deoxyglucose (FDG) uptake areas of the esophageal GTV. METHODS: Patients
with esophageal squamous cell carcinoma were treated with escalating radiation
dose of 4 levels, with a simultaneous integrated boost (SIB) to the pre-treatment
50% SUVmax area of the primary tumor. Patients received 4 monthly cycles of
cisplatin and fluorouracil. Dose-limiting toxicity (DLT) was defined as any Grade
3 or higher acute toxicities causing continuous interruption of radiation for
over 1 week. RESULTS: From April 2012 to February 2014, dose has been escalated
up to LEVEL 4 (70Gy). All of the 25 patients finished the prescribed dose without
DLT, and 10 of them developed Grade 3 acute esophagitis. One patient of LEVEL 2
died of esophageal hemorrhage within 1 month after completion of radiotherapy,
which was not definitely correlated with treatment yet. Late toxicities remained
under observation. With median follow up of 8.9months, one-year overall survival
and local control was 69.2% and 77.4%, respectively. CONCLUSIONS: Dose escalation
in esophageal cancer based on (18)FDG-PET/CT has been safely achieved up to 70Gy
using the SIB technique. Acute toxicities were well tolerated, whereas late
toxicities and long-term outcomes deserved further observation.
PMID- 25586955
TI - Blood transfusion at the time of the First World War--practice and promise at the
birth of transfusion medicine.
AB - The centenary of the start of the First World War has stirred considerable
interest in the political, social, military and human factors of the time and how
they interacted to produce and sustain the material and human destruction in the
4 years of the war and beyond. Medical practice may appear distant and static and
perhaps seems to have been somewhat ineffectual in the face of so much trauma and
in the light of the enormous advances in medicine and surgery over the last
century. However, this is an illusion of time and of course medical, surgical and
psychiatric knowledge and procedures were developing rapidly at the time and the
war years accelerated implementation of many important advances. Transfusion
practice lay at the heart of resuscitation, and although direct transfusion from
donor to recipient was still used, Geoffrey Keynes from Britain, Oswald Robertson
from America and his namesake Lawrence Bruce Robertson from Canada, developed
methods for indirect transfusion from donor to recipient by storing blood in
bottles and also blood-banking that laid the foundation of modern transfusion
medicine. This review explores the historical setting behind the development of
blood transfusion up to the start of the First World War and on how they
progressed during the war and afterwards. A fresh look may renew interest in how
a novel medical speciality responded to the needs of war and of post-war society.
PMID- 25586956
TI - Profound sustained reticulocytopenia and anaemia in an adult patient with sickle
cell disease.
PMID- 25586958
TI - Osteonecrosis of the Jaw in Patients With Metastatic Renal Cell Cancer Treated
With Bisphosphonates and Targeted Agents: Results of an Italian Multicenter Study
and Review of the Literature.
AB - Osteonecrosis of the jaw (ONJ) associated with the use of bisphosphonates has
been rarely reported in metastatic renal cell cancer (RCC) patients. Since the
introduction of combined therapies consisting of nitrogen-containing
bisphosphonates (NBPs) and targeted agents, an increasing number of RCC patients
were reported to develop ONJ, suggesting that therapeutic angiogenesis
suppression might increase the risk of ONJ in NBPs users. We performed a
multicenter retrospective study and reviewed literature data to assess the
occurrence and to investigate the nature of ONJ in RCC patients taking NBPs and
targeted agents. Nine Italian Centers contributed to the data collection.
Patients with exposed and nonexposed ONJ were eligible for the study if they had
been taking NBPs and were receiving targeted agents at the time of ONJ diagnosis.
Forty-four RCC patients were studied. Patients were mostly male (82%), with a
median age of 63 years (range, 45-85 years). Zoledronic acid (93%) and sunitinib
(80%) were the most frequently used NBP and antiangiogenic agent, respectively.
Other agents included Pamidronate, ibandronate, sorafenib, bevacizumab, mammalian
target of rapamycin inhibitors. Forty-nine sites of ONJ were encountered, with
the mandible being the preferred site of ONJ (52%); both jaws were affected in 5
cases (12%). The most common precipitating event was dental/periodontal infection
(34%), followed by tooth extraction (30%). Oral triggers of ONJ were missing in
10 cases (23%). This unexpectedly high number of ONJ cases, in comparison with
literature data, suggests that frequency of ONJ in RCC patients might be largely
underestimated and suggests a potential role for targeted agents in the
incremental risk of ONJ.
PMID- 25586959
TI - Multimodal neuroimaging evidence linking memory and attention systems during
visual search cued by context.
AB - Visual search can be facilitated by the learning of spatial configurations that
predict the location of a target among distractors. Neuropsychological and
functional magnetic resonance imaging (fMRI) evidence implicates the medial
temporal lobe (MTL) memory system in this contextual cueing effect, and
electroencephalography (EEG) studies have identified the involvement of visual
cortical regions related to attention. This work investigated two questions: (1)
how memory and attention systems are related in contextual cueing; and (2) how
these systems are involved in both short- and long-term contextual learning. In
one session, EEG and fMRI data were acquired simultaneously in a contextual
cueing task. In a second session conducted 1 week later, EEG data were recorded
in isolation. The fMRI results revealed MTL contextual modulations that were
correlated with short- and long-term behavioral context enhancements and
attention-related effects measured with EEG. An fMRI-seeded EEG source analysis
revealed that the MTL contributed the most variance to the variability in the
attention enhancements measured with EEG. These results support the notion that
memory and attention systems interact to facilitate search when spatial context
is implicitly learned.
PMID- 25586961
TI - Toxicity of the conventional energetics TNT and RDX relative to new insensitive
munitions constituents DNAN and NTO in Rana pipiens tadpoles.
AB - An initiative within the US military is targeting the replacement of traditional
munitions constituents with insensitive munitions to reduce risk of accidental
detonation. The purpose of the present study was to comparatively assess toxicity
of the traditional munitions constituents 2,4,6-trinitrotoluene (TNT) and 1,3,5
trinitroperhydro-1,3,5-triazine (RDX) with the new insensitive munitions
constituents 2,4-dinitroanisole (DNAN) and 3-nitro-1,2,4-triazol-5-one (NTO). The
following exposure durations were performed with Rana pipiens (leopard frog)
tadpoles: TNT and DNAN, 96 h and 28 d; RDX, 10 d and 28 d; NTO, 28 d. The 96-h
50% lethal concentration (LC50) values and 95% confidence intervals for TNT and
DNAN were 4.4 mg/L (4.2 mg/L, 4. 7 mg/L) and 24.3 mg/L (21.3 mg/L, 27.6 mg/L),
respectively. No significant impacts on survival were observed in the 10-d
exposure to RDX up to 25.3 mg/L. Effects on tadpole swimming distance were
observed with a lowest-observed-effect concentration (LOEC) of 5.9 mg/L RDX. In
the 28-d exposures, the LOECs for survival for TNT, DNAN, and NTO were 0.003
mg/L, 2.4 mg/L, and 5.0 mg/L, respectively. No significant mortality was observed
in the RDX chronic 28-d exposure up to the highest treatment level tested of 28.0
mg/L. Neither tadpole developmental stage nor growth was significantly affected
in any of the 28-d exposures. Rana pipiens were very sensitive to chronic TNT
exposure, with an LOEC 3 orders of magnitude lower than those for insensitive
munitions constituents DNAN and NTO.
PMID- 25586963
TI - Erratum to: Role of sirtuins in chronic obstructive pulmonary disease.
PMID- 25586960
TI - Pak2 regulates hematopoietic progenitor cell proliferation, survival, and
differentiation.
AB - p21-Activated kinase 2 (Pak2), a serine/threonine kinase, has been previously
shown to be essential for hematopoietic stem cell (HSC) engraftment. However,
Pak2 modulation of long-term hematopoiesis and lineage commitment remain
unreported. Using a conditional Pak2 knockout mouse model, we found that
disruption of Pak2 in HSCs induced profound leukopenia and a mild macrocytic
anemia. Although loss of Pak2 in HSCs leads to less efficient short- and long
term competitive hematopoiesis than wild-type cells, it does not affect HSC self
renewal per se. Pak2 disruption decreased the survival and proliferation of
multicytokine stimulated immature progenitors. Loss of Pak2 skewed lineage
differentiation toward granulocytopoiesis and monocytopoiesis in mice as
evidenced by (a) a three- to sixfold increase in the percentage of peripheral
blood granulocytes and a significant increase in the percentage of granulocyte
monocyte progenitors in mice transplanted with Pak2-disrupted bone marrow (BM);
(b)Pak2-disrupted BM and c-kit(+) cells yielded higher numbers of more mature
subsets of granulocyte-monocyte colonies and polymorphonuclear neutrophils,
respectively, when cultured in the presence of granulocyte-macrophage colony
stimulating factor. Pak2 disruption resulted, respectively, in decreased and
increased gene expression of transcription factors JunB and c-Myc, which may
suggest underlying mechanisms by which Pak2 regulates granulocyte-monocyte
lineage commitment. Furthermore, Pak2 disruption led to (a) higher percentage of
CD4(+) CD8(+) double positive T cells and lower percentages of CD4(+) CD8(-) or
CD4(-) CD8(+) single positive T cells in thymus and (b) decreased numbers of
mature B cells and increased numbers of Pre-Pro B cells in BM, suggesting defects
in lymphopoiesis.
PMID- 25586962
TI - Gene pyramiding enhances durable blast disease resistance in rice.
AB - Effective control of blast, a devastating fungal disease of rice, would increase
and stabilize worldwide food production. Resistance mediated by quantitative
trait loci (QTLs), which usually have smaller individual effects than R-genes but
confer broad-spectrum or non-race-specific resistance, is a promising alternative
to less durable race-specific resistance for crop improvement, yet evidence that
validates the impact of QTL combinations (pyramids) on the durability of plant
disease resistance has been lacking. Here, we developed near-isogenic
experimental lines representing all possible combinations of four QTL alleles
from a durably resistant cultivar. These lines enabled us to evaluate the QTLs
singly and in combination in a homogeneous genetic background. We present
evidence that pyramiding QTL alleles, each controlling a different response to M.
oryzae, confers strong, non-race-specific, environmentally stable resistance to
blast disease. Our results suggest that this robust defence system provides
durable resistance, thus avoiding an evolutionary "arms race" between a crop and
its pathogen.
PMID- 25586964
TI - Anti-inflammatory activity of sappanchalcone isolated from Caesalpinia sappan L.
in a collagen-induced arthritis mouse model.
AB - Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia
sappan L. possesses anti-inflammatory effects. We studied the efficacy of
sappanchalcone in attenuating collagen-induced arthritis (CIA) in a mouse model
of rheumatoid arthritis. Sappanchalcone was purified to homogeneity from the
chloroform fraction of the methanolic extract of C. sappan, and identified using
mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. CIA-induced
male DBA/1J mice were divided into control, sappanchalcone-treated, and
methotrexate-treated groups (n = 10 per group). Paw swelling, arthritis severity,
radiographic and histomorphometric changes were assessed to measure the
protective role of sappanchalcone against chronic disease progression.
Sappanchalcone administration significantly reduced clinical arthritis and
inflammatory edema in paws. Bone mineral density and trabecular structure were
maintained in CIA mice administered sappanchalcone. The levels of pro
inflammatory cytokines (TNF-alpha, IL-6, and 1L-1beta) were significantly lower
in the serum of sappanchalcone-treated mice as compared with the control group.
Our results suggest that sappanchalcone could be used as an anti-inflammatory and
bone-protective agent during the treatment of rheumatoid arthritis.
PMID- 25586967
TI - Size dependence of phase transitions in aerosol nanoparticles.
AB - Phase transitions of nanoparticles are of fundamental importance in atmospheric
sciences, but current understanding is insufficient to explain observations at
the nano-scale. In particular, discrepancies exist between observations and model
predictions of deliquescence and efflorescence transitions and the hygroscopic
growth of salt nanoparticles. Here we show that these discrepancies can be
resolved by consideration of particle size effects with consistent thermodynamic
data. We present a new method for the determination of water and solute
activities and interfacial energies in highly supersaturated aqueous solution
droplets (Differential Kohler Analysis). Our analysis reveals that particle size
can strongly alter the characteristic concentration of phase separation in mixed
systems, resembling the influence of temperature. Owing to similar effects,
atmospheric secondary organic aerosol particles at room temperature are expected
to be always liquid at diameters below ~20 nm. We thus propose and demonstrate
that particle size should be included as an additional dimension in the
equilibrium phase diagram of aerosol nanoparticles.
PMID- 25586969
TI - Clinical Obesity - a new journal for a new clinical era.
PMID- 25586966
TI - The alveolar ridge splitting/expansion technique: a systematic review.
AB - PURPOSE: The aim of this systematic review was to evaluate clinical, radiological
and histological outcomes of the alveolar ridge splitting/expansion technique
(ARST) with or without GBR. MATERIALS AND METHODS: A screening of two databases
MEDLINE (PubMed) and EMBASE (OVID) and hand search of articles were performed.
Human and animal studies reporting on dental implants placed with simultaneous
ARST up to May 31st 2014 were considered. Quality assessment of selected full
text articles was performed according to the ARRIVE guidelines and the Cochrane
collaboration's tool to assess risk of bias. RESULTS: Overall, 18 human and six
animal studies (risk of bias: high/unclear) were included in this review. No
randomized controlled trials were found. Due to the heterogeneity of study
designs, definitions of success criteria, outcome variables, observation times
and surgical procedures, no meta-analysis was performed. Reported survival (18
studies) and success (nine studies) rates ranged from 91.7 to 100% and 88.2 to
100%, respectively, with a mean follow-up of 1-10 years. Crestal bone level
changes (?CBL) in some studies indicate slightly higher bone loss before and
after loading. Histologic and histomorphometric data from six animal studies
confirm the crestal bone loss, particularly at buccal sites. CONCLUSIONS: Within
the limitations of this review, ARST seems to be a well-functioning one-stage
alternative to extended two-stage horizontal grafting procedures. Data indicate
that during healing and first year of loading, increased ?CBL particularly at
buccal sites must be anticipated. Additional horizontal GBR can help to preserve
buccal bone height and width.
PMID- 25586968
TI - Construction of a high-mannose-type glycan library by a renewed top-down chemo
enzymatic approach.
AB - A comprehensive method for the construction of a high-mannose-type glycan library
by systematic chemo-enzymatic trimming of a single Man9-based precursor was
developed. It consists of the chemical synthesis of a non-natural
tridecasaccharide precursor, the orthogonal demasking of the non-reducing ends,
and trimming by glycosidases, which enabled a comprehensive synthesis of high
mannose-type glycans in their mono- or non-glucosylated forms. It employed
glucose, isopropylidene, and N-acetylglucosamine groups for blocking the A-, B-,
and C-arms, respectively. After systematic trimming of the precursor, thirty
seven high-mannose-type glycans were obtained. The power of the methodology was
demonstrated by the enzymatic activity of human recombinant N
acetylglucosaminyltransferase-I toward M7-M3 glycans, clarifying the substrate
specificity in the context of high-mannose-type glycans.
PMID- 25586965
TI - Impairment of chaperone-mediated autophagy leads to selective lysosomal
degradation defects in the lysosomal storage disease cystinosis.
AB - Metabolite accumulation in lysosomal storage disorders (LSDs) results in impaired
cell function and multi-systemic disease. Although substrate reduction and
lysosomal overload-decreasing therapies can ameliorate disease progression, the
significance of lysosomal overload-independent mechanisms in the development of
cellular dysfunction is unknown for most LSDs. Here, we identify a mechanism of
impaired chaperone-mediated autophagy (CMA) in cystinosis, a LSD caused by
defects in the cystine transporter cystinosin (CTNS) and characterized by cystine
lysosomal accumulation. We show that, different from other LSDs, autophagosome
number is increased, but macroautophagic flux is not impaired in cystinosis while
mTOR activity is not affected. Conversely, the expression and localization of the
CMA receptor LAMP2A are abnormal in CTNS-deficient cells and degradation of the
CMA substrate GAPDH is defective in Ctns(-/-) mice. Importantly, cysteamine
treatment, despite decreasing lysosomal overload, did not correct defective CMA
in Ctns(-/-) mice or LAMP2A mislocalization in cystinotic cells, which was
rescued by CTNS expression instead, suggesting that cystinosin is important for
CMA activity. In conclusion, CMA impairment contributes to cell malfunction in
cystinosis, highlighting the need for treatments complementary to current
therapies that are based on decreasing lysosomal overload.
PMID- 25586970
TI - Review of current guidelines on adolescent bariatric surgery.
AB - A variety of European, North American and, recently, Middle East and Australasian
guidelines are now available for clinicians treating obese children and
adolescents. This review aims to synthesize recommendations from recent guidance
to provide direction to clinicians on the appropriate use of bariatric surgery in
adolescents. A literature search for English-language guidelines endorsed by
national governments or professional health associations or societies was
conducted, and subject experts were consulted to identify the most recently
released guidance. Fifteen sets of guidelines were found, released in the past 6
years, of which nearly all suggested that bariatric surgery is indicated for
obese paediatric patients after previous failed attempts at weight loss. Guidance
was broadly similar in terms of the categories addressed (patient selection
criteria, requirements of the surgical team and institution, and suggested
preoperative and postoperative protocols), although relatively little consensus
was evident among the criteria specified within these categories. Recommendations
differed regarding the appropriate age and degree of obesity at which to
intervene. Fewer guidelines addressed preoperative and postoperative care
requirements, and of those that did the emphasis varied between familial care and
involvement, psychological state and patient motivation, and the importance of
long term care. There is a lack of uniformity in the guidance in this area,
indicative of the complex nature of obesity management for younger patients.
While guidance is necessary to inform and update clinicians, obese paediatric
patients require individualized assessment and care.
PMID- 25586971
TI - Effectiveness and cost-effectiveness of paediatric bariatric surgery: a
systematic review.
AB - Strong evidence for successful and cost-effective obesity management strategies
is still generally lacking, leading the medical profession to rely increasingly
on surgical options to treat obesity in children and adolescents. We performed a
systematic review to examine the effectiveness of surgical interventions to treat
obese children and adolescents, and whether they are cost-effective. We searched
PubMed, ISI Web of Science, Embase and the Cochrane Library to 6 September 2010,
and hand-searched bibliographies. We included articles with English abstracts if
they examined subjects <=19 years of age, reported at least one postoperative
weight loss measure and at least 1 year of postoperative follow-up. Thirty-seven
relevant papers on bariatric surgery effectiveness in 831 children or adolescents
were included, spanning 36 years. Thirteen studies examined gastric banding, with
mean body mass index (BMI) reductions ranging from 8.5 to 43 kg m(-2) . Weight
gain was reported in one case study. Eight papers examined Roux-en-Y gastric
bypass, with mean BMI reductions ranging from 9 to 25 kg m(-2) . Fourteen
publications studied other forms of bariatric surgery: sleeve gastrectomies,
vertical banded gastroplasty, biliopancreatic diversion or a combination of
procedures. Mean BMI reductions ranged from 9 to 24 kg m(-2) . Three surgery
related mortalities were reported, as was weight regain in several cases. The
majority of studies reported resolution or improvement of comorbid conditions. A
range of postoperative complications were identified across surgery types,
including: ulcers, intestinal leakage, wound infection, anastomotic stricture,
nutritional deficiencies, bowel obstruction, pulmonary embolism, disrupted staple
lines, band slippage, psychological intolerance and repeated vomiting. Evidence
on cost-effectiveness was limited to one Australian modelling project, which
deemed laparoscopic adjustable gastric banding cost-effective for adolescents.
Existing evidence - although based generally on underpowered, retrospective
studies - suggests that bariatric surgery in older children results in
significant weight loss and improvements in comorbidities and quality of life.
However, postoperative complications, compliance and follow-up may be more
problematic in adolescents than adults, and availability of long-term data on
safety, effectiveness and cost-effectiveness remains largely unknown. Pending an
improvement in the quality of available evidence, a cautious approach to child
and adolescent bariatric surgery is warranted, and reversible techniques are
advisable compared to approaches that permanently alter anatomy.
PMID- 25586972
TI - Does medically induced weight loss improve obstructive sleep apnoea in the obese:
review of randomized trials.
AB - Obstructive sleep apnoea is characterized by repeated periods of breathing
cessation during sleep. Obstructive sleep apnoea is both common and
underdiagnosed in the obese. A recent study found that as many as 86% of older
obese type 2 diabetics had obstructive sleep apnoea. Obesity is independently
associated with developing obstructive sleep apnoea, and the reverse may also
occur. The prevalence of obstructive sleep apnoea is therefore expected to rise
in the wake of the obesity epidemic. The number of partial (hypopnoea) or
complete (apnoea) airway obstructions per hour (apnoea-hypopnoea index) is used
to classify obstructive sleep apnoea as mild (5-14 events per hour), moderate (15
30) or severe (>30). Severe obstructive sleep apnoea is associated with a two to
sixfold increase in all-cause mortality; the impact of mild and moderate
obstructive sleep apnoea is less clear. Until recently, the evidence supporting a
beneficial effect of weight loss on obstructive sleep apnoea has been limited by
a lack of randomized trials. In 2009, at least three randomized controlled trials
evaluated whether medically induced weight loss improves obstructive sleep
apnoea. The treatment effect ranged from 42% to 62% improvement, although the
highest estimate was seen in a very short duration study (9 weeks). Patients who
either lost 10-15 kg or more, or had severe obstructive sleep apnoea at baseline,
benefited most from treatment.
PMID- 25586973
TI - Comparison of a low-energy diet and a very low-energy diet in sedentary obese
individuals: a pragmatic randomized controlled trial.
AB - There is no consensus on whether 'very low-energy diets' (VLED; <800 kcal d(-1) )
cause greater weight loss in obese individuals than 'low-energy diets' (LED; 800
1200 kcal d(-1) ). The objective was to determine whether a very low-energy
formula diet would cause greater weight loss than a formula 810 kcal d(-1) LED in
older sedentary individuals. This is a pragmatic randomized controlled trial.
INCLUSION CRITERIA: obesity (body mass index [BMI] > 30); age >50 years, with
knee osteoarthritis. Participants were randomized to VLED (420-554 kcal d(-1) )
or LED (810 kcal d(-1) ) for 8 weeks, followed by a fixed-energy (1200 kcal d(-1)
) diet with food and two diet products daily for 8 weeks. In all, 192
participants were randomized. Mean age was 63 years (standard deviation: 6), mean
weight 103.2 kg (15.0) and BMI of 37.3 kg m(-2) (4.8) at baseline. Mean weight
losses in VLED and LED groups were 11.4 kg (standard error: 0.5) and 10.7 kg
(0.5) at week 8 and 13.3 kg (0.7) and 12.2 kg (0.6) at week 16. Mean differences
between groups were 0.76 kg (95% confidence interval: -0.59 to 2.10; P = 0.27)
and 1.08 kg (-0.66 to 2.81; P = 0.22) at 8 and 16 weeks, respectively. Loss of
lean body mass was 2.1 kg (0.2) and 1.2 kg (0.4) (17% and 11% of the weight lost,
respectively) at week 16 in the VLED and LED group with a mean difference of 0.85
kg (0.01 to 1.69; P = 0.047). Significant adverse effects comparing VLED and LED,
were bad breath: 34 (35%) vs. 21 (22%), intolerance to cold: 39 (41%) vs. 17
(18%) and flatulence: 43 (45%) vs. 28 (29%) for VLED and LED at 8 weeks (P < 0.05
in all cases). The VLED and LED regimens were equally successful in inducing
weight loss. The significantly lower loss of lean tissue in the LED group
together with more frequently reported side effects in the VLED group, favours
the choice of low-energy diet (LED) for the treatment of obesity.
PMID- 25586975
TI - Osteoarthritis - a role for weight management in rheumatology practice: an
update.
AB - Osteoarthritis (OA) and obesity are related diseases, which occur in a large
proportion of the population. Epidemiological evidence show that weight is of
great importance for the development of OA in the knee, and to some extent also
in hip and finger joints. Once acquired, the OA contributes to further weight
problems by decreasing the daily activity level. Weight loss will be beneficial
for the knee and experimental data point at a highly significant effect on knee
function and recent results even point at a positive effect on the cartilage of
the knee joint. Recommending patients with a combination of knee OA and obesity
to lose at least 5% body weight, and aim for 10% is predicted to correspond to
26% improvement in physical function. A programme for this weight loss has been
tested with good results applying an initial formula diet with maintenance
therapy in groups during follow-up.
PMID- 25586974
TI - VLED and formula LED in the management of type 2 diabetes: defining the clinical
need and research requirements.
AB - It has been known for many years that substantial weight loss, achieved by
bariatric surgery or non-surgical means can mean normalize glucose tolerance.
Recent randomized controlled trial evidence indicates that >15 kg weight loss is
necessary, to this and it may lead to near normalization (doubling) of life
expectancy. Less than 5% of patients achieve this through even the best, evidence
based medical weight management programme (Counterweight
http://www.counterweight.org). A weight loss of >15 kg is easily achievable by 8
weeks very low-energy diet (VLED)/LELD (Low energy Liquid-formula Diet) in
compliant patients, with little difference between 400 and 800 kcal day(-1) , but
weight maintenance after VLED has until recently been so poor that VLED is not,
at present, recommended in clinical guidelines. However, mean weight loss close
to >15 kg can be maintained 18-24 months using a variety of maintenance
strategies. These include a structured reintroduction of foods linked to an
education programme with behavioural strategies, intermittent VLED use and
prescribable anti-obesity drugs (dexfenfluramine, orlistat, sibutramine). Most of
these studies have been in non-diabetic subjects. A new 'curative' paradigm in
type 2 diabetes mellitus management, aiming to normalize glucose tolerance and
health risks by achieving and maintaining >15 kg loss, as soon as possible after
diagnosis, should be highly acceptable to patients, generating many additional
Quality Adjusted Life Years (QALYs). It is likely to be highly cost-effective by
avoiding the current recommended, mainly palliative, model, using polypharmacy
which provides an overall risk reduction of only 5-10%. Clinical trials are on
going to establish the feasibility of delivering formula (LELD) and a maintenance
programme to large numbers of patients within routine primary care. There is
urgent need, to run similar studies in diabetic patients. New approaches to long
term (lifelong) maintenance of weight loss and a non-diabetic state may include
anti-obesity drugs.
PMID- 25586976
TI - A 60-year-old obese woman with osteoarthritis of the knee: a case-report.
AB - A case is presented of a 60-year-old woman with concomitant obesity and knee
osteoarthritis. The bad knees prevented the patient from exercising; however,
with a focused dietary intervention employing food supplements for the first
period of 8 weeks, an ordinary low-energy diet for another 8 weeks, the patient
lost 17.3 kg; and a further weight loss was achieved during 1-year follow-up
totalling 30.6 kg. Lean body mass only changed slightly, 96.8% of the weight loss
being fat mass. Along with this her metabolic syndrome decreased and her gait
improved. It is suggested that a major weight loss is the treatment of choice in
patients with this combination of diseases.
PMID- 25586977
TI - Effect of a very low-energy diet on moderate and severe obstructive sleep apnoea:
case reports.
AB - In this article, we report two cases from our study in which we investigated the
effect of a very low-energy diet (VLED) for 9 weeks followed by a weight
maintenance program for a total duration of 1 year in obese men with moderate to
severe obstructive sleep apnea. The first case was a 43-year-old man with a body
weight of 126 kg and a body mass index (BMI) of 38.8 kg/m(2) at baseline. Over
the 1-year treatment program he lost 26% of his initial weight and his apnea
hypopnea index (AHI) was improved by 60%. The second case was at baseline a 54
year-old man with a weight of 87 kg and BMI of 32.1 kg/m(2) . Over the 1-year
treatment program he lost 10% of his initial weight and his AHI improved by 66%.
In summary, treatment with a VLED followed by a weight maintenance program
significantly improved obstructive sleep apnea in both cases.
PMID- 25586979
TI - Neuroretinitis secondary to Bartonella henselae in the emergent setting.
PMID- 25586980
TI - Cryolipolysis for safe and effective inner thigh fat reduction.
AB - BACKGROUND AND OBJECTIVES: While cryolipolysis initially received FDA clearance
for fat reduction in the abdomen and flanks, there was significant interest in
non-surgical fat reduction for other sites, such as the inner and outer thighs.
This article reports the results of an inner thigh study which contributed to FDA
clearance of cryolipolysis for treatment of thighs. STUDY DESIGN/MATERIAL AND
METHODS: A flat cup vacuum applicator (CoolFit applicator, CoolSculpting System)
was used to treat 45 subjects bilaterally in the inner thighs. Single cycle
treatments were delivered at Cooling Intensity Factor (CIF) 41.6 for 60 minutes
followed by 2 minutes of manual massage. Follow-up visits were conducted at 8 and
16 weeks. Efficacy was assessed by ultrasound imaging, circumference
measurements, and photographs. Safety was assessed by monitoring adverse events.
Patient satisfaction was evaluated by questionnaire. RESULTS: Data is presented
for n = 42 patients that completed the 16 week study follow-up and maintained
their weight within 5 lbs. of baseline. Independent photo review from three
blinded physicians found 91% correct identification of baseline clinical
photographs. Ultrasound data indicate fat layer reduction of 2.8 mm.
Circumferential measurements indicate mean reduction of 0.9 cm. Patient
questionnaires reveal 93% were satisfied with the CoolSculpting procedure; 84%
noticed visible fat reduction; 89% would recommend to a friend; and 91% were
likely to have a second treatment. There were no device- or procedure-related
serious adverse events. CONCLUSION: The CoolFit flat cup vacuum applicator was
found to deliver safe and effective cryolipolysis treatment to reduce inner thigh
fat. Completed 16-week data from 42 subjects show 2.8 mm reduction in fat
thickness and 0.9 cm reduction in circumference. Assessment of clinical
photographs found 91% correct identification of baseline images. The results of
this prospective, multi-center, interventional clinical study contributed to FDA
clearance of cryolipolysis for treatment of thighs in April 2014.
PMID- 25586978
TI - Disruptions in follicle cell functions in the ovaries of rhesus monkeys during
summer.
AB - Oocytes isolated from female rhesus monkeys following standard ovarian
stimulation protocols during the summer months displayed a reduced capacity to
mature compared with stimulation during the normal breeding season. Because the
gene expression profiles of oocyte-associated cumulus cells and mural granulosa
cells (CCs and GCs) are indicative of altered oocyte quality and can provide
insight into intrafollicular processes that may be disrupted during oogenesis, we
performed array-based transcriptome comparisons of CCs and GCs from summer and
normal breeding season stimulation cycles. Summer CCs and GCs both display
deficiencies in expression of mRNAs related to cell proliferation, angiogenesis,
and endocrine signaling, as well as reduced expression of glycogen phosphorylase.
Additionally, CCs display deficiencies in expression of mRNAs related to stress
response. These results provide the first insight into the specific molecular
pathways and processes that are disrupted in the follicles of rhesus macaque
females during the summer season. Some of the changes seen in summer GCs and CCs
have been reported in humans and in other model mammalian species. This suggests
that the seasonal effects seen in the rhesus monkey may help us to understand
better the mechanisms that contribute to reduced oocyte quality and fertility in
humans.
PMID- 25586981
TI - Detection of minimal residual disease in mantle cell lymphoma-establishment of
novel eight-color flow cytometry approach.
AB - BACKGROUND: Minimal residual disease (MRD) detection is an essential tool for
therapy response assessment in a considerable number of hematooncologic
disorders, including mantle cell lymphoma (MCL). Flow cytometry (FCM) ranks among
the most effective approaches, which allows rapid sample processing and compete
successfully with highly sensitive molecular methods like polymerase chain
reaction. Because FCM is ordinarily applied to detect MRD in B-lineage diseases
like chronic lymphocytic leukemia, a similar method could be used in MCL. We
decided to test our novel eight-color FCM approach in MCL MRD detection. METHODS:
Using an eight-color FCM protocol designed by us, the expression of 24 selected
surface antigens in a cohort of 30 patients with newly diagnosed leukemic MCL and
20 normal controls were compared to establish markers that can reliably
distinguish normal B-lymphocytes from the MCL population. The sensitivity of the
designed protocol was tested using serial dilution studies. RESULTS: Although MCL
presents high immunophenotypic variability, the combination of
CD20/23/5/19/200/62L/3/45 seems to be very favorable in flow cytometric MRD
measurement. CONCLUSIONS: Our eight-color FCM protocol could easily detect MRD in
MCL patients, and reaches a sensitivity of up to 2 * 10(-4) .
PMID- 25586982
TI - Non-work-related use of personal mobile phones by hospital registered nurses.
AB - BACKGROUND: Personal mobile phones and other personal communication devices
(smartphones and tablet computers) provide users with an ever-increasing number
and diversity of non-work-related activities while at work. In hospitals, where
the vigilance of health care workers is essential for patient care, the potential
distraction of these devices could be hazardous to patients. OBJECTIVE: The
objective of this study was to determine the frequency of non-work-related use of
personal mobile phones and other personal communication devices among hospital
registered nurses. METHODS: In March 2014, a previously validated 30-question
survey was emailed to the 10,978 members of the Academy of Medical Surgical
Nurses. There were 825 respondents who met the inclusion criteria. RESULTS: The
use of a personal mobile phone or other personal communication device while
working (excluding meal times and breaks) was reported by 78.1% (644/825) of
respondents. Nurses reported regularly (sometimes, often, or always) sending
personal emails and text messages (38.6%, 318/825), reading news (25.7%,
212/825), checking/posting on social networking sites (20.8%, 172/825), shopping
(9.6%, 79/825), and playing games (6.5%, 54/825) while working. CONCLUSIONS: This
study found that hospital nurses frequently use their personal mobile phones or
other personal communication devices for non-work-related activities at work. The
primary activity reported was to send personal emails and text messages to family
and friends.
PMID- 25586984
TI - Incorporating microarray assessment of HER2 status in clinical practice supports
individualised therapy in early-stage breast cancer.
AB - Accurate determination of human epidermal growth factor receptor-2 (HER2) status
is essential for optimal selection of breast cancer patients for gene targeted
therapy. The analytical performance of microarray analysis using TargetPrint for
assessment of HER2 status was evaluated in 138 breast tumours, including 41 fresh
and 97 formalin-fixed paraffin embedded (FFPE) specimens. Reflex testing using
immunohistochemistry/in situ hybridization (IHC/ISH) in four discordant cases
confirmed the TargetPrint results, achieving 100% agreement regardless of whether
fresh tissue or FFPE specimens were used. One equivocal IHC/ISH case was
classified as HER2-positive based on the microarray result. The proven clinical
utility in resolving equivocal and borderline cases justifies modification of the
testing algorithm under these circumstances, to obtain a definitive positive or
negative test result with the use of microarrays. Determination of HER2 status
across three assay platforms facilitated improved quality assurance and led to a
higher level of confidence on which to base treatment decisions.
PMID- 25586983
TI - Digital storytelling: an innovative legacy-making intervention for children with
cancer.
AB - BACKGROUND: This study examined the feasibility of a legacy-making intervention
in children with cancer and the preliminary effects on outcomes related to
quality of life. PROCEDURE: Children (N = 28) ages 7-17 years completed a
baseline QOL questionnaire (PedsQL) at T1. After baseline, the intervention group
(n = 15) completed a randomized intervention that guided children to answer
questions about legacy-making and create a digital story about themselves. A
final copy of the digital story was provided to the families. A control group (n
= 13) received customary care. Children repeated the questionnaire at T2. Parents
(N = 22) of children who completed the intervention completed follow-up survey
questions regarding intervention effects. RESULTS: Feasibility was strong (78%
participation; 1 attrition). While differences between the groups in physical,
emotional, social, or school functioning change was not statistically
significant, the intervention group showed slightly better emotional and school
functioning compared to controls. Parents reported that their child's digital
story provided emotional comfort to them (n = 11, 46%), facilitated communication
between parents and children (n = 9, 38%), and was a coping strategy for them (n
= 4, 17%). Parents reported that the intervention helped children express their
feelings (n = 19, 79%), cope (n = 6, 27%), and feel better emotionally (n = 5,
23%). CONCLUSIONS: Our intervention is feasible for children with cancer, is
developmentally appropriate for children 7-17 years of age, and demonstrates
promise to improve quality of life outcomes for children with cancer and their
parents.
PMID- 25586986
TI - Infection control: beyond the horizon.
AB - This article will consider possible future directions for innovation and research
in infection prevention and control, and will make the case for the importance of
including clinical and cost-effectiveness evaluation in such research.
Opportunities for studies in a number of broad subject areas will be considered,
including prevention and control of existing and emerging infection hazards, the
challenges posed by changes in the way that medical care is being delivered,
technological developments that could be harnessed for infection prevention and
control, how new laboratory diagnostic technologies might benefit infection
prevention and control, cleaning and decontamination, and the infection control
aspects of hospital design. The need for robust economic data to support the wide
and timely implementation of evidence-based practice is emphasized.
PMID- 25586987
TI - Sociocognitive predictors of the intention of healthcare workers to receive the
influenza vaccine in Belgian, Dutch and German hospital settings.
AB - BACKGROUND: Influenza vaccination of healthcare workers (HCWs) is recommended to
prevent the transmission of influenza to vulnerable patients. Nevertheless,
vaccination coverage rates of HCWs in European countries have been low. AIM: To
investigate the relative and combined strength of sociocognitive variables, from
past research, theory and a qualitative study, in explaining the motivation of
HCWs to receive the influenza vaccine. METHODS: An anonymous, online
questionnaire was distributed among HCWs in hospital settings in Belgium, Germany
and the Netherlands between February and April 2013. FINDINGS: Attitude and past
vaccination uptake explained a considerable amount of variance in the intention
of HCWs to receive the influenza vaccine. Moreover, low perceived social norms,
omission bias, low moral norms, being older, having no patient contact, and being
Belgian or Dutch (compared with German) increased the probability of having no
intention to receive the influenza vaccine compared with being undecided about
vaccination. High intention to receive the influenza vaccine was shown to be more
likely than being undecided about vaccination when HCWs had high perceived
susceptibility of contracting influenza, low naturalistic views, and lower
motivation to receive the vaccine solely for self-protection. CONCLUSION: Country
specific interventions and a focus on different sociocognitive variables
depending on the intention/lack of intention of HCWs to receive the influenza
vaccine may be beneficial to promote vaccination uptake.
PMID- 25586988
TI - Comparison of different hand-drying methods: the potential for airborne microbe
dispersal and contamination.
AB - Efficient washing and drying of hands is important in prevention of the transfer
of micro-organisms. However, knowledge surrounding the potential for microbial
contamination according to hand-drying methods is limited. This study assessed
the potential for airborne microbe dispersal during hand drying by four methods
(paper towels, roller towel, warm air and jet air dryer) using three different
models. The jet air dryer dispersed liquid from users' hands further and over a
greater range (up to 1.5m) than the other drying methods (up to 0.75 m),
demonstrating the differing potential risks for airborne microbe dissemination,
particularly if handwashing is suboptimal.
PMID- 25586989
TI - Letter to the editor: An intriguing relationship between lipid droplets,
cholesterol-binding protein CD133 and Wnt/beta-catenin signaling pathway in
carcinogenesis.
PMID- 25586990
TI - Successful rapid desensitization to the antibody-drug conjugate brentuximab
vedotin in a patient with refractory Hodgkin lymphoma.
PMID- 25586991
TI - TRIB2 as a biomarker for diagnosis and progression of melanoma.
AB - Malignant melanoma is the most deadly form of skin cancer. There is a critical
need to identify the patients that could be successfully treated by surgery alone
and those that require adjuvant treatment. In this study, we demonstrate that the
expression of tribbles2 (TRIB2) strongly correlates with both the presence and
progression of melanocyte-derived malignancies. We examined the expression of
TRIB2 in addition to 12 previously described melanoma biomarkers across three
independent full genome microarray studies. TRIB2 expression was consistently and
significantly increased in benign nevi and melanoma, and was highest in samples
from patients with metastatic melanoma. The expression profiles for the 12
biomarkers were poorly conserved throughout these studies with only TYR, S100B
and SPP1 showing consistently elevated expression in metastatic melanoma versus
normal skin. Strikingly we confirmed these findings in 20 freshly obtained
primary melanoma tissue samples from metastatic lesions where the expression of
these biomarkers were evaluated revealing that TRIB2 expression correlated with
disease stage and clinical prognosis. Our results suggest that TRIB2 is a
meaningful biomarker reflecting diagnosis and progression of melanoma, as well as
predicting clinical response to chemotherapy.
PMID- 25586994
TI - Response to: Letter to the editor by C Benn, A Fisker and P Aaby.
PMID- 25586993
TI - Brain-derived neurotrophic factor deficiency restricts proliferation of
oligodendrocyte progenitors following cuprizone-induced demyelination.
AB - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2
(TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in
oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well
understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice
following cuprizone-elicited demyelination. Here, we investigate whether these
blunted increases in OPCs are associated with changes in proliferation. BDNF+/+
and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects
on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRalpha)+ or
NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine
(EdU) was injected intraperitoneally and colocalized with PDGFRalpha+ cells.
Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with
PDGFRalpha or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/-
animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers
of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also
were not significantly different, suggesting that neither the DNA synthesis phase
(S phase) nor the proliferative pool size was different between genotypes. In
contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in
OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference
in elevations in cell number was accompanied by decreases in EdU labeling and
PCNA labeling without changes in cell death, indicating a reduction in the DNA
synthesis and the proliferative pool. Therefore, levels of BDNF influence the
proliferation of OPCs resulting from a demyelinating lesion.
PMID- 25586995
TI - Effect on child cognitive function of increasing household expenditure in
Indonesia: application of a marginal structural model and simulation of a cash
transfer programme.
AB - BACKGROUND: Parental investments in children are an important determinant of
human capability formation. We investigated the causal effect of household
expenditure on Indonesian children's cognitive function between 2000 and 2007. We
also investigated the effect of change in mean cognitive function from a
simulation of a hypothetical cash transfer intervention. METHODS: A longitudinal
analysis using data from the Indonesian Family Life Survey (IFLS) was conducted
including 6136 children aged 7 to 14 years in 2000 and still alive in 2007. We
used the inverse probability of treatment weighting of a marginal structural
model to estimate the causal effect of household expenditure on children's
cognitive function. RESULTS: Cumulative household expenditure was positively
associated with cognitive function z-score. From the marginal structural model, a
74534 rupiah/month (about US$9) increase in household expenditure resulted in a
0.03 increase in cognitive function z-score [beta=0.32, 95% confidence interval
(CI) 0.30-0.35] Based on our simulations, among children in the poorest
households in 2000 an additional ~ US$6-10 of cash transfer resulted in a 0.01
unit increase in cognitive function z-score, equivalent to about 6% increase from
the mean z-score prior to cash transfer. In contrast, children in the poorest
household in 2007 did not benefit from an additional ~ US$10 cash transfer. We
found no overall effect of cash transfers at the total population level.
CONCLUSIONS: Greater household expenditure had a small causal effect on
children's cognitive function. Although cash transfer interventions had a
positive effect for poor children, this effect was quite small. Multi-faceted
interventions that combine nutrition, cash transfer, improved living conditions
and women's education are required to benefit children's cognitive development in
Indonesia.
PMID- 25586999
TI - Description of an Automated Method for Urea Nitrogen Determination in
Bronchoalveolar Lavage Fluid (BALF) of Neonates and Infants.
AB - Bronchoalveolar lavage (BAL) partially recovers both the instilled saline and the
alveolar fluid, so-called epithelial lining fluid (ELF), but a correction for the
dilution due to the BAL technique itself is needed to know the amount of
recovered ELF. In this regard, urea nitrogen may be useful and has been proposed
to calculate ELF. The aim of the present study was to develop and validate a new
method to measure urea nitrogen in BAL fluid (BALF). We used 19 BALF samples
obtained from neonates and infants with different respiratory conditions. The
urea nitrogen assay was carried out on Cobas c311 analyzer (Roche Diagnostics). A
validation study shows that the method is perfectly linear (R(2) = 0.999),
sensitive (limit of detection = 0.055 mg/dL; limit of quantification = 0.16
mg/dL), repeatable (low = 0.15 +/- 0.02, 13.3%; high = 1.80 +/- 0.02, 1.1%),
reproducible (low = 0.14 +/- 0.02, 14.2 %; high = 1.76 +/- 0.04, 2.2 %) with
accuracy ranging between 93-96%. Our results support the robustness of validated
procedure since the described method appears simple, precise, rapid, and suitable
for routine analysis. Thus, it may be used to correct concentration of various
noncellular BAL components and calculate their ELF amounts in neonates and
infants.
PMID- 25587000
TI - An Overview on Prenatal Screening for Chromosomal Aberrations.
AB - This article is a review of current and emerging methods used for prenatal
detection of chromosomal aneuploidies. Chromosomal anomalies in the developing
fetus can occur in any pregnancy and lead to death prior to or shortly after
birth or to costly lifelong disabilities. Early detection of fetal chromosomal
aneuploidies, an atypical number of certain chromosomes, can help parents
evaluate their pregnancy options. Current diagnostic methods include maternal
serum sampling or nuchal translucency testing, which are minimally invasive
diagnostics, but lack sensitivity and specificity. The gold standard,
karyotyping, requires amniocentesis or chorionic villus sampling, which are
highly invasive and can cause abortions. In addition, many of these methods have
long turnaround times, which can cause anxiety in mothers. Next-generation
sequencing of fetal DNA in maternal blood enables minimally invasive, sensitive,
and reasonably rapid analysis of fetal chromosomal anomalies and can be of
clinical utility to parents. This review covers traditional methods and next
generation sequencing techniques for diagnosing aneuploidies in terms of clinical
utility, technological characteristics, and market potential.
PMID- 25587001
TI - The clinical pattern of diabetes Insipidus in a large university hospital in the
Middle East.
AB - Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients
were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi
Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of
high serum osmolality, hypernatremia and low urine osmolality due to increased
urine output confirmed the diagnosis. Water deprivation test was required in some
cases with non-classic presentations. Appropriate brain imaging was performed
whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients,
15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were
included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7%
(17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic
diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was
due to variable aetiology. Though CDI was the commonest, NDI was not a rare
encounter in our community, possibly because of high consanguineous marriages.
PMID- 25586998
TI - TEER measurement techniques for in vitro barrier model systems.
AB - Transepithelial/transendothelial electrical resistance (TEER) is a widely
accepted quantitative technique to measure the integrity of tight junction
dynamics in cell culture models of endothelial and epithelial monolayers. TEER
values are strong indicators of the integrity of the cellular barriers before
they are evaluated for transport of drugs or chemicals. TEER measurements can be
performed in real time without cell damage and generally are based on measuring
ohmic resistance or measuring impedance across a wide spectrum of frequencies.
The measurements for various cell types have been reported with commercially
available measurement systems and also with custom-built microfluidic
implementations. Some of the barrier models that have been widely characterized
using TEER include the blood-brain barrier (BBB), gastrointestinal (GI) tract,
and pulmonary models. Variations in these values can arise due to factors such as
temperature, medium formulation, and passage number of cells. The aim of this
article is to review the different TEER measurement techniques and analyze their
strengths and weaknesses, determine the significance of TEER in drug toxicity
studies, examine the various in vitro models and microfluidic organs-on-chips
implementations using TEER measurements in some widely studied barrier models
(BBB, GI tract, and pulmonary), and discuss the various factors that can affect
TEER measurements.
PMID- 25586992
TI - Inherited variants in the inner centromere protein (INCENP) gene of the
chromosomal passenger complex contribute to the susceptibility of ER-negative
breast cancer.
AB - The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of
cell division. Therefore, inherited CPC variability could influence tumor
development. The present candidate gene approach investigates the relationship
between single nucleotide polymorphisms (SNPs) in genes encoding key CPC
components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB,
BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control
studies of the Breast Cancer Association Consortium. Possible associations were
investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon
7 of INCENP was associated with overall breast cancer risk [per A allele odds
ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and
particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR
0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed
based on 1000 Genomes. The SNPs rs1047739 in the 3' untranslated region and
rs144045115 downstream of INCENP showed the strongest association signals for
overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative
breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two
genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP
rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest
that INCENP in the CPC pathway contributes to ER-negative breast cancer
susceptibility in the European population. In spite of a modest contribution of
CPC-inherited variants to the total burden of sporadic and familial breast
cancer, their potential as novel targets for breast cancer treatment should be
further investigated.
PMID- 25587004
TI - Efficacy of jollab in the treatment of depression in dyspeptic patients: a
randomized double-blind controlled trial.
AB - The current study aimed to evaluate the efficacy of jollab, a well-known beverage
from traditional Persian medicine in the treatment of depression among patients
suffering from functional dyspepsia. In a randomized, double-blind, placebo
controlled trial, a pair of 80 patients were enrolled in 2 parallel groups as
Jollab and placebo. The Beck Depression Inventory-II questionnaire was used for
the assessment. At all, 133 patients enrolling in the treatment and placebo
groups ended the protocol. According to the outcomes, changes in scores between
the 2 groups were statistically significant at the end of trial (P <= .001).
Taken as a whole, treatment group was significantly more effective than the
placebo. Focusing on nutritional and pharmaceutical properties, jollab may be
introduced not only as a medication for depression and allied ailment but also a
pleasant daily drink.
PMID- 25587003
TI - MET1 is a thylakoid-associated TPR protein involved in photosystem II
supercomplex formation and repair in Arabidopsis.
AB - Photosystem II (PSII) requires constant disassembly and reassembly to accommodate
replacement of the D1 protein. Here, we characterize Arabidopsis thaliana MET1, a
PSII assembly factor with PDZ and TPR domains. The maize (Zea mays) MET1 homolog
is enriched in mesophyll chloroplasts compared with bundle sheath chloroplasts,
and MET1 mRNA and protein levels increase during leaf development concomitant
with the thylakoid machinery. MET1 is conserved in C3 and C4 plants and green
algae but is not found in prokaryotes. Arabidopsis MET1 is a peripheral thylakoid
protein enriched in stroma lamellae and is also present in grana. Split-ubiquitin
assays and coimmunoprecipitations showed interaction of MET1 with stromal loops
of PSII core components CP43 and CP47. From native gels, we inferred that MET1
associates with PSII subcomplexes formed during the PSII repair cycle. When grown
under fluctuating light intensities, the Arabidopsis MET1 null mutant (met1)
showed conditional reduced growth, near complete blockage in PSII supercomplex
formation, and concomitant increase of unassembled CP43. Growth of met1 in high
light resulted in loss of PSII supercomplexes and accelerated D1 degradation. We
propose that MET1 functions as a CP43/CP47 chaperone on the stromal side of the
membrane during PSII assembly and repair. This function is consistent with the
observed differential MET1 accumulation across dimorphic maize chloroplasts.
PMID- 25587002
TI - Transposition of a rice Mutator-like element in the yeast Saccharomyces
cerevisiae.
AB - Mutator-like transposable elements (MULEs) are widespread in plants and are well
known for their high transposition activity as well as their ability to duplicate
and amplify host gene fragments. Despite their abundance and importance, few
active MULEs have been identified. In this study, we demonstrated that a rice
(Oryza sativa) MULE, Os3378, is capable of excising and reinserting in yeast
(Saccharomyces cerevisiae), suggesting that yeast harbors all the host factors
for the transposition of MULEs. The transposition activity induced by the wild
type transposase is low but can be altered by modification of the transposase
sequence, including deletion, fusion, and substitution. Particularly, fusion of a
fluorescent protein to the transposase enhanced the transposition activity,
representing another approach to manipulate transposases. Moreover, we identified
a critical region in the transposase where the net charge of the amino acids
seems to be important for activity. Finally, transposition efficiency is also
influenced by the element and its flanking sequences (i.e., small elements are
more competent than their large counterparts). Perfect target site duplication is
favorable, but not required, for precise excision. In addition to the potential
application in functional genomics, this study provides the foundation for
further studies of the transposition mechanism of MULEs.
PMID- 25587005
TI - Severe maternal morbidity associated with maternal birthplace in three high
immigration settings.
AB - BACKGROUND: Maternal mortality and morbidity vary substantially worldwide. It is
unknown if these geographic differences translate into disparities in severe
maternal morbidity among immigrants from various world regions. We assessed
disparities in severe maternal morbidity between immigrant women from various
world regions giving birth in three high-immigration countries. METHODS: We used
population-based delivery data from Victoria; Australia and Ontario, Canada and
national data from Denmark, in the most recent 10-year period ending in 2010
available to each participating centre. Each centre provided aggregate data
according to standardized definitions of the outcome, maternal regions of birth
and covariates for pooled analyses. We used random effects and stratified
logistic regression to obtain odds ratios (ORs) with 95% confidence intervals
(95% CIs), adjusted for maternal age, parity and comparability scores. RESULTS:
We retrieved 2,322,907 deliveries in all three receiving countries, of which
479,986 (21%) were to immigrant women. Compared with non-immigrants, only Sub
Saharan African women were consistently at higher risk of severe maternal
morbidity in all three receiving countries (pooled adjusted OR: 1.67; 95% CI:
1.43, 1.95). In contrast, both Western and Eastern European immigrants had lower
odds (OR: 0.82; 95% CI: 0.70, 0.96 and OR: 0.64; 95% CI: 0.49, 0.83,
respectively). The most common diagnosis was severe pre-eclampsia followed by
uterine rupture, which was more common among Sub-Saharan Africans in all three
settings. CONCLUSIONS: Immigrant women from Sub-Saharan Africa have higher rates
of severe maternal morbidity. Other immigrant groups had similar or lower rates
than the majority locally born populations.
PMID- 25587006
TI - A case of intestinal duplication.
PMID- 25587007
TI - Nutrition rehabilitation in the intensive care unit.
AB - The maintenance of homeostasis after severe injury requires the restoration of
the physiological regulation of food intake. A wide array of functional
alterations can hinder the intake of adequate amounts of nutrients to support the
recovery from critical illness. These alterations encompass changes in the
preprandial phase, reflected by a loss of appetite; changes in the prandial
phase, yielding swallowing disorders; and changes in the postprandial phase,
including impairments of gastric emptying, gut motility, and satiety. This
tutorial aims to review these often overlooked features and to suggest
recommendations for the nutrition rehabilitation of the critically ill.
PMID- 25587008
TI - One-Step Insertion of Low-Profile Gastrostomy in Pediatric Patients vs Pull
Percutaneous Endoscopic Gastrostomy: Retrospective Analysis of Outcomes.
AB - BACKGROUND: Standard care for initiation of enteral feeding in children has been
pull percutaneous endoscopic gastrostomy (pull-PEG). As an alternative to pull
PEG, a 1-step endoscopic procedure for inserting a low-profile gastrostomy tube
"button" has been developed that allows initial placement of a balloon-retained
device. This report presents outcomes of metrics used to compare button placement
with pull-PEG in a pediatric population. METHODS: Data were generated from
procedural experiences of surgeons on pediatric patients (n = 374) with a variety
of clinical indications for gastrostomy. Study population ages ranged from 6 days
to 16 years, while weights were from 2-84 kg. RESULTS: The button was
successfully placed by the 1-step procedure in 98% of the respective study
population, and median procedural times were 20 and 15 minutes for button and
pull-PEG placements, respectively. Median times to first feeds were equivalent
for the 1-step procedure and pull-PEG (6 hours), while times to first nutrition
feeds were 12.5 and 10 hours, respectively. Stoma site complications within each
study group were similar. Healthy stoma proportions were 65.2% and 73.2% in the 1
step procedure and pull-PEG groups, respectively, at first follow-up.
CONCLUSIONS: Similar study outcomes between the 1-step procedure and pull-PEG
groups suggest that the former is a feasible alternative to pull-PEG for initial
tube placement in children. The 1-step method involves a single procedure and
reduces patient exposure to anesthesia, operating room time, and the potential
for complications compared with a pull-PEG requirement for multiple procedures.
PMID- 25587009
TI - Taurine Concentrations Decrease in Critically Ill Patients With Shock Given
Enteral Nutrition.
AB - BACKGROUND: Nutrition studies in the intensive care unit (ICU) have shown that
adequate enteral nutrition (EN) support has clinical benefits. However, the
course of amino acid concentrations in plasma has never been investigated in
patients admitted with shock receiving EN. We hypothesized that plasma
concentrations, when deficit, increase during EN and that persistent deficiency
is associated with poor outcome. METHODS: In 33 septic or cardiogenic shock
patients receiving EN, plasma amino acid concentrations were measured during 5
days. Changes in amino acid concentrations, correlations with clinical outcome
variables, and regression analyses were studied. RESULTS: On ICU admission,
several plasma concentrations were deficient. Plasma concentrations of almost all
amino acids increased. In contrast, taurine decreased by >50%, from 47.6 umol/L
on admission to 20.0 umol/L at day 1, and remained low at day 5. Taurine
(admission) correlated with time on mechanical ventilation (R = -0.42, P = .015).
Taurine decrease within 24 hours correlated with Acute Physiology and Chronic
Health Evaluation II predicted mortality (R = 0.43, P = .017) and Sequential
Organ Failure Assessment score (R = 0.36, P = .05). Regression analyses confirmed
correlations. CONCLUSIONS: Several amino acids were deficient in plasma on ICU
admission but increased during EN. Taurine concentrations declined and were
associated with longer periods of mechanical ventilation and ICU support. Fast
taurine decline correlated with severity of organ failure. These findings support
the role of taurine during ischemia, reperfusion, and inflammation. Taurine may
be an essential candidate to enrich nutrition support for critically ill
patients, although more research is required.
PMID- 25587010
TI - Genomic avenue to avian colisepticemia.
AB - Here we present an extensive genomic and genetic analysis of Escherichia coli
strains of serotype O78 that represent the major cause of avian colisepticemia,
an invasive infection caused by avian pathogenic Escherichia coli (APEC) strains.
It is associated with high mortality and morbidity, resulting in significant
economic consequences for the poultry industry. To understand the genetic basis
of the virulence of avian septicemic E. coli, we sequenced the entire genome of a
clinical isolate of serotype O78-O78:H19 ST88 isolate 789 (O78-9)-and compared it
with three publicly available APEC O78 sequences and one complete genome of APEC
serotype O1 strain. Although there was a large variability in genome content
between the APEC strains, several genes were conserved, which are potentially
critical for colisepticemia. Some of these genes are present in multiple copies
per genome or code for gene products with overlapping function, signifying their
importance. A systematic deletion of each of these virulence-related genes
identified three systems that are conserved in all septicemic strains examined
and are critical for serum survival, a prerequisite for septicemia. These are the
plasmid-encoded protein, the defective ETT2 (E. coli type 3 secretion system 2)
type 3 secretion system ETT2sepsis, and iron uptake systems. Strain O78-9 is the
only APEC O78 strain that also carried the regulon coding for yersiniabactin, the
iron binding system of the Yersinia high-pathogenicity island. Interestingly,
this system is the only one that cannot be complemented by other iron uptake
systems under iron limitation and in serum. IMPORTANCE: Avian colisepticemia is a
severe systemic disease of birds causing high morbidity and mortality and
resulting in severe economic losses. The bacteria associated with avian
colisepticemia are highly antibiotic resistant, making antibiotic treatment
ineffective, and there is no effective vaccine due to the multitude of serotypes
involved. To understand the disease and work out strategies to combat it, we
performed an extensive genomic and genetic analysis of Escherichia coli strains
of serotype O78, the major cause of the disease. We identified several potential
virulence factors, conserved in all the colisepticemic strains examined, and
determined their contribution to growth in serum, an absolute requirement for
septicemia. These findings raise the possibility that specific vaccines or drugs
can be developed against these critical virulence factors to help combat this
economically important disease.
PMID- 25587011
TI - An intracellular nanotrap redirects proteins and organelles in live bacteria.
AB - Owing to their small size and enhanced stability, nanobodies derived from
camelids have previously been used for the construction of intracellular
"nanotraps," which enable redirection and manipulation of green fluorescent
protein (GFP)-tagged targets within living plant and animal cells. By taking
advantage of intracellular compartmentalization in the magnetic bacterium
Magnetospirillum gryphiswaldense, we demonstrate that proteins and even entire
organelles can be retargeted also within prokaryotic cells by versatile nanotrap
technology. Expression of multivalent GFP-binding nanobodies on magnetosomes
ectopically recruited the chemotaxis protein CheW1-GFP from polar chemoreceptor
clusters to the midcell, resulting in a gradual knockdown of aerotaxis.
Conversely, entire magnetosome chains could be redirected from the midcell and
tethered to one of the cell poles. Similar approaches could potentially be used
for building synthetic cellular structures and targeted protein knockdowns in
other bacteria. IMPORTANCE: Intrabodies are commonly used in eukaryotic systems
for intracellular analysis and manipulation of proteins within distinct
subcellular compartments. In particular, so-called nanobodies have great
potential for synthetic biology approaches because they can be expressed easily
in heterologous hosts and actively interact with intracellular targets, for
instance, by the construction of intracellular "nanotraps" in living animal and
plant cells. Although prokaryotic cells also exhibit a considerable degree of
intracellular organization, there are few tools available equivalent to the well
established methods used in eukaryotes. Here, we demonstrate the ectopic
retargeting and depletion of polar membrane proteins and entire organelles to
distinct compartments in a magnetotactic bacterium, resulting in a gradual
knockdown of magneto-aerotaxis. This intracellular nanotrap approach has the
potential to be applied in other bacteria for building synthetic cellular
structures, manipulating protein function, and creating gradual targeted
knockdowns. Our findings provide a proof of principle for the universal use of
fluorescently tagged proteins as targets for nanotraps to fulfill these tasks.
PMID- 25587012
TI - Comparative genomics suggests primary homothallism of Pneumocystis species.
AB - Pneumocystis species are fungal parasites of mammal lungs showing host
specificity. Pneumocystis jirovecii colonizes humans and causes severe pneumonia
in immunosuppressed individuals. In the absence of in vitro cultures, the life
cycle of these fungi remains poorly known. Sexual reproduction probably occurs,
but the system of this process and the mating type (MAT) genes involved are not
characterized. In the present study, we used comparative genomics to investigate
the issue in P. jirovecii and Pneumocystis carinii, the species infecting rats,
as well as in their relative Taphrina deformans. We searched sex-related genes
using 103 sequences from the relative Schizosaccharomyces pombe as queries. Genes
homologous to several sex-related role categories were identified in all species
investigated, further supporting sexuality in these organisms. Extensive in
silico searches identified only three putative MAT genes in each species
investigated (matMc, matMi, and matPi). In P. jirovecii, these genes clustered on
the same contig, proving their contiguity in the genome. This organization seems
compatible neither with heterothallism, because two different MAT loci on
separate DNA molecules would have been detected, nor with secondary homothallism,
because the latter involves generally more MAT genes. Consistently, we did not
detect cis-acting sequences for mating type switching in secondary homothallism,
and PCR revealed identical MAT genes in P. jirovecii isolates from six patients.
A strong synteny of the genomic region surrounding the putative MAT genes exists
between the two Pneumocystis species. Our results suggest the hypothesis that
primary homothallism is the system of reproduction of Pneumocystis species and T.
deformans. IMPORTANCE: Sexual reproduction among fungi can involve a single
partner (homothallism) or two compatible partners (heterothallism). We
investigated the issue in three pathogenic fungal relatives: Pneumocystis
jirovecii, which causes severe pneumonia in immunocompromised humans;
Pneumocystis carinii, which infects rats; and the plant pathogen Taphrina
deformans. The nature, the number, and the organization within the genome of the
genes involved in sexual reproduction were determined. The three species appeared
to harbor a single genomic region gathering only three genes involved in sexual
differentiation, an organization which is compatible with sexual reproduction
involving a single partner. These findings illuminate the strategy adopted by
fungal pathogens to infect their hosts.
PMID- 25587013
TI - Reversible antibiotic tolerance induced in Staphylococcus aureus by concurrent
drug exposure.
AB - Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to
increasing use of the glycopeptide antibiotic vancomycin as a life-saving
treatment for major S. aureus infections. Coinfection by an unrelated bacterial
species may necessitate concurrent treatment with a second antibiotic that
targets the coinfecting pathogen. While investigating factors that affect
bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus
to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide
antimicrobial employed to treat infections by Gram-negative pathogens. We show
that colistin-induced vancomycin tolerance persists only as long as the inducer
is present and is accompanied by gene expression changes similar to those
resulting from mutations that produce stably inherited reduction of vancomycin
sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin
induced vancomycin tolerance is reversible, it may not be detected by routine
sensitivity testing and may be responsible for treatment failure at vancomycin
doses expected to be clinically effective based on such routine testing.
IMPORTANCE: Commonly, antibiotic resistance is associated with permanent genetic
changes, such as point mutations or acquisition of resistance genes. We show that
phenotypic resistance can arise where changes in gene expression result in
tolerance to an antibiotic without any accompanying genetic changes.
Specifically, methicillin-resistant Staphylococcus aureus (MRSA) behaves like
vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is
currently used against infections by Gram-negative bacteria. Vancomycin is a last
resort drug for treatment of serious S. aureus infections, and VISA is associated
with poor clinical prognosis. Phenotypic and reversible resistance will not be
revealed by standard susceptibility testing and may underlie treatment failure.
PMID- 25587015
TI - Erratum for kang et Al., flexibility and symmetry of prokaryotic genome
rearrangement reveal lineage-associated core-gene-defined genome organizational
frameworks.
PMID- 25587014
TI - Inactivation of a foodborne norovirus outbreak strain with nonthermal atmospheric
pressure plasma.
AB - Human norovirus (NoV) is the most frequent cause of epidemic nonbacterial acute
gastroenteritis worldwide. We investigated the impact of nonthermal or cold
atmospheric pressure plasma (CAPP) on the inactivation of a clinical human
outbreak NoV, GII.4. Three different dilutions of a NoV-positive stool sample
were prepared and subsequently treated with CAPP for various lengths of time, up
to 15 min. NoV viral loads were quantified by quantitative real-time reverse
transcription PCR (RT-qPCR). Increased CAPP treatment time led to increased NoV
reduction; samples treated for the longest time had the lowest viral load. From
the initial starting quantity of 2.36 * 10(4) genomic equivalents/ml, sample
exposure to CAPP reduced this value by 1.23 log10 and 1.69 log10 genomic
equivalents/ml after 10 and 15 min, respectively (P < 0.01). CAPP treatment of
surfaces carrying a lower viral load reduced NoV by at least 1 log10 after CAPP
exposure for 2 min (P < 0.05) and 1 min (P < 0.05), respectively. Our results
suggest that NoV can be inactivated by CAPP treatment. The lack of cell culture
assays prevents our ability to estimate infectivity. It is possible that some
detectable, intact virus particles were rendered noninfectious. We conclude that
CAPP treatment of surfaces may be a useful strategy to reduce the risk of NoV
transmission in crowded environments. IMPORTANCE: Human gastroenteritis is most
frequently caused by noroviruses, which are spread person to person and via
surfaces, often in facilities with crowds of people. Disinfection of surfaces
that come into contact with infected humans is critical for the prevention of
cross-contamination and further transmission of the virus. However, effective
disinfection cannot be done easily in mass catering environments or health care
facilities. We evaluated the efficacy of cold atmospheric pressure plasma, an
innovative airborne disinfection method, on surfaces inoculated with norovirus.
We used a clinically relevant strain of norovirus from an outbreak in Germany.
Cold plasma was able to inactivate the virus on the tested surfaces, suggesting
that this method could be used for continuous disinfection of contaminated
surfaces. The use of a clinical strain of norovirus strengthens the reliability
of our results as it is a strain relevant to outbreaks in humans.
PMID- 25587016
TI - The Ordospora colligata genome: Evolution of extreme reduction in microsporidia
and host-to-parasite horizontal gene transfer.
AB - Microsporidia are a group of obligate intracellular parasites that are best known
for their unique infection mechanism and their unparalleled levels of genomic
reduction and compaction. We sequenced the genome of Ordospora colligata, a gut
parasite of the microcrustacean Daphnia sp. and the closest known relative to the
microsporidia characterized by the most extreme genomic reduction, the model
genus Encephalitozoon. We found that the O. colligata genome is as compact as
those of Encephalitozoon spp., featuring few introns and a similar complement of
about 2,000 genes, altogether showing that the extreme reduction took place
before the origin of Encephalitozoon spp. and their adaptation to vertebrate
hosts. We also found that the O. colligata genome has acquired by horizontal
transfer from its animal host a septin that is structurally analogous to septin
7, a protein that plays a major role in the endocytosis-based invasion mechanism
of the fungal pathogen Candida albicans. Microsporidian invasion is most often
characterized by injection through a projectile tube, but microsporidia are also
known to invade cells by inducing endocytosis. Given the function of septins in
other systems, we hypothesize that the acquired septin could help O. colligata
induce its uptake by mimicking host receptors. IMPORTANCE: The smallest known
eukaryotic genomes are found in members of the Encephalitozoon genus of
microsporidian parasites. Their extreme compaction, however, is not
characteristic of the group, whose genomes can differ by an order of magnitude.
The processes and evolutionary forces that led the Encephalitozoon genomes to
shed so much of their ancestral baggage are unclear. We sequenced the genome of
Ordospora colligata, a parasite of the water flea Daphnia sp. and the closest
known relative of Encephalitozoon species, and show that this extreme reduction
predated the split between the two lineages. We also found that O. colligata has
acquired a septin gene by host-to-parasite horizontal transfer and predicted that
the encoded protein folds like a septin 7, which plays a major role in
endocytosis. We hypothesize that this acquisition could help O. colligata
parasitize its hosts by facilitating endocytic infection, a mechanism that occurs
in microsporidia but that is not yet well understood.
PMID- 25587017
TI - Can a novel clinical risk score improve pneumonia prediction in acute stroke
care? A UK multicenter cohort study.
AB - BACKGROUND: Pneumonia frequently complicates stroke and has a major impact on
outcome. We derived and internally validated a simple clinical risk score for
predicting stroke-associated pneumonia (SAP), and compared the performance with
an existing score (A(2)DS(2)). METHODS AND RESULTS: We extracted data for
patients with ischemic stroke or intracerebral hemorrhage from the Sentinel
Stroke National Audit Programme multicenter UK registry. The data were randomly
allocated into derivation (n=11 551) and validation (n=11 648) samples. A
multivariable logistic regression model was fitted to the derivation data to
predict SAP in the first 7 days of admission. The characteristics of the score
were evaluated using receiver operating characteristics (discrimination) and by
plotting predicted versus observed SAP frequency in deciles of risk
(calibration). Prevalence of SAP was 6.7% overall. The final 22-point score
(ISAN: prestroke Independence [modified Rankin scale], Sex, Age, National
Institutes of Health Stroke Scale) exhibited good discrimination in the ischemic
stroke derivation (C-statistic 0.79; 95% CI 0.77 to 0.81) and validation (C
statistic 0.78; 95% CI 0.76 to 0.80) samples. It was well calibrated in ischemic
stroke and was further classified into meaningful risk groups (low 0 to 5, medium
6 to 10, high 11 to 14, and very high >=15) associated with SAP frequencies of
1.6%, 4.9%, 12.6%, and 26.4%, respectively, in the validation sample.
Discrimination for both scores was similar, although they performed less well in
the intracerebral hemorrhage patients with an apparent ceiling effect.
CONCLUSIONS: The ISAN score is a simple tool for predicting SAP in clinical
practice. External validation is required in ischemic and hemorrhagic stroke
cohorts.
PMID- 25587018
TI - Persistent recovery of normal left ventricular function and dimension in
idiopathic dilated cardiomyopathy during long-term follow-up: does real healing
exist?
AB - BACKGROUND: An important number of patients with idiopathic dilated
cardiomyopathy have dramatically improved left ventricular function with optimal
treatment; however, little is known about the evolution and long-term outcome of
this subgroup, which shows apparent healing. This study assesses whether real
healing actually exists in dilated cardiomyopathy. METHODS AND RESULTS:
Persistent apparent healing was evaluated among 408 patients with dilated
cardiomyopathy receiving tailored medical treatment and followed over the very
long-term. Persistent apparent healing was defined as left ventricular ejection
fraction >=50% and indexed left ventricular end-diastolic diameter <=33 mm/m(2)
at both mid-term (19+/-4 months) and long-term (103+/-9 months) follow-up. At mid
term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9%of the whole
population) showed persistent apparent healing at long-term evaluation. No
predictors of persistent apparent healing were found. Patients with persistent
apparent healing showed better heart transplant-free survival at very long-term
follow-up (95% versus 71%; P=0.014) compared with nonpersistently normalized
patients. Nevertheless, in the very longterm, 37% of this subgroup experienced
deterioration of left ventricular systolic function, and 5% died or had heart
transplantation. CONCLUSIONS: Persistent long-term apparent healing was evident
in a remarkable proportion of dilated cardiomyopathy patients receiving optimal
medical treatment and was associated with stable normalization of main clinical
and laboratory features. This condition can be characterized by a decline of left
ventricular function over the very long term, highlighting the relevance of
serial nd individualized follow-up in all patients with dilated cardiomyopathy,
especially considering the absence of predictors for longterm apparent healing.
PMID- 25587019
TI - Weighing the risk of drug resistance with the benefits of HIV preexposure
prophylaxis.
PMID- 25587022
TI - Saphenous nerve injury after endovenous laser ablation of incompetent greater
saphenous vein: An electroneuromyography study.
AB - AIM: To determine whether endovenous laser ablation of incompetent greater
saphenous vein causes a detectable impairment in saphenous nerve conduction.
MATERIAL AND METHODS: Thirty-five patients (mean age: 44.78 +/- 8.6, male/female
ratio: 16/19) who were operated on for incompetent greater saphenous veins,
underwent electroneuromyography before and two weeks after the operation.
Dysesthesia was questioned as to whether having unpleasant abnormal sensation
after the operation. Positive electroneuromyography findings for saphenous nerve
injury included a sensory nerve action potential amplitude <2 uV or a nerve
conduction velocity <48.0 m/s or a latency onset >5.0 ms. RESULTS: Thirty-four
patients were available at two-week follow-up. All patients achieved complete
proximal closure. Three patients (8.8%) had dysesthesia at two weeks. Mean
electroneuromyography values were not significantly different between
preoperative and postoperative period. Postoperatively, none of the patients had
abnormal sensory nerve action potential or latency onset, whereas nerve
conduction velocity decreased below the lower limit in two patients. These two
patients were not among those having dysesthesia and they had no other
complaints. CONCLUSION: Injury to saphenous nerve seems not likely during
endovenous laser ablation of incompetent greater saphenous veins, as evidenced by
normal electroneuromyography values found after the operation.
PMID- 25587020
TI - Risk of drug resistance among persons acquiring HIV within a randomized clinical
trial of single- or dual-agent preexposure prophylaxis.
AB - BACKGROUND: Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir
disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human
immunodeficiency virus (HIV) acquisition. Understanding the risk of
antiretroviral resistance selected by PrEP during breakthrough infections is
important because of the risk of treatment failure during subsequent
antiretroviral use. METHODS: Within the largest randomized trial of FTC/TDF
versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations
associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454
sequencing. RESULTS: Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received
TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP
use during or after HIV acquisition, of which 5 had virus with resistance
mutations associated with their PrEP regimen. Among those with PrEP drug detected
during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]),
compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated
mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP
randomization, and 2 were HIV negative at enrollment. CONCLUSIONS: These results
suggest that resistance selected by PrEP is rare but can occur both with PrEP
initiation during acute seronegative HIV infection and in PrEP breakthrough
infections and that FTC is associated with a greater frequency of resistance
mutations than TDF.
PMID- 25587021
TI - Habitat visualization and genomic analysis of "Candidatus Pantoea carbekii," the
primary symbiont of the brown marmorated stink bug.
AB - Phytophagous pentatomid insects can negatively impact agricultural productivity
and the brown marmorated stink bug (Halyomorpha halys) is an emerging invasive
pest responsible for damage to many fruit crops and ornamental plants in North
America. Many phytophagous stink bugs, including H. halys, harbor
gammaproteobacterial symbionts that likely contribute to host development, and
characterization of symbiont transmission/acquisition and their contribution to
host fitness may offer alternative strategies for managing pest species.
"Candidatus Pantoea carbekii" is the primary occupant of gastric ceca lumina
flanking the distal midgut of H. halys insects and it is acquired each generation
when nymphs feed on maternal extrachorion secretions following hatching. Insects
prevented from symbiont uptake exhibit developmental delays and aberrant
behaviors. To infer contributions of Ca. P. carbekii to H. halys, the complete
genome was sequenced and annotated from a North American H. halys population.
Overall, the Ca. P. carbekii genome is nearly one-fourth (1.2 Mb) that of free
living congenerics, and retains genes encoding many functions that are
potentially host-supportive. Gene content reflects patterns of gene
loss/retention typical of intracellular mutualists of plant-feeding insects.
Electron and fluorescence in situ microscopic imaging of H. halys egg surfaces
revealed that maternal extrachorion secretions were populated with Ca. P.
carbekii cells. The reported findings detail a transgenerational mode of symbiont
transmission distinct from that observed for intracellular insect mutualists and
illustrate the potential additive functions contributed by the bacterial symbiont
to this important agricultural pest.
PMID- 25587023
TI - Hypoxia-inducible factor 1 mediates TAZ expression and nuclear localization to
induce the breast cancer stem cell phenotype.
AB - Intratumoral hypoxia, which is associated with breast cancer metastasis and
patient mortality, increases the percentage of breast cancer stem cells (BCSCs)
but the underlying molecular mechanisms have not been delineated. Here we report
that hypoxia-inducible factor 1 (HIF-1) triggers the expression and activity of
TAZ, a transcriptional co-activator that is required for BCSC maintenance,
through two discrete mechanisms. First, HIF-1 binds directly to the WWTR1 gene
and activates transcription of TAZ mRNA. Second, HIF-1 activates transcription of
the SIAH1 gene, which encodes a ubiquitin protein ligase that is required for the
hypoxia-induced ubiquitination and proteasome-dependent degradation of LATS2, a
kinase that inhibits the nuclear localization of TAZ. Inhibition of HIF-1alpha,
TAZ, or SIAH1 expression by short hairpin RNA blocked the enrichment of BCSCs in
response to hypoxia. Human breast cancer database analysis revealed that
increased expression (greater than the median) of both TAZ and HIF-1 target
genes, but neither one alone, is associated with significantly increased patient
mortality. Taken together, these results establish a molecular mechanism for
induction of the BCSC phenotype in response to hypoxia.
PMID- 25587024
TI - A unifying gene signature for adenoid cystic cancer identifies parallel MYB
dependent and MYB-independent therapeutic targets.
AB - MYB activation is proposed to underlie development of adenoid cystic cancer
(ACC), an aggressive salivary gland tumor with no effective systemic treatments.
To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of
12 ACC with matched normal tissues, and compared these data with 14
mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We
detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top
scoring gene (18-fold induction), however we observed the same signature in ACC
without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among
our 12 cases and 3 from public databases) with negligible MYB expression that
retained the same ACC mRNA signature including over-expression of extracellular
matrix (ECM) genes. Integration of this signature with somatic mutational
analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM
elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB
expression in human salivary gland cells alters cell morphology and cell adhesion
in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC
tumor culture. In summary, we identified a unique ACC signature with parallel MYB
dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a
potential target.
PMID- 25587025
TI - MYC regulates the non-coding transcriptome.
AB - Using RNA-seq (RNA sequencing) of ribosome-depleted RNA, we have identified 1,273
lncRNAs (long non-coding RNAs) in P493-6 human B-cells. Of these, 534 are either
up- or downregulated in response to MYC overexpression. An increase in MYC
occupancy near their TSS (transcription start sites) was observed for MYC
responsive lncRNAs suggesting these are direct MYC targets. MYC binds to the same
TSS across several cell lines, but the number of TSS bound depends on cellular
MYC levels and increases with higher MYC concentrations. Despite this concordance
in promoter binding, a majority of expressed lncRNAs are specific for one cell
line, suggesting a determinant role of additional, possibly differentiation
specific factors in the activity of MYC-bound lncRNA promoters. A significant
fraction of the lncRNA transcripts lack polyadenylation. The RNA-seq data were
confirmed on eight selected lncRNAs by NRO (nuclear run-on) and RT-qPCR
(quantitative reverse transcription PCR).
PMID- 25587026
TI - Neutrophils with protumor potential could efficiently suppress tumor growth after
cytokine priming and in presence of normal NK cells.
AB - In tumor-bearing state, the function of neutrophils is converted from tumor
suppressing to tumor-promoting. Here we report that priming with IFN-gamma and
TNF-alpha could convert the potential of neutrophils from tumor-promoting to
tumor-suppressing. The neutrophils with protumor potential have not lost their
responsiveness to IFN-gamma and TNF-alpha. After priming with IFN-gamma and TNF
alpha, the potential of the neutrophils to express Bv8 and Mmp9 genes was
reduced. Conversely, the tumor-promotional neutrophils recovered the expression
of Rab27a and Trail, resumed the activation levels of PI3K and p38 MAPK pathways
in response to stimuli, and expressed higher levels of IL-18 and NK-activating
ligands such as RAE-1, MULT-1, and H60. Therefore, the anti-tumor function of the
neutrophils was augmented, including the cytotoxicity to tumor cells, the
capability of degranulation, and the capacity to activate NK cells. Since the
function of NK cells is impaired in tumor-bearing state, the administration of
normal NK cells could significantly augment the efficiency of tumor therapy based
on neutrophil priming. These findings highlight the reversibility of neutrophil
function in tumor-bearing state, and suggest that neutrophil priming by IFN
gamma/TNF-alpha might be a potential approach to eliminate residual tumor cells
in comprehensive strategy for tumor therapy.
PMID- 25587027
TI - The p53 transcriptional pathway is preserved in ATMmutated and NOTCH1mutated
chronic lymphocytic leukemias.
AB - By using next generation sequencing, we have analyzed 108 B chronic lymphocytic
leukemia (B-CLL) patients. Among genes involved in the TP53 pathway, we found
frequent mutations in ATM (n=18), TP53 (n=10) and NOTCH1 (n=10) genes, rare
mutations of NOTCH2 (n=2) and CDKN1A/p21 (n=1) and no mutations in BAX, MDM2,
TNFRSF10A and TNFRSF10B genes. The in vitro treatment of primary B-CLL cells with
the activator of p53 Nutlin-3 induced the transcription of p53 target genes,
without significant differences between the B-CLL without mutations and those
harboring either ATM or NOTCH1mutations. On the other hand, the subgroup of
TP53mutated B-CLL exhibited a significantly lower induction of the p53 target
genes in response to Nutlin-3 as compared to the other B-CLL samples. However,
among the TP53mutated B-CLL, those showing mutations in the high hot spot region
of the DNA binding domain [273-280 aa] maintained a significantly higher p53
dependent transcriptional activity as compared to the other TP53mutated B-CLL
samples. Since the ability to elicit a p53-dependent transcriptional activity in
vitro has a positive prognostic significance, our data suggest that ATMmutated,
NOTCH1mutated and surprisingly, also a subset of TP53mutated B-CLL patients might
benefit from therapeutic combinations including small molecule activator of the
p53 pathway.
PMID- 25587028
TI - Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2
dependent glycolysis in melanoma.
AB - Reliance on glycolysis is a characteristic of malignancy, yet the development of
resistance to BRAF inhibitors in melanoma is associated with gain of
mitochondrial function. Concurrent attenuation of oxidative phosphorylation and
HIF-1alpha/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen
dependent cell death that we term ferroxitosis. The redox cycling agent menadione
causes a robust increase in oxygen consumption, accompanied by significant loss
of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation
or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of
K213Q HIF-1alpha mutant blunts the effects of menadione. However, knockdown of
HIF-1alpha or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly,
exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2
inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions.
Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity
in melanoma.
PMID- 25587029
TI - Mislocalization of p27 to the cytoplasm of breast cancer cells confers resistance
to anti-HER2 targeted therapy.
AB - As a cell cycle inhibitor and tumor suppressor, p27 is frequently misregulated in
human cancers. Increased degradation is the most common mechanism of
misregulation, however in some cancers, p27 is mislocalized from its cell cycle
inhibitory location in the nucleus, to the cytoplasm. In normal cells cytoplasmic
p27 has functions that are distinct from its cell cycle-regulatory nuclear
functions. Therefore, an important question is whether localization of p27 to the
cytoplasm in tumor cells is primarily a mechanism for cancelling its inhibitory
effect on cell proliferation, or whether cytoplasmic p27 has more direct
oncogenic actions. To study p27 mislocalization in human cancers we screened a
panel of common breast cancer cell lines. We observed that p27 accumulated in the
cytoplasm exclusively in cell lines that are Her2+. To address the significance
of p27 mislocalization in Her2+ breast cancer cells we interrogated the cellular
response to the dual-Her2/EGFR kinase inhibitor, lapatinib. Knockdown of p27
using shRNA sensitized Her2+ cells to lapatinib-induced apoptosis. Moreover,
expression of a constitutively cytoplasmic form of p27 (p27DeltaNLS) reversed the
lapatinib-induced apoptosis, suggesting that cytoplasmic p27 contributed to
lapatinib resistance in Her2+ breast cancer cells by suppressing apoptosis. Our
results suggest that p27 localization may be useful as a predictive biomarker of
therapeutic response in patients with Her2+ breast cancers.
PMID- 25587031
TI - The angular structure of ONC201, a TRAIL pathway-inducing compound, determines
its potent anti-cancer activity.
AB - We previously identified TRAIL-inducing compound 10 (TIC10), also known as
NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that
has potent anti-tumor efficacy and a benign safety profile in preclinical cancer
models. The chemical structure that was originally published by Stahle, et. al.
in the patent literature was described as an imidazo[1,2-a]pyrido[4,3
d]pyrimidine derivative. The NCI and others generally accepted this as the
correct structure, which was consistent with the mass spectrometry analysis
outlined in the publication by Allen et. al. that first reported the molecule's
anticancer properties. A recent publication demonstrated that the chemical
structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the
originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray
structural analysis of the dihydrochloride salt form that the ONC201 material
produced by Oncoceutics is the angular [3,4-e] structure and not the linear
structure originally depicted in the patent literature and by the NCI. Similarly,
in accordance with our biological evaluation, the previously disclosed anti
cancer activity is associated with the angular structure and not the linear
isomer. Together these studies confirm that ONC201, produced by Oncoceutics or
obtained from the NCI, possesses an angular [3,4-e] structure that represents the
highly active anti-cancer compound utilized in prior preclinical studies and now
entering clinical trials in advanced cancers.
PMID- 25587030
TI - Tumor promoter-induced cellular senescence: cell cycle arrest followed by
geroconversion.
AB - Phorbol ester (PMA or TPA), a tumor promoter, can cause either proliferation or
cell cycle arrest, depending on cellular context. For example, in SKBr3 breast
cancer cells, PMA hyper-activates the MEK/MAPK pathway, thus inducing p21 and
cell cycle arrest. Here we showed that PMA-induced arrest was followed by
conversion to cellular senescence (geroconversion). Geroconversion was associated
with active mTOR and S6 kinase (S6K). Rapamycin suppressed geroconversion,
maintaining quiescence instead. In this model, PMA induced arrest (step one of a
senescence program), whereas constitutively active mTOR drove geroconversion
(step two). Without affecting Akt phosphorylation, PMA increased phosphorylation
of S6K (T389) and S6 (S240/244), and that was completely prevented by rapamycin.
Yet, T421/S424 and S235/236 (p-S6K and p-S6, respectively) phosphorylation became
rapamycin-insensitive in the presence of PMA. Either MEK or mTOR was sufficient
to phosphorylate these PMA-induced rapamycin-resistant sites because co-treatment
with U0126 and rapamycin was required to abrogate them. We next tested whether
activation of rapamycin-insensitive pathways would shift quiescence towards
senescence. In HT-p21 cells, cell cycle arrest was caused by IPTG-inducible p21
and was spontaneously followed by mTOR-dependent geroconversion. Rapamycin
suppressed geroconversion, whereas PMA partially counteracted the effect of
rapamycin, revealing the involvement of rapamycin-insensitive gerogenic pathways.
In normal RPE cells arrested by serum withdrawal, the mTOR/pS6 pathway was
inhibited and cells remained quiescent. PMA transiently activated mTOR, enabling
partial geroconversion. We conclude that PMA can initiate a senescent program by
either inducing arrest or fostering geroconversion or both. Rapamycin can
decrease gero-conversion by PMA, without preventing PMA-induced arrest. The tumor
promoter PMA is a gero-promoter, which may be useful to study aging in mammals.
PMID- 25587032
TI - Peripheral primitive neuroectodermal tumor: dynamic CT, MRI and
clinicopathological characteristics--analysis of 36 cases and review of the
literature.
AB - BACKGROUND: The peripheral primitive neuroectodermal tumor (pPNET) is a rare
malignant tumor originating from neuroectoderm. The accurate diagnosis is
essential for the treatment of pPNET. METHODS: we performed the largest cases of
retrospective analysis thus far to review the unique computed tomography (CT),
magnetic resonance imaging (MRI), and clinicopathological features of pPNET. The
tumor location, morphological features, signal intensity, contrast enhancement
characteristics, and involvement of local soft tissues of 36 pPNETs were
assessed. RESULTS: Our results showed that there were more men (25/36) than women
pPNETs patients. Unenhanced MRI (16 cases) showed that 14 cases were isointense
and 2 cases were hypointense on T1WI. Nine cases were isointense and 7 were
hyperintense on T2WI. Most pPNETs had heterogeneous signal intensity with small
necrosis (CT: 31/36; MRI: 14/16) as well as heterogeneous enhancement (CT: 34/30;
MRI: 15/16). The tumors usually had ill-defined borders and irregular shapes (CT:
30/36; MRI: 15/16). Pathologic exam showed small areas of necrosis in all tumors.
CONCLUSIONS: The diagnosis of pPNET should be suggested in young men when the
imaging depicts a single large ill-defined solid mass with small area of
necrosis, especially for those whose images show iso-intense on T1WI and T2WI and
have heterogeneous enhancement.
PMID- 25587033
TI - Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its
binding affinity and specificity.
AB - Src homology 2 (SH2) domains are modular protein structures that bind
phosphotyrosine (pY)-containing polypeptides and regulate cellular functions
through protein-protein interactions. Proteomics analysis showed that the SH2
domains of Src family kinases are themselves tyrosine phosphorylated in blood
system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia,
and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we
found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the
affinity and specificity of SH2 domain binding to pY-containing peptides and
proteins. Analysis of the Lyn SH2 domain crystal structure supports a model
wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket
that engages amino acid side chains at the pY+2/+3 position. These data indicate
another level of regulation wherein SH2-mediated protein-protein interactions are
modulated by SH2 kinases and phosphatases.
PMID- 25587034
TI - Proteomic study of microsomal proteins reveals a key role for Arabidopsis annexin
1 in mediating heat stress-induced increase in intracellular calcium levels.
AB - To understand the early signaling steps in the response of plant cells to
increased environmental temperature, 2-D difference gel electrophoresis was used
to study the proteins in microsomes of Arabidopsis seedlings that are regulated
early during heat stress. Using mass spectrometry, 19 microsomal proteins that
showed an altered expression level within 5 min after heat treatment were
identified. Among these proteins, annexin 1 (AtANN1) was one of those up
regulated rapidly after heat-shock treatment. Functional studies show loss-of
function mutants for AtANN1 and its close homolog AtANN2 were more sensitive to
heat-shock treatment, whereas plants overexpressing AtANN1 showed more resistance
to this treatment. Correspondingly, the heat-induced expression of heat-shock
proteins and heat-shock factors is inhibited in ann1/ann2 double mutant, and the
heat-activated increase in cytoplasmic calcium concentration ([Ca(2+)]cyt) is
greatly impaired in the ann1 mutant and almost undetectable in ann1/ann2 double
mutant. Taken together these results suggest that AtANN1 is important in
regulating the heat-induced increase in [Ca(2+)]cyt and in the response of
Arabidopsis seedlings to heat stress.
PMID- 25587037
TI - How I treat relapsed myeloma.
AB - Multiple myeloma (MM) is a plasma cell malignancy leading to significant life
expectancy shortening. Although the incorporation of the novel agents
thalidomide, bortezomib, and lenalidomide in the front-line therapy has resulted
in significant improvement, almost all patients relapse, making the treatment of
relapse a real challenge. In the present article, when and how to treat relapsed
MM is discussed. Treatment can be safely delayed in a subset of patients with
asymptomatic relapse, whereas those with symptomatic relapse, advanced disease at
diagnosis, or significant paraproteinemic increase require prompt rescue therapy.
The benefit of retreatment and the use of a sequential approach for successive
relapses considering drug synergism are highlighted. For patients with aggressive
relapses and for those who have exhausted all available options, continued
therapy until disease progression is recommended, particularly when using
regimens with a long-term safety profile. Patients with a duration response to a
first autologous stem cell transplantation (ASCT) longer than 2 years may benefit
from a second ASCT. Patients with aggressive disease and/or poor cytogenetics at
diagnosis relapsing within the first 2 years from ASCT should be considered for
an allogeneic transplantation. Finally, a number of newer promising drugs are
being actively investigated and the enrolment of patients in clinical trials is
encouraged.
PMID- 25587035
TI - Elevated adenosine signaling via adenosine A2B receptor induces normal and sickle
erythrocyte sphingosine kinase 1 activity.
AB - Erythrocyte possesses high sphingosine kinase 1 (SphK1) activity and is the major
cell type supplying plasma sphingosine-1-phosphate, a signaling lipid regulating
multiple physiological and pathological functions. Recent studies revealed that
erythrocyte SphK1 activity is upregulated in sickle cell disease (SCD) and
contributes to sickling and disease progression. However, how erythrocyte SphK1
activity is regulated remains unknown. Here we report that adenosine induces
SphK1 activity in human and mouse sickle and normal erythrocytes in vitro. Next,
using 4 adenosine receptor-deficient mice and pharmacological approaches, we
determined that the A2B adenosine receptor (ADORA2B) is essential for adenosine
induced SphK1 activity in human and mouse normal and sickle erythrocytes in
vitro. Subsequently, we provide in vivo genetic evidence that adenosine deaminase
(ADA) deficiency leads to excess plasma adenosine and elevated erythrocyte SphK1
activity. Lowering adenosine by ADA enzyme therapy or genetic deletion of ADORA2B
significantly reduced excess adenosine-induced erythrocyte SphK1 activity in ADA
deficient mice. Finally, we revealed that protein kinase A-mediated extracellular
signal-regulated kinase 1/2 activation functioning downstream of ADORA2B
underlies adenosine-induced erythrocyte SphK1 activity. Overall, our findings
reveal a novel signaling network regulating erythrocyte SphK1 and highlight
innovative mechanisms regulating SphK1 activity in normal and SCD.
PMID- 25587038
TI - Interaction of kindlin-2 with integrin beta3 promotes outside-in signaling
responses by the alphaVbeta3 vitronectin receptor.
AB - The bidirectional signaling and hemostatic functions of platelet alphaIIbbeta3
are regulated by kindlin-3 through interactions with the beta3 cytoplasmic tail.
Little is known about kindlin regulation of the related "vitronectin receptor,"
alphaVbeta3. These relationships were investigated in endothelial cells, which
express alphaVbeta3 and kindlin-2 endogenously. "beta3DeltaRGT" knock-in mice
lack the 3 C-terminal beta3 tail residues, whereas in "beta3/beta1(EGK)" mice,
RGT is replaced by the corresponding residues of beta1. The wild-type beta3 tail
pulled down kindlin-2 and c-Src in vitro, whereas beta3DeltaRGT bound neither
protein and beta3/beta1(EGK) bound kindlin-2, but not c-Src. beta3DeltaRGT
endothelial cells, but not beta3/beta1(EGK) endothelial cells, exhibited
migration and spreading defects on vitronectin and reduced sprouting in 3
dimensional fibrin. Short hairpin RNA silencing of kindlin-2, but not c-Src,
blocked sprouting by beta3 wild-type endothelial cells. Moreover, defective
sprouting by beta3DeltaRGT endothelial cells could be rescued by conditional,
forced interaction of alphaVbeta3DeltaRGT with kindlin-2. Stimulation of
beta3DeltaRGT endothelial cells led to normal extracellular ligand binding to
alphaVbeta3, pin-pointing their defect to one of outside-in alphaVbeta3
signaling. beta3DeltaRGT mice, but not beta3/beta1(EGK) mice, exhibited defects
in both developmental and tumor angiogenesis, responses that require endothelial
cell function. Thus, the beta3/kindlin-2 interaction promotes outside-in
alphaVbeta3 signaling selectively, with biological consequences in vivo.
PMID- 25587036
TI - Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on
hemogenic endothelium.
AB - Hematopoietic and vascular development share many common features, including cell
surface markers and sites of origin. Recent lineage-tracing studies have
established that definitive hematopoietic stem and progenitor cells arise from
vascular endothelial-cadherin(+) hemogenic endothelial cells of the aorta-gonad
mesonephros region, but the genetic programs underlying the specification of
hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch
induction enhances hematopoietic potential and promotes the specification of
hemogenic endothelium in differentiating cultures of mouse embryonic stem cells,
and we identified Foxc2 as a highly upregulated transcript in the hemogenic
endothelial population. Studies in zebrafish and mouse embryos revealed that
Foxc2 and its orthologs are required for the proper development of definitive
hematopoiesis and function downstream of Notch signaling in the hemogenic
endothelium. These data establish a pathway linking Notch signaling to Foxc2 in
hemogenic endothelial cells to promote definitive hematopoiesis.
PMID- 25587039
TI - Activated factor XI increases the procoagulant activity of the extrinsic pathway
by inactivating tissue factor pathway inhibitor.
AB - Activation of coagulation factor XI (FXI) may play a role in hemostasis. The
primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa)
and thrombin generation. However, recent studies suggest the hemostatic role of
FXI may not be restricted to the activation of FIX. We explored whether FXI could
interact with and inhibit the activity of tissue factor pathway inhibitor (TFPI).
TFPI is an essential reversible inhibitor of activated factor X (FXa) and also
inhibits the FVIIa-TF complex. We found that FXIa neutralized both endothelium-
and platelet-derived TFPI by cleaving the protein between the Kunitz (K) 1 and K2
domains (Lys86/Thr87) and at the active sites of the K2 (Arg107/Gly108) and K3
(Arg199/Ala200) domains. Addition of FXIa to plasma was able to reverse the
ability of TFPI to prolong TF-initiated clotting times in FXI- or FIX-deficient
plasma, as well as FXa-initiated clotting times in FX-deficient plasma. Treatment
of cultured endothelial cells with FXIa increased the generation of FXa and
promoted TF-dependent fibrin formation in recalcified plasma. Together, these
results suggest that the hemostatic role of FXIa may be attributed not only to
activation of FIX but also to promoting the extrinsic pathway of thrombin
generation through inactivation of TFPI.
PMID- 25587041
TI - Parmodulins inhibit thrombus formation without inducing endothelial injury caused
by vorapaxar.
AB - Protease-activated receptor-1 (PAR1) couples the coagulation cascade to platelet
activation during myocardial infarction and to endothelial inflammation during
sepsis. This receptor demonstrates marked signaling bias. Its activation by
thrombin stimulates prothrombotic and proinflammatory signaling, whereas its
activation by activated protein C (APC) stimulates cytoprotective and
antiinflammatory signaling. A challenge in developing PAR1-targeted therapies is
to inhibit detrimental signaling while sparing beneficial pathways. We now
characterize a novel class of structurally unrelated small-molecule PAR1
antagonists, termed parmodulins, and compare the activity of these compounds to
previously characterized compounds that act at the PAR1 ligand-binding site. We
find that parmodulins target the cytoplasmic face of PAR1 without modifying the
ligand-binding site, blocking signaling through Galphaq but not Galpha13 in vitro
and thrombus formation in vivo. In endothelium, parmodulins inhibit prothrombotic
and proinflammatory signaling without blocking APC-mediated pathways or inducing
endothelial injury. In contrast, orthosteric PAR1 antagonists such as vorapaxar
inhibit all signaling downstream of PAR1. Furthermore, exposure of endothelial
cells to nanomolar concentrations of vorapaxar induces endothelial cell barrier
dysfunction and apoptosis. These studies demonstrate how functionally selective
antagonism can be achieved by targeting the cytoplasmic face of a G-protein
coupled receptor to selectively block pathologic signaling while preserving
cytoprotective pathways.
PMID- 25587043
TI - Paternalistic breaches of confidentiality in prison: mental health professionals'
attitudes and justifications.
AB - AIM: This manuscript presents mental health practitioners' (MHPs) practice,
attitudes and justifications for breaching confidentiality when imprisoned
patients disclose suicidal thoughts or abuse by others. METHODS: 24 MHPs working
in Swiss prisons shared their experiences regarding confidentiality practices.
The data were analysed qualitatively and MHPs' attitudes and course of action
were identified. RESULTS: Analysis revealed paternalistic breaches of
confidentiality. When patients reported suicidal thoughts and abuse, MHPs
believed that forgoing confidentiality is necessary to protect patients,
providing several justifications for it. Patients were informed that such
information will be transmitted without their consent to medical and non-medical
prison personnel. With reference to suicidal attempts, MHPs resorted to methods
that may reduce suicidal attempts such as transfer to hospital or internal
changes in living arrangements, which would require provision of certain
information to prison guards. In cases of abuse, some MHPs convinced patients to
accept intervention or sometimes overrode competent patients' refusals to report.
Also in the case of abuse, provision of limited information to other prison
personnel was seen as an acceptable method to protect patients from further harm.
DISCUSSION: Breaches of confidentiality, whether limited or full, remain
unethical, when used for competent patients based solely on paternalistic
justifications. Institutionalising ethical and legal procedures to address
suicidal and abuse situations would be helpful. Education and training to help
both medical and prison personnel to respond to such situations in an appropriate
manner that ensures confidentiality and protects patients from suicide and abuse
are necessary.
PMID- 25587042
TI - JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone
formation in mice.
AB - JMJD3 (KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated
transcription repression. However, the function of JMJD3 in vivo is not well
understood. Here we show that JMJD3 is highly expressed in cells of the
chondrocyte lineage, especially in prehypertrophic and hypertrophic chondrocytes,
during endochondral ossification. Homozygous deletion of Jmjd3 results in
severely decreased proliferation and delayed hypertrophy of chondrocytes, and
thereby marked retardation of endochondral ossification in mice. Genetically,
JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of
chondrocytes. Biochemically, JMJD3 associates with and enhances RUNX2 activity by
derepression of Runx2 and Ihh transcription through its H3K27me3 demethylase
activity. These results demonstrate that JMJD3 is a key epigenetic regulator in
the process of cartilage maturation during endochondral bone formation.
PMID- 25587044
TI - Role of Hic-5 in the formation of microvilli-like structures and the monocyte
endothelial interaction that accelerates atherosclerosis.
AB - AIMS: The adhesion of circulating monocytes to endothelial cells (ECs) is an
early and critical event in the formation of atherosclerotic plaques. Hydrogen
peroxide-inducible clone 5 (Hic-5) serves as an adaptor molecule in cell adhesion
complexes. However, the role of endothelial Hic-5 in monocyte-EC interaction and
atherogenesis remains unclear. We examined the roles of endothelial Hic-5 in
monocyte-EC interaction and atherogenesis using mouse models of atherosclerosis
and cultured human umbilical vein endothelial cells (HUVECs). METHODS AND
RESULTS: Hic-5 was expressed in ECs, but not in monocytes/macrophages. An ex vivo
monocyte adhesion assay revealed that adhesion of THP-1 monocytes to aortas
isolated from Apoe(-/-) and LDLR(-/-) mice stimulated by TNF-alpha or oxidized
LDL was suppressed by Hic-5 deficiency. Scanning electron microscopic
observations of aortas harvested from Apoe(-/-) mice revealed that TNF-alpha- or
oxidized LDL-induced microvilli-like structures were markedly suppressed by Hic-5
deficiency. Relative Hic-5 deficiency suppressed 60% of the atherosclerotic
lesions in aortas from Apoe(-/-) and LDLR(-/-) mice. In contrast, overexpression
of Hic-5 in HUVECs promoted induction of microvilli-like structures and adherence
of THP-1 cells in an adhesion receptor such as intercellular adhesion molecule-1-
and vascular cell adhesion molecule-1-dependent manner. CONCLUSION: Hic-5 in ECs
plays an important role in the formation of microvilli-like structures and in the
interaction between ECs and monocytes, leading to monocyte recruitment and
subsequent development of atherosclerosis.
PMID- 25587045
TI - Syndecan-4 is a key determinant of collagen cross-linking and passive myocardial
stiffness in the pressure-overloaded heart.
AB - AIMS: Diastolic dysfunction is central to the development of heart failure. To
date, there is no effective treatment and only limited understanding of its
molecular basis. Recently, we showed that the transmembrane proteoglycan syndecan
4 increases in the left ventricle after pressure overload in mice and man, and
that syndecan-4 via calcineurin/nuclear factor of activated T-cells (NFAT)
promotes myofibroblast differentiation and collagen production upon mechanical
stress. The aim of this study was to investigate whether syndecan-4 affects
collagen cross-linking and myocardial stiffening in the pressure-overloaded
heart. METHODS AND RESULTS: Aortic banding (AB) caused concentric hypertrophy and
increased passive tension of left ventricular muscle strips, responses that were
blunted in syndecan-4(-/-) mice. Disruption of titin anchoring by salt extraction
of actin and myosin filaments revealed that the effect of syndecan-4 on passive
tension was due to extracellular matrix remodelling. Expression and activity of
the cross-linking enzyme lysyl oxidase (LOX) increased with mechanical stress and
was lower in left ventricles and cardiac fibroblasts from syndecan-4(-/-) mice,
which exhibited less collagen cross-linking after AB. Expression of osteopontin
(OPN), a matricellular protein able to induce LOX in cardiac fibroblasts, was up
regulated in hearts after AB, in mechanically stressed fibroblasts and in
fibroblasts overexpressing syndecan-4, calcineurin, or NFAT, but down-regulated
in fibroblasts lacking syndecan-4 or after NFAT inhibition. Interestingly, the
extracellular domain of syndecan-4 facilitated LOX-mediated collagen cross
linking. CONCLUSIONS: Syndecan-4 exerts a dual role in collagen cross-linking,
one involving its cytosolic domain and NFAT signalling leading to collagen, OPN,
and LOX induction in cardiac fibroblasts; the other involving the extracellular
domain promoting LOX-dependent cross-linking.
PMID- 25587047
TI - Systemic gene transfer enables optogenetic pacing of mouse hearts.
AB - AIMS: Optogenetic pacing of the heart has been demonstrated in transgenic animals
expressing channelrhodopsin-2 (ChR2). However, for the clinical use of
optogenetics to treat cardiac arrhythmias, gene transfer to non-transgenic hearts
is required. The aim of this study was to describe a reliable method for gene
transfer of ChR2 into a sufficient percentage of cardiomyocytes to overcome the
electrical sink of all the coupled non-expressing cardiomyocytes during optical
pacing of the whole heart in vivo. METHODS AND RESULTS: Adeno-associated virus
(AAV) with cardiac tropism for expression of ChR2 in fusion with mCherry was
systemically injected into wild-type mouse hearts. Bright mCherry fluorescence
was detected in the whole heart 4-10 weeks later. Single-cell dissociation
revealed that on average 58% cardiomyocytes were mCherry-positive. These showed
light-induced inward currents, action potentials, and contractions. Pulsed
illumination of the left ventricle induced ventricular pacing in vivo in 74% of
mice, and higher light intensities were required for reduced pulse duration or
size of illumination. Non-responding hearts showed low AAV expression, and the
threshold for optical pacing was estimated to be 35-40% ChR2-expressing
cardiomyocytes. Optical pacing in vivo was stable over extended periods without
negative effects on normal sinus rhythm and ECG parameters after termination of
stimulation indicating sufficient cardiac output during pacing. CONCLUSIONS: Gene
transfer generates sufficient ChR2 photocurrent for reliable optogenetic pacing
in vivo and lays out the basis for future optogenetic pacemaker and pain-free
defibrillation therapies.
PMID- 25587046
TI - Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration
and ameliorates intimal hyperplasia.
AB - AIMS: Vascular smooth muscle cell (VSMC) migration in response to arterial wall
injury is a critical process in the development of intimal hyperplasia. Cell
migration is an energy-demanding process that is predicted to require
mitochondrial function. Mitochondria are morphologically dynamic, undergoing
continuous shape change through fission and fusion. However, the role of
mitochondrial morphology in VSMC migration is not well understood. The aim of the
study is to understand how mitochondrial fission contributes to VSMC migration
and provides its in vivo relevance in the mouse model of intimal hyperplasia.
METHODS AND RESULTS: In primary mouse VSMCs, the chemoattractant PDGF induced
mitochondrial shortening through the mitochondrial fission protein dynamin-like
protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the
dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF
induced lamellipodia formation and VSMC migration, indicating that mitochondrial
fission is an important process in VSMC migration. PDGF induced an augmentation
of mitochondrial energetics as well as ROS production, both of which were found
to be necessary for VSMC migration. Mechanistically, the inhibition of
mitochondrial fission induced an increase of mitochondrial inner membrane proton
leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS
increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing
DLP1-K38A displayed markedly reduced ROS levels and neointima formation in
response to femoral artery wire injury. CONCLUSIONS: Mitochondrial fission is an
integral process in cell migration, and controlling mitochondrial fission can
limit VSMC migration and the pathological intimal hyperplasia by altering
mitochondrial energetics and ROS levels.
PMID- 25587049
TI - Without mandatory regulation, clinical physiologists put patients at risk.
PMID- 25587050
TI - A constructionist review of morality and emotions: no evidence for specific links
between moral content and discrete emotions.
AB - Morality and emotions are linked, but what is the nature of their correspondence?
Many "whole number" accounts posit specific correspondences between moral content
and discrete emotions, such that harm is linked to anger, and purity is linked to
disgust. A review of the literature provides little support for these specific
morality-emotion links. Moreover, any apparent specificity may arise from global
features shared between morality and emotion, such as affect and conceptual
content. These findings are consistent with a constructionist perspective of the
mind, which argues against a whole number of discrete and domain-specific mental
mechanisms underlying morality and emotion. Instead, constructionism emphasizes
the flexible combination of basic and domain-general ingredients such as core
affect and conceptualization in creating the experience of moral judgments and
discrete emotions. The implications of constructionism in moral psychology are
discussed, and we propose an experimental framework for rigorously testing
morality-emotion links.
PMID- 25587048
TI - Atrial fibrillation: effects beyond the atrium?
AB - Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is
associated with significant morbidity, mostly secondary to heart failure and
stroke, and an estimated two-fold increase in premature death. Efforts to
increase our understanding of AF and its complications have focused on
unravelling the mechanisms of electrical and structural remodelling of the atrial
myocardium. Yet, it is increasingly recognized that AF is more than an atrial
disease, being associated with systemic inflammation, endothelial dysfunction,
and adverse effects on the structure and function of the left ventricular
myocardium that may be prognostically important. Here, we review the molecular
and in vivo evidence that underpins current knowledge regarding the effects of
human or experimental AF on the ventricular myocardium. Potential mechanisms are
explored including diffuse ventricular fibrosis, focal myocardial scarring, and
impaired myocardial perfusion and perfusion reserve. The complex relationship
between AF, systemic inflammation, as well as endothelial/microvascular
dysfunction and the effects of AF on ventricular calcium handling and oxidative
stress are also addressed. Finally, consideration is given to the clinical
implications of these observations and concepts, with particular reference to
rate vs. rhythm control.
PMID- 25587052
TI - Is widespread screening for hepatitis C justified?
PMID- 25587040
TI - Role of allogeneic stem cell transplantation in adult patients with Ph-negative
acute lymphoblastic leukemia.
AB - Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic
Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with
Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic
stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL
2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at
least 1 conventional high-risk factor were candidates for SCT in first complete
remission. Among these, 282 (54%) received a transplant in first complete
remission. At 3 years, posttransplant cumulative incidences of relapse,
nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%,
15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a
significant difference in RFS between SCT and no-SCT cohorts. However, SCT was
associated with longer RFS in patients with postinduction minimal residual
disease (MRD) >=10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B
cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion
(hazard ratio, 0.42). This article shows that poor early MRD response, in
contrast to conventional ALL risk factors, is an excellent tool to identify
patients who may benefit from allogeneic SCT in the context of intensified adult
ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as
#NCT00222027; GRAALL-2005 was registered as #NCT00327678.
PMID- 25587051
TI - Association of the colorectal CpG island methylator phenotype with molecular
features, risk factors, and family history.
AB - BACKGROUND: The CpG island methylator phenotype (CIMP) represents a subset of
colorectal cancers characterized by widespread aberrant DNA hypermethylation at
select CpG islands. The risk factors and environmental exposures contributing to
etiologic heterogeneity between CIMP and non-CIMP tumors are not known. METHODS:
We measured the CIMP status of 3,119 primary population-based colorectal cancer
tumors from the multinational Colon Cancer Family Registry. Etiologic
heterogeneity was assessed by a case-case study comparing risk factor frequency
of colorectal cancer cases with CIMP and non-CIMP tumors using logistic
regression to estimate the case-case odds ratio (ccOR). RESULTS: We found
associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E
mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P < 0.0001), female
sex [ccOR = 1.8; 95% confidence interval (CI), 1.5-2.1], older age (ccOR = 4.0
comparing over 70 years vs. under 50; 95% CI, 3.0-5.5), and family history of CRC
(ccOR = 0.6; 95% CI, 0.5-0.7). While use of NSAIDs varied by tumor CIMP status
for both males and females (P = 0.0001 and P = 0.02, respectively), use of
multivitamin or calcium supplements did not. Only for female colorectal cancer
was CIMP status associated with increased pack-years of smoking (Ptrend < 0.001)
and body mass index (BMI; Ptrend = 0.03). CONCLUSIONS: The frequency of several
colorectal cancer risk factors varied by CIMP status, and the associations of
smoking and obesity with tumor subtype were evident only for females. IMPACT:
Differences in the associations of a unique DNA methylation-based subgroup of
colorectal cancer with important lifestyle and environmental exposures increase
understanding of the molecular pathologic epidemiology of this heavily methylated
subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512-9.
(c)2015 AACR.
PMID- 25587055
TI - Degeneration and regeneration of corneal nerves in response to HSV-1 infection.
AB - PURPOSE: Herpes simplex virus type 1 (HSV-1) infection is one cause of
neurotrophic keratitis, characterized by decreases in corneal sensation, blink
reflex, and tear secretion as consequence of damage to the sensory fibers
innervating the cornea. Our aim was to characterize changes in the corneal nerve
network and its function in response to HSV-1 infection. METHODS: C57BL/6J mice
were infected with HSV-1 or left uninfected. Corneas were harvested at
predetermined times post infection (pi) and assessed for beta III tubulin,
substance P, calcitonin gene-related peptide, and neurofilament H staining by
immunohistochemistry (IHC). Corneal sensitivity was evaluated using a Cochet
Bonnet esthesiometer. Expression of genes associated with nerve repair was
determined in corneas by real time RT-PCR, Western blotting, and IHC. Semaphorin
7A (SEMA 7A) neutralizing antibody or isotype control was subconjunctivally
administered to infected mice. RESULTS: The area of cornea occupied by beta III
tubulin immunoreactivity and sensitivity significantly decreased by day 8 pi.
Modified reinnervation was observed by day 30 pi without recovery of corneal
sensation. Sensory fibers were lost by day 8 pi and were still absent or abnormal
at day 30 pi. Expression of SEMA 7A increased at day 8 pi, localizing to corneal
epithelial cells. Neutralization of SEMA 7A resulted in defective reinnervation
and lower corneal sensitivity. CONCLUSIONS: Corneal sensory nerves were lost,
consistent with loss of corneal sensation at day 8 pi. At day 30 pi, the cornea
reinnervated but without recovering the normal arrangement of its fibers or
function. SEMA 7A expression was increased at day 8pi, likely as part of a nerve
regeneration mechanism.
PMID- 25587057
TI - Papillomacular bundle and inner retinal thicknesses correlate with visual acuity
in nonarteritic anterior ischemic optic neuropathy.
AB - PURPOSE: To evaluate the ability of the papillomacular bundle (PMB) retinal nerve
fiber layer and macular inner retinal layer thickness measurements with
Spectralis optical coherence tomography (OCT) to differentiate eyes with
nonarteritic anterior ischemic optic neuropathy (NAION) from uninvolved eyes and
to evaluate whether their thicknesses correlate with visual acuity. METHODS: An
observational, cross-sectional study was performed, including 29 eyes with NAION
and 29 uninvolved eyes from 29 patients. Eyes underwent scanning with Cirrus OCT
(peripapillary and macular scanning) and Spectralis OCT (N-site axonal
peripapillary scan and a new automated segmentation macular scan to measure
individual retinal layers) in both eyes. RESULTS: The NAION eyes showed
significant thinning versus uninvolved eyes in the macular retinal nerve fiber (P
< 0.05), ganglion cell layer (GCL; P < 0.001), and inner plexiform layer (IPL; P
< 0.01) by Spectralis and in the GCL-IPL by Cirrus (P < 0.02). Average and
sectors of peripapillary retinal nerve fiber layer (pRNFL) and total macular
thickness (TMT) were significantly reduced in NAION eyes, with both Spectralis
and Cirrus OCT (P < 0.05). Spectralis temporal (rhoSpearman = -0.768; P < 0.001)
and PMB pRNFL thicknesses (rhoSpearman = -0.675; P < 0.001), as well as central
macular IPL thickness (rhoSpearman = -0.735; P < 0.001), correlated strongly with
best corrected visual acuity (BCVA). Quadratic regression using outer nasal TMT
by Cirrus OCT and temporal pRNFL thickness by Spectralis were the best models to
predict BCVA. CONCLUSIONS: Macular segmentation by Spectralis and Cirrus OCT
revealed inner retinal layer atrophy in NAION eyes. The temporal and PMB pRNFL
thicknesses and central macular IPL thickness by Spectralis-OCT and outer nasal
TMT by Cirrus were strongly correlated with BCVA in NAION eyes.
PMID- 25587053
TI - Progesterone action in breast, uterine, and ovarian cancers.
AB - Progesterone and progesterone receptors (PRs) are essential for the development
and cyclical regulation of hormone-responsive tissues including the breast and
reproductive tract. Altered functions of PR isoforms contribute to the
pathogenesis of tumors that arise in these tissues. In the breast, progesterone
acts in concert with estrogen to promote proliferative and pro-survival gene
programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the
uterus and protects the ovary from neoplastic transformation. Progesterone
dependent actions and associated biology in diverse tissues and tumors are
mediated by two PR isoforms, PR-A and PR-B. These isoforms are subject to altered
transcriptional activity or expression levels, differential crosstalk with growth
factor signaling pathways, and distinct post-translational modifications and
cofactor-binding partners. Herein, we summarize and discuss the recent literature
focused on progesterone and PR isoform-specific actions in breast, uterine, and
ovarian cancers. Understanding the complexity of context-dependent PR actions in
these tissues is critical to developing new models that will allow us to advance
our knowledge base with the goal of revealing novel and efficacious therapeutic
regimens for these hormone-responsive diseases.
PMID- 25587056
TI - Adaptive optics microperimetry and OCT images show preserved function and
recovery of cone visibility in macular telangiectasia type 2 retinal lesions.
AB - PURPOSE: To evaluate visual function and disease progression in the retinal
structural abnormalities of three patients from two unrelated families with
macular telangiectasia (MacTel) type 2. METHODS: Adaptive optics scanning laser
ophthalmoscopy (AOSLO) and AOSLO microperimetry (AOMP) were used to evaluate the
structure and function of macular cones in three eyes with MacTel type 2. Cone
spacing was estimated using histogram analysis of intercone distances, and
registered spectral-domain optical coherence tomography (SD-OCT) scans were used
to evaluate retinal anatomy. AOMP was used to assess visual sensitivity in and
around areas of apparent cone loss. RESULTS: Although overall lesion surface area
increased, some initially affected regions subsequently showed clear, contiguous,
and normally spaced cone mosaics with recovered photoreceptor inner/outer segment
(IS/OS) reflectivity (two of two eyes). The AOMP test sites fell within three
categories: normal-appearing cones (N), dimly reflecting cones (D), and RPE cell
mosaics (R). At N sites, AOMP threshold values (arbitrary units [au]) increased
with increasing eccentricity (slope = 0.054 au/degree, r(2) = 0.77). The N
thresholds ranged from 0.04 to 0.27 au, D thresholds from 0.04 to 0.33 au, and R
thresholds from 0.14 to 1.00 au. There was measurable visual sensitivity
everywhere except areas without intact external limiting membrane (ELM) and with
diffuse scattering in the IS/OS and posterior tips of the outer segments (PTOS)
regions on OCT. CONCLUSIONS: Visual sensitivity and recovery of cone visibility
in areas of apparent focal cone loss suggests that MacTel type 2 lesions with a
preserved ELM may contain functioning cones with abnormal scattering and/or
waveguiding characteristics. (ClinicalTrials.gov number, NCT00254605.).
PMID- 25587058
TI - Evaluation of 12 myopia-associated genes in Chinese patients with high myopia.
AB - PURPOSE: Two recent large-scale genome-wide association studies identified
significant associations between myopia and single nucleotide polymorphisms
(SNPs) near the PRSS56, BMP3, KCNQ5, LAMA2, TOX, TJP2, RDH5, ZIC2, RASGRF1, GJD2,
RBFOX1, and SHISA6 genes. Our study is to examine whether rare variants in these
genes contribute to high myopia. METHODS: Whole-exome sequencing was performed on
samples of 298 probands with early-onset high myopia (eoHM; spherical refraction
in each meridian <= -6.00 [diopters] D in both eyes; age of onset < 7 years) and
195 controls (different forms of retinal degeneration including Leber congenital
amaurosis, cone-rod dystrophy, and familial exudative vitroretinopathy).
Potential variations in these genes were selected for further validation and
comparison to the controls. Moreover, Sanger sequencing was used to evaluate the
coding regions and the upstream 800 bps of GJD2 in 395 additional subjects with
late-onset moderate to high myopia (loMHM; spherical refraction in each meridian
<= -4.00 D; age of onset >= 7 years) and 403 healthy controls (-0.50 D +/- 1.00
D). RESULTS: Exome sequencing of the 298 probands with eoHM identified 25 rare
variants that were predicted to affect coding residues. The segregation analysis
and the distribution of rare variants between patients and controls did not
provide evidence to support their involvement in myopia. Sanger sequencing of
GJD2 in an additional 395 subjects with loMHM and 403 healthy controls did not
identify myopia-associated variants. CONCLUSIONS: We did not find evidence to
support the association of myopia with rare variants in these genes, probably due
to our limited sample size. Additional studies are expected to validate these
results.
PMID- 25587054
TI - Genetic regulation of murine pituitary development.
AB - Significant progress has been made recently in unravelling the embryonic events
leading to pituitary morphogenesis, both in vivo and in vitro. This includes
dissection of the molecular mechanisms controlling patterning of the ventral
diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch.
There is also a better characterisation of processes that underlie maintenance of
pituitary progenitors, specification of endocrine lineages and the three
dimensional organisation of newly differentiated endocrine cells. Furthermore, a
population of adult pituitary stem cells (SCs), originating from embryonic
progenitors, have been described and shown to have not only regenerative
potential, but also the capacity to induce tumour formation. Finally, the
successful recapitulation in vitro of embryonic events leading to generation of
endocrine cells from embryonic SCs, and their subsequent transplantation,
represents exciting advances towards the use of regenerative medicine to treat
endocrine deficits. In this review, an up-to-date description of pituitary
morphogenesis will be provided and discussed with particular reference to
pituitary SC studies.
PMID- 25587059
TI - Choroidal thickness in geographic atrophy secondary to age-related macular
degeneration.
AB - PURPOSE: To analyze choroidal thickness (CT) in eyes with geographic atrophy (GA)
secondary to age-related macular degeneration (AMD). METHODS: A total of 72 eyes
of 72 patients (mean age, 75.97 +/- 7.09 years) with GA and 37 eyes of 37 healthy
controls (73.89 +/- 6.19 years) were examined by confocal scanning laser
ophthalmoscopy and enhanced depth imaging (EDI) spectral-domain optical coherence
tomography. Choroidal thickness was measured at 25 defined points in horizontal
and vertical scans. Geographic atrophy size was determined in fundus
autofluorescence (FAF) images and GA subtypes were classified based on abnormal
FAF in the perilesional zone. RESULTS: In GA, subfoveal CT (fCT) was
significantly thinner compared to controls (173.03 +/- 90.22 vs. 253.95 +/- 69.19
MUm, P < 0.001). Analysis of averaged measurements of all 25 points obtained per
patient (mCT) revealed similar results (162.07 +/- 76.26 vs. 228.00 +/- 66.24
MUm, P < 0.001). Spatial differences in CT between both groups were largest
superior to the fovea. Addressing "diffuse-trickling" (n = 15) and "non-diffuse
trickling" (n = 57) GA independently, fCT was 114.67 +/- 43.32 and 188.39 +/-
93.26 MUm, respectively (P = 0.002), with both groups being significantly thinner
than controls (P < 0.001 for "diffuse-trickling" and P < 0.001 for "?non-diffuse
trickling"). Similar results were obtained for mCT, which was 110.21 +/- 29.66
MUm in "diffuse-trickling," 175.72 +/- 79.02 MUm in "?non-diffuse-trickling" and
228.00 +/- 66.24 MUm in controls. Differences were significant with P = 0.002
between both GA groups and P <= 0.001 toward controls for each GA group.
CONCLUSIONS: The results indicate that the choroid in eyes with GA is thinner
compared to normal eyes of similar age. Hereby, the extent of thinning is most
pronounced in a specific subtype of GA identified by FAF imaging ("diffuse
trickling"). Such GA subtype-related differences in choroidal thickness may
reflect heterogeneity in the pathogenesis of disease. (ClinicalTrials.gov number,
NCT02051998.).
PMID- 25587061
TI - An analysis of the factors influencing the residual refractive astigmatism after
cataract surgery with toric intraocular lenses.
AB - PURPOSE: To investigate the influence of posterior corneal astigmatism,
surgically-induced corneal astigmatism (SICA), intraocular lens (IOL)
orientation, and effective lens position on the refractive outcome of toric IOLs.
METHODS: Five models were prospectively investigated. Keratometric astigmatism
and an intended SICA of 0.2 diopters (D) were entered into model 1. Total corneal
astigmatism, measured by a rotating Scheimpflug camera, was used instead of
keratometric astigmatism in model 2. The mean postoperative SICA, the actual
postoperative IOL orientation, and the influence of the effective lens position
were added, respectively, into models 3, 4, and 5. Astigmatic data were
vectorially described by meridional and torsional powers. A set of equations was
developed to describe the error in refractive astigmatism (ERA) as the difference
between the postoperative refractive astigmatism and the target refractive
astigmatism. RESULTS: We enrolled 40 consecutive eyes. In model 1, ERA
calculations revealed significant cylinder overcorrection in with-the-rule (WTR)
eyes (meridional power = -0.59 +/- 0.34 D, P < 0.0001) and undercorrection in
against-the-rule (ATR) eyes (0.32 +/- 0.42 D, P = 0.01). When total corneal
astigmatism was used instead of keratometric astigmatism (model 2), the ERA
meridional power decreased in WTR (-0.13 +/- 0.42 D) and ATR (0.07 +/- 0.59 D)
eyes, both values being not statistically significant. Models 3 to 5 did not lead
to significant improvement. CONCLUSIONS: Posterior corneal astigmatism exerts the
highest influence on the ERA after toric IOL implantation. Basing calculations on
total corneal astigmatism rather than keratometric astigmatism improves the
prediction of the residual refractive astigmatism.
PMID- 25587060
TI - Neuroprotective effects of transcription factor Brn3b in an ocular hypertension
rat model of glaucoma.
AB - PURPOSE: Glaucoma is an optic neuropathy commonly associated with elevated
intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss,
and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in
blindness. Brn3b is a class-4 POU domain transcription factor that plays a key
role in RGC development, axon outgrowth, and pathfinding. Previous studies
suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The
goal of this study was to determine if adeno-associated virus (AAV)-directed
overexpression of the Brn3b protein could have neuroprotective effects following
elevated IOP-mediated neurodegeneration. METHODS: Intraocular pressure was
elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the
IOP-elevated eyes were intravitreally injected with AAV constructs encoding
either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV
hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity
markers and neuroprotection was assessed by RGC counts and visual acuity tests.
RESULTS: Adeno-associated virus-mediated expression of the Brn3b protein in IOP
elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP
43), actin binding LIM protein (abLIM) and acetylated alpha-tubulin (ac-Tuba)
both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity
score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats
compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats.
Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored
the visual optomotor response in IOP-elevated rat eyes. CONCLUSIONS: Adeno
associated virus-mediated Brn3b protein expression may be a suitable approach for
promoting neuroprotection in animal models of glaucoma.
PMID- 25587062
TI - Evidence for lymphatics in the developing and adult human choroid.
AB - PURPOSE: Lymphatics subserve many important functions in the human body including
maintenance of fluid homeostasis, immune surveillance, and tumor metastasis. Our
aim was to provide structural and phenotypic evidence of lymphatic-like
structures in the human choroid, including details of its development. METHODS:
Using multiple-marker immunohistochemistry (IHC), choroids from human fetal eyes
(8-26 weeks gestation) and adults (17-74 years) were examined with lymphatic- and
vascular-specific markers: prospero homeobox-1 (PROX-1), lymphatic vascular
endothelium receptor-1 (LYVE-1), podoplanin, D2-40, endomucin, VEGF-C, vascular
endothelial growth factor receptor-3 (VEGFR-3 or Flt4), UEA lectin, platelet
endothelial cell adhesion molecule-1 (PECAM-1), CD34, and CD39. Transmission
electron microscopy (TEM) was used to establish evidence for choroidal
lymphatics, and to provide details of stratification and relative frequency of
lymphatics compared to choroidal blood vessels. RESULTS: Immunohistochemistry and
TEM indicated a central-to-peripheral topography of lymphatic formation, with
numerous blind-ended lymph sacs just external to the choriocapillaris, as well as
the presence of infrequent precollector and collector lymphatic channels.
Characteristic ultrastructural features of lymphatics in adult human choroid
included anchoring filaments, luminal flocculent protein but absence of
erythrocytes, fragmented and/or absent basal lamina, absence of intracellular
Weibel-Palade bodies, infrequent pericyte ensheathment, and lack of fenestrae.
CONCLUSIONS: The system of blind-ended initial lymphatic segments seen just
external to the fenestrated vessels of the choriocapillaris is ideally placed for
recirculating extracellular fluid and strategically placed for immune
surveillance. The presence of a system of lymphatic-like channels in the human
choroid provides an anatomical basis for antigen presentation in the posterior
eye, with a possible route from the eye to the sentinel lymph nodes, similar to
that already described for anterior eye lymphatics.
PMID- 25587063
TI - Delay in retinal photoreceptor development in very preterm compared to term
infants.
AB - PURPOSE: We compared photoreceptor development from spectral domain optical
coherence tomography (SD-OCT) imaging in very preterm infants (VPT, <32 weeks
gestational age) with those of term infants. METHODS: The microanatomy of foveal
SD-OCT images obtained at the bedside at 37 to 42 weeks term equivalent
postmenstrual age (TEA) was reviewed with qualitative and quantitative analysis
of retinal and especially photoreceptor layers in the macula. Measures of
maturity included presence of the cone outer segment tips (COST) or the ellipsoid
zone (EZ) at foveal center, distance from Bruch's membrane (BM) to the EZ at the
foveal center, and radial distance from foveal center to first appearance of the
EZ. RESULTS: The incidence of the EZ developed at the foveal center was lower in
VPT infants (9/64, 14%) versus term infants (22/47, 47%, P < 0.001) and lower in
VPT infants with macular edema (3/46) versus VPT without edema (6/18, P = 0.01).
Mean +/- SD distance from the foveal center to the visible EZ was 783 +/- 440 MUm
in VPT, and 492 +/- 501 MUm in term infants, P = 0.002. The height of the BM-to
EZ at the foveal center did not differ in VPT versus term infants. The COST band
was not visible in any infant. CONCLUSIONS: Photoreceptor inner and outer segment
development in VPT infants appears delayed when compared to term infants, and the
photoreceptor RPE junction remains immature in all infants at TEA. Delayed
maturation of photoreceptors could contribute to differences in visual function
in some VPT infants.
PMID- 25587064
TI - SeqHBase: a big data toolset for family based sequencing data analysis.
AB - BACKGROUND: Whole-genome sequencing (WGS) and whole-exome sequencing (WES)
technologies are increasingly used to identify disease-contributing mutations in
human genomic studies. It can be a significant challenge to process such data,
especially when a large family or cohort is sequenced. Our objective was to
develop a big data toolset to efficiently manipulate genome-wide variants,
functional annotations and coverage, together with conducting family based
sequencing data analysis. METHODS: Hadoop is a framework for reliable, scalable,
distributed processing of large data sets using MapReduce programming models.
Based on Hadoop and HBase, we developed SeqHBase, a big data-based toolset for
analysing family based sequencing data to detect de novo, inherited homozygous,
or compound heterozygous mutations that may contribute to disease manifestations.
SeqHBase takes as input BAM files (for coverage at every site), variant call
format (VCF) files (for variant calls) and functional annotations (for variant
prioritisation). RESULTS: We applied SeqHBase to a 5-member nuclear family and a
10-member 3-generation family with WGS data, as well as a 4-member nuclear family
with WES data. Analysis times were almost linearly scalable with number of data
nodes. With 20 data nodes, SeqHBase took about 5 secs to analyse WES familial
data and approximately 1 min to analyse WGS familial data. CONCLUSIONS: These
results demonstrate SeqHBase's high efficiency and scalability, which is
necessary as WGS and WES are rapidly becoming standard methods to study the
genetics of familial disorders.
PMID- 25587066
TI - Long working hours are linked to risky alcohol consumption.
PMID- 25587067
TI - GPs rarely use interventions for weight management in obese and overweight
patients, study finds.
PMID- 25587065
TI - Long working hours and alcohol use: systematic review and meta-analysis of
published studies and unpublished individual participant data.
AB - OBJECTIVE: To quantify the association between long working hours and alcohol
use. DESIGN: Systematic review and meta-analysis of published studies and
unpublished individual participant data. DATA SOURCES: A systematic search of
PubMed and Embase databases in April 2014 for published studies, supplemented
with manual searches. Unpublished individual participant data were obtained from
27 additional studies. REVIEW METHODS: The search strategy was designed to
retrieve cross sectional and prospective studies of the association between long
working hours and alcohol use. Summary estimates were obtained with random
effects meta-analysis. Sources of heterogeneity were examined with meta
regression. RESULTS: Cross sectional analysis was based on 61 studies
representing 333,693 participants from 14 countries. Prospective analysis was
based on 20 studies representing 100,602 participants from nine countries. The
pooled maximum adjusted odds ratio for the association between long working hours
and alcohol use was 1.11 (95% confidence interval 1.05 to 1.18) in the cross
sectional analysis of published and unpublished data. Odds ratio of new onset
risky alcohol use was 1.12 (1.04 to 1.20) in the analysis of prospective
published and unpublished data. In the 18 studies with individual participant
data it was possible to assess the European Union Working Time Directive, which
recommends an upper limit of 48 hours a week. Odds ratios of new onset risky
alcohol use for those working 49-54 hours and >= 55 hours a week were 1.13 (1.02
to 1.26; adjusted difference in incidence 0.8 percentage points) and 1.12 (1.01
to 1.25; adjusted difference in incidence 0.7 percentage points), respectively,
compared with working standard 35-40 hours (incidence of new onset risky alcohol
use 6.2%). There was no difference in these associations between men and women or
by age or socioeconomic groups, geographical regions, sample type (population
based v occupational cohort), prevalence of risky alcohol use in the cohort, or
sample attrition rate. CONCLUSIONS: Individuals whose working hours exceed
standard recommendations are more likely to increase their alcohol use to levels
that pose a health risk.
PMID- 25587069
TI - Epigenetic Changes Induced by Hypoxia-Inducible Factor: a Long Way Still To Go as
a Target for Therapy?
PMID- 25587070
TI - US court cannot force tobacco companies to say they are "unscrupulous villains,"
claims industry appeal.
PMID- 25587071
TI - Impact commentaries. Subacute necrotising encephalomyelopathy (Leigh's disease;
Leigh syndrome).
PMID- 25587068
TI - MicroRNA-687 Induced by Hypoxia-Inducible Factor-1 Targets Phosphatase and Tensin
Homolog in Renal Ischemia-Reperfusion Injury.
AB - Ischemia-reperfusion injury contributes to tissue damage and organ failure in
clinical settings, but the underlying mechanism remains elusive and effective
therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key
regulator and therapeutic target in renal ischemia-reperfusion injury. We show
that miR-687 is markedly upregulated in the kidney during renal ischemia
reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687
induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF
1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and
tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis.
Blockade of miR-687 preserved PTEN expression and attenuated cell cycle
activation and renal apoptosis, resulting in protection against kidney injury in
mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling
pathway in ischemia-reperfusion injury that may be targeted for therapy.
PMID- 25587072
TI - Lateralising value of experiential hallucinations in temporal lobe epilepsy.
AB - OBJECTIVES: Ever since John Hughlings Jackson first described the so-called
'dreamy state' during temporal lobe epilepsy, that is, the sense of an abnormal
familiarity (deja vu) or vivid memory-like hallucinations from the past
(experiential hallucinations), these phenomena have been studied and repeatedly
linked to mesial temporal lobe structures. However, little is known about the
lateralising value of either deja vu or experiential hallucinations. METHODS: We
analysed a sample of 28 patients with intractable focal epilepsy suffering from
either deja vu or experiential hallucinations. All the patients underwent
thorough presurgical examination, including MRI, positron emission tomography,
single-photon emission CT, EEG and neuropsychological examination. RESULTS: While
deja vu was due to right or left mesial temporal lobe epilepsy, experiential
hallucinations were strongly lateralised to the left mesial temporal lobe.
Moreover, there was a significant effect for interictal language deficits being
more frequent in patients suffering from experiential hallucinations.
CONCLUSIONS: These results suggest a lateralising value for experiential
hallucinations to the left temporal lobe.
PMID- 25587074
TI - Modified 16S-23S rRNA intergenic region restriction endonuclease analysis for
species identification of Enterococcus strains isolated from pigs, compared with
identification using classical methods and matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry.
AB - Fast and reliable identification of bacteria to at least the species level is
currently the basis for correct diagnosis and appropriate treatment of
infections. This is particularly important in the case of bacteria of the genus
Enterococcus, whose resistance profile is often correlated with their species
(e.g. resistance to vancomycin). In this study, we evaluated restriction
endonuclease analysis of the 16S-23S rRNA gene intergenic transcribed spacer
(ITS) region for species identification of Enterococcus. The utility of the
method was compared with that of phenotypic methods [biochemical profile
evaluation and matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOF MS)]. Identification was based on 21 Enterococcus
reference strains, of the species E. faecalis, E. faecium, E. hirae, E. durans,
E. casseliflavus, E. gallinarum, E. avium, E. cecorum and E. columbae, and 47
Enterococcus field strains isolated from pigs. Restriction endonuclease analysis
of the ITS-PCR product using HinfI, RsaI and MboI, in the order specified,
enabled species differentiation of the Enterococcus reference and field strains,
and in the case of the latter, the results of species identification were
identical (47/47) to those obtained by MALDI-TOF MS. Moreover, as a result of
digestion with MboI, a unique restriction profile was also obtained for the
strains (3/3) identified by MALDI-TOF MS as E. thailandicus. In our opinion,
restriction endonuclease analysis of the 16S-23S rRNA gene ITS region of
Enterococcus may be a simple and relatively fast (less than 4 h) alternative
method for identifying the species occurring most frequently in humans and
animals.
PMID- 25587080
TI - Faecal levels of zonula occludens toxin in paediatric patients with Crohn's
disease and their association with the intestinal microbiota.
PMID- 25587073
TI - Comparison of turnaround time and time to oseltamivir discontinuation between two
respiratory viral panel testing methodologies.
PMID- 25587081
TI - High prevalence of Escherichia coli sequence type 131 among antimicrobial
resistant E. coli isolates from geriatric patients.
AB - Previous work on the subclones within Escherichia coli ST131 predominantly
involved isolates from Western countries. This study assessed the prevalence and
antimicrobial resistance attributed to this clonal group. A total of 340
consecutive, non-duplicated urinary E. coli isolates originating from four
clinical laboratories in Hong Kong in 2013 were tested. ST131 prevalence among
the total isolates was 18.5 % (63/340) and was higher among inpatient isolates
(23.0 %) than outpatient isolates (11.8 %, P<0.001), and higher among isolates
from patients aged >=65 years than from patients aged 18-50 years and 51-64 years
(25.4 vs 3.4 and 4.0 %, respectively, P<0.001). Of the 63 ST131 isolates, 43
(68.3 %) isolates belonged to the H30 subclone, whereas the remaining isolates
belonged to H41 (n = 17), H54 (n = 2) and H22 (n = 1). All H30 isolates were
ciprofloxacin-resistant, of which 18.6 % (8/43) belonged to the H30-Rx subclone.
Twenty-six (41.3 %) ST131 isolates were ESBL-producers, of which 19 had blaCTX-M
14 (12 non-H30-Rx, two H30-Rx and five H41), six had blaCTX-M-15 (five non-H30-Rx
and one H30-Rx) and one was blaCTX-M-negative (H30). In conclusion, ST131
accounts for a large share of the antimicrobial-resistant E. coli isolates from
geriatric patients. Unlike previous reports, ESBL-producing ST131 strains mainly
belonged to non-H30-Rx rather than the H30-Rx subclone, with blaCTX-M-14 as the
dominant enzyme type.
PMID- 25587082
TI - Phenotypic and molecular characterization of Malassezia japonica isolated from
psoriasis vulgaris patients.
AB - Malassezia species, which are skin colonizers, are being debated as to their
pathogenic role in various cutaneous diseases. Species identification of
Malassezia is important as particular species have been implicated in or
associated with specific diseases. Malassezia japonica, a relatively newly
described species, has not been completely characterized owing to the rarity of
its isolation. In the present study we describe phenotypic and molecular
characterization of six M. japonica strains isolated from patients with psoriasis
vulgaris. In contrast to the physiological and biochemical properties of the M.
japonica type strain, CBS9348, all our isolates assimilated Tween 20 and showed
positive beta-glucosidase activity, and the Cremophor EL utilization test was
negative. However, the sequences of the D1/D2 region of rDNA, ITS2 and IGS1
regions of all our isolates clustered with the type strain of M. japonica.
PMID- 25587083
TI - Multiplex assay (Mikrogen recomBead) for detection of serum IgG and IgM
antibodies to 13 recombinant antigens of Borrelia burgdorferi sensu lato in
patients with neuroborreliosis: the more the better?
AB - A multiplex-bead-based assay for the detection of serum antibodies to Borrelia
burgdorferi sensu lato was evaluated. The assay contained 13 different antigens
in both the IgG and the IgM assay; thus, a total of 26 measurement results were
available from each sample. A total of 49 Danish patients with Lyme
neuroborreliosis (LNB), 218 Danish blood donor controls, a set of 61 Swedish
patients with LNB and 139 Swedish non-LNB patients investigated for suspected LNB
were used. There are four parts developed in this study: a characterization of
the sero-epidemiological antibody-response pattern, the construction of a
diagnostic score, evaluation of the scoring method using an independent dataset
and an assessment of the analytical quality of the multiplex assay. The VlsE IgG
had the highest diagnostic value with an AUC (area under the curve) of 96% on the
receiver operating characteristic curve. The OspC IgM had AUCs just above 80%.
All the other antigens had both low quantitative reactivity and lower contrast in
the patients with LNB compared to controls. The diagnostic value of the assay may
be improved by using a logistic model giving a sensitivity of 90 and 79% for the
specificities at 92 and 98%, respectively. Overall, the patients with LNB had
serum reactivity in IgG VlsE, but modest antibody reactivity in the remaining 12
IgG and 13 IgM antibody measurements. Using a logistic regression model with five
IgG and two IgM antigens, the sensitivity and specificity of the assay was
improved; but the IgG VlsE component alone contributed most of the diagnostic
contrast.
PMID- 25587084
TI - A prospective study of mucormycosis in north India: experience from a tertiary
care hospital.
AB - Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous
filamentous fungi of the Order Mucorales and class of Mucormycetes. We conducted
a prospective study of 38 patients who were diagnosed as having mucormycosis in a
tertiary care hospital during January 2010 to June 2011. The cases were analyzed
regarding the site of involvement, underlying disease and species of fungi
isolated, antifungal susceptibility pattern of the isolates, and outcome of
therapy. The mean age of the patients was 40.43 years, with 72% male. Rhino
orbital mucormycosis (61.5%) was the most common presentation followed by
cutaneous manifestations (31%), gastrointestinal symptoms (5%), and pulmonary
(2.5%). Diabetes mellitus (56%) was the significant risk factor in rhino-orbito
cerebral presentation (OR = 7.55, P = 0.001). Among 23 culture isolates, Rhizopus
arrhizus (37.5%) was the most common, followed by Apophysomyces variabilis
(29.2%), Lichtheimia ramosa (16.7%), Rhizopus microsporus (4.2%), Rhizomucor
pusillus (4.2%), and Apophysomyces elegans (4.2%). Rhizopus arrhizus was most
commonly isolated from rhino-orbito-cerebral mucormycosis and Apophysomyces
species were generally obtained from cutaneous mucormycosis. In vitro antifungal
susceptibility showed that 16 isolates were sensitive to amphotericin B (MIC less
than 1 MUg/ml), while in contrast, all isolates were found to be resistant to
voriconazole (MIC- 0.25 to >8), fluconazole (MIC > 32), flucytosine (MIC > 32).
Treatment regimens included antifungal therapy, reversal of underlying
predisposing risk factors, and surgical debridement. Combination of surgery and
medical treatment with amphotericin B was significantly better (OR = 0.2, P <
0.04) than amphotericin B alone (61.5% vs. 10.3% patient survival). The awareness
of fungal diseases amongst clinicians is required to decrease the fatal outcome
of disease.
PMID- 25587086
TI - Photo quiz. Breast mass in a 45-year-old man.
PMID- 25587089
TI - Should proton pump inhibitors be withheld from patients taking clopidogrel? The
issue that has been giving me heartburn!
PMID- 25587085
TI - LEF1 Targeting EMT in Prostate Cancer Invasion Is Regulated by miR-34a.
AB - The microRNA-34a (miR-34a), a tumor-suppressive microRNA (miRNA), is implicated
in epithelial-mesenchymal transition (EMT) and cancer stem cells. Lymphoid
enhancer-binding factor-1 (LEF1) is a key transcription factor in the Wnt
signaling pathway, and has been suggested to be involved in regulation of cell
proliferation and invasion. Here, the molecular mechanism of miR-34a and LEF1 in
cooperatively regulating prostate cancer cell invasion is described. Molecular
profiling analysis of miRNA levels in prostate cancer cells revealed a negative
correlation between miR-34a and LEF1 expression, and the downregulation of LEF1
by miR-34a was confirmed by luciferase assays. Furthermore, miR-34a specifically
repressed LEF1 expression through direct binding to its 3'-untranslated regions
(3'-UTR). miR-34a modulated the levels of LEF1 to regulate EMT in prostate cancer
cells. Functionally, miR-34a negatively correlated with the migration and
invasion of prostate cancer cells through LEF1. An analysis of miR-34a expression
levels in matched human tumor and benign tissues demonstrated consistent and
statistically significant downregulation of miR-34a in primary prostate cancer
specimens. These data strongly suggest that miR-34a/LEF1 regulation of EMT plays
an important role in prostate cancer migration and invasion. IMPLICATIONS: The
miR-34a-LEF1 axis represents a potential molecular target for novel therapeutic
strategies in prostate cancer.
PMID- 25587088
TI - Interventions to reduce dependency in personal activities of daily living in
community dwelling adults who use homecare services: a systematic review.
AB - OBJECTIVES: To identify interventions that aim to reduce dependency in activities
of daily living (ADL) in homecare service users. To determine: content;
effectiveness in improving ability to perform ADL; and whether delivery by
qualified occupational therapists influences effectiveness. DATA SOURCES: The
Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL,
PsycINFO, OTseeker, PEDro, Web of Science, CIRRIE, and ASSIA. REVIEW METHODS: We
included: randomised controlled trials, non-randomised controlled trials and
controlled before and after studies. Two reviewers independently screened studies
for inclusion, assessed risk of bias and extracted data. A narrative synthesis of
the findings was conducted. RESULTS: Thirteen studies were included, totalling
4975 participants. Ten (77%) were judged to have risk of bias. Interventions were
categorised as those termed 're-ablement' or 'restorative homecare' (n=5/13); and
those involving separate components which were not described using this
terminology (n=8/13). Content of the intervention and level of health
professional input varied within and between studies. Effectiveness on ADL: eight
studies included an ADL outcome, five favoured the intervention group, only two
with statistical significance, both these were controlled before and after
studies judged at high risk of bias. ADL outcome was reported using seven
different measures. Occupational therapy: there was insufficient evidence to
determine whether involvement of qualified occupational therapists influenced
effectiveness. CONCLUSION: There is limited evidence that interventions targeted
at personal ADL can reduce homecare service users' dependency with activities,
the content of evaluated interventions varies greatly.
PMID- 25587090
TI - Effect of a computer-guided, quality improvement program for cardiovascular
disease risk management in primary health care: the treatment of cardiovascular
risk using electronic decision support cluster-randomized trial.
AB - BACKGROUND: Despite effective treatments to reduce cardiovascular disease risk,
their translation into practice is limited. METHODS AND RESULTS: Using a parallel
arm cluster-randomized controlled trial in 60 Australian primary healthcare
centers, we tested whether a multifaceted quality improvement intervention
comprising computerized decision support, audit/feedback tools, and staff
training improved (1) guideline-indicated risk factor measurements and (2)
guideline-indicated medications for those at high cardiovascular disease risk.
Centers had to use a compatible software system, and eligible patients were
regular attendees (Aboriginal and Torres Strait Islander people aged >= 35 years
and others aged >= 45 years). Patient-level analyses were conducted using
generalized estimating equations to account for clustering. Median follow-up for
38,725 patients (mean age, 61.0 years; 42% men) was 17.5 months. Mean monthly
staff support was <1 hour/site. For the coprimary outcomes, the intervention was
associated with improved overall risk factor measurements (62.8% versus 53.4%
risk ratio; 1.25; 95% confidence interval, 1.04-1.50; P=0.02), but there was no
significant differences in recommended prescriptions for the high-risk cohort
(n=10,308; 56.8% versus 51.2%; P=0.12). There were significant treatment
escalations (new prescriptions or increased numbers of medicines) for
antiplatelet (17.9% versus 2.7%; P<0.001), lipid-lowering (19.2% versus 4.8%;
P<0.001), and blood pressure-lowering medications (23.3% versus 12.1%; P=0.02).
CONCLUSIONS: In Australian primary healthcare settings, a computer-guided quality
improvement intervention, requiring minimal support, improved cardiovascular
disease risk measurement but did not increase prescription rates in the high-risk
group. Computerized quality improvement tools offer an important, albeit partial,
solution to improving primary healthcare system capacity for cardiovascular
disease risk management. CLINICAL TRIAL REGISTRATION URL:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336630.
Australian New Zealand Clinical Trials Registry No. 12611000478910.
PMID- 25587092
TI - Association of discharge summary quality with readmission risk for patients
hospitalized with heart failure exacerbation.
PMID- 25587091
TI - Hospital variation in quality of discharge summaries for patients hospitalized
with heart failure exacerbation.
AB - BACKGROUND: Single-site studies have demonstrated inadequate quality of discharge
summaries in timeliness, transmission, and content, potentially contributing to
adverse outcomes. However, degree of hospital-level variation in discharge
summary quality for patients hospitalized with heart failure (HF) is uncertain.
METHODS AND RESULTS: We analyzed discharge summaries of patients enrolled in the
Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) study. We assessed
hospital-level performance on timeliness (fraction of summaries completed on the
day of discharge), documented transmission to the follow-up physician, and
content (presence of components suggested by the Transitions of Care Consensus
Conference). We obtained 1501 discharge summaries from 1640 (91.5%) patients
discharged alive from 46 hospitals. Among hospitals contributing >= 10 summaries,
the median hospital dictated 69.2% of discharge summaries on the day of discharge
(range, 0.0%-98.0%; P<0.001); documented transmission of 33.3% of summaries to
the follow-up physician (range, 0.0%-75.7%; P<0.001); and included 3.6 of 7
Transitions of Care Consensus Conference elements (range, 2.9-4.5; P<0.001).
Hospital course was typically included (97.2%), but summaries were less likely to
include discharge condition (30.7%), discharge volume status (16.0%), or
discharge weight (15.7%). No discharge summary included all 7 Transitions of Care
Consensus Conference-endorsed content elements, was dictated on the day of
discharge, and was sent to a follow-up physician. CONCLUSIONS: Even at the
highest performing hospital, discharge summary quality is insufficient in terms
of timeliness, transmission, and content. Improvements in all aspects of
discharge summary quality are necessary to enable the discharge summary to serve
as an effective transitional care tool.
PMID- 25587093
TI - Validity of international classification of disease codes to identify ischemic
stroke and intracranial hemorrhage among individuals with associated diagnosis of
atrial fibrillation.
AB - BACKGROUND: Because of its association with death and disability, stroke is a
focus of outcomes in atrial fibrillation (AF) research. International
Classification of Disease-Ninth Revision (ICD-9) edition codes are commonly used
to identify stroke in research, particularly in large administrative data. We
sought to assess the validity of ICD-9 codes in stroke case ascertainment and for
AF across 3 institutions. METHODS AND RESULTS: Participating centers included
Boston Medical Center (safety net hospital), Geisinger Health System (rural
Pennsylvania), and the University of Alabama (academic center in the southeastern
stroke belt). ICD-9 codes for ischemic stroke (433-434, 436) and intracranial
hemorrhage (430-432) identified 1812 stroke cases with an associated code for AF
(427.31) from 2006 to 2010. Cases were vetted through chart review with final
adjudication by a stroke neurologist. Review considered 94.2% of ICD-9 identified
stroke cases valid with decreased accuracy for concurrent AF diagnosis (82.28%)
and stroke attributable to AF (72.8%). Among events with "without infarction"
modifiers, 7.2% were valid strokes. ICD-9 stroke code accuracy did not differ by
stroke type or site. Stroke code 434 displayed higher accuracy than 433 (94.4%
versus 85.2%; P<0.01), and primary stroke codes were more accurate than
nonprimary codes (97.2% versus 83.7%; P<0.0001). CONCLUSIONS: Using ICD-9 stroke
and AF codes to identify patients with stroke plus AF resulted in inaccuracies.
Given the expanded financial and policy implications of patient-oriented
research, conclusions derived solely from administrative data without validation
of outcome events should be interpreted with caution.
PMID- 25587095
TI - Age-specific performance of the revised cardiac risk index for predicting
cardiovascular risk in elective noncardiac surgery.
AB - BACKGROUND: The revised cardiac risk index (RCRI) holds a central role in
preoperative cardiac risk stratification in noncardiac surgery. Its performance
in unselected populations, including different age groups, has, however, not been
systematically investigated. We assessed the relationship of RCRI with major
adverse cardiovascular events in an unselected cohort of patients undergoing
elective, noncardiac surgery overall and in different age groups. METHODS AND
RESULTS: We followed up all individuals >= 25 years who underwent major elective
noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30
day risk of major adverse cardiovascular events (ischemic stroke, myocardial
infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of
74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse
cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable
odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence
interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart
failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin
therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI
classes as a continuous variable, C statistic was highest among age group 56 to
65 years (0.772) and lowest for those aged >85 years (0.683). Sensitivity of RCRI
class >I (ie, having >= 1 risk factor) for capturing major adverse cardiovascular
events was 59%, 71%, 64%, 66%, and 67% in patients aged <= 55, 56 to 65, 66 to
75, 76 to 85, and >85 years, respectively; the negative predictive values were
>98% across all age groups. CONCLUSIONS: In a nationwide unselected cohort, the
performance of the RCRI was similar to that of the original cohort. Having >= 1
risk factor was of moderate sensitivity, but high negative predictive value for
all ages.
PMID- 25587094
TI - Conflicting results between randomized trials and observational studies on the
impact of proton pump inhibitors on cardiovascular events when coadministered
with dual antiplatelet therapy: systematic review.
AB - BACKGROUND: Discordant results have been reported on the effects of concomitant
use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for
cardiovascular outcomes. We conducted a systematic review comparing the
effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge
treatment of unstable angina/non-ST-segment-elevation myocardial infarction
patients. METHODS AND RESULTS: We searched for clinical studies in MEDLINE,
EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012.
Reviewers screened and extracted data, assessed applicability and quality, and
graded the strength of evidence. We performed meta-analyses of direct comparisons
when outcomes and follow-up periods were comparable. Thirty-five studies were
eligible. Five (4 randomized controlled trials and 1 observational) assessed the
effect of omeprazole when added to DAPT; the other 30 (observational) assessed
the effect of PPIs as a class when compared with no PPIs. Random-effects meta
analyses of the studies assessing PPIs as a class consistently reported higher
event rates in patients receiving PPIs for various clinical outcomes at 1 year
(composite ischemic end points, all-cause mortality, nonfatal MI, stroke,
revascularization, and stent thrombosis). However, the results from randomized
controlled trials evaluating omeprazole compared with placebo showed no
difference in ischemic outcomes, despite a reduction in upper gastrointestinal
bleeding with omeprazole. CONCLUSIONS: Large, well-conducted observational
studies of PPIs and randomized controlled trials of omeprazole seem to provide
conflicting results for the effect of PPIs on cardiovascular outcomes when
coadministered with DAPT. Prospective trials that directly compare
pharmacodynamic parameters and clinical events among specific PPI agents in
patients with unstable angina/non-ST-segment-elevation myocardial infarction
treated with DAPT are warranted.
PMID- 25587096
TI - Cellular postconditioning: allogeneic cardiosphere-derived cells reduce infarct
size and attenuate microvascular obstruction when administered after reperfusion
in pigs with acute myocardial infarction.
AB - BACKGROUND: Intracoronary delivery of cardiosphere-derived cells (CDCs) has been
demonstrated to be safe and effective in porcine and human chronic myocardial
infarction. However, intracoronary delivery of CDCs after reperfusion in acute
myocardial infarction has never been assessed in a clinically-relevant large
animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine
model of myocardial infarction. METHODS AND RESULTS: First, escalating doses (5,
7.5, and 10 million cells) of allogeneic CDCs were administered intracoronary 30
minutes after reperfusion. Forty-eight hours later, left ventriculography was
performed and animals euthanized to measure area at risk, infarct size (IS), and
microvascular obstruction. Second, identical end points were measured in a
pivotal study of minipigs (n=14) that received 8.5 to 9 million allogeneic CDCs,
placebo solution, or sham. Multiple indicators of cardioprotection were observed
with 7.5 and 10 million allogeneic CDCs, but not 5 million CDCs, relative to
control. In the pivotal study, IS, microvascular obstruction, cardiomyocyte
apoptosis, and adverse left ventricular remodeling were all smaller in the CDC
group than in sham or placebo groups. In addition, serum troponin I level at 24
hours was lower after CDC infusion than that in the placebo or sham groups,
consistent with the histologically-demonstrated reduction in IS. CONCLUSIONS:
Intracoronary delivery of allogeneic CDCs is safe, feasible, and effective in
cardioprotection, reducing IS, preventing microvascular obstruction, and
attenuating adverse acute remodeling. This novel cardioprotective effect, which
we call cellular postconditioning, differs from previous strategies to reduce IS
in that it works even when initiated with significant delay after reflow.
PMID- 25587098
TI - lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing
endogenous RNA.
AB - RATIONALE: Pathological angiogenesis is a critical component of diseases, such as
ocular disorders, cancers, and atherosclerosis. It is usually caused by the
abnormal activity of biological processes, such as cell proliferation, cell
motility, immune, or inflammation response. Long noncoding RNAs (lncRNAs) have
emerged as critical regulators of these biological processes. However, the role
of lncRNA in diabetes mellitus-induced microvascular dysfunction is largely
unknown. OBJECTIVE: To elucidate whether lncRNA-myocardial infarction-associated
transcript (MIAT) is involved in diabetes mellitus-induced microvascular
dysfunction. METHODS AND RESULTS: Using quantitative polymerase chain reaction,
we demonstrated increased expression of lncRNA-MIAT in diabetic retinas and
endothelial cells cultured in high glucose medium. Visual electrophysiology
examination, TUNEL staining, retinal trypsin digestion, vascular permeability
assay, and in vitro studies revealed that MIAT knockdown obviously ameliorated
diabetes mellitus-induced retinal microvascular dysfunction in vivo, and
inhibited endothelial cell proliferation, migration, and tube formation in vitro.
Bioinformatics analysis, luciferase assay, RNA immunoprecipitation, and in vitro
studies revealed that MIAT functioned as a competing endogenous RNA, and formed a
feedback loop with vascular endothelial growth factor and miR-150-5p to regulate
endothelial cell function. CONCLUSIONS: This study highlights the involvement of
lncRNA-MIAT in pathological angiogenesis and facilitates the development of
lncRNA-directed diagnostics and therapeutics against neovascular diseases.
PMID- 25587097
TI - Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal
transition.
AB - RATIONALE: Endocardial fibroelastosis (EFE) is a unique form of fibrosis, which
forms a de novo subendocardial tissue layer encapsulating the myocardium and
stunting its growth, and which is typically associated with congenital heart
diseases of heterogeneous origin, such as hypoplastic left heart syndrome.
Relevance of EFE was only recently highlighted through the establishment of
staged biventricular repair surgery in infant patients with hypoplastic left
heart syndrome, where surgical removal of EFE tissue has resulted in improvement
in the restrictive physiology leading to the growth of the left ventricle in
parallel with somatic growth. However, pathomechanisms underlying EFE formation
are still scarce, and specific therapeutic targets are not yet known. OBJECTIVE:
Here, we aimed to investigate the cellular origins of EFE tissue and to gain
insights into the underlying molecular mechanisms to ultimately develop novel
therapeutic strategies. METHODS AND RESULTS: By utilizing a novel EFE model of
heterotopic transplantation of hearts from newborn reporter mice and by analyzing
human EFE tissue, we demonstrate for the first time that fibrogenic cells within
EFE tissue originate from endocardial endothelial cells via aberrant endothelial
to mesenchymal transition. We further demonstrate that such aberrant endothelial
to mesenchymal transition involving endocardial endothelial cells is caused by
dysregulated transforming growth factor beta/bone morphogenetic proteins
signaling and that this imbalance is at least in part caused by aberrant promoter
methylation and subsequent transcriptional suppression of bone morphogenetic
proteins 5 and 7. Finally, we provide evidence that supplementation of exogenous
recombinant bone morphogenetic proteins 7 effectively ameliorates endothelial to
mesenchymal transition and experimental EFE in rats. CONCLUSIONS: In summary, our
data point to aberrant endothelial to mesenchymal transition as a common
denominator of infant EFE development in heterogeneous, congenital heart
diseases, and to bone morphogenetic proteins 7 as an effective treatment for EFE
and its restriction of heart growth.
PMID- 25587099
TI - Predicting graft loss by 1 year in pediatric heart transplantation candidates: an
analysis of the Pediatric Heart Transplant Study database.
AB - BACKGROUND: Pediatric data on the impact of pre-heart transplantation (HTx) risk
factors on early post-HTx outcomes remain inconclusive. Thus, among patients with
previous congenital heart disease or cardiomyopathy, disease-specific risk models
for graft loss were developed with the use pre-HTx recipient and donor
characteristics. METHODS AND RESULTS: Patients enrolled in the Pediatric Heart
Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis
into cardiomyopathy and congenital heart disease cohorts. Logistic regression
identified independent, pre-HTx risk factors. Risk models were constructed for 1
year post-HTx graft loss. Donor factors were added for model refinement. The
models were validated with the use of patients transplanted from 2007 to 2009.
Risk factors for graft loss were identified in patients with cardiomyopathy
(n=896) and congenital heart disease (n=965). For cardiomyopathy, independent
risk factors were earlier year of transplantation, nonwhite race, female sex,
diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and
panel reactive antibody >10%. The recipient characteristic risk model had good
accuracy in the validation cohort, with predicted versus actual survival of 97.5%
versus 95.3% (C statistic, 0.73). For patients with congenital heart disease,
independent risk factors were nonwhite race, history of Fontan, ventilator
dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower
body surface area. The risk model was less accurate, with 86.6% predicted versus
92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor
characteristics did not enhance model precision. CONCLUSIONS: Risk factors for 1
year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis.
Modeling effectively stratifies the risk of graft loss in patients with
cardiomyopathy and may be an adjunctive tool in allocation policies and center
performance metrics.
PMID- 25587100
TI - Systematic review of patients presenting with suspected myocardial infarction and
nonobstructive coronary arteries.
AB - BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA)
is a puzzling clinical entity with no previous evaluation of the literature. This
systematic review aims to (1) quantify the prevalence, risk factors, and 12-month
prognosis in patients with MINOCA, and (2) evaluate potential pathophysiological
mechanisms underlying this disorder. METHODS AND RESULTS: Quantitative assessment
of 28 publications using a meta-analytic approach evaluated the prevalence,
clinical features, and prognosis of MINOCA. The prevalence of MINOCA was 6% [95%
confidence interval, 5%-7%] with a median patient age of 55 years (95% confidence
interval, 51-59 years) and 40% women. However, in comparison with those with
myocardial infarction associated with obstructive coronary artery disease, the
patients with MINOCA were more likely to be younger and female but less likely to
have hyperlipidemia, although other cardiovascular risk factors were similar. All
cause mortality at 12 months was lower in MINOCA (4.7%; 95% confidence interval,
2.6%-6.9%) compared with myocardial infarction associated with obstructive
coronary artery disease (6.7%, 95% confidence interval, 4.3%-9.0%). Qualitative
assessment of 46 publications evaluating the underlying pathophysiology
responsible for MINOCA revealed the presence of a typical myocardial infarct on
cardiac magnetic resonance imaging in only 24% of patients, with myocarditis
occurring in 33% and no significant abnormality in 26%. Coronary artery spasm was
inducible in 27% of MINOCA patients, and thrombophilia disorders were detected in
14%. CONCLUSIONS: MINOCA should be considered as a working diagnosis with
multiple potential causes that require evaluation so that directed therapies may
improve its guarded prognosis.
PMID- 25587101
TI - Inhibition of PKR impairs angiogenesis through a VEGF pathway.
AB - Peripheral artery disease (PAD) is a common clinical problem, and its
pathophysiological mechanisms are incompletely understood. Double-stranded RNA
activated protein kinase (PKR) is a ubiquitously expressed serine/threonine
protein kinase. Although PKR has been reported in antivirus and the immune
system, the role of PKR in vascular function, especially in angiogenesis, is
still unclear. PKR(-/-) mice were used in our experiments. Blood flow recovery
was significantly delayed in PKR(-/-) vs. WT mice (Laser Doppler detection, n =
9, P < 0.01), accompanied by 34% reduced CD31-positive stain in ischemic muscle
28 days after procedure (immunohistochemistry, n = 9, P < 0.05). PKR expression
decreased in the first 12 h and increased to peak at 24 h in human umbilical vein
endothelial cells (HUVECs) in response to hypoxia (Western blot analyses, n = 3,
P < 0.05). Accordingly, phospho-PKR expression increased in HUVECs 24 h after
treatment with hypoxia (Western blot analyses, n = 3, P < 0.05). Inhibition of
PKR (siRNA transfection) reduced microtubule formation (Matrigel tube formation,
n = 3, vs. control siRNA, P < 0.05) and migration (wound healing, n = 3, vs.
control siRNA, P < 0.05) by 33 and 59%, respectively. Vascular endothelial growth
factor (VEGF) expression in ischemic muscle from PKR(-/-) mice was significantly
decreased by 54% 1 day after procedure (n = 3, P < 0.05, vs. WT) and by 63% 7
days after procedure (n = 3, P < 0.01, vs. WT), respectively. At the same time,
VEGF expression in HUVECs decreased by 21% (n = 3, P < 0.05, PKR siRNA vs.
control siRNA). These findings demonstrate that PKR mediates angiogenesis through
a VEGF pathway, which may form the basis for future intervention of PAD.
PMID- 25587103
TI - Alternative strategies needed to improve vascular access outcomes.
PMID- 25587104
TI - Preventing aristolochic acid nephropathy.
PMID- 25587106
TI - News feature: The search for what sets humans apart.
PMID- 25587105
TI - Provider visit frequency and vascular access interventions in hemodialysis.
AB - BACKGROUND AND OBJECTIVES: Medicare reimbursement policy encourages frequent
provider visits to patients with ESRD undergoing hemodialysis. This study sought
to determine whether more frequent face-to-face provider (physician and advanced
practitioner) visits lead to more procedures and therapeutic interventions aimed
at preserving arteriovenous fistulas and grafts, improved vascular access
outcomes, and fewer related hospitalizations. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: Multivariable regression was used to evaluate the association
between provider (physician and advanced practitioner) visit frequency and
interventions aimed at preserving vascular access, vascular access survival,
hospitalization for vascular access infection, and outpatient antibiotic use in a
cohort of 63,488 Medicare beneficiaries receiving hemodialysis in the United
States. Medicare claims were used to identify the type of vascular access used,
access-related events, and vascular access failure. RESULTS: One additional
provider (physician and advanced practitioner) visit per month was associated
with a 13% higher odds of receiving an intervention to preserve vascular access
(95% confidence interval [95% CI], 12% to 14%) but was not associated with
vascular access survival (hazard ratio, 1.01; 95% CI, 0.99 to 1.03). One
additional provider visit was associated with a 9% (95% CI, 5% to 14%) lower odds
of hospitalization for vascular access infection and a corresponding 9% (95% CI,
5% to 14%) higher odds of outpatient intravenous antibiotic administration.
However, the associated changes in absolute probabilities of hospitalization and
antibiotic administration were small. CONCLUSIONS: More frequent face-to-face
provider (physician and advanced practitioner) visits were associated with more
procedures and therapeutic interventions aimed at preserving vascular accesses,
but not with prolonged vascular access survival and only a small decrease in
hospitalization for vascular access.
PMID- 25587102
TI - Chronic dietary exposure to aristolochic acid and kidney function in native
farmers from a Croatian endemic area and Bosnian immigrants.
AB - BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have
reduced exposure to consumption of aristolochic acid-contaminated flour and
development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that
Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago
would be at lower risk of developing endemic nephropathy because of reduced
exposure to aristolochic acid. To test this hypothesis, past and present exposure
to aristolochic acid, proximal tubule damage as a hallmark of endemic
nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN,
SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational
study from 2005 to 2010, 2161 farmers were divided into groups: indigenous
inhabitants from endemic nephropathy and nonendemic nephropathy villages and
Bosnian immigrants; alpha-1 microglobulin-to-creatinine ratio >31.5 mg/g and
eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and
proximal tubule damage prevalence was significantly lower in Bosnian immigrants
than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001;
1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants
observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%)
and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than
homemade bread compared with Croatian farmers from endemic nephropathy villages
(38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants
observe significantly fewer Aristolochia plants growing in their fields compared
with 15-30 years ago. Prior aristolochic acid exposure was associated with
proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58;
P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence
interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent
negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence
interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and
autochthonous Croats residing in endemic areas are exposed significantly less to
ingestion of aristolochic acid than in the past. The prevalence of endemic
nephropathy and its associated urothelial cancers is predicted to decrease over
time.
PMID- 25587109
TI - An epidemiologic review of marijuana and cancer: an update.
AB - Marijuana use is legal in two states and additional states are considering
legalization. Approximately 18 million Americans are current marijuana users.
There is currently no consensus on whether marijuana use is associated with
cancer risk. Our objective is to review the epidemiologic studies on this
possible association. We identified 34 epidemiologic studies on upper
aerodigestive tract cancers (n = 11), lung cancer (n = 6), testicular cancer (n =
3), childhood cancers (n = 6), all cancers (n = 1), anal cancer (n = 1), penile
cancer (n = 1), non-Hodgkin lymphoma (n = 2), malignant primary gliomas (n = 1),
bladder cancer (n = 1), and Kaposi sarcoma (n = 1). Studies on head and neck
cancer reported increased and decreased risks, possibly because there is no
association, or because risks differ by human papillomavirus status or geographic
differences. The lung cancer studies largely appear not to support an association
with marijuana use, possibly because of the smaller amounts of marijuana
regularly smoked compared with tobacco. Three testicular cancer case-control
studies reported increased risks with marijuana use [summary ORs, 1.56; 95%
confidence interval (CI), 1.09-2.23 for higher frequency and 1.50 (95% CI, 1.08
2.09) for >=10 years]. For other cancer sites, there is still insufficient data
to make any conclusions. Considering that marijuana use may change due to
legalization, well-designed studies on marijuana use and cancer are warranted.
PMID- 25587112
TI - Correction: Androgen Receptor CAG Repeat Polymorphism and Risk of TMPRSS2:ERG
Positive Prostate Cancer.
PMID- 25587110
TI - Sun protection practices and sun exposure among children with a parental history
of melanoma.
AB - BACKGROUND: First-degree relatives of melanoma survivors have a substantially
higher lifetime risk for melanoma than individuals with no family history.
Exposure to ultraviolet radiation (UVR) is the primary modifiable risk factor for
the disease. Reducing UV exposure through sun protection may be particularly
important for children with a parental history of melanoma. Nonetheless, limited
prior research has investigated sun protection practices and sun exposure among
these children. METHODS: The California Cancer Registry was used to identify
melanoma survivors eligible to participate in a survey to assess their children's
sun protection practices and sun exposure. The survey was administered by mail,
telephone, or web to Latino and non-Latino white melanoma survivors with at least
one child (0-17 years; N = 324). RESULTS: Sun exposure was high and the rate of
sunburn was equivalent to or higher than estimates from average-risk populations.
Use of sun protection was suboptimal. Latino children were less likely to wear
sunscreen and hats and more likely to wear sunglasses, although these differences
disappeared in adjusted analyses. Increasing age of the child was associated with
lower sun protection and higher risk for sunburn, whereas higher objective risk
for melanoma predicted improved sun protection and a higher risk for sunburns.
Perception of high barriers to sun protection was the strongest modifiable
correlate of sun protection. CONCLUSIONS: Interventions to improve sun protection
and reduce sun exposure and sunburns in high-risk children are needed. IMPACT:
Intervening in high-risk populations may help reduce the burden of melanoma in
the United States.
PMID- 25587113
TI - Correction: weight change and survival after breast cancer in the after breast
cancer pooling project.
PMID- 25587111
TI - Metabolic syndrome and risk of endometrial cancer in the united states: a study
in the SEER-medicare linked database.
AB - BACKGROUND: Metabolic syndrome and its component feature, central obesity, are
associated with endometrial cancer risk. It remains unclear whether associations
with the other metabolic factors that comprise metabolic syndrome are independent
of the obesity-endometrial cancer association. Furthermore, the link with
specific endometrial cancer subtypes remains ill-defined, despite evidence of
etiologic heterogeneity among these tumors. METHODS: In a case-control study
within the SEER-Medicare linked database, we examined whether metabolic factors,
individually or combined, were associated with endometrial cancer. Cases (n =
16,323) were women diagnosed with endometrial cancer from 1993 through 2007.
Controls (n = 100,751) were a 5% sample of female Medicare enrollees residing in
the same SEER registry area as cases. Metabolic syndrome was defined using ICD-9
CM codes from inpatient/outpatient diagnoses 1 to 3 years before case diagnosis
and a comparable time period in controls. ORs and 95% confidence intervals (CI)
were estimated using logistic regression. RESULTS: Endometrial cancer risk was
associated with metabolic syndrome [OR (95% CI): 1.39 (1.32-1.47)] and its
component factors: overweight/obesity [1.95 (1.80-2.11)], impaired fasting
glucose [1.36 (1.30-1.43)], high blood pressure [1.31 (1.25-1.36)], and high
triglycerides [1.13 (1.08-1.18)]. After adjusting for overweight/obesity, the
increased risks associated with the metabolic syndrome factors remained.
Heterogeneity of associations by subtype were not identified (Pheterogeneity =
0.82). CONCLUSIONS: Among women age 65 and older in the United States, metabolic
syndrome, and its component factors, increased endometrial cancer risk similarly
across endometrial cancer subtypes. IMPACT: Strategies to reduce the prevalence
of metabolic syndrome factors might have a favorable effect on endometrial cancer
incidence.
PMID- 25587114
TI - Laser speckle contrast imaging reveals large-scale synchronization of cortical
autoregulation dynamics influenced by nitric oxide.
AB - Synchronization of tubuloglomerular feedback (TGF) dynamics in nephrons that
share a cortical radial artery is well known. It is less clear whether
synchronization extends beyond a single cortical radial artery or whether it
extends to the myogenic response (MR). We used LSCI to examine cortical perfusion
dynamics in isoflurane-anesthetized, male Long-Evans rats. Inhibition of nitric
oxide synthases by N(omega)-nitro-l-arginine methyl ester (l-NAME) was used to
alter perfusion dynamics. Phase coherence (PC) was determined between all
possible pixel pairs in either the MR or TGF band (0.09-0.3 and 0.015-0.06 Hz,
respectively). The field of view (~4 * 5 mm) was segmented into synchronized
clusters based on mutual PC. During the control period, the field of view was
often contained within one cluster for both MR and TGF. PC was moderate for TGF
and modest for MR, although significant in both. In both MR and TGF, PC exhibited
little spatial variation. After l-NAME, the number of clusters increased in both
MR and TGF. MR clusters became more strongly synchronized while TGF clusters
showed small highly coupled, high-PC regions that were coupled with low PC to the
remainder of the cluster. Graph theory analysis probed modularity of
synchronization. It confirmed weak synchronization of MR during control that
probably was not physiologically relevant. It confirmed extensive and long
distance synchronization of TGF during control and showed increased modularity,
albeit with larger modules seen in MR than in TGF after l-NAME. The results show
widespread synchronization of MR and TGF that is differentially affected by
nitric oxide.
PMID- 25587115
TI - Expression of a dominant negative PKA mutation in the kidney elicits a diabetes
insipidus phenotype.
AB - PKA plays a critical role in water excretion through regulation of the production
and action of the antidiuretic hormone arginine vasopressin (AVP). The AVP
prohormone is produced in the hypothalamus, where its transcription is regulated
by cAMP. Once released into the circulation, AVP stimulates antidiuresis through
activation of vasopressin 2 receptors in renal principal cells. Vasopressin 2
receptor activation increases cAMP and activates PKA, which, in turn,
phosphorylates aquaporin (AQP)2, triggering apical membrane accumulation,
increased collecting duct permeability, and water reabsorption. We used single
minded homolog 1 (Sim1)-Cre recombinase-mediated expression of a dominant
negative PKA regulatory subunit (RIalphaB) to disrupt kinase activity in vivo and
assess the role of PKA in fluid homeostasis. RIalphaB expression gave rise to
marked polydipsia and polyuria; however, neither hypothalamic Avp mRNA expression
nor urinary AVP levels were attenuated, indicating a primary physiological effect
on the kidney. RIalphaB mice displayed a marked deficit in urinary concentrating
ability and greatly reduced levels of AQP2 and phospho-AQP2. Dehydration induced
Aqp2 mRNA in the kidney of both control and RIalphaB-expressing mice, but AQP2
protein levels were still reduced in RIalphaB-expressing mutants, and mice were
unable to fully concentrate their urine and conserve water. We conclude that
partial PKA inhibition in the kidney leads to posttranslational effects that
reduce AQP2 protein levels and interfere with apical membrane localization. These
findings demonstrate a distinct physiological role for PKA signaling in both
short- and long-term regulation of AQP2 and characterize a novel mouse model of
diabetes insipidus.
PMID- 25587117
TI - Shear stress is normalized in glomerular capillaries following 5/6 nephrectomy.
AB - Loss of significant functional renal mass results in compensatory structural and
hemodynamic adaptations in the nephron. While these changes have been
characterized in several injury models, how they affect hemodynamic forces at the
glomerular capillary wall has not been adequately characterized, despite their
potential physiological significance. Therefore, we used intravital multiphoton
microscopy to measure the velocity of red blood cells in individual glomerular
capillaries of normal rats and rats subjected to 5/6 nephrectomy. Glomerular
capillary blood flow rate and wall shear stress were then estimated using
previously established experimental and mathematical models to account for
changes in hematocrit and blood rheology in small vessels. We found little change
in the hemodynamic parameters in glomerular capillaries immediately following
injury. At 2 wk postnephrectomy, significant changes in individual capillary
blood flow velocity and volume flow rate were present. Despite these changes,
estimated capillary wall shear stress was unchanged. This was a result of an
increase in capillary diameter and changes in capillary blood rheology in
nephrectomized rats.
PMID- 25587116
TI - Prolactin stimulates sodium and chloride ion channels in A6 renal epithelial
cells.
AB - Many hormonal pathways contribute to the regulation of renal epithelial sodium
channel (ENaC) function, a key process for maintaining blood volume and
controlling blood pressure. In the present study, we examined whether the peptide
hormone prolactin (PRL) regulates ENaC function in renal epithelial cells (A6).
Basolateral application of several different concentrations of PRL dramatically
stimulated the transepithelial current in A6 cells, increasing both amiloride
sensitive (ENaC) and amiloride-insensitive currents. Using cell-attached patch
clamp, we determined that PRL increased both the number (N) and open probability
(Po) of ENaC present in the apical membrane. Inhibition of PKA with H-89
abolished the effect of PRL on amiloride-sensitive and insensitive
transepithelial currents and eliminated the increase in ENaC NPo with PRL
exposure. PRL also increased cAMP in A6 cells, consistent with signaling through
the cAMP-dependent PKA pathway. We also identified that PRL induced activity of a
2-pS anion channel with outward rectification, electrophysiological properties
consistent with ClC4 or ClC5. RT-PCR only detected ClC4, but not ClC5
transcripts. Here, we show for the first time that PRL activates sodium and
chloride transport in renal epithelial cells via ENaC and ClC4.
PMID- 25587118
TI - Chloride channel ClC-5 binds to aspartyl aminopeptidase to regulate renal albumin
endocytosis.
AB - ClC-5 is a chloride/proton exchanger that plays an obligate role in albumin
uptake by the renal proximal tubule. ClC-5 forms an endocytic complex with the
albumin receptor megalin/cubilin. We have identified a novel ClC-5 binding
partner, cytosolic aspartyl aminopeptidase (DNPEP; EC 3.4.11.21), that catalyzes
the release of N-terminal aspartate/glutamate residues. The physiological role of
DNPEP remains largely unresolved. Mass spectrometric analysis of proteins binding
to the glutathione-S-transferase (GST)-ClC-5 C terminus identified DNPEP as an
interacting partner. Coimmunoprecipitation confirmed that DNPEP and ClC-5 also
associated in cells. Further experiments using purified GST-ClC-5 and His-DNPEP
proteins demonstrated that the two proteins bound directly to each other. In
opossum kidney (OK) cells, confocal immunofluorescence studies revealed that
DNPEP colocalized with albumin-containing endocytic vesicles. Overexpression of
wild-type DNPEP increased cell-surface levels of ClC-5 and albumin uptake.
Analysis of DNPEP-immunoprecipitated products from rat kidney lysate identified
beta-actin and tubulin, suggesting a role for DNPEP in cytoskeletal maintenance.
A DNase I inhibition assay showed a significant decrease in the amount of G actin
when DNPEP was overexpressed in OK cells, suggesting a role for DNPEP in
stabilizing the cytoskeleton. DNPEP was not present in the urine of healthy rats;
however, it was readily detected in the urine in rat models of mild and heavy
proteinuria (diabetic nephropathy and anti-glomerular basement membrane disease,
respectively). Urinary levels of DNPEP were found to correlate with the severity
of proteinuria. Therefore, we have identified another key molecular component of
the albumin endocytic machinery in the renal proximal tubule and describe a new
role for DNPEP in stabilizing the actin cytoskeleton.
PMID- 25587119
TI - Urinary proteins induce lysosomal membrane permeabilization and lysosomal
dysfunction in renal tubular epithelial cells.
AB - Lysosomal membrane permeabilization (LMP) has been shown to cause the release of
cathepsins and other hydrolases from the lysosomal lumen to the cytosol and
initiate a cell death pathway. Whether proteinuria triggers LMP in renal tubular
epithelial cells (TECs) to accelerate the progression of renal tubulointerstitial
injury remains unclear. In the present study, we evaluated TEC injury as well as
changes in lysosomal number, volume, activity, and membrane integrity after
urinary protein overload in vivo and in vitro. Our results revealed that
neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels
were significantly increased in the urine of patients with minimal change
nephrotic syndrome (MCNS) and the culture supernatant of HK-2 cells treated by
urinary proteins extracted from MCNS patients. Urinary protein overload also
induced apoptotic cell death in HK-2 cells. Importantly, we found that lysosomal
volume and number were markedly increased in TECs of patients with MCNS and HK-2
cells overloaded with urinary proteins. However, lysosome function, as assessed
by proteolytic degradation of DQ-ovalbumin and cathepsin-B and cathepsin-L
activities, was decreased in HK-2 cells overloaded with urinary proteins.
Furthermore, urinary protein overload led to a diffuse cytoplasmic immunostaining
pattern of cathepsin-B and irregular immunostaining of lysosome-associated
membrane protein-1, accompanying a reduction in intracellular acidic components,
which could be improved by pretreatment with antioxidant. Taken together, our
results indicate that overloading of urinary proteins caused LMP and lysosomal
dysfunction at least partly via oxidative stress in TECs.
PMID- 25587120
TI - Mitochondrial dysfunction in uremic cardiomyopathy.
AB - Uremic cardiomyopathy (UCM) is characterized by metabolic remodelling,
compromised energetics, and loss of insulin-mediated cardioprotection, which
result in unsustainable adaptations and heart failure. However, the role of
mitochondria and the susceptibility of mitochondrial permeability transition pore
(mPTP) formation in ischemia-reperfusion injury (IRI) in UCM are unknown. Using a
rat model of chronic uremia, we investigated the oxidative capacity of
mitochondria in UCM and their sensitivity to ischemia-reperfusion mimetic oxidant
and calcium stressors to assess the susceptibility to mPTP formation. Uremic
animals exhibited a 45% reduction in creatinine clearance (P < 0.01), and cardiac
mitochondria demonstrated uncoupling with increased state 4 respiration.
Following IRI, uremic mitochondria exhibited a 58% increase in state 4
respiration (P < 0.05), with an overall reduction in respiratory control ratio (P
< 0.01). Cardiomyocytes from uremic animals displayed a 30% greater vulnerability
to oxidant-induced cell death determined by FAD autofluorescence (P < 0.05) and
reduced mitochondrial redox state on exposure to 200 MUM H2O2 (P < 0.01). The
susceptibility to calcium-induced permeability transition showed that maximum
rates of depolarization were enhanced in uremia by 79%. These results demonstrate
that mitochondrial respiration in the uremic heart is chronically uncoupled.
Cardiomyocytes in UCM are characterized by a more oxidized mitochondrial network,
with greater susceptibility to oxidant-induced cell death and enhanced
vulnerability to calcium-induced mPTP formation. Collectively, these findings
indicate that mitochondrial function is compromised in UCM with increased
vulnerability to calcium and oxidant-induced stressors, which may underpin the
enhanced predisposition to IRI in the uremic heart.
PMID- 25587121
TI - Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation.
AB - Unique situations in female physiology require volume retention. Accordingly, a
dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC)
has been reported, with a higher activity in females than in males. However,
little is known about the hormones and mechanisms involved. Here, we present
evidence that estrogens, progesterone, and prolactin stimulate NCC expression and
phosphorylation. The sex difference in NCC abundance, however, is species
dependent. In rats, NCC phosphorylation is higher in females than in males, while
in mice both NCC expression and phosphorylation is higher in females, and this is
associated with increased expression and phosphorylation of full-length STE-20
proline-alanine-rich kinase (SPAK). Higher expression/phosphorylation of NCC was
corroborated in humans by urinary exosome analysis. Ovariectomy in rats resulted
in decreased expression and phosphorylation of the cotransporter and promoted the
shift of SPAK isoforms toward the short inhibitory variant SPAK2. Conversely,
estradiol or progesterone administration to ovariectomized rats restored NCC
phosphorylation levels and shifted SPAK expression and phosphorylation towards
the full-length isoform. Estradiol administration to male rats induced a
significant increase in NCC phosphorylation. NCC is also modulated by prolactin.
Administration of this peptide hormone to male rats induced increased
phosphorylation of NCC, an effect that was observed even using the ex vivo kidney
perfusion strategy. Our results indicate that estradiol, progesterone, and
prolactin, the hormones that are involved in sexual cycle, pregnancy and
lactation, upregulate the activity of NCC.
PMID- 25587124
TI - Transdermal contraception and the renin-angiotensin-aldosterone system in
premenopausal women.
AB - The oral contraceptive pill (OCP) activates the renin-angiotensin-aldosterone
system (RAAS) through first-pass hepatic metabolism. Although usually benign,
RAAS activation may have detrimental effects on renal and hemodynamic function in
some women. Since combined hormonal contraception with the transdermal patch
(EVRA) does not undergo first-pass hepatic metabolism, we hypothesized that the
RAAS response would be different from that of OCP subjects. Thirty-five
nonsmoking, premenopausal women (15 control subjects, 10 OCP subjects, and 10
contraceptive patch subjects) without evidence of cardiovascular disease, renal
disease, or diabetes were studied. Baseline angiotensinogen, renin, angiotensin
II, aldosterone, and plasma renin activity were assessed along with hormonal and
hemodynamic responses to simulated orthostatic stress using incremental lower
body negative pressure (LBNP; -15, -25, and -40 mmHg). Baseline levels of
angiotensinogen, angiotensin II, and plasma renin activity were significantly
higher in OCP subjects compared with normotensive control and contraceptive patch
subjects (P < 0.05), whereas aldosterone was significantly higher in OCP versus
control subjects only (P < 0.05). Plasma renin levels were significantly lower at
baseline in contraceptive patch subjects compared with normotensive control and
OCP subjects (P < 0.05). In response to LBNP, increases in renin, angiotensin II,
and aldosterone were attenuated in contraceptive patch subjects in conjunction
with an exaggerated decline in mean arterial pressure (P < 0.05 vs. control and
OCP subjects). The contraceptive patch in healthy premenopausal women is
associated with an impaired ability to maintain blood pressure in response to
LBNP, possibly due to insensitivity of the endogenous RAAS. Further evaluation
may be beneficial in women with kidney disease.
PMID- 25587122
TI - Flow regulation of endothelin-1 production in the inner medullary collecting
duct.
AB - Collecting duct-derived endothelin (ET)-1 is an autocrine inhibitor of Na(+) and
water reabsorption; its deficiency causes hypertension and water retention.
Extracellular fluid volume expansion increases collecting duct ET-1, thereby
promoting natriuresis and diuresis; however, how this coupling between volume
expansion and collecting duct ET-1 occurs is incompletely understood. One
possibility is that volume expansion increases tubular fluid flow. To investigate
this, cultured IMCD3 cells were subjected to static or flow conditions. Exposure
to a shear stress of 2 dyn/cm(2) for 2 h increased ET-1 mRNA content by ~2.3
fold. Absence of perfusate Ca(2+), chelation of intracellular Ca(2+), or
inhibition of Ca(2+) signaling (calmodulin, Ca(2+)/calmodulin-dependent kinase,
calcineurin, PKC, or phospholipase C) prevented the flow response. Evaluation of
possible flow-activated Ca(2+) entry pathways revealed no role for transient
receptor potential (TRP)C3, TRPC6, and TRPV4; however, cells with TRPP2
(polycystin-2) knockdown had no ET-1 flow response. Flow increased intracellular
Ca(2+) was blunted in TRPP2 knockdown cells. Nonspecific blockade of P2
receptors, as well as specific inhibition of P2X7 and P2Y2 receptors, prevented
the ET-1 flow response. The ET-1 flow response was not affected by inhibition of
either epithelial Na(+) channels or the mitochondrial Na(+)/Ca(2+) exchanger.
Taken together, these findings provide evidence that in IMCD3 cells, flow, via
polycystin-2 and P2 receptors, engages Ca(2+)-dependent signaling pathways that
stimulate ET-1 synthesis.
PMID- 25587126
TI - His and hers hypertension-down to a T?
PMID- 25587123
TI - Ret is critical for podocyte survival following glomerular injury in vivo.
AB - Podocyte injury and loss directly cause proteinuria and the progression to
glomerulosclerosis. Elucidation of the mechanisms of podocyte survival and
recovery from injury is critical for designing strategies to prevent the
progression of glomerular diseases. Glial cell line-derived neurotrophic factor
(GDNF) and its receptor tyrosine kinase, Ret, are upregulated in both nonimmune
and immune-mediated in vitro and in vivo models of glomerular diseases. We
investigated whether Ret, a known receptor tyrosine kinase critical for kidney
morphogenesis and neuronal growth and development, is necessary for glomerular
and podocyte development and survival in vivo. Since deletions of both GDNF and
Ret result in embryonic lethality due to kidney agenesis, we examined the role of
Ret in vivo by generating mice with a conditional deletion of Ret in podocytes
(Ret(flox/flox); Nphs2-Cre). In contrast to the lack of any developmental and
maintenance deficits, Ret(flox/flox); Nphs2-Cre mice showed a significantly
enhanced susceptibility to adriamycin nephropathy, a rodent model of focal
segmental glomerulosclerosis. Thus, these findings demonstrated that the Ret
signaling pathway is important for podocyte survival and recovery from glomerular
injury in vivo.
PMID- 25587125
TI - Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1
accelerates podocyte loss via uPAR-mediated beta1-integrin endocytosis.
AB - Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration
barrier. The present study investigated the endothelial response to podocyte
injury and its subsequent role in glomerulosclerosis using the podocyte-specific
injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local
podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an
increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and
aberrant endothelial PAI-1 protein already on day 1, before thrombosis and
proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and
preserved podocyte numbers in NEP25/LMB2 mice by stabilization of beta1-integrin
translocation. Heparin loading significantly reduced thrombotic formation,
whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes
treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused
significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or
with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody
failed to cause detachment. Confocal microscopy and cell surface biotinylation
experiments showed that internalized beta1-integrin was found together with uPAR
in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking
antibody protected cultured podocytes from cell detachment. In conclusion, PAI
1/uPA complex-mediated uPAR-dependent podocyte beta1-integrin endocytosis
represents a novel mechanism of glomerular injury leading to progressive
podocytopenia. This aberrant cross-talk between podocytes and endothelial cells
represents a feedforward injury response driving podocyte loss and progressive
glomerulosclerosis.
PMID- 25587127
TI - Mechanism-based inhibitory and peroxisome proliferator-activated receptor alpha
dependent modulating effects of silybin on principal hepatic drug-metabolizing
enzymes.
AB - Silybin, a major pharmacologically active compound in silymarin, has been widely
used in combination with other prescriptions in the clinic to treat hepatitis and
a host of other diseases. Previous studies suggested that silybin is a potential
inhibitor of multiple drug-metabolizing enzymes (DMEs); however, the in vitro to
in vivo translation and the mechanisms involved remain established. The aim of
this study was to provide a mechanistic understanding of the regulatory effects
of silybin on principal DMEs. Silybin (50 or 150 mg/kg/d) was administered to
mice for a consecutive 14 days. The plasma and hepatic exposure of silybin were
detected; the mRNA, protein levels, and enzyme activities of principal DMEs were
determined. The results demonstrated that the enzyme activities of CYP1A2, CYP2C,
CYP3A11, and UGT1A1 were significantly repressed, whereas little alteration of
the mRNA and protein levels was observed. Silybin inhibits these DMEs in a
mechanism-based and/or substrate-competitive manner. More importantly, silybin
was found to be a weak agonist of peroxisome proliferator-activated receptor
(PPAR)alpha, as evidenced from the molecular docking, reporter gene assay, and
the targeting gene expression analysis. However, silybin could significantly
compromise the activation of PPARalpha by fenofibrate, characterized with
significantly repressed expression of PPARalpha targeting genes, including L
FABP, ACOX1, and UGT1A6. This study suggests that silybin, despite its low
bioavailability, may inhibit enzyme activities of multiple DMEs in a mechanism
based mode, and more importantly, may confer significant drug-drug interaction
with PPARalpha agonists via the repression of PPARalpha activation in a
competitive mode.
PMID- 25587128
TI - Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug
interactions: practical recommendations for clinical victim and perpetrator drug
drug interaction study design.
AB - Breast cancer resistance protein (BCRP; ABCG2) limits intestinal absorption of
low-permeability substrate drugs and mediates biliary excretion of drugs and
metabolites. Based on clinical evidence of BCRP-mediated drug-drug interactions
(DDIs) and the c.421C>A functional polymorphism affecting drug efficacy and
safety, both the US Food and Drug Administration and European Medicines Agency
recommend preclinical evaluation and, when appropriate, clinical assessment of
BCRP-mediated DDIs. Although many BCRP substrates and inhibitors have been
identified in vitro, clinical translation has been confounded by overlap with
other transporters and metabolic enzymes. Regulatory recommendations for BCRP
mediated clinical DDI studies are challenging, as consensus is lacking on the
choice of the most robust and specific human BCRP substrates and inhibitors and
optimal study design. This review proposes a path forward based on a
comprehensive analysis of available data. Oral sulfasalazine (1000 mg, immediate
release tablet) is the best available clinical substrate for intestinal BCRP,
oral rosuvastatin (20 mg) for both intestinal and hepatic BCRP, and intravenous
rosuvastatin (4 mg) for hepatic BCRP. Oral curcumin (2000 mg) and lapatinib (250
mg) are the best available clinical BCRP inhibitors. To interrogate the worst
case clinical BCRP DDI scenario, study subjects harboring the BCRP c.421C/C
reference genotype are recommended. In addition, if sulfasalazine is selected as
the substrate, subjects having the rapid acetylator phenotype are recommended. In
the case of rosuvastatin, subjects with the organic anion-transporting
polypeptide 1B1 c.521T/T genotype are recommended, together with monitoring of
rosuvastatin's cholesterol-lowering effect at baseline and DDI phase. A proof-of
concept clinical study is being planned by a collaborative consortium to evaluate
the proposed BCRP DDI study design.
PMID- 25587129
TI - Associations of HSD11B1 polymorphisms with tacrolimus concentrations in Chinese
renal transplant recipients with prednisone combined therapy.
AB - Tacrolimus requires close therapeutic drug monitoring because of its narrow
therapeutic index and marked interindividual pharmacokinetic variation. In this
study, we investigated the associations of polymorphisms in the gene encoding
11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) with tacrolimus
concentrations in Chinese renal transplant recipients during the early
posttransplantation stage. A total of 258 renal transplant recipients receiving
tacrolimus with prednisone (30 mg) combined therapy were genotyped for HSD11B1
rs846908, rs846910, rs4844880, and CYP3A5*3 polymorphisms. Tacrolimus trough
concentrations were determined on days 6-9 after transplantation, measured by a
chemiluminescent microparticle immunoassay. Among the CYP3A5 expressers, the dose
adjusted trough concentration (C0/D) of tacrolimus in HSD11B1 rs846908 AA
homozygous individuals was considerably lower than found in GG+GA carriers [56.2
(23.9-86.6) versus 76.7 (12.6-220.0) (ng/ml)/(mg/kg), P = 0.0204]; HSD11B1
rs846910 AA homozygotes had a lower tacrolimus C0/D compared with GG+GA carriers
[51.2 (23.9-86.6) versus 76.3 (12.6-220.0) (ng/ml)/(mg/kg), P = 0.0367]; carriers
with the HSD11B1 rs4844880 AA genotype had a significantly lower tacrolimus C0/D
with respect to carriers of TT+TA genotypes [61.3 (23.9-97.5) versus 77.2 (12.6
220.0) (ng/ml)/(mg/kg), P = 0.0002]; the HSD11B1 AA-AA-AA haplotype carriers had
a lower tacrolimus C0/D than noncarriers [51.2 (23.9-86.6) versus 76.3 (12.6
220.0) (ng/ml)/(mg/kg), P = 0.0367]. These findings illustrate that the HSD11B1
genotypes are closely correlated with tacrolimus trough concentrations,
suggesting that these polymorphisms may be useful for safer dosing of tacrolimus.
PMID- 25587130
TI - Home blood pressure monitoring with patient-initiated drug titration reduces
blood pressure in high-risk patients with hypertension.
PMID- 25587131
TI - 64Cu antibody-targeting of the T-cell receptor and subsequent internalization
enables in vivo tracking of lymphocytes by PET.
AB - T cells are key players in inflammation, autoimmune diseases, and immunotherapy.
Thus, holistic and noninvasive in vivo characterizations of the temporal
distribution and homing dynamics of lymphocytes in mammals are of special
interest. Herein, we show that PET-based T-cell labeling facilitates
quantitative, highly sensitive, and holistic monitoring of T-cell homing patterns
in vivo. We developed a new T-cell receptor (TCR)-specific labeling approach for
the intracellular labeling of mouse T cells. We found that continuous TCR plasma
membrane turnover and the endocytosis of the specific (64)Cu-monoclonal antibody
(mAb)-TCR complex enables a stable labeling of T cells. The TCR-mAb complex was
internalized within 24 h, whereas antigen recognition was not impaired. Harmful
effects of the label on the viability, DNA-damage and apoptosis-necrosis
induction, could be minimized while yielding a high contrast in in vivo PET
images. We were able to follow and quantify the specific homing of systemically
applied (64)Cu-labeled chicken ovalbumin (cOVA)-TCR transgenic T cells into the
pulmonary and perithymic lymph nodes (LNs) of mice with cOVA-induced airway
delayed-type hypersensitivity reaction (DTHR) but not into pulmonary and
perithymic LNs of naive control mice or mice diseased from turkey or pheasant OVA
induced DTHR. Our protocol provides consequent advancements in the detection of
small accumulations of immune cells in single LNs and specific homing to the
sites of inflammation by PET using the internalization of TCR-specific mAbs as a
specific label of T cells. Thus, our labeling approach is applicable to other
cells with constant membrane receptor turnover.
PMID- 25587133
TI - Representing "stuff" in visual cortex.
PMID- 25587132
TI - Genomic and proteomic characterization of "Candidatus Nitrosopelagicus brevis":
an ammonia-oxidizing archaeon from the open ocean.
AB - Thaumarchaeota are among the most abundant microbial cells in the ocean, but
difficulty in cultivating marine Thaumarchaeota has hindered investigation into
the physiological and evolutionary basis of their success. We report here a
closed genome assembled from a highly enriched culture of the ammonia-oxidizing
pelagic thaumarchaeon CN25, originating from the open ocean. The CN25 genome
exhibits strong evidence of genome streamlining, including a 1.23-Mbp genome, a
high coding density, and a low number of paralogous genes. Proteomic analysis
recovered nearly 70% of the predicted proteins encoded by the genome,
demonstrating that a high fraction of the genome is translated. In contrast to
other minimal marine microbes that acquire, rather than synthesize, cofactors,
CN25 encodes and expresses near-complete biosynthetic pathways for multiple
vitamins. Metagenomic fragment recruitment indicated the presence of DNA
sequences >90% identical to the CN25 genome throughout the oligotrophic ocean. We
propose the provisional name "Candidatus Nitrosopelagicus brevis" str. CN25 for
this minimalist marine thaumarchaeon and suggest it as a potential model system
for understanding archaeal adaptation to the open ocean.
PMID- 25587135
TI - Altruism, self-interest, and energy consumption.
PMID- 25587134
TI - The NMR-Rosetta capsid model of M13 bacteriophage reveals a quadrupled
hydrophobic packing epitope.
AB - Filamentous phage are elongated semiflexible ssDNA viruses that infect bacteria.
The M13 phage, belonging to the family inoviridae, has a length of ~1 MUm and a
diameter of ~7 nm. Here we present a structural model for the capsid of intact
M13 bacteriophage using Rosetta model building guided by structure restraints
obtained from magic-angle spinning solid-state NMR experimental data. The C5
subunit symmetry observed in fiber diffraction studies was enforced during model
building. The structure consists of stacked pentamers with largely alpha helical
subunits containing an N-terminal type II beta-turn; there is a rise of 16.6-16.7
A and a tilt of 36.1-36.6 degrees between consecutive pentamers. The packing of
the subunits is stabilized by a repeating hydrophobic stacking pocket; each
subunit participates in four pockets by contributing different hydrophobic
residues, which are spread along the subunit sequence. Our study provides, to our
knowledge, the first magic-angle spinning NMR structure of an intact filamentous
virus capsid and further demonstrates the strength of this technique as a method
of choice to study noncrystalline, high-molecular-weight molecular assemblies.
PMID- 25587136
TI - The value of monitoring to control evolving populations.
AB - Populations can evolve to adapt to external changes. The capacity to evolve and
adapt makes successful treatment of infectious diseases and cancer difficult.
Indeed, therapy resistance has become a key challenge for global health.
Therefore, ideas of how to control evolving populations to overcome this threat
are valuable. Here we use the mathematical concepts of stochastic optimal control
to study what is needed to control evolving populations. Following established
routes to calculate control strategies, we first study how a polymorphism can be
maintained in a finite population by adaptively tuning selection. We then
introduce a minimal model of drug resistance in a stochastically evolving cancer
cell population and compute adaptive therapies. When decisions are in this manner
based on monitoring the response of the tumor, this can outperform established
therapy paradigms. For both case studies, we demonstrate the importance of high
resolution monitoring of the target population to achieve a given control
objective, thus quantifying the intuition that to control, one must monitor.
PMID- 25587137
TI - Reply to Scahill: Behavioral outcome measures in autism.
PMID- 25587138
TI - Uncommon use of common measures in sulforaphane trial.
PMID- 25587139
TI - Reply to Evans and Bar-Oz et al.: Recovering ecological pattern and process in
Ancient Egypt.
PMID- 25587140
TI - Ancient Egypt's fluctuating fauna: ecological events or cultural constructs?
PMID- 25587141
TI - Mammalian extinction in ancient Egypt, similarities with the southern Levant.
PMID- 25587143
TI - On measuring the bending strength of septate grass stems.
AB - * PREMISE OF THE STUDY: Reliable testing methodologies are a fundamental tenet of
scientific research. However, very little information is found in the literature
explaining how to accurately measure the structural bending strength of plant
stems. It was hypothesized that the most commonly employed loading configuration
used in bending experiments (placement of loading anvil at an internodal region
of the stem or stalk) may significantly alter test results and introduce errors
in bending strength measurements of plant stems.* METHODS: Four types of
mechanical tests were performed on bamboo (Phyllostachys aurea), giant reed
(Arundo donax), and maize (Zea mays) to investigate how different loading
configurations employed during three-point bending experiments affect test
results of septate grass stems and to develop a testing protocol that provides
reliable measures of stalk bending strength.* RESULTS: RESULTS confirmed the
hypothesis that internodal-loaded three-point bending test can produce erroneous
bending strength measurements. This testing methodology causes plant stems to
break prematurely and produces failure types and patterns incongruent with stalks
that broke in their natural (in situ) environment. In contrast, a modified test
configuration produces natural failure patterns and more accurate measurements of
bending strength.* CONCLUSION: Reliable measurements of stalk bending strength
can be obtained by maximizing the span length of bending tests and placing the
loading anvil at stronger and denser nodal tissues. These results are relevant to
ecological and evolutionary plant biomechanics studies as well as agronomic
breeding studies focused on measuring plant phenotypes such as stalk lodging
strength, or on improving bending strength of septate plant stems.
PMID- 25587144
TI - Multiscale stress-strain characterization of onion outer epidermal tissue in wet
and dry states.
AB - * PREMISE OF THE STUDY: Quantitative measurements of water's effects on the
tension response of plant tissue will assist in understanding the regulatory
mechanism underlying expansive growth. Such measurements should be multiscale in
nature to account for plants' hierarchical structure.* METHODS: Outer onion
epidermal tissues were cut and bonded to uniaxial displacement-controlled
mechanical loading devices to apply and measure the force on the sample.
Fluorescent polystyrene beads (500 nm in diameter) were dispersed on the sample
surface under various levels of tensile load conditions to obtain displacement
maps with a confocal fluorescent microscope. The resulting strain was measured
using a digital image correlation technique by tracking individual bead
displacements. The applied forces were obtained by measuring the displacement of
the calibrated force-sensing device. Tissue- and cell-scale mechanical properties
were quantified by calculating the applied stress and the corresponding global
and local strains.* KEY RESULTS: The Young's modulus values of individual cell
walls of dehydrated and rehydrated samples were 3.0 +/- 1.0 GPa and 0.4 +/- 0.2
GPa, respectively, and are different from the Young's modulus values of the
global tissue-scale dehydrated and rehydrated samples, which were 1.9 +/- 0.3 GPa
and 0.08 +/- 0.02 GPa, respectively. Poisson's ratio increased more than 3-fold
due to hydration.* CONCLUSION: The results on global, cell-to-cell, and point-to
point mechanical property variations suggest the importance of the mechanical
contribution of extracellular features including the middle lamella, cell shape,
and dimension. This study shows that a multiscale investigation is essential for
fundamental insights into the hierarchical deformation of biological systems.
PMID- 25587145
TI - Transcriptional response of Arabidopsis seedlings during spaceflight reveals
peroxidase and cell wall remodeling genes associated with root hair development.
AB - * PREMISE OF THE STUDY: Plants will be an important component of advanced life
support systems during space exploration missions. Therefore, understanding their
biology in the spacecraft environment will be essential before they can be used
for such systems.* METHODS: Seedlings of Arabidopsis thaliana were grown for 2 wk
in the Biological Research in Canisters (BRIC) hardware on board the second to
the last mission of the space shuttle Discovery (STS-131). Transcript profiles
between ground controls and space-grown seedlings were compared using stringent
selection criteria.* KEY RESULTS: Expression of transcripts associated with
oxidative stress and cell wall remodeling was repressed in microgravity. These
downregulated genes were previously shown to be enriched in root hairs consistent
with seedling phenotypes observed in space. Mutations in genes that were
downregulated in microgravity, including two uncharacterized root hair-expressed
class III peroxidase genes (PRX44 and PRX57), led to defective polar root hair
growth on Earth. PRX44 and PRX57 mutants had ruptured root hairs, which is a
typical phenotype of tip-growing cells with defective cell walls and those
subjected to stress.* CONCLUSIONS: Long-term exposure to microgravity negatively
impacts tip growth by repressing expression of genes essential for normal root
hair development. Whereas changes in peroxidase gene expression leading to
reduced root hair growth in space are actin-independent, root hair development
modulated by phosphoinositides could be dependent on the actin cytoskeleton.
These results have profound implications for plant adaptation to microgravity
given the importance of tip growing cells such as root hairs for efficient
nutrient capture.
PMID- 25587147
TI - An invasive plant alters pollinator-mediated phenotypic selection on a native
congener.
AB - * PREMISE OF STUDY: Recent studies suggest that invasive plants compete
reproductively with native plants by reducing the quantity or quality of
pollinator visits. Although these studies have revealed ecological consequences
of pollinator-mediated competition between invasive and native plants, the
evolutionary outcomes of these interactions remain largely unexplored.* METHODS:
We studied the ecological and evolutionary impact of pollinator-mediated
competition with an invasive jewelweed, Impatiens glandulifera, on a co-occurring
native congener, I. capensis. Using a pollinator choice experiment, a hand
pollination experiment, and a selection analysis, we addressed the following
questions: (1) Do native pollinators show preference for the invasive or native
jewelweed, and do they move between the two species? (2) Does invasive jewelweed
pollen inhibit seed production in the native plant? (3) Does the invasive
jewelweed alter phenotypic selection on the native plant's floral traits?* KEY
RESULTS: The pollinator choice experiment showed that pollinators strongly
preferred the invasive jewelweed. The hand pollination experiment demonstrated
that invasive pollen inhibited seed production in the native plant. The selection
analysis showed that the presence of the invasive jewelweed altered phenotypic
selection on corolla height in the native plant.* CONCLUSIONS: Invasive plants
have the potential to alter phenotypic selection on floral traits in native plant
populations. If native plants can evolve in response to this altered selection
pressure, the evolution of floral traits may play an important role in permitting
long-term coexistence of native and invasive plants.
PMID- 25587146
TI - Ecological niche differentiation of polyploidization is not supported by
environmental differences among species in a cosmopolitan grass genus.
AB - * PREMISE OF THE STUDY: Polyploidization frequently results in the creation of
new plant species, the establishment of which is thought to often be facilitated
by ecological niche differentiation from the diploid species. We tested this
hypothesis using the cosmopolitan grass genus Phalaris (Poaceae), consisting of
19 species that range from diploid to tetraploid to hexaploid. Specifically, we
tested whether (1) polyploids occupy more extreme environments and/or (2) have
broader niche breadths and/or (3) whether the polyploid species' distributions
indicate a niche shift from diploid species.* METHODS: We employed a
bootstrapping approach using distribution data for each species and eight
environmental variables to investigate differences between species in the means,
extremes, and breadths of each environmental variable. We used a kernel smoothing
technique to quantify niche overlap between species.* KEY RESULTS: Although we
found some support for the three hypotheses for a few diploid-polyploid pairs and
for specific environmental variables, none of these hypotheses were generally
supported.* CONCLUSIONS: Our results suggest that these commonly held hypotheses
about the effects of polyploidization on ecological distributions are not
universally applicable. Correlative biogeographic studies like ours provide a
necessary first step for suggesting specific hypotheses that require experimental
verification. A combination of genetic, physiological, and ecological studies
will be required to achieve a better understanding of the role of
polyploidization in niche evolution.
PMID- 25587148
TI - Dynamic extrafloral nectar production: the timing of leaf damage affects the
defensive response in Senna mexicana var. chapmanii (Fabaceae).
AB - * PREMISE OF THE STUDY: Extrafloral nectar (EFN) mediates food for protection
mutualisms between plants and defensive insects. Understanding sources of
variation in EFN production is important because such variations may affect the
number and identity of visitors and the effectiveness of plant defense. We
investigated the influence of plant developmental stage, time of day, leaf age,
and leaf damage on EFN production in Senna mexicana var. chapmanii. The observed
patterns of variation in EFN production were compared with those predicted by
optimal defense theory.* METHODS: Greenhouse experiments with potted plants were
conducted to determine how plant age, time of day, and leaf damage affected EFN
production. A subsequent field study was conducted to determine how leaf damage,
and the resulting increase in EFN production, affected ant visitation in S.
chapmanii.* KEY RESULTS: More nectar was produced at night and by older plants.
Leaf damage resulted in increased EFN production, and the magnitude of the
response was greater in plants damaged in the morning than those damaged at
night. Damage to young leaves elicited a stronger defensive response than damage
to older leaves, in line with optimal defense theory. Damage to the leaves of S.
chapmanii also resulted in significantly higher ant visitation in the field.*
CONCLUSIONS: Extrafloral nectar is an inducible defense in S. chapmanii.
Developmental variations in its production support the growth differentiation
balance hypothesis, while within-plant variations and damage responses support
optimal defense theory.
PMID- 25587149
TI - Pollen limitation and the contribution of autonomous selfing to fruit and seed
set in a rewarding orchid.
AB - * PREMISE OF THE STUDY: Although rewarding orchids are believed to have a high
pollination efficiency, pollination success is often low, suggesting that
rewarding orchids may be prone to pollen limitation. Assuming that selfing
contributes significantly to fruit and seed set (i.e., reproductive assurance)
and that the quality of selfed seeds is high (i.e., low inbreeding depression),
it can be hypothesized that under these circumstances populations evolve to
facultative or even complete self-pollination.* METHODS: In this study, we
performed emasculation and pollen supplementation experiments in the field to
assess the extent of outcross pollen limitation and the contribution of
autonomous self-pollination to fruit and seed set in the rewarding orchid
Epipactis palustris. Hand-pollinations using cross and self-pollen were performed
in the greenhouse to investigate the impact of selfing on seed set and seed
quality and to assess the magnitude of inbreeding depression.* KEY RESULTS: Fruit
set under natural conditions was high: ca. 70% of all flowers set fruit.
Percentage fruit set of emasculated plants was 56%, implying that fruit set in
about 14% of all flowers was the result of autonomous self-pollination. Pollen
supplementation significantly increased fruit and seed set, indicating strong
outcross pollen limitation. Hand-pollination with cross pollen resulted in
significantly higher seed set and seed quality compared with manual self
pollination, indicating high levels of early inbreeding depression (delta = 0.46
+/- 0.08).* CONCLUSIONS: Overall, these results indicate that, despite the high
pollination efficiency, populations of this rewarding orchid species were
strongly pollen limited. Costs of early inbreeding depression, on the other hand,
were high, which may prevent rapid evolution of complete selfing.
PMID- 25587151
TI - Direct and indirect effects of environmental variability on growth and
survivorship of pre-reproductive Joshua trees, Yucca brevifolia Engelm.
(Agavaceae).
AB - * PREMISE OF STUDY: Accurate demographic information about long-lived plant
species is important for understanding responses to large-scale disturbances,
including climate change. It is challenging to obtain these data from desert
perennial plants because seedling establishment is exceptionally rare, and
estimates of survival are lacking for their vulnerable early stages. Desert
wildfires, urbanization, and climate change influence the persistence of the long
lived Yucca brevifolia. Quantitative demographic attributes are crucial for
understanding how populations will respond to disturbances and where populations
will recede or advance under future climate scenarios.* METHODS: We measured
survival in a cohort of 53 pre-reproductive Y. brevifolia at Yucca Flat, Nevada,
USA, for 22 yr and recorded their growth, nurse-plant relationships, and
herbivory.* KEY RESULTS: Herbivory by black-tailed jackrabbits (Lepus
californicus) caused severe losses of plants during the first and second years
(45% and 31%, respectively). Surviving plants experienced <2.5% annual mortality.
Survival for the population was 19% over 22 yr. Plants <25 cm in height had lower
life expectancy. Average growth rate (+/- SD) for plants that survived to the
last census was 3.12 +/- 1.96 cm yr(-1), and growth rates were positively
associated with precipitation. Thirty-year-old Y. brevifolia had not yet
reproduced.* CONCLUSIONS: A rare establishment event for Y. brevifolia during
1983-1984, triggered by above-average summer rainfall, provided a unique
opportunity to track early survival and growth. Infrequent but acute episodes of
herbivory during drought influenced demography for decades. Variability in
survival among young Y. brevifolia indicates that size-dependent demographic
variables will improve forecasts for this long-lived desert species under
predicted regional climate change.
PMID- 25587150
TI - Plastic responses of native plant root systems to the presence of an invasive
annual grass.
AB - * PREMISE OF THE STUDY: The ability to respond to environmental change via
phenotypic plasticity may be important for plants experiencing disturbances such
as climate change and plant invasion. Responding to belowground competition
through root plasticity may allow native plants to persist in highly invaded
systems such as the cold deserts of the Intermountain West, USA.* METHODS: We
investigated whether Poa secunda, a native bunchgrass, could alter root
morphology in response to nutrient availability and the presence of a competitive
annual grass. Seeds from 20 families were grown with high and low nutrients and
harvested after 50 d, and seeds from 48 families, grown with and without Bromus
tectorum, were harvested after ~2 or 6 mo. We measured total biomass, root mass
fraction, specific root length (SRL), root tips, allocation to roots of varying
diameter, and plasticity in allocation.* KEY RESULTS: Plants had many parallel
responses to low nutrients and competition, including increased root tip
production, a trait associated with tolerance to reduced resources, though
families differed in almost every trait and correlations among trait changes
varied among experiments, indicating flexibility in plant responses. Seedlings
actively increased SRL and fine root allocation under competition, while older
seedlings also increased coarse root allocation, a trait associated with
increased tolerance, and increased root mass fraction.* CONCLUSIONS: The high
degree of genetic variation for root plasticity within natural populations could
aid in the long-term persistence of P. secunda because phenotypic plasticity may
allow native species to persist in invaded and fluctuating resource environments.
PMID- 25587152
TI - Environmental correlates of cytotype distribution in Andropogon gerardii
(Poaceae).
AB - * PREMISE OF THE STUDY: Information about geographic distribution of cytotypes
can provide insight into the origin and maintenance of autopolyploid complexes
and builds a foundation for understanding cytotype differentiation and the
dynamics of mixed-ploidy populations. Here, we investigate environmental
correlates of the geographic distributions of 6x and 9x individuals in the
ecologically dominant grass Andropogon gerardii to examine the role of climate in
shaping patterns of cytotype distribution in this species.* METHODS: Flow
cytometry was used to estimate ploidy level in 352 individuals from 32
populations across North America. Ecological differentiation of cytotypes was
tested by relating BIOCLIM variables to cytotype distribution using principal
components analysis and partial linear regression.* KEY RESULTS: Broad geographic
sampling confirmed two primary cytotypes-6x (hexaploid) and 9x (enneaploid)-and
revealed that 9x plants are more common than previously thought. Enneaploids
occur frequently in the southern portions of the range, with hexaploids
dominating in northern regions. Mixed-ploidy populations were common (46.9%).
Principal components analysis and partial linear regression indicated that
reduced summer precipitation and increased variation in diurnal and seasonal
temperature range were significant predictors of the frequency of 9x plants in a
population.* CONCLUSIONS: Results indicate that (1) geographic distribution of 6x
and 9x individuals is nonrandom; (2) environmental variables are associated with
cytotype distribution in A. gerardii; and (3) nearly half of populations surveyed
include both 6x and 9x individuals. The persistence of mixed-ploidy populations
may reflect a combination of recurrent polyploid formation and the prevalence of
clonal reproduction.
PMID- 25587153
TI - Sequoia maguanensis, a new Miocene relative of the coast redwood, Sequoia
sempervirens, from China: implications for paleogeography and paleoclimate.
AB - * PREMISE OF THE STUDY: The paleogeographical origin of the relict North American
Sequoia sempervirens is controversial. Fossil records indicate a Neogene origin
for its foliage characteristics. Although several fossils from the Miocene
sediments in eastern Asia have been considered to have close affinities with the
modern S. sempervirens, they lack the typical features of a leafy twig bearing
linear as well as scale leaves, and the fertile shoots terminating by a cone. The
taxonomic status of these fossils has remained unclear.* METHODS: New better
preserved fossils from the upper Miocene of China indicate a new species of
Sequoia. This finding not only confirms the former presence of this genus in
eastern Asia, but it also confirms the affinity of this Asian form to the modern
relict S. sempervirens.* KEY RESULTS: The principal foliage characteristics of S.
sempervirens had already originated by the late Miocene. The eastern Asian
records probably imply a Beringian biogeographic track of the ancestor of S.
sempervirens in the early Neogene, at a time when the land bridge was not too
cool for this thermophilic conifer to spread between Asia and North America.*
CONCLUSIONS: The climatic context of the new fossil Sequoia in Southeast Yunnan,
based on other floristic elements of the fossil assemblage in which it is found,
is presumed to be warm and humid. Following the uplift of the Qinghai-Tibet
Plateau, this warm, humid climate was replaced by the present monsoonal climate
with dry winter and spring. This change may have led to the disappearance of this
hygrophilous conifer from eastern Asia.
PMID- 25587154
TI - Analysis of nuclear microsatellites reveals limited differentiation between
Colchic and Hyrcanian populations of the wind-pollinated relict tree Zelkova
carpinifolia (Ulmaceae).
AB - * PREMISE OF THE STUDY: The Caucasus represents one of the world's biodiversity
hotspots and includes the climatic refugia Hyrcan on the southern coast of the
Caspian Sea and Colchis on the eastern coast of the Black Sea, where different
species survived during the Quaternary climatic oscillations. We evaluated the
genetic diversity of the relict tree Zelkova carpinifolia shared between the two
refugia and distributed throughout the Caucasus and adjacent areas.* METHODS:
Specimens were collected from 30 geographical sites in Azerbaijan, Georgia, Iran,
and Turkey and screened for variability at eight nuclear microsatellite loci. The
genetic diversity among and within populations was assessed using a set of
statistical measures.* KEY RESULTS: We detected 379 different genotypes from a
total of 495 individuals with varying degrees of clonal reproduction at the
different sites. Low to intermediate levels of genetic diversity were observed at
all sites, and strong differentiation between sampling sites was absent. In
addition, we observed no clear genetic differentiation between the Colchis and
Hyrcan. Bayesian clustering of the genotypes revealed three populations with high
levels of admixture between the sampling sites.* CONCLUSIONS: The lack of strong
genetic structure of studied populations of Z. carpinifolia contrasts with a
previous study based on chloroplast markers and suggests that long-distance
pollen dispersal is an important factor of gene flow among populations of Z.
carpinifolia. The present study does not reveal any particular site with
particularly isolated genotypes that would deserve more attention for
conservation purposes than others, although some sites should be considered for
further investigation.
PMID- 25587155
TI - The potential for crop to wild hybridization in eggplant (Solanum melongena;
Solanaceae) in southern India.
AB - * PREMISE OF THE STUDY: In India and elsewhere, transgenic Bt eggplant (Solanum
melongena) has been developed to reduce insect herbivore damage, but published
studies of the potential for pollen-mediated, crop- to- wild gene flow are scant.
This information is useful for risk assessments as well as in situ conservation
strategies for wild germplasm.* METHODS: In 2010-2014, we surveyed 23 populations
of wild/weedy eggplant (Solanum insanum; known as wild brinjal), carried out hand
pollination experiments, and observed pollinators to assess the potential for
crop- to- wild gene flow in southern India.* KEY RESULTS: Wild brinjal is a
spiny, low-growing perennial commonly found in disturbed sites such as roadsides,
wastelands, and sparsely vegetated areas near villages and agricultural fields.
Fourteen of the 23 wild populations in our study occurred within 0.5 km of
cultivated brinjal and at least nine flowered in synchrony with the crop. Hand
crosses between wild and cultivated brinjal resulted in seed set and viable F1
progeny. Wild brinjal flowers that were bagged to exclude pollinators did not set
fruit, and fruit set from manual self-pollination was low. The exserted stigmas
of wild brinjal are likely to promote outcrossing. The most effective pollinators
appeared to be bees (Amegilla, Xylocopa, Nomia, and Heterotrigona spp.), which
also were observed foraging for pollen on crop brinjal.* CONCLUSION: Our findings
suggest that hybridization is possible between cultivated and wild brinjal in
southern India. Thus, as part of the risk assessment process, we assume that
transgenes from the crop could spread to wild brinjal populations that occur
nearby.
PMID- 25587156
TI - Genetic diversity and population structure of wild/weedy eggplant (Solanum
insanum, Solanaceae) in southern India: implications for conservation.
AB - * PREMISE OF THE STUDY: Crop wild relatives represent important genetic resources
for crop improvement and the preservation of native biodiversity. Eggplant
(Solanum melongena), known as brinjal in India, ranks high among crops whose wild
gene pools are underrepresented in ex situ collections and warrant urgent
conservation. Knowledge of outcrossing rates and patterns of genetic variation
among wild populations can aid in designing strategies for both in situ and ex
situ preservation.* METHODS: We used 14 microsatellite (simple sequence repeat)
markers to examine genetic diversity, population structure, and outcrossing in 10
natural populations of wild/weedy eggplant (S. insanum = S. melongena var.
insanum) and three cultivated populations in southern India.* KEY RESULTS:
Multilocus FST analyses revealed strong differentiation among populations and
significant isolation by distance. Bayesian model-based clustering, principal
coordinate analysis, and hierarchical cluster analysis grouped the wild/weedy
populations into three major clusters, largely according to their geographic
origin. The three crop populations were similar to each other and grouped with
two wild/weedy populations that occurred nearby. Outcrossing rates among the
wild/weedy populations ranged from 5-33%, indicating a variable mixed-mating
system.* CONCLUSION: Geographic isolation has played a significant role in
shaping the contemporary patterns of genetic differentiation among these
populations, many of which represent excellent candidates for in situ
conservation. In two cases, close genetic affinity between cultivars and nearby
wild/weedy populations suggests that gene flow has occurred between them. To our
knowledge, this is the first study investigating population-level patterns of
genetic diversity in wild relatives of eggplant.
PMID- 25587157
TI - The roles of history and ecology in chloroplast phylogeographic patterns of the
bird-dispersed plant parasite Phoradendron californicum (Viscaceae) in the
Sonoran Desert.
AB - * PREMISE OF THE STUDY: A recurrent explanation for phylogeographic
discontinuities in the Baja California Peninsula and the Sonoran Desert Region
has been the association of vicariant events with Pliocene and Pleistocene seaway
breaks. Nevertheless, despite its relevance for plant dispersal, other
explanations such as ecological and paleoclimatic factors have received little
attention. Here, we analyzed the role of several of these factors to describe the
phylogeographic patterns of the desert mistletoe, Phoradendron californicum.*
METHODS: Using noncoding chloroplast regions, we assess the marginal probability
of 19 a priori hypotheses related to geological and ecological factors to predict
the cpDNA variation in P. californicum using a Bayesian coalescent framework.
Complementarily, we used the macrofossil record and niche model projections on
Last Glacial Maximum climatic conditions for hosts, mistletoe, and a bird
specialist to interpret phylogeographic patterns.* KEY RESULTS: Genealogical
reconstructions revealed five clades, which suggest a combination of cryptic
divergence, long-distance seed dispersal, and isolating postdivergence events.
Bayesian hypothesis test favored a series of Pliocene and Pleistocene geological
events related to the formation of the Baja California Peninsula and seaways
across the peninsula as the most supported explanation for this genealogical
pattern. However, age estimates, niche projections, and fossil records show
dynamic host-mistletoe interactions and evidence of host races, indicating that
ecological and geological factors have been interacting during the formation and
structuring of phylogeographic divergence.* CONCLUSIONS: Variation in cpDNA
across the species range results from the interplay of vicariant events, past
climatic oscillations, and more dynamic factors related to ecological processes
at finer temporal and spatial scales.
PMID- 25587159
TI - Neurally adjusted ventilatory assist improves patient-ventilator synchrony in a
patient with tetanus and unstable diaphragmatic electrical activity.
AB - A 79-y-old man with generalized tetanus was admitted to the ICU. A left-forearm
wound was surgically debrided, and the wound was closed. On postoperative day 1,
after the patient experienced opisthotonos and convulsions, endotracheal
intubation was performed. Propofol and diazepam were infused but failed to stop
the convulsions. Morphine, midazolam, dantrolene, and rocuronium were used to
ameliorate the muscle spasms. Magnesium sulfate was also infused. On
postoperative day 15, patient-ventilator asynchrony was apparent. The patient
showed recurrent tachypnea and bradypnea, which seemed typical of Cheyne-Stokes
respiration. A neurally adjusted ventilatory assist (NAVA) catheter was inserted
transnasally, and electrical activity of the diaphragm (Edi) was monitored.
Readings showed regular attempts to breathe at 40-50 breaths/min with periodic
changes in Edi amplitude. NAVA mode improved patient-ventilator synchrony.
Periodic breathing continued for 2 weeks. We stopped monitoring Edi on
postoperative day 39. He began respiratory rehabilitation and was transferred to
a hospital for rehabilitation on postoperative day 80. We encountered periodic
respiration in a patient with tetanus. Edi monitoring revealed periodic amplitude
change. The cause of the periodic breathing pattern in this patient could not be
determined but may be attributable to side effects of the pharmacologic
interventions or the natural history of the disease itself. NAVA mode improved
patient-ventilator synchrony.
PMID- 25587160
TI - Evaluation of an oxygen mask-based capnometry device in subjects extubated after
abdominal surgery.
AB - BACKGROUND: For early detection of respiratory and hemodynamic changes during
anesthesia, continuous end-tidal carbon dioxide concentration (PETCO2) is
monitored by capnometry. However, the accuracy of CO2 monitoring during
spontaneous breathing in extubated patients remains undetermined. Therefore, we
aimed to compare P(ETCO2) measured by capnometry using an oxygen mask with a
carbon dioxide sampling port (capnometry-type oxygen mask) and P(CO2) in
extubated subjects who had undergone abdominal surgery. Furthermore, we
investigated whether spontaneous deep breathing affected dissociation between
P(aCO2) and P(ETCO2). METHODS: Adult post-abdominal surgery subjects admitted to
the ICU were enrolled in this study. After extubation, oxygen was supplied at 6
L/min using the capnometry-type oxygen mask. After 30 min of oxygen supply,
P(aCO2) blood gas analysis was performed, and P(ETCO2) was measured under resting
and deep-breathing conditions. For both resting and deep-breathing conditions,
the correlation between P(aCO2) and P(ETCO2) was analyzed. Furthermore, bias,
precision, and limits of agreement were calculated using the Bland-Altman method.
RESULTS: Twenty-five subjects (15 men, 10 women) with a mean age of 62 y
(interquartile range of 57-76 y) and body mass index of 20-24 kg/m(2) were
studied. The correlation (r) between P(aCO2) and P(ETCO2) under resting and deep
breathing conditions was 0.50 and 0.56, respectively. Compared with P(aCO2), the
bias and limits of agreement were -12.6 (-20.6 to -4.6) for resting P(ETCO2) and
9.1 (-16.0 to -2.1) for deep-breathing P(ETCO2). The association between P(aCO2)
and deep-breathing P(ETCO2) was significantly smaller compared with resting
P(ETCO2) (P = .002). CONCLUSIONS: It is possible to measure the P(ETCO2) under
varying breathing conditions with the capnometry-type oxygen mask in subjects
receiving oxygen supplementation after extubation following upper abdominal
surgery to determine whether they are properly ventilating. (ClinicalTrials.gov
registration UMIN000011925.).
PMID- 25587161
TI - Muscle impairment in neuromuscular disease using an expiratory/inspiratory
pressure ratio.
AB - BACKGROUND: Neuromuscular diseases (NMDs) lead to different weakness patterns,
and most patients with NMDs develop respiratory failure. Inspiratory and
expiratory muscle strength can be measured by maximum static inspiratory pressure
(PImax) and maximum static expiratory pressure (PEmax), and the relationship
between them has not been well described in healthy subjects and subjects with
NMDs. Our aim was to assess expiratory/inspiratory muscle strength in NMDs and
healthy subjects and calculate PEmax/PImax ratio for these groups. METHODS:
Seventy (35 males) subjects with NMDs (amyotrophic lateral sclerosis, myasthenia
gravis, and myotonic dystrophy), and 93 (47 males) healthy individuals 20-80 y of
age were evaluated for anthropometry, pulmonary function, PImax, and PEmax,
respectively. RESULTS: Healthy individuals showed greater values for PImax and
PEmax when compared with subjects with NMDs. PEmax/PImax ratio for healthy
subjects was 1.31 +/- 0.26, and PEmax%/PImax% was 1.04 +/- 0.05; for subjects
with NMDs, PEmax/PImax ratio was 1.45 +/- 0.65, and PEmax%/PImax% ratio was 1.42
+/- 0.67. We found that PEmax%/PImax% for myotonic dystrophy was 0.93 +/- 0.24,
for myasthenia gravis 1.94 +/- 0.6, and for amyotrophic lateral sclerosis 1.33 +/
0.62 when we analyzed them separately. All healthy individuals showed higher
PEmax compared with PImax. For subjects with NMDs, the impairment of PEmax and
PImax is different among the 3 pathologies studied (P < .001). CONCLUSIONS:
Healthy individuals and subjects with NMDs showed higher PEmax in comparison to
PImax regarding the PEmax/PImax ratio. Based on the ratio, it is possible to
state that NMDs show different patterns of respiratory muscle strength loss.
PEmax/PImax ratio is a useful parameter to assess the impairment of respiratory
muscles in a patient and to customize rehabilitation and treatment.
PMID- 25587162
TI - A comparison of metered-dose inhaled albuterol versus endotracheal liquid bolus
albuterol for the treatment of bronchoconstriction.
AB - INTRODUCTION: Aerosolized albuterol delivery is a mainstay treatment for
bronchoconstriction; however, almost no data exist that evaluate the clinical
outcome of instillation of an endotracheal liquid bolus (ELB) of a bronchodilator
directly into the airway. METHODS: This randomized trial sought to evaluate the
efficacy of albuterol lavage via artificial airway with accompanied patient
positioning. Subjects receiving mechanical ventilation for acute respiratory
failure with clinical manifestations of bronchoconstriction were assigned to
initially receive either traditional albuterol via metered-dose inhaler (MDI) or
albuterol via ELB lavage with follow-up administration of the other therapy after
a 4-h washout period. Clinical data were collected at baseline and at 5 and 30
min post-treatment. RESULTS: Fourteen subjects (5 males, 9 females; mean age of
57.5 y) were included in this study. In the group receiving initial ELB, peak
airway pressure decreased significantly (P = .02), and a significant decrease in
airway resistance mean scores was seen from baseline to 30 min post-treatment (P
< .001) and from 5 to 30 min post-treatment (P = .003), with no significant
effects seen with follow-up MDI. In the initial MDI treatment group, no
significant effect on peak airway pressure or airway resistance was noted. S(pO2)
increased at 5 min post-treatment with ELB. In contrast, S(pO2) decreased 30 min
post-treatment with MDI. Mean arterial pressure decreased post-treatment with
ELB. The pattern in heart rate change post-treatment with ELB was similar to that
post-treatment with MDI, with a significant increase at the 5-min interval from
baseline (P < .01), followed by a significant decrease at the 30-min interval (P
< .001). There were no differences in dynamic compliance at each time interval
following administration of both the MDI (P = .92) and ELB conditions (P = .18).
CONCLUSIONS: ELB albuterol lavage may be a viable option to reverse
bronchoconstriction in intubated patients with limited response to traditional
aerosolized albuterol via MDI.
PMID- 25587163
TI - Spirometry quality in adults with very severe lung function impairment.
AB - BACKGROUND: Some technologists worry that patients with very severe lung disease
are unable to complete several spirometry maneuvers, which require considerable
effort. METHODS: We retrospectively selected all spirometry tests with an FEV1 <
35% predicted done by adult subjects sent to our pulmonary function laboratory
during a 3-y period. We determined the rates and correlates of poor quality test
sessions. RESULTS: Approximately 90% of the tests done by the 558 subjects with
very severe lung-function impairment (of > 30,000 subjects tested during the 3-y
period) had adequate quality spirometry. Subjects with airway obstruction were
less likely to meet FVC repeatability goals. A poor spirometry quality grade was
associated with a very low FVC and a low body mass index, but not older age.
CONCLUSIONS: Severe lung disease should not be used as an excuse for not meeting
spirometry quality goals.
PMID- 25587164
TI - Clinical predictors of obesity hypoventilation syndrome in obese subjects with
obstructive sleep apnea.
AB - BACKGROUND: Arterial blood gas (ABG) analysis is not a routine test in sleep
laboratories due to its invasive nature. Therefore, the diagnosis of obesity
hypoventilation syndrome (OHS) is underestimated. We aimed to evaluate the
differences in subjects with OHS and pure obstructive sleep apnea (OSA) and to
determine clinical predictors of OHS in obese subjects. METHODS: Demographics,
body mass index (BMI), Epworth Sleepiness Scale score, polysomnographic data,
ABG, spirometric measurements, and serum bicarbonate levels were recorded.
RESULTS: Of 152 obese subjects with OSA (79 females/73 males, mean age of 50.3 +/
10.6 y, BMI of 40.1 +/- 5.6 kg/m(2), 51.9% with severe OSA), 42.1% (n = 64) had
OHS. Subjects with OHS had higher BMI (P = .02), neck circumference (P < .001),
waist circumference (P < .001), waist/hip ratio (P = .02), Epworth Sleepiness
Scale scores (P = .036), ABG and serum bicarbonate levels (P < .001), apnea
hypopnea index (P = .01), oxygen desaturation index (P < .001), and total sleep
time with S(pO2) < 90% (P < .001) compared with subjects with pure OSA (n = 88).
They also had lower daytime PaO2 (P < .001), sleep efficiency (P = .032), mean
S(pO2) (P < .001), and nadir S(pO2) (P < .001). Serum bicarbonate levels and
nadir S(pO2) were the only independent predictive factors for OHS. A serum
bicarbonate level of >= 27 mmol/L as the cutoff gives a satisfactory
discrimination for the diagnosis of OHS (sensitivity of 76.6%, specificity of
74.6%, positive predictive value of 54.5%, negative predictive value of 88.9%). A
nadir S(pO2) of < 80% as the cutoff gives a satisfactory discrimination for the
diagnosis of OHS (sensitivity of 82.8%, specificity of 54.5%, positive predictive
value of 56.9%, negative predictive value of 81.4%). When we used a serum
bicarbonate level of >= 27 mmol/L and/or a nadir S(pO2) of < 80% as a screening
measure, only 3 of 64 subjects with OHS were missed. CONCLUSIONS: Serum
bicarbonate level and nadir saturation were independent predictive factors for
the diagnosis of OHS.
PMID- 25587165
TI - Successful Colchicine Therapy in a Patient With Follicular Bronchiolitis Presumed
to Be Asthma.
AB - Follicular bronchiolitis (FB) is a rare small-airway pathology that is associated
mainly with connective tissue diseases. This case report presents a new,
diagnosed, different airway disease in a non-smoker with rheumatoid arthritis in
remission who was treated for presumed asthma, but was not controlled. She was
ultimately diagnosed with FB after video-assisted thoracoscopic surgery. The
clinical findings of FB were controlled successfully by colchicine after she did
not respond to systemic steroid therapy. This is the first case report of FB
associated with rheumatoid arthritis that responded to colchicine.
PMID- 25587166
TI - Pneumothoraces Post Mechanical Cardiopulmonary Resuscitation: A Case Series.
AB - The incidence of pneumothoraces with automated cardiopulmonary resuscitation
(CPR) is unknown. Herein, we present 4 cases of pneumothoraces occurring in the
setting of automated mechanical CPR (AM-CPR) in a 2-month period since
incorporating mechanical devices into our resuscitation program. Two of the cases
were in-hospital cardiac arrests, whereas the other 2 were out-of-hospital
cardiac arrests. The Life-Stat 1008 device was utilized for AM-CPR in all cases.
All cases demonstrated confirmed pneumothoraces on post-resuscitation imaging.
Several factors may have contributed to the observed pneumothoraces. Two of the
cases presented with obstructive lung disease, whereas the other 2 had underlying
malignancy. Suboptimal positioning and failure to secure the included shoulder
straps could have led to migration of the piston over the ribs. Further study is
needed to determine the incidence of complications for all FDA-approved AM-CPR
devices compared with manual chest compressions.
PMID- 25587167
TI - In Vitro Evaluation of Aerosols Delivered via the Nasal Route.
AB - BACKGROUND: Infants and young children are obligate nose breathers; therefore, a
transnasal route seems the logical delivery method of inhaled aerosols. The
efficiency of aerosol delivery depends on several factors, such as interface,
type of nebulizer, and patient age and breathing pattern. We hypothesized that
the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head
model and breathing pattern of an older child would result in a higher lung dose.
We also hypothesized that the use of an anatomically correct model would more
accurately reflect lung dose than models that do not include airways. METHODS: A
model comprising a breathing simulator and an anatomically correct model of a 7
month-old infant and a 5-y-old child with an interposed collection filter (lung
dose) were used. Breathing patterns of a newborn, infant, and child were used
with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded
with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol
mass was determined via spectrophotometer (276 nm). RESULTS: Lung dose varied
between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh
nebulizer. The front-loaded mask was the most efficient interface. We also found
that higher tidal volumes were associated with higher lung doses and that the use
of a larger airway model resulted in a lower lung dose. Finally, the model showed
a good correlation with in vivo data and rendered lung doses severalfold lower
than previous data obtained with oral models. CONCLUSIONS: Careful pairing of the
aerosol generator and interface is very important during transnasal aerosol
delivery.
PMID- 25587168
TI - Diffuse Interstitial Pulmonary Infiltrates in Malignant Melanoma.
AB - Only a few cases of sarcoidosis-like reaction to a pharmacologic compound have
been reported in patients with melanoma in the literature. Long-term treatment
with interferon alpha may be assumed. We report a case of a 25-y-old man who
presented to our department with diffuse interstitial pulmonary infiltrates and
slightly enlarged mediastinal lymph nodes as determined by computed tomography.
He had a history of malignant melanoma with 18 months of interferon alpha-2
therapy. Histological analysis of a transbronchial biopsy revealed sarcoidosis
like reactions.
PMID- 25587169
TI - Systematic and endothelial inflammation and endothelial progenitor cell levels in
emphysematous rats exposed to intermittent hypoxia.
AB - BACKGROUND: This study aimed to develop an overlap syndrome rat model with
intermittent hypoxia (IH) exposure as seen in obstructive sleep apnea, on a base
of preexisting emphysema caused by 16 wk of smoke exposure to determine whether
IH and emphysema existing simultaneously play overlapped roles on
systematic/endothelial inflammation and endothelial damage. METHODS: Sixty male
Wistar rats were divided into 4 groups of 15 each, labeled according to exposure
conditions as control, IH, emphysema, and overlap groups. In these animals,
electroencephalogram monitoring and preliminary experiments to obtain arterial
blood gas values were performed. Serum concentrations of tumor necrosis factor
(TNF)-alpha and interleukin (IL)-6, TNF-alpha and IL-6 concentrations in the
culture medium, Ras homology A mRNA expression levels of endothelial cells from
right common carotid artery, and ratio of carotid intima-media thickness of whole
thickness of vascular wall expressed in percent (C-IMT) (%) values were
evaluated. Subsequently, circulating endothelial progenitor cells (EPCs) within
rat peripheral blood and bone marrow were measured with flow cytometry. RESULTS:
The serum and endothelial concentrations of TNF-alpha and IL-6 and the levels of
endothelial Ras homology A mRNA have statistically significant results described
as overlap>emphysema>IH>control. The levels of EPCs in rat peripheral blood and
bone marrow have statistically significant results described as
overlap>IH>emphysema>control. C-IMT (%) values from right common carotid artery
are the highest in the overlap group and the lowest in the control group. There
is no statistical difference when comparing the IH and the emphysema groups.
CONCLUSIONS: Regardless of whether IH and emphysema exposure are mechanistically
synergistic, this overlap elicits a more severe systematic/endothelial
inflammation and endothelial damage; meanwhile, a robust mobilization of EPCs is
demonstrated, which is not to mean a robust adherent and repairing capability.
PMID- 25587170
TI - Removal of the CPAP Therapy Device During Sleep and Its Association With Body
Position Changes and Oxygen Desaturations.
AB - BACKGROUND: Some patients with obstructive sleep apnea syndrome remove the CPAP
device during sleep, although they start CPAP at bedtime. We hypothesized that
body position changes and oxygen desaturations may be associated with patient
removal of the CPAP device. METHODS: We consecutively enrolled 36 poor CPAP
adherers and 25 good CPAP adherers. Body positions and oxygen desaturations were
evaluated when these subjects used CPAP during sleep for 2 nights, permitting the
removal of the CPAP device during the recording. RESULTS: Twelve poor CPAP
adherers exhibited subject removal of the CPAP device within 4 h from the start
of body position recording. The frequency of body position changes was
significantly higher within 15 min before the CPAP removal than during other
periods when CPAP was used. At the same time, oxygen desaturations were
significantly more frequent within 15 min before CPAP removal than during other
periods when CPAP was used. In addition, the majority (66.7%) of the CPAP removal
events were followed by a change from a supine position to a non-supine position
within 5 min. The number of body position changes during the first 4-h recording
was significantly higher in the poor CPAP adherers who had removed their CPAP
device compared with the poor CPAP adherers who had not removed their device.
However, the number of body position changes or oxygen desaturation index under
CPAP during the first 4-h recording was not significantly different between the
poor CPAP adherers and good CPAP adherers. CONCLUSIONS: Our findings are the
first to indicate associations among CPAP removal, body position changes, and
oxygen desaturations during sleep in poor CPAP adherers. However, our findings
also indicated that most good CPAP adherers make frequent body position changes
without removal of CPAP device, suggesting that patients can adapt to the
discomfort of CPAP therapy at the time of body position changes.
PMID- 25587171
TI - Distractive Auditory Stimuli Alleviate the Perception of Dyspnea Induced by Low
Intensity Exercise in Elderly Subjects With COPD.
AB - BACKGROUND: Although recent studies have shown that distractive auditory stimuli
(DAS) in the form of music increase adherence to exercise in subjects with COPD,
the effect of DAS on dyspnea induced by low-intensity, constant-load exercise in
elderly patients with COPD has not been elucidated. Therefore, the purpose of
this study was to investigate the effect of DAS on the perception of dyspnea
induced by low-intensity, constant-load exercise in elderly subjects with COPD.
METHODS: We enrolled 16 male out-patients with COPD. Subjects completed cycling
exercises with and without DAS at 40% maximum oxygen consumption. They were asked
to rate their perception of dyspnea using the modified Borg scale every 3 min
during exercise and every 1 min during the recovery period. RESULTS: Dyspnea
perception during low-intensity exercise showed a significant correlation between
the exercise condition (DAS and control) and exercise duration (P = .04).
Exercise-induced dyspnea perception under the DAS condition was significantly
lower than that under the control condition from 18 min after the start of
exercise to 3 min after the end of exercise (18, 20, 21, 22, and 23 min, P = .01,
P < .001, P = .009, P = .006, and P = .006, respectively). However, oxygen
consumption and ventilation in response to low-intensity exercise did not
significantly differ in the DAS and control conditions (P = .39 and .14,
respectively) CONCLUSIONS: Our results suggest that DAS is a non-pharmacologic
therapy that can be used to reduce the dyspneic sensation in elderly patients
with COPD.
PMID- 25587172
TI - Influence of ambient music on perceived exertion during a pulmonary
rehabilitation session: a randomized crossover study.
AB - BACKGROUND: Pulmonary rehabilitation is a key element in the treatment of COPD.
Music has been shown to have a positive effect on parameters related to a
decrease in exercise tolerance. The aim of this study was to evaluate the effect
of listening to ambient music on perceived exertion during a pulmonary
rehabilitation session for COPD subjects. METHODS: COPD subjects randomly
performed a session of pulmonary rehabilitation with or without ambient music.
Perceived exertion (Borg scales), anxiety (Hospital Anxiety and Depression Scale
Anxiety Subscale), dyspnea (visual analog scale), and cardiorespiratory
parameters were compared at the end of both sessions. RESULTS: Forty-one subjects
were analyzed. The characteristics of the COPD subjects were as follows: age,
70.5 +/- 8.4 y; body mass index, 22.7 +/- 3.9 kg/m(2); and FEV1, 38.6 +/- 12.5 %
predicted. Perceived exertion was not modified by ambient music, but anxiety was
improved (P = .02). Dyspnea, fatigue and cardiorespiratory parameters were not
influenced by music during a typical session of the pulmonary rehabilitation
program. CONCLUSIONS: This study demonstrates that perceived exertion during one
pulmonary rehabilitation session was not influenced by ambient music. However, a
positive effect on anxiety was observed. (ClinicalTrials.gov registration
NCT01833260.).
PMID- 25587173
TI - Home mechanical ventilation in Canada: a national survey.
AB - BACKGROUND: No comprehensive Canadian national data describe the prevalence of
and service provision for ventilator-assisted individuals living at home, data
critical to health-care system planning for appropriate resourcing. Our objective
was to generate national data profiling service providers, users, types of
services, criteria for initiation and monitoring, ventilator servicing
arrangements, education, and barriers to home transition. METHODS: Eligible
providers delivering services to ventilator-assisted individuals (adult and
pediatric) living at home were identified by our national provider inventory and
referrals from other providers. The survey was administered via a web link from
August 2012 to April 2013. RESULTS: The survey response rate was 152/171 (89%).
We identified 4,334 ventilator-assisted individuals: an estimated prevalence of
12.9/100,000 population, with 73% receiving noninvasive ventilation (NIV) and 18%
receiving intermittent mandatory ventilation (9% not reported). Services were
delivered by 39 institutional providers and 113 community providers. We
identified variation in initiation criteria for NIV, with polysomnography
demonstrating nocturnal hypoventilation (57%), daytime hypercapnia (38%), and
nocturnal hypercapnia (32%) as the most common criteria. Various models of
ventilator servicing were reported. Most providers (64%) stated that caregiver
competency was a prerequisite for home discharge; however, repeated competency
assessment and retraining were offered by only 45%. Important barriers to home
transition were: insufficient funding for paid caregivers, equipment, and
supplies; a shortage of paid caregivers; and negotiating public funding
arrangements. CONCLUSIONS: Ventilatory support in the community appears well
established, with most individuals managed with NIV. Although caregiver
competency is a prerequisite to discharge, ongoing assessment and retraining were
infrequent. Funding and caregiver availability were important barriers to home
transition.
PMID- 25587176
TI - Chronic exposure of grandparents to poverty and body mass index trajectories of
grandchildren: a prospective intergenerational study.
AB - In this study, I used the growth curve model to examine the association between
grandparents' (first generation (G1)) life-course exposure to chronic poverty and
grandchildren's (third generation (G3)) body mass index (BMI; weight (kg)/height
(m)(2)) growth trajectories. This association was estimated separately for male
and female grandchildren. Analyses were based on prospective data from a US
longitudinal survey, the Panel Study of Income Dynamics (1968-2011), and 2 of its
supplemental studies: the Child Development Supplement (1997-2011) and the
Transition into Adulthood Study (1997-2011). A prospectively enrolled nationally
representative cohort of 2,613 G3 youth (1,323 male, 1,290 female) sampled in the
2 supplemental studies was linked to 1,719 grandparents from the Panel Study of
Income Dynamics core sample. Chronic exposure to poverty among grandparents was
prospectively ascertained annually over a 30-year period prior to the collection
of data on grandchildren. Findings suggested that grandparents' chronic poverty
exposure was positively associated with the slope of the BMI trajectory among
granddaughters (beta = 0.10, 95% confidence interval: 0.03, 0.17) but not among
grandsons (beta = 0.02, 95% confidence interval: -0.04, 0.08). The association
between grandparents' chronic poverty exposure and granddaughters' BMI growth
slope remained even after controlling for parental (second generation (G2))
socioeconomic status and BMI.
PMID- 25587174
TI - Urinary melatonin concentration and the risk of breast cancer in Nurses' Health
Study II.
AB - Experimental and epidemiologic data support a protective role for melatonin in
breast cancer etiology, yet studies in premenopausal women are scarce. In a case
control study nested within the Nurses' Health Study II cohort, we measured the
concentration of melatonin's major urinary metabolite, 6-sulfatoxymelatonin
(aMT6s), in urine samples collected between 1996 and 1999 among 600 breast cancer
cases and 786 matched controls. Cases were predominantly premenopausal women who
were diagnosed with incident breast cancer after urine collection and before June
1, 2007. Using multivariable conditional logistic regression, we computed odds
ratios and 95% confidence intervals. Melatonin levels were not significantly
associated with total breast cancer risk (for the fourth (top) quartile (Q4) of
aMT6s vs. the first (bottom) quartile (Q1), odds ratio (OR) = 0.91, 95%
confidence interval (CI): 0.64, 1.28; Ptrend = 0.38) or risk of invasive or in
situ breast cancer. Findings did not vary by body mass index, smoking status,
menopausal status, or time between urine collection and diagnosis (all
Pinteraction values >= 0.12). For example, the odds ratio for total breast cancer
among women with <=5 years between urine collection and diagnosis was 0.74 (Q4
vs. Q1; 95% CI: 0.45, 1.20; Ptrend = 0.09), and it was 1.20 (Q4 vs. Q1; 95% CI:
0.72, 1.98; Ptrend = 0.70) for women with >5 years. Our data do not support an
overall association between urinary melatonin levels and breast cancer risk.
PMID- 25587177
TI - Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients
in a dose-dependent manner: a population-based cohort study.
AB - OBJECTIVE: SLE is associated with increased risk of diabetes mellitus. Treatment
for SLE requires high-dose glucocorticoids that may worsen glucose homoeostasis.
HCQ can reduce diabetes risk in RA. This study aimed to investigate the
association of HCQ use and diabetes mellitus risk in SLE patients. METHODS: This
nationwide, population-based cohort study was conducted using the Taiwan National
Health Insurance Research Database. In the period 2001-10, 8628 newly diagnosed
SLE patients were identified after excluding those with a previous diagnosis of
RA, psoriasis or diabetes mellitus. Incidence of diabetes mellitus was identified
as a new diagnostic code using a diabetes mellitus-specific medication. RESULTS:
Two hundred and twenty-one newly diagnosed diabetes mellitus patients were
identified among SLE patients (6795 had taken HCQ and 1833 had never taken HCQ),
with an average follow-up period of 5.6 years. Compared with patients without HCQ
treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a
cumulative dose >=129 g was reduced [HR 0.26 (95% CI 0.18, 0.37), P < 0.001].
Daily glucocorticoid >=10 mg prednisolone-equivalent dose was associated with
increased risk of developing diabetes mellitus [HR 2.47 (95% CI 1.44, 4.23), P =
0.001], which was minimized by concomitant HCQ use at a cumulative dose >=129 g.
CONCLUSION: In SLE patients, the use of HCQ is associated with reduced risk of
incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids
increase the risk of diabetes, which can be decreased by concomitant HCQ use.
PMID- 25587178
TI - Does reduction of disease activity improve early markers of cardiovascular
disease in newly diagnosed rheumatoid arthritis patients?
AB - OBJECTIVE: The incidence of cardiovascular disease (CVD) is increased in RA. This
study was designed to evaluate whether a reduction in disease activity influences
early markers of CVD. METHODS: In a prospective longitudinal study, 58 newly
diagnosed RA patients and 58 age- and sex-matched healthy controls (HCs) were
included. Endothelial dysfunction was measured by small artery elasticity (SAE)
and endothelial cell activation was assessed by measuring soluble vascular
cellular activation molecule 1(sVCAM-1) and von Willebrand factor (vWF). Advanced
glycation end products (AGEs) were quantified by skin autofluorescence. After 1
year, measurements were repeated in all RA patients. RESULTS: At entry, SAE was
decreased in RA vs HCs [median 3.4 ml/mmHg100 (range 1.2-9.0) vs 6.1 (range 5.0
15.3), P < 0.0001] and sVCAM-1 and vWF were increased: 391 ng/ml (range 256-680)
vs 341 (range 223-691) (P = 0.0015) and 120 ng/ml (range 26.5-342) vs 99 (range
22-298) (P = 0.02), respectively. SAE was inversely correlated with the 28-joint
DAS (DAS28; r = -0.31, P = 0.016). AGEs were increased by 2.55 arbitrary units
(range 1.29-4.65) vs 2.12 (range 1.32-3.82) in HCs (P = 0.003). In multivariate
analysis, the presence of RA, age and systolic blood pressure were independently
and inversely related to SAE. After 1 year, SAE had significantly improved in RA,
from 3.4 (range 1.2-9.0) to 3.8 (range 1.5-10.3) (P = 0.03). CONCLUSION:
Endothelial dysfunction is present in newly diagnosed RA patients, independently
of traditional risk factors and is inversely correlated with disease activity. By
reducing disease activity, endothelial dysfunction improves, although not to
normal values. Also, a reduction in disease activity targeting traditional risk
factors remains important in preventing CVD in RA.
PMID- 25587179
TI - IgG4-related periaortitis vs idiopathic periaortitis: is there a role for
atherosclerotic plaque in the pathogenesis of IgG4-related periaortitis?
AB - OBJECTIVE: The diagnosis of (isolated) IgG4-related periaortitis is often based
on elevated serum IgG4 levels since in tissues such as the aorta, biopsies cannot
be easily performed. However, the role for serum IgG4 as a biomarker for IgG4
related periaortitis is indistinct. The main purpose of our study was to identify
clinical differences between periaortitis with elevated vs normal serum IgG4
levels. METHODS: A retrospective study was performed on 68 non-infectious
periaortitis patients. We compared demographic, clinical, biochemical and
radiological data in patients with elevated serum IgG4 levels with data from
patients with normal serum IgG4 levels. The calcium content of the aortic wall
was calculated to determine the amount of atherosclerosis. RESULTS: After
applying exclusion criteria, our study population consisted of nine IgG4-related
periaortitis patients and eight idiopathic periaortitis patients. Striking
significant differences were male predominance (P = 0.001) and multifocal organ
involvement (P = 0.004) in IgG4-related periaortitis patients compared with the
idiopathic periaortitis group. The calcium content of the total aortic wall was
significantly higher in IgG4-related periaortitis patients (P = 0.005). No other
significant differences were found. CONCLUSION: Elevated serum IgG4 levels, male
gender, a higher calcium content of the aortic wall and multifocal organ
involvement are features that might provide a higher probability for IgG4-related
periaortitis compared with idiopathic periaortitis. Our study results might be
compatible with the hypothesis of Mitchinson and Parums that atherosclerotic
plaque plays a role in the pathogenesis of chronic periaortitis.
PMID- 25587180
TI - Structural basis for recognition of intron branchpoint RNA by yeast Msl5 and
selective effects of interfacial mutations on splicing of yeast pre-mRNAs.
AB - Saccharomyces cerevisiae Msl5 orchestrates spliceosome assembly by binding the
intron branchpoint sequence 5'-UACUAAC and, with its heterodimer partner protein
Mud2, establishing cross intron-bridging interactions with the U1 snRNP at the 5'
splice site. Here we define the central Msl5 KH-QUA2 domain as sufficient for
branchpoint RNA recognition. The 1.8 A crystal structure of Msl5-(KH-QUA2) bound
to the branchpoint highlights an extensive network of direct and water-mediated
protein-RNA and intra-RNA atomic contacts at the interface that illuminate how
Msl5 recognizes each nucleobase of the UACUAAC element. The Msl5 structure
rationalizes a large body of mutational data and inspires new functional studies
herein, which reveal how perturbations of the Msl5.RNA interface impede the
splicing of specific yeast pre-mRNAs. We also identify interfacial mutations in
Msl5 that bypass the essentiality of Sub2, a DExD-box ATPase implicated in
displacing Msl5 from the branchpoint in exchange for the U2 snRNP. These studies
establish an atomic resolution framework for understanding splice site selection
and early spliceosome dynamics.
PMID- 25587181
TI - Cross-sectional survey comparing HIV risk behaviours of adolescent and young
adult men who have sex with men only and men who have sex with men and women in
the U.S. and Puerto Rico.
AB - OBJECTIVE: To examine the HIV risk behaviours of men who have sex with men only
(MSMO) and men who have sex with men and women (MSMW), aged 12-24 years, in five
US cities and in San Juan, Puerto Rico. METHODS: Data were collected through four
annual cross-sectional anonymous surveys at community venues and included
questions about sexual partnerships, sexual practices including condom use and
substance use. Demographic and risk profiles were summarised for both groups.
RESULTS: A total of 1198 men were included in this analysis, including 565 MSMO
and 633 MSMW. There were statistically significant differences between the two
groups for many risk factors examined in multivariable models. MSMW were more
likely to identify as bisexual, be in a long-term relationship, have a history of
homelessness, have ever used marijuana, have ever been tested for HIV and to have
been tested for HIV within the past 6 months. MSMW may be more likely to ever
exchange sex for money and ever have a sexually transmitted infection than MSMO.
CONCLUSIONS: MSMW were more likely to report several markers of socioeconomic
vulnerability or behaviours associated with increased risk for HIV than MSMO.
MSMW contribute to HIV prevalence in the USA, and better understanding of the
risk profile of this group is essential to understand heterosexual HIV
transmission. MSMW, particularly those who identify as bisexual or questioning,
may feel uncomfortable participating in programmes that are designed for gay
identified men. Therefore, prevention strategies need to target distinct
subgroups that compose the population of MSM.
PMID- 25587183
TI - Distal femoral fracture after double-bundle anterior cruciate ligament
reconstruction surgery.
PMID- 25587182
TI - Measuring child awareness for adult symptomatic HIV using a verbal assessment
tool: concordance between adult-child dyads on adult HIV-associated symptoms and
illnesses.
AB - OBJECTIVES: This study assessed children's awareness for adult HIV-associated
symptoms and illnesses using a verbal assessment tool by analysing inter-rater
reliability between adult-child dyads. This study also evaluated sociodemographic
and household characteristics associated with child awareness of adult
symptomatic HIV. METHODS: A cross-sectional survey using a representative
community sample of adult-child dyads (N=2477 dyads) was conducted in KwaZulu
Natal, South Africa. Analyses focused on a subsample (n=673 adult-child dyads)
who completed verbal assessment interviews for symptomatic HIV. We used an
existing validated verbal autopsy approach, originally designed to determine AIDS
related deaths by adult proxy reporters. We adapted this approach for use by
child proxy reporters for reporting on HIV-associated symptoms and illnesses
among living adults. Analyses assessed whether children could reliably report on
adult HIV-associated symptoms and illnesses and adult provisional HIV status.
RESULTS: Adult-child pairs concurred above the 65th percentile for 9 of the 10
HIV-associated symptoms and illnesses with sensitivities ranging from 10% to 100%
and specificities ranging from 20% to 100%. Concordant reporting between adult
child dyads for the adult's provisional HIV status was 72% (sensitivity=68%,
specificity=73%). Children were more likely to reliably match adult's reports of
provisional HIV status when they lived in households with more household members,
and households with more robust socioeconomic indicators including access to
potable water, food security and television. CONCLUSIONS: Children demonstrate
awareness of HIV-associated symptoms and illnesses experienced by adults in their
household. Children in households with greater socioeconomic resources and more
household members were more likely to reliably report on the adult's provisional
HIV status.
PMID- 25587184
TI - Intra- and interobserver agreement in the classification and treatment of distal
third clavicle fractures.
AB - BACKGROUND: In treatment of distal third clavicle fractures, the Neer
classification system, based on the location of the fracture in relation to the
coracoclavicular ligaments, has traditionally been used to determine fracture
pattern stability. PURPOSE: To determine the intra- and interobserver reliability
in the classification of distal third clavicle fractures via standard plain
radiographs and the intra- and interobserver agreement in the preferred treatment
of these fractures. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3.
METHODS: Thirty radiographs of distal clavicle fractures were randomly selected
from patients treated for distal clavicle fractures between 2006 and 2011. The
radiographs were distributed to 22 shoulder/sports medicine fellowship-trained
orthopaedic surgeons. Fourteen surgeons responded and took part in the study. The
evaluators were asked to measure the size of the distal fragment, classify the
fracture pattern as stable or unstable, assign the Neer classification, and
recommend operative versus nonoperative treatment. The radiographs were reordered
and redistributed 3 months later. Inter- and intrarater agreement was determined
for the distal fragment size, stability of the fracture, Neer classification, and
decision to operate. Single variable logistic regression was performed to
determine what factors could most accurately predict the decision for surgery.
RESULTS: Interrater agreement was fair for distal fragment size, moderate for
stability, fair for Neer classification, slight for type IIB and III fractures,
and moderate for treatment approach. Intrarater agreement was moderate for distal
fragment size categories (kappa = 0.50, P < .001) and Neer classification (kappa
= 0.42, P < .001) and substantial for stable fracture (kappa = 0.65, P < .001)
and decision to operate (kappa = 0.65, P < .001). Fracture stability was the best
predictor of treatment, with 89% accuracy (P < .001). CONCLUSION: Fracture
stability determination and the decision to operate had the highest interobserver
agreement. Fracture stability was the key determinant of treatment, rather than
the Neer classification system or the size of the distal fragment.
PMID- 25587185
TI - The prevalence and combined prevalences of anatomic factors associated with
recurrent patellar dislocation: a magnetic resonance imaging study.
AB - BACKGROUND: Anatomic factors, including patella alta, increased tibial tubercle
trochlear groove (TT-TG) distance, rotational deformities, and trochlear
dysplasia, are associated with dislocation of the patella. Identifying the
presence of these anatomic factors both in isolation and in combination may
influence treatment in patients with patellar dislocation. PURPOSE: The aim of
this study was to compare the prevalence and combined prevalences of these
anatomic factors using magnetic resonance imaging in a group of patients with and
without histories of recurrent dislocation of the patella. STUDY DESIGN: Case
control study; Level of evidence, 3. METHODS: The prevalence and combined
prevalences of patella alta, increased TT-TG distance, rotational deformity, and
trochlear dysplasia on magnetic resonance imaging were reported and compared in
60 patients (60 knees) with and 120 patients (120 knees) without histories of
recurrent patellar dislocation. RESULTS: Patients with recurrent patellar
dislocation possessed higher rates of patella alta (60.0% vs. 20.8%), increased
TT-TG distance (42.0% vs. 3.2%), rotational deformity (26.7% vs. 2.5%), and
trochlear dysplasia (68.3% vs. 5.8%) compared with patients without histories of
patellar dislocation. Multiple anatomic factors were identified in 58.3% of
patients (35/60) with recurrent dislocation compared with only 1.7% of controls
(2/120). CONCLUSION: Recurrent patellar dislocation is associated with an
increased prevalence of patella alta, increased TT-TG distance, rotational
deformity, and trochlear dysplasia compared with patients with no histories of
patellar dislocation. Multiple anatomic factors were identified in the majority
of patients with recurrent dislocation. Further research may identify which
factors play a greater role in patellar stability and may allow physicians to
predict which first-time dislocation patients are more likely to sustain
recurrence.
PMID- 25587187
TI - Characterization of size-specific particulate matter emission rates for a
simulated medical laser procedure--a pilot study.
AB - Prior investigation on medical laser interaction with tissue has suggested device
operational parameter settings influence laser generated air contaminant
emission, but this has not been systematically explored. A laboratory-based
simulated medical laser procedure was designed and pilot tested to determine the
effect of laser operational parameters on the size-specific mass emission rate of
laser generated particulate matter. Porcine tissue was lased in an emission
chamber using two medical laser systems (CO2, lambda = 10,600 nm; Ho:YAG, lambda
= 2100 nm) in a fractional factorial study design by varying three operational
parameters (beam diameter, pulse repetition frequency, and power) between two
levels (high and low) and the resultant plume was measured using two real-time
size-selective particle counters. Particle count concentrations were converted to
mass emission rates before an analysis of variance was used to determine the
influence of operational parameter settings on size-specific mass emission rate.
Particle shape and diameter were described for a limited number of samples by
collecting particles on polycarbonate filters, and photographed using a scanning
electron microscope (SEM) to examine method of particle formation. An increase in
power and decrease in beam diameter led to an increase in mass emission for the
Ho:YAG laser at all size ranges. For the CO2 laser, emission rates were dependent
on particle size and were not statistically significant for particle ranges
between 5 and 10 um. When any parameter level was increased, emission rate of the
smallest particle size range also increased. Beam diameter was the most
influential variable for both lasers, and the operational parameters tested
explained the most variability at the smallest particle size range. Particle
shape was variable and some particles observed by SEM were likely created from
mechanical methods. This study provides a foundation for future investigations to
better estimate size-specific mass emission rates and particle characteristics
for additional laser operational parameters in order to estimate occupational
exposure, and to inform control strategies.
PMID- 25587186
TI - What Is the Association Between Sports Participation and the Development of
Proximal Femoral Cam Deformity? A Systematic Review and Meta-analysis.
AB - BACKGROUND: Femoroacetabular impingement (FAI) is recognized as a common cause of
hip pain and intra-articular disorders in athletes. Studies have suggested a link
between participation in athletics during adolescence and the development of cam
type deformities of the proximal femoral head-neck junction. PURPOSE: To
investigate the association of sporting activity participation during adolescence
and the development of cam deformity. STUDY DESIGN: Systematic review. METHODS:
The PubMed, EMBASE, and Cochrane databases were searched to identify potential
studies. Abstracts and manuscripts (when applicable) were independently reviewed
by 2 reviewers. Nine studies met the inclusion criteria, including 8 studies that
compared the prevalence of cam deformity in athletes with that in controls and 3
studies that compared the prevalence of cam deformity before and after physeal
closure (2 with both). A meta-analysis was performed with pooling of data and
random-effects modeling to compare rates of cam deformity between athletes and
controls. RESULTS: High-level male athletes are 1.9 to 8.0 times more likely to
develop a cam deformity than are male controls. The pooled prevalence rate (by
hip) of cam deformity in male athletes was 41%, compared with 17% for male
controls. The pooled mean alpha angle among male athletes was 61 degrees ,
compared with 51 degrees for male controls. CONCLUSION: Males participating in
specific high-level impact sports (hockey, basketball, and possibly soccer) are
at an increased risk of physeal abnormalities of the anterosuperior head-neck
junction that result in a cam deformity at skeletal maturity.
PMID- 25587189
TI - The mitotic checkpoint protein kinase BUB1 is an engine in the TGF-beta signaling
apparatus.
AB - The transforming growth factor-beta (TGF-beta) pathway mediates critical events
in cell behavior that contribute to development and disease. The mitotic
checkpoint guarantees faithful chromosomal segregation during cell division. In
the 6 January 2015 issue of Science Signaling, Nyati et al. reported that the
mitotic checkpoint kinase BUB1 promotes the activity of TGF-beta receptors, which
adds new molecular links between these fundamental biological processes.
PMID- 25587188
TI - Extensive glycosylation of ACPA-IgG variable domains modulates binding to
citrullinated antigens in rheumatoid arthritis.
AB - OBJECTIVES: To understand the molecular features distinguishing anti
citrullinated protein antibodies (ACPA) from 'conventional' antibodies in
rheumatoid arthritis (RA). METHODS: Serum of ACPA-positive RA patients was
fractionated by size exclusion chromatography and analysed for the presence of
ACPA-IgG by ELISA. ACPA-IgG and non-citrulline-specific IgG were affinity
purified from serum, plasma and/or synovial fluid and analysed by gel
electrophoresis. Electrophoresis bands were excised, enzymatically digested and
analysed by mass spectrometry. Binding affinity to citrullinated antigens was
measured by ELISA and imaging surface plasmon resonance using recombinant
monoclonal ACPA with molecular modifications. RESULTS: In all donor samples
studied (n=24), ACPA-IgG exhibited a 10-20 kDa higher molecular weight compared
with non-autoreactive IgG. This feature also distinguished ACPA-IgG from
antibodies against recall antigens or other disease-specific autoantibodies.
Structural analysis revealed that a high frequency of N-glycans in the
(hyper)variable domains of ACPA is responsible for this observation. In line with
their localisation, these N-glycans were found to modulate binding avidity of
ACPA to citrullinated antigens. CONCLUSIONS: The vast majority of ACPA-IgG
harbour N-glycans in their variable domains. As N-linked glycosylation requires
glycosylation consensus sites in the protein sequence and as these are lacking in
the 'germline-counterparts' of identified variable domains, our data indicate
that the N-glycosylation sites in ACPA variable domains have been introduced by
somatic hypermutation. This finding also suggests that ACPA-hyperglycosylation
confers a selective advantage to ACPA-producing B cells. This unique and
completely novel feature of the citrulline-specific immune response in RA
elucidates our understanding of the underlying B cell response.
PMID- 25587190
TI - STIM2 enhances receptor-stimulated Ca2+ signaling by promoting recruitment of
STIM1 to the endoplasmic reticulum-plasma membrane junctions.
AB - A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+)
entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in
endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response
to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated
activation of SOCE by promoting STIM1 clustering in ER-PM junctions at low
stimulus intensities. Targeted deletion of STIM2 in mouse salivary glands
diminished fluid secretion in vivo and SOCE activation in dispersed salivary
acinar cells stimulated with low concentrations of muscarinic receptor agonists.
STIM2 knockdown in human embryonic kidney (HEK) 293 cells diminished agonist
induced Ca(2+) signaling and nuclear translocation of NFAT (nuclear factor of
activated T cells). STIM2 lacking five carboxyl-terminal amino acid residues did
not promote formation of STIM1 puncta at low concentrations of agonist, whereas
coexpression of STIM2 with STIM1 mutant lacking the polybasic region STIM1DeltaK
resulted in co-clustering of both proteins. Together, our findings suggest that
STIM2 recruits STIM1 to ER-PM junctions at low stimulus intensities when ER
Ca(2+) stores are mildly depleted, thus increasing the sensitivity of Ca(2+)
signaling to agonists.
PMID- 25587191
TI - Annotation of human cancers with EGFR signaling-associated protein complexes
using proximity ligation assays.
AB - Strategies to measure functional signaling-associated protein complexes have the
potential to augment current molecular biomarker assays, such as genotyping and
expression profiling, used to annotate diseases. Aberrant activation of epidermal
growth factor receptor (EGFR) signaling contributes to diverse cancers. We used a
proximity ligation assay (PLA) to detect EGFR in a complex with growth factor
receptor-bound protein 2 (GRB2), the major signaling adaptor for EGFR. We used
multiple lung cancer cell lines to develop and characterize EGFR:GRB2 PLA and
correlated this assay with established biochemical measures of EGFR signaling. In
a panel of patient-derived xenografts in mice, the intensity of EGFR:GRB2 PLA
correlated with the reduction in tumor size in response to the EGFR inhibitor
cetuximab. In tumor biopsies from three cohorts of lung cancer patients, positive
EGFR:GRB2 PLA was observed in patients with and without EGFR mutations, and the
intensity of EGFR:GRB2 PLA was predictive of overall survival in an EGFR
inhibitor-treated cohort. Thus, we established the feasibility of using PLA to
measure EGFR signaling-associated protein complexes in patient-based materials,
suggesting the potential for similar assays for a broader array of receptor
tyrosine kinases and other key signaling molecules.
PMID- 25587193
TI - Rotational thromboelastometry in prediction of bleeding after cardiac surgery.
AB - BACKGROUND: Reexploration and its associated complications significantly affect
hospital mortality and morbidity. Therefore, to prevent postoperative bleeding
and its related complications, using an appropriate modality is essential during
cardiac surgery. METHODS: Four hundred patients (296 males and 104 females, mean
age 60.8 +/- 9 years) scheduled for first-time coronary artery bypass graft
surgery were prospectively enrolled. Blood samples were obtained for ROTEM
testing before surgery and 30 min after heparin reversal. The patients were
divided into 2 groups: group 1 was patients with no abnormal postoperative
bleeding and group 2 was patients who required reexploration for abnormal
postoperative bleeding. Group 2 patients were divided into 2 subgroups: 2a was
patients with surgical bleeding and group 2b was patients with nonsurgical
bleeding. Variables were compared between groups. RESULTS: Among the 400
patients, 42 were reexplored. Hospital stay was significantly longer and hospital
deaths more frequent in group 2 patients (p < 0.001 and p = 0.010, respectively).
Ten (2.8%) patients had abnormal preoperative results of ROTEM in group 1
compared to 14 (33.3%) in group 2 (p < 0.001). After surgery, the number of
patients with abnormal ROTEM results was significantly different between the 2
groups: 6 (1.7%) in group 1 vs. 14 (33.3%) in group 2 (p < 0.001). Four (12.5%)
patients in group 2a had abnormal preoperative ROTEM results compared to 10
(100%) in group 2a (p < 0.001). CONCLUSION: Measuring coagulation factors by
ROTEM both before surgery and after heparin reversal can identify patients at
increased risk of postoperative bleeding.
PMID- 25587195
TI - Effects of disturbance on vegetation by sand accretion and erosion across coastal
dune habitats on a barrier island.
AB - Coastal geomorphology and vegetation are expected to be particularly sensitive to
climate change, because of disturbances caused by sea-level rise and increased
storm frequency. Dunes have critical reciprocal interactions with vegetation;
dunes create habitats for plants, while plants help to build dunes and promote
geomorphological stability. These interactions are also greatly affected by
disturbances associated with sand movement, either in accretion (dune building)
or in erosion. The magnitude and intensity of disturbances are expected to vary
with habitat, from the more exposed and less stable foredunes, to low-lying and
flood-prone interdunes, to the protected and older backdunes. Permanent plots
were established at three different spatial scales on St George Island, FL, USA,
where the vegetation and dune elevation were quantified annually from 2011 to
2013. Change in elevation, either through accretion or erosion, was used as a
measure of year-to-year disturbance over the 2 years of the study. At the scale
of different dune habitats, foredunes were found to have the greatest
disturbance, while interdunes had the least. Elevation and habitat (i.e.
foredune, interdune, backdune) were significantly correlated with plant community
composition. Generalized linear models conducted within each habitat show that
the change in elevation (disturbance) is also significantly correlated with the
plant community, but only within foredunes and interdunes. The importance of
disturbance in exposed foredunes was expected and was found to be related to an
increasing abundance of a dominant species (Uniola paniculata) in eroding areas.
The significant effect of disturbance in the relatively stable interdunes was
surprising, and may be due to the importance of flooding associated with small
changes in elevation in these low-lying areas. Overall, this study documents
changes in the plant community associated with elevation, and demonstrates that
the foredune and interdune communities are also associated with the responses of
specific species to local changes in elevation due to accretion or erosion.
PMID- 25587194
TI - Influence of sulfur and cadmium on antioxidants, phytochelatins and growth in
Indian mustard.
AB - Soils in many parts of the world are contaminated with heavy metals, leading to
multiple, deleterious effects on plants and threats to world food production
efficiency. Cadmium (Cd) is one such metal, being toxic at relatively low
concentrations as it is readily absorbed and translocated in plants. Sulfur-rich
compounds are critical to the impact of Cd toxicity, enabling plants to increase
their cellular defence and/or sequester Cd into vacuoles mediated by
phytochelatins (PCs). The influence of sulfur on Cd-induced stress was studied in
the hyperaccumulator plant Indian mustard (Brassica juncea) using two sulfur
concentrations (+S, 300 uM [Formula: see text] and S-deficient -S, [Formula: see
text]) with and without the addition of Cd (100 uM CdCl2) at two different time
intervals (7 and 14 days after treatment). Compared with control plants (+S/-Cd),
levels of oxidative stress were higher in S-deficient (-S/-Cd) plants, and
greatest in S-deficient Cd-treated (-S/+Cd) plants. However, additional S
(+S/+Cd) helped plants cope with oxidative stress. Superoxide dismutase emerged
as a key player against Cd stress under both -S and +S conditions. The activity
of ascorbate peroxidase, glutathione reductase and catalase declined in Cd
treated and S-deficient plants, but was up-regulated in the presence of sulfur.
Sulfur deficiency mediated a decrease in ascorbate and glutathione (GSH) content
but changes in ascorbate (reduced : oxidized) and GSH (reduced : oxidized) ratios
were alleviated by sulfur. Our data clearly indicate that a sulfur pool is needed
for synthesis of GSH, non-protein thiols and PCs and is also important for
growth. Sulfur-based defence mechanisms and the cellular antioxidant pathway,
which are critical for tolerance and growth, collapsed as a result of a decline
in the sulfur pool.
PMID- 25587192
TI - MAPK feedback encodes a switch and timer for tunable stress adaptation in yeast.
AB - Signaling pathways can behave as switches or rheostats, generating binary or
graded responses to a given cell stimulus. We evaluated whether a single
signaling pathway can simultaneously encode a switch and a rheostat. We found
that the kinase Hog1 mediated a bifurcated cellular response: Activation and
commitment to adaptation to osmotic stress are switchlike, whereas protein
induction and the resolution of this commitment are graded. Through
experimentation, bioinformatics analysis, and computational modeling, we
determined that graded recovery is encoded through feedback phosphorylation and a
gene induction program that is both temporally staggered and variable across the
population. This switch-to-rheostat signaling mechanism represents a versatile
stress adaptation system, wherein a broad range of inputs generate an "all-in"
response that is later tuned to allow graded recovery of individual cells over
time.
PMID- 25587196
TI - Fluorosis and periostitis deformans as complications of prolonged voriconazole
treatment.
AB - We describe a case of development of painful periostitis deformans in a 39-year
old woman who was receiving long-term voriconazole treatment for Aspergillus
infection as a complication of orthotopic liver transplant. Measurement of
fluoride levels strongly supports fluorosis to be the mechanism of the
voriconazole-induced periostitis deformans and supports the concept that such
measurements might be of use in predicting this complication of long-term
voriconazole treatment.
PMID- 25587197
TI - Plasma capric acid concentrations in healthy subjects determined by high
performance liquid chromatography.
AB - BACKGROUND: Capric acid (FA10:0, decanoic acid) is a medium-chain fatty acid
abundant in tropical oils such as coconut oil, whereas small amounts are present
in milk of goat, cow, and human. Orally ingested FA10:0 is transported to the
liver and quickly burnt within it. Only few reports are available for FA10:0
concentrations in human plasma. METHODS: Fasting (n = 5, male/female = 3/2, age
31 +/- 9.3 years old) and non-fasting (n = 106, male/female = 44/62, age 21.9 +/-
3.2 years old) blood samples were collected from apparently healthy Japanese
volunteers. The total FA10:0 in the plasma were measured by high-performance
liquid chromatography after derivatization with 2-nitrophenylhydrazine followed
by UV detection. RESULTS: Inter and intra-assay coefficient of variation of
FA10:0 assay at three different concentrations ranged in 1.7-3.9 and 1.3-5.4%,
respectively, with an analytical recovery of 95.2-104.0%. FA10:0 concentration
was below detection limit (0.1 umol/L) in each fasting human plasma. FA10:0 was
not detected in 50 (47.2%) of 106 non-fasting blood samples, while 29 (27.4%)
plasma samples contained FA10:0 less than or equal to 0.5 umol/L (0.4 +/- 0.1),
and 27 (25.5%) contained it at more than 0.5 umol/L (0.9 +/- 0.3). CONCLUSION: A
half of the non-fasting plasma samples contained detectable FA10:0. This simple,
precise, and accurate high-performance liquid chromatography method might be
useful for monitoring plasma FA10:0 during medium-chain triglycerides therapy.
PMID- 25587198
TI - The interference by HbF on HbA1c (BM Test HbA1c) measurement in enzymatic method.
AB - BACKGROUND: High performance liquid chromatography and immunological and
enzymatic methods are known as the methods for HbA1c measurement. However, the
differences in the principles of the methods may cause slight discrepancies,
which become problems especially in the regions where hemoglobinopathies that
have high HbF concentrations are commonly seen. In this report, we discuss the
effect of HbF on the HbA1c measurement by the enzymatic method (BM Test HbA1c)
which can be applied to automatic analyzer of high sample throughput. METHODS:
Thirty-five samples (HbF concentration: between 1.4 and 90.1%) and 68 samples
(HbF concentration: <1.0%) were analyzed by high performance liquid
chromatography (Tosoh G8) and BM Test HbA1c. The results by BM Test HbA1c were
compared with those by the high performance liquid chromatography and
International Federation of Clinical Chemistry reference method. RESULTS: The
high and positive correlation coefficient was demonstrated between the enzymatic
and International Federation of Clinical Chemistry methods for the samples with
normal HbF concentration. The samples with high HbF concentration exhibited high
and positive correlation coefficient, although the figure is lower than that of
the normal HbF concentration group. CONCLUSIONS: BM Test HbA1c revealed a high
and positive correlation with high performance liquid chromatography and
International Federation of Clinical Chemistry reference methods. However, the
HbA1c values by BM Test HbA1c and high performance liquid chromatography method
were lower than those by International Federation of Clinical Chemistry reference
method when the HbF concentration was high. BM Test HbA1c had some deviation from
the International Federation of Clinical Chemistry reference method, while no
significant interference was seen when the HbF values were less than 15%. When
HbF is higher than 15%, however, the interpretation of HbA1c by BM Test may
require some special consideration.
PMID- 25587199
TI - The Pot Calling the Kettle Black? A Comparison of Measures of Current Tobacco
Use.
AB - Researchers often use the discrepancy between self-reported and biochemically
assessed active smoking status to argue that self-reported smoking status is not
reliable, ignoring the limitations of biochemically assessed measures and
treating it as the gold standard in their comparisons. Here, we employ
econometric techniques to compare the accuracy of self-reported and biochemically
assessed current tobacco use, taking into account measurement errors with both
methods. Our approach allows estimating and comparing the sensitivity and
specificity of each measure without directly observing true smoking status. The
results, robust to several alternative specifications, suggest that there is no
clear reason to think that one measure dominates the other in accuracy.
PMID- 25587200
TI - Pseudo-empirical Likelihood-Based Method Using Calibration for Longitudinal Data
with Drop-Out.
AB - In observational studies, interest mainly lies in estimation of the population
level relationship between the explanatory variables and dependent variables, and
the estimation is often undertaken using a sample of longitudinal data. In some
situations, the longitudinal data sample features biases and loss of estimation
efficiency due to non-random drop-out. However, inclusion of population-level
information can increase estimation efficiency. In this paper we propose an
empirical likelihood-based method to incorporate population-level information in
a longitudinal study with drop-out. The population-level information is
incorporated via constraints on functions of the parameters, and non-random drop
out bias is corrected by using a weighted generalized estimating equations
method. We provide a three-step estimation procedure that makes computation
easier. Some commonly used methods are compared in simulation studies, which
demonstrate that our proposed method can correct the non-random drop-out bias and
increase the estimation efficiency, especially for small sample size or when the
missing proportion is high. In some situations, the efficiency improvement is
substantial. Finally, we apply this method to an Alzheimer's disease study.
PMID- 25587201
TI - Whole-body cortisol response of zebrafish to acute net handling stress.
AB - Zebrafish, Danio rerio, are frequently handled during husbandry and experimental
procedures in the laboratory, yet little is known about the physiological
responses to such stressors. We measured the whole-body cortisol levels of adult
zebrafish subjected to net stress and air exposure at intervals over a 24 h
period; cortisol recovered to near control levels by about 1 h post-net-stress
(PNS). We then measured cortisol at frequent intervals over a 1 h period.
Cortisol levels were more than 2-fold higher in net stressed fish at 3 min PNS
and continued to increase peaking at 15 min PNS, when cortisol levels were 6-fold
greater than the control cortisol. Mean cortisol declined from 15 to 60 min PNS,
and at 60 min, net-stressed cortisol was similar to control cortisol. Because the
age of fish differed between studies, we examined resting cortisol levels of fish
of different ages (3, 7, 13, and 19 months). The resting cortisol values among
tanks with the same age fish differed significantly but there was no clear effect
of age. Our study is the first to report the response and recovery of cortisol
after net handling for laboratory-reared zebrafish.
PMID- 25587202
TI - Trait Rumination Is Associated with Enhanced Recollection of Negative Words.
AB - Rumination is associated with Major Depressive Disorder (MDD). To better
understand this association, researchers have begun to investigate the
relationship between rumination and cognitive biases that are linked to MDD. To
date, several studies have found that rumination is related to negatively biased
memory, but it is not clear whether this relationship is independent of
depressive symptoms. To address this question, the present study examined 97
healthy Caucasian women between the ages of 18 and 25. Participants performed an
encoding task of self-referent adjectives, followed by a recognition task. The
recognition task utilized a remember/know paradigm to separately examine
recollection-based memory and familiarity-based memory. Trait rumination was
assessed using the ruminative response scale (RRS). Results indicate that high
trait rumination is associated with selective enhancement of recollection for
negative words compared to neutral words and a trend toward selective enhancement
for recollection for negative words compared to positive words. Trait rumination
does not affect biases in overall recognition sensitivity or familiarity.
PMID- 25587203
TI - A Methodology for Robust Multiproxy Paleoclimate Reconstructions and Modeling of
Temperature Conditional Quantiles.
AB - Great strides have been made in the field of reconstructing past temperatures
based on models relating temperature to temperature-sensitive paleoclimate
proxies. One of the goals of such reconstructions is to assess if current climate
is anomalous in a millennial context. These regression based approaches model the
conditional mean of the temperature distribution as a function of paleoclimate
proxies (or vice versa). Some of the recent focus in the area has considered
methods which help reduce the uncertainty inherent in such statistical
paleoclimate reconstructions, with the ultimate goal of improving the confidence
that can be attached to such endeavors. A second important scientific focus in
the subject area is the area of forward models for proxies, the goal of which is
to understand the way paleoclimate proxies are driven by temperature and other
environmental variables. One of the primary contributions of this paper is novel
statistical methodology for (1) quantile regression with autoregressive residual
structure, (2) estimation of corresponding model parameters, (3) development of a
rigorous framework for specifying uncertainty estimates of quantities of
interest, yielding (4) statistical byproducts that address the two scientific
foci discussed above. We show that by using the above statistical methodology we
can demonstrably produce a more robust reconstruction than is possible by using
conditional-mean-fitting methods. Our reconstruction shares some of the common
features of past reconstructions, but we also gain useful insights. More
importantly, we are able to demonstrate a significantly smaller uncertainty than
that from previous regression methods. In addition, the quantile regression
component allows us to model, in a more complete and flexible way than least
squares, the conditional distribution of temperature given proxies. This
relationship can be used to inform forward models relating how proxies are driven
by temperature.
PMID- 25587204
TI - Immigrants' children's transition to secondary school in Italy.
AB - Choosing a secondary school represents an important step in the lives of students
in Italy, in that it has a strong bearing on their ultimate educational
achievement and labor force trajectory. In this paper, we analyze the effect of
generational status and length of residence on the transition to secondary school
among immigrants living in Italy. Using data from the ITAGEN2 follow-up, we
analyze scholastic results from the middle school final exam and the choice of
secondary school among the adolescents in Italy. Children of immigrants are more
likely to have inferior outcomes on the middle school exam and to enroll in
vocational and polytechnic schools. Our multivariate results indicate that, after
controlling for the family's human capital and other key background factors,
immigrant students show greater propensity to choose a vocational path.
Differences between immigrants and natives in secondary school tracks are also
manifest when previous scholastic results are taken into account.
PMID- 25587205
TI - Association of polymorphisms of genes involved in lipid metabolism with blood
pressure and lipid values in mexican hypertensive individuals.
AB - Hypertension and dyslipidemia exhibit an important clinical relationship because
an increase in blood lipids yields an increase in blood pressure (BP). We
analyzed the associations of seven polymorphisms of genes involved in lipid
metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC
rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in
Mexican hypertensive (HT) patients. A total of 160 HT patients and 160
normotensive individuals were included. Genotyping was performed through PCR
RFLP, PCR-AIRS, and sequencing. The results showed significant associations in
the HT group and HT subgroups classified as normolipemic and hyperlipemic. The
alleles FABP2 p.55T, LIPC -514T, and MTTP -493T were associated with elevated
systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T
were associated with decreased total cholesterol and LDL-C, respectively; APOA5
p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased
triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides.
The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17
2.93; P = 0.001) under the dominant model. These findings indicate that
polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and
may be important in the development of essential hypertension and dyslipidemia in
Mexican HT patients.
PMID- 25587207
TI - Mobile, Social, and Wearable Computing and the Evolution of Psychological
Practice.
AB - Psychological assessment and intervention are extending from the clinic into
daily life. Multiple forces are at play: Advances in mobile technology,
constrained clinical care, and consumer demand for contextualized,
nonstigmatizing, and low-cost alternatives are beginning to change the face of
psychological assessment and interventions. Mobile, social, and wearable
technologies are now enabling individuals to measure themselves and to integrate
myriad forms of help and entertainment. The massive data sets generated by self
tracking of mood and passive sensing of voice, activity, and physiology may
eventually reorganize taxonomies of mental health concerns. Compelling mobile
therapies will also emerge, involving contextually appropriate, entertaining, and
dynamic feedback to provide help in the context of daily life. The efficacy of
such applications will be tested through citizen science as well as clinical
trials. This article reviews technical advances that can be applied to enhance
assessment and intervention and dramatically increase access to psychotherapy. It
is recommended that, in addition to exploring clinically oriented products,
practitioners should support patients' use of direct-to-consumer applications in
ways that align with therapeutic objectives.
PMID- 25587206
TI - Stepwise application of urine markers to detect tumor recurrence in patients
undergoing surveillance for non-muscle-invasive bladder cancer.
AB - BACKGROUND: The optimal use of urine markers in the surveillance of non-muscle
invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to
investigate the combined and stepwise use of the four most broadly available
urine markers to detect tumor recurrence in patients undergoing surveillance of
NMIBC. PATIENTS AND METHODS: 483 patients with history of NMIBC were included.
Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology
(uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy.
Characteristics of single tests and combinations were assessed by contingency
analysis. RESULTS: 128 (26.5%) patients had evidence of tumor recurrence.
Sensitivities and negative predictive values (NPVs) of the single tests ranged
between 66.4-74.3 and 82.3-88.2%. Two-marker combinations showed sensitivities
and NPVs of 80.5-89.8 and 89.5-91.2%. A stepwise application of the two-test
combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+
and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and
99.1%, respectively. CONCLUSIONS: Combinations of cytology, FISH, immunocytology,
and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test
combinations of cytology, FISH, and immunocytology have a low probability of
missing a high-risk tumor. The high sensitivities may justify the use of these
combinations in prospective studies assessing the use of urine markers to
individualize intervals between cystoscopies during follow-up.
PMID- 25587208
TI - Acute exercise-induced response of monocyte subtypes in chronic heart and renal
failure.
AB - PURPOSE: Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation
associated with high cardiovascular morbidity and mortality of patients with
chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an
acute exercise bout on monocyte subsets in the setting of systemic inflammation
is currently unknown. This study aims (1) to evaluate baseline distribution of
monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate
the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are
related to the Mon1-2-3 response. METHODS: Twenty CHF patients, 20 CKD patients,
and 15 HS were included. Before and after a maximal cardiopulmonary exercise
test, monocyte subsets were quantified by flow cytometry: CD14(++)CD16(-)CCR2(+)
(Mon1), CD14(++)CD16(+)CCR2(+) (Mon2), and CD14(+)CD16(++)CCR2(-) (Mon3). Serum
levels of IL-6 and MCP-1 were determined by ELISA. RESULTS: Baseline distribution
of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2
and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and
in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only,
MCP-1 levels increased following exercise; IL-6 levels were unchanged.
Circulatory power was a strong and independent predictor of the changes in Mon1
(beta = -0.461, P < 0.001) and Mon3 (beta = 0.449, P < 0.001); and baseline LVEF
of the change in Mon2 (beta = 0.441, P < 0.001). CONCLUSION: The response of
monocytes to acute exercise is characterized by an increase in proangiogenic and
proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise
induced monocyte subset response is mainly driven by hemodynamic changes and not
by preexistent low-grade inflammation.
PMID- 25587209
TI - Brain-derived neurotrophic factor in chronic periodontitis.
AB - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor
family. Outside the nervous system, BDNF has been shown to be expressed in
various nonneural tissues, such as periodontal ligament, dental pulp, and
odontoblasts. Although a role for BDNF in periodontal regeneration has been
suggested, a function for BDNF in periodontal disease has not yet been studied.
The aim of this study was to analyze the BDNF levels in periodontal tissues of
patients with chronic periodontitis (CP) and periodontally healthy controls (HC).
All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms.
Periodontal tissues were collected for ELISA, myeloperoxidase (MPO), and
microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were
increased in CP patients compared to HC subjects. A negative correlation was
observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium.
No differences in frequencies of BDNF genotypes between CP and HC subjects were
observed. However, BDNF genotype GG was associated with increased levels of BDNF,
TNF-alpha, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated
with periodontal disease process, but the specific role of BDNF still needs to be
clarified.
PMID- 25587210
TI - Outcomes of the use of fully covered esophageal self-expandable stent in the
management of colorectal anastomotic strictures and leaks.
AB - Introduction. Colorectal anastomotic leak or stricture is a dreaded complication
leading to significant morbidity and mortality. The novel use of self-expandable
metal stents (SEMS) in the management of postoperative colorectal anastomotic
leaks or strictures can avoid surgical reintervention. Methods. Retrospective
study with particular attention to the indications, operative or postoperative
complications, and clinical outcomes of SEMS placement for patients with either a
colorectal anastomotic stricture or leak. Results. Eight patients had SEMS
(WallFlex stent) for the management of postoperative colorectal anastomotic leak
or stricture. Five had a colorectal anastomotic stricture and 3 had a colorectal
anastomotic leak. Complete resolution of the anastomotic stricture or leak was
achieved in all patients. Three had recurrence of the anastomotic stricture on 3
month flexible sigmoidoscopy follow-up after the initial stent was removed. Two
of these patients had a stricture that was technically too difficult to place
another stent. Stent migration was noted in 2 patients, one at day 3 and the
other at day 14 after stent placement that required a larger 23 mm stent to be
placed. Conclusions. The use of SEMS in the management of colorectal anastomotic
leaks or strictures is feasible and is associated with high technical and
clinical success rate.
PMID- 25587211
TI - Modeling Light Scattering in Tissue as Continuous Random Media Using a Versatile
Refractive Index Correlation Function.
AB - Optical interactions with biological tissue provide powerful tools for study,
diagnosis, and treatment of disease. When optical methods are used in
applications involving tissue, scattering of light is an important phenomenon. In
imaging modalities, scattering provides contrast, but also limits imaging depth,
so models help optimize an imaging technique. Scattering can also be used to
collect information about the tissue itself providing diagnostic value. Therapies
involving focused beams require scattering models to assess dose distribution. In
all cases, models of light scattering in tissue are crucial to correctly
interpreting the measured signal. Here, we review a versatile model of light
scattering that uses the Whittle-Matern correlation family to describe the
refractive index correlation function Bn (rd ). In weakly scattering media such
as tissue, Bn (rd ) determines the shape of the power spectral density from which
all other scattering characteristics are derived. This model encompasses many
forms such as mass fractal and the Henyey-Greenstein function as special cases.
We discuss normalization and calculation of optical properties including the
scattering coefficient and anisotropy factor. Experimental methods using the
model are also described to quantify tissue properties that depend on length
scales of only a few tens of nanometers.
PMID- 25587212
TI - Preperitoneal surgery using a self-adhesive mesh for inguinal hernia repair.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic preperitoneal hernia repair with mesh has
been reported to result in improved patient outcomes. However, there are few
published data on the use of a totally extraperitoneal (TEP) approach. The
purpose of this study was to present our experience and evaluate early outcomes
of TEP inguinal hernia repair with self-adhesive mesh. METHODS: This cohort study
was a retrospective review of patients who underwent laparoscopic TEP inguinal
hernial repair from April 4, 2010, through July 22, 2014. Data assessed were age,
sex, body mass index (BMI), hernia repair indications, hernia type, pain,
paresthesia, occurrence (bilateral or unilateral), recurrence, and patient
satisfaction. Descriptive and regression analyses were performed. RESULTS: Six
hundred forty patients underwent laparoscopic preperitoneal hernia surgery with
self-adhesive mesh. The average age was 56 years, nearly all were men (95.8%),
and the mean BMI was 26.2 kg/m(2). Cases involved primary hernia more frequently
than recurrent hernia (94% vs 6%; P < .05). After surgery, 92% of the patients
reported no more than minimal pain, <1% reported paresthesia, and 0.2% had early
recurrence. There were 7 conversions to an open procedure. The patients had no
adverse reactions to anesthesia and no bladder injury. Postoperative acute pain
or recurrence was not explained by demographics, BMI, or preoperative pain. There
were significant associations of hernia side, recurrence, occurrence, and sex
with composite end points. Nearly all patients (98%) were satisfied with the
outcome. CONCLUSION: The use of self-adhesive, Velcro-type mesh in laparoscopic
TEP inguinal hernia repair is associated with reduced pain; low rates of early
recurrence, infection, and hematoma; and improved patient satisfaction.
PMID- 25587213
TI - Outcomes of conversion of laparoscopic colorectal surgery to open surgery.
AB - OBJECTIVES: There is limited data regarding the outcomes of patients who undergo
conversion to open surgery during a laparoscopic operation in colorectal
resection. We sought to identify the outcomes of such patients. METHODS: The NIS
(National Inpatient Sample) database was used to identify patients who had
conversion from laparoscopic to open colorectal surgery during the 2009 to 2012
period. Multivariate regression analysis was performed to identify risk-adjusted
outcomes of conversion to open surgery. RESULTS: We sampled 776 007 patients who
underwent colorectal resection. 337 732 (43.5%) of the patients had laparoscopic
resection. Of these, 48 265 procedures (14.3%) were converted to open surgery.
The mortality of converted patients was increased, when compared with
successfully completed laparoscopic operations, but was still lower than that of
open procedures (0.6% vs. 1.4% vs. 3.9%, respectively; adjusted odds ratio [AOR],
1.61 and 0.58, respectively; P < .01). The most common laparoscopic colorectal
procedure was right colectomy (41.2%). The lowest rate of conversion is seen with
right colectomy while proctectomy had the highest rate of conversion (31.2% vs.
12.9%, AOR, 2.81, P < .01). Postsurgical complications including intra-abdominal
abscess (AOR, 2.64), prolonged ileus (AOR, 1.50), and wound infection (AOR, 2.38)
were higher in procedures requiring conversion (P < .01). CONCLUSIONS: Conversion
of laparoscopic to open colorectal resection occurs in 14.3% of cases. Compared
with patients who had laparoscopic operations, patients who had conversion to
open surgery had a higher mortality, higher overall morbidity, longer length of
hospitalization, and increased hospital charges. The lowest conversion rate was
in right colectomy and the highest was in proctectomy procedures. Wound infection
in converted procedures is higher than in laparoscopic and open procedures.
PMID- 25587214
TI - Laparoscopic techniques enable peritoneal dialysis in the difficult abdomen.
AB - BACKGROUND AND OBJECTIVES: Continuous ambulatory peritoneal dialysis has become
an increasingly popular modality of renal replacement therapy. Laparoscopic
placement of peritoneal dialysis catheters may help overcome previous barriers to
peritoneal dialysis, such as previous abdominal surgical procedures or the
presence of hernias, without incurring substantially greater risks. METHODS: We
performed a retrospective review of 120 consecutive patients who underwent
attempted laparoscopic peritoneal dialysis catheter placement between July 2009
and June 2014 by a single surgeon. Patient and catheter characteristics and
outcomes were compared between patients with and without complications, as well
as between patients with a history of major abdominal surgery and those without
such a history. RESULTS: Laparoscopic peritoneal dialysis catheter placement was
aborted in 4 patients because of an inability to safely achieve sufficient access
to the abdominal cavity through dissection; these patients were excluded from
subsequent analysis. The mean follow-up period was 18.8 +/- 12.9 months. Fifty
five patients had a history of major abdominal surgery compared with 61 without
such a history. No significant difference was observed with respect to age, race,
sex, or body mass index between groups. Notably, more adjunctive procedures were
required in patients with previous abdominal surgery, including adhesiolysis
(60.0% vs 4.9%, P < .0001) and hernia repair (12.7% vs 1.6%, P = .026).
Postoperative catheter complications were not significantly different between
patients with and patients without a history of abdominal surgery (29.1% vs
32.8%, P = .667). Both unassisted (56.8% vs 65.0%, P = .397) and overall (72.7%
vs 76.7%, P = .647) 1-year catheter survival rates were similar between patients
with and patients without previous surgery, and the overall 1-year survival rate
improved to 83.9% on exclusion of patients who stopped peritoneal dialysis for
nonsurgical reasons. CONCLUSIONS: Laparoscopic peritoneal dialysis catheter
placement offers a chance to establish peritoneal dialysis access in patients
traditionally viewed as noncandidates for this modality. Despite the potential
risks incurred because of additional procedures at the time of catheter placement
in these complicated cases, these patients can achieve good long-term peritoneal
dialysis access with an aggressive surgical approach.
PMID- 25587215
TI - Trends in splenectomy: where does laparoscopy stand?
AB - BACKGROUND AND OBJECTIVES: Laparoscopic splenectomy (LS) has been shown to offer
superior outcomes when compared to open splenectomy (OS). Despite the potential
advantages associated with the minimally invasive technique, laparoscopy appears
to be underused. We sought to evaluate the nationwide trends in LS. METHODS: The
Nationwide Inpatient Sample (NIS) database was queried for both OS and LS
procedures performed from 2005 through 2010. Partial splenectomies and those
performed for traumatic injury, vascular anomaly, or as part of a pancreatectomy
were excluded. The included cases were examined for age of the patient and
comorbid conditions. We then evaluated the postoperative complications, overall
morbidity, mortality, and length of hospital stay. RESULTS: A total of 37,006
splenectomies were identified. Of those, OS accounted for 30,108 (81.4%) cases,
LS for 4,938 (13.3%), and conversion to open surgery (CS) for 1,960 (5.3%). The
overall rate of morbidity was significantly less in the LS group than in the OS
group (7.4% vs 10.4%; P < .0001). The LS group had less mortality (1.3% vs 2.5%,
P < .05) and a shorter length of stay (5.6 +/- 8 days vs 7.5 +/- 9 days).
CONCLUSIONS: Despite the benefits conferred by LS, it appears to be underused in
the United States. There has been an improvement in the rate of splenectomies
completed laparoscopically when compared to NIS data from the past (8.8% vs 13%;
P < .05). The conversion rate is appreciably higher for LS than for other
laparoscopic procedures, suggesting that splenectomies require advanced
laparoscopic skills and that consideration should be given to referring patients
in need of the procedure to appropriately experienced surgeons.
PMID- 25587217
TI - Current clinical practice: differential management of uveal melanoma in the era
of molecular tumor analyses.
AB - OBJECTIVE: Assess current clinical practices for uveal melanoma (UM) and the
impact of molecular prognostic testing on treatment decisions. DESIGN: Cross
sectional survey and sequential medical records review. PARTICIPANTS:
Ophthalmologists who treat UM. METHODS: (A) Medical records review of all
Medicare beneficiaries tested by UM gene expression profile in 2012, conducted
under an institutional review board-approved protocol. (B) 109 ophthalmologists
specializing in the treatment of UM were invited to participate in 24-question
survey in 2012; 72 were invited to participate in a 23-question survey in 2014.
MAIN OUTCOME MEASURES: Responses analyzed by descriptive statistics, frequency
analyses (percentages, Tukey, histograms), and Fisher's exact test. Descriptive
presentation of essay answers. RESULTS: The review of Medicare medical records
included 191 evaluable patients, 88 (46%) with documented medical treatment
actions or institutional policies related to surveillance plans. Of these 88, all
gene expression profiling (GEP) Class 1 UM patients were treated with low
intensity surveillance. All GEP Class 2 UM patients were treated with high
intensity surveillance (P<0.0001 versus Class 1). There were 36 (19%) with
information concerning referrals after initial diagnosis. Of these 36, all 23
Class 2 patients were referred to medical oncology; however, none of the 13 Class
1 patients were referred (P<0.0001 versus Class 1). Only Class 2 patients were
recommended for adjunctive treatment regimens. 2012 survey: 50 respondents with
an annual median of 35 new UM patients. The majority of respondents (82%)
performed molecular analysis of UM tumors after fine needle biopsy (FNAB);
median: 15 FNAB per year; 2014 survey: 35 respondents with an annual median of 30
new UM patients. The majority offered molecular analyses of UM tumor samples to
most patients. Patients with low metastatic risk (disomy 3 or GEP Class 1) were
generally assigned to less frequent (every 6 or 12 months) and less intensive
clinical visits. Patients with high metastatic risk (monosomy 3 or GEP Class 2)
were assigned to more frequent surveillance with hepatic imaging and liver
function testing every 3-6 months. High-risk patients were considered more
suitable for adjuvant treatment protocols. CONCLUSION: The majority of
ophthalmologists treating UM have adopted molecular diagnostic tests for the
purpose of designing risk-appropriate treatment strategies.
PMID- 25587216
TI - Cationic liposome-nucleic acid complexes for gene delivery and gene silencing.
AB - Cationic liposomes (CLs) are studied worldwide as carriers of DNA and short
interfering RNA (siRNA) for gene delivery and gene silencing, and related
clinical trials are ongoing. Optimization of transfection efficiency and
silencing efficiency by cationic liposome carriers requires a comprehensive
understanding of the structures of CL-nucleic acid complexes and the nature of
their interactions with cell membranes as well as events leading to release of
active nucleic acids within the cytoplasm. Synchrotron x-ray scattering has
revealed that CL-nucleic acid complexes spontaneously assemble into distinct
liquid crystalline phases including the lamellar, inverse hexagonal, hexagonal,
and gyroid cubic phases, and fluorescence microscopy has revealed CL-DNA pathways
and interactions with cells. The combining of custom synthesis with
characterization techniques and gene expression and silencing assays has begun to
unveil structure-function relations in vitro. As a recent example, this review
will briefly describe experiments with surface-functionalized PEGylated CL-DNA
nanoparticles. The functionalization, which is achieved through custom synthesis,
is intended to address and overcome cell targeting and endosomal escape barriers
to nucleic acid delivery faced by PEGylated nanoparticles designed for in vivo
applications.
PMID- 25587218
TI - A single blind randomized control trial on support groups for Chinese persons
with mild dementia.
AB - PURPOSE: Persons with mild dementia experience multiple losses and manifest
depressive symptoms. This research study aimed to evaluate the effectiveness of a
support group led by a social worker for Chinese persons with mild dementia.
RESEARCH METHODS: Participants were randomly assigned to either a ten-session
support group or a control group. Standardized assessment tools were used for
data collection at pretreatment and post-treatment periods by a research
assistant who was kept blind to the group assignment of the participants. Upon
completion of the study, 20 treatment group participants and 16 control group
participants completed all assessments. RESULTS: At baseline, the treatment and
control groups did not show any significant difference on all demographic
variables, as well as on all baseline measures; over one-half (59%) of all the
participants reported having depression, as assessed by a Chinese Geriatric
Depression Scale score >=8. After completing the support group, the depressive
mood of the treatment group participants reduced from 8.83 (standard deviation
=2.48) to 7.35 (standard deviation =2.18), which was significant (Wilcoxon signed
rank test; P=0.017, P<0.05), while the control group's participants did not show
any significant change. CONCLUSION: This present study supports the efficacy and
effectiveness of the support group for persons with mild dementia in Chinese
society. In particular, this present study shows that a support group can reduce
depressive symptoms for participants.
PMID- 25587220
TI - Induction of multiple drug resistance in HMEC-1 endothelial cells after long-term
exposure to sunitinib.
AB - Multiple drug resistance is still an unsolved problem in cancer therapy. Our
previous study demonstrated that the chemotherapeutic drug doxorubicin (Dox)
induced upregulation of P-glycoprotein (P-gp) in endothelial cells, resulting in
a 20-fold increase in drug resistance and reduced efficiency of Dox treatment in
a mice tumor model. In this study, we exposed human microvascular endothelial
cells (HMEC-1) to sunitinib, a tyrosine kinase receptor inhibitor, to induce drug
resistance. The results show that sunitinib treatment induced multiple drug
resistance in these cells. They became resistant not only to sunitinib but also
to Dox, paclitaxel, and vinblastine. Significant increases in P-gp (9.3-fold),
ABCG2 (breast cancer resistance protein, 1.9-fold), and multidrug resistance
associated protein 1 (2.7-fold) gene transcription were found by quantitative
polymerase chain reaction quantification, and their protein expression was
confirmed by Western blot. These increases gave rise to an approximately five
fold increase in half maximal inhibitory concentration in these cells in response
to sunitinib treatment in vitro. The inhibitors of adenosine triphosphate-binding
cassette transporters did not reverse the drug resistance in sunitinib-resistant
HMEC-1 cells, assumedly because of a blockage of the pump function caused by
sunitinib. Our study indicates that the antiangiogenic drug sunitinib induces
multiple drug resistance in endothelial cells. The induction of adenosine
triphosphate-binding cassette transporters seems not to be responsible for
observed multiple drug resistance, and the underlying mechanisms remain unknown.
PMID- 25587222
TI - Dr Noni E MacDonald Award.
PMID- 25587219
TI - Prevalence and correlates of suicide ideation in patients with COPD: a mixed
methods study.
AB - PURPOSE: The purpose of this study was to examine the prevalence and correlates
of suicidal ideation (SI) in patients with stable moderate to very severe chronic
obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We conducted an
exploratory mixed methods analysis of data from participants in a longitudinal
observational study of depression in COPD. We measured depression with the
Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared
participants with and without SI in relation to sociodemographics, symptoms,
anxiety, and healthcare resource use with independent t-tests and chi-square
tests. Content analysis was performed on qualitative data gathered during a
structured SI safety assessment. RESULTS: Of 202 participants, 121 (60%) had
depressive symptoms (PHQ >=6); 51 (25%) had a PHQ-9 >=10, indicating a high
likelihood of current major depression; and 22 (11%) reported SI. Compared to the
99 depressed participants without SI, those with SI were more likely to be female
(59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P<0.001), and
anxiety (P=0.003); and were also more likely to have received treatment for
depression and/or anxiety (82% vs 40%, P<0.001) and more hospitalizations for
COPD exacerbations (P=0.03) but had similar levels of airflow obstruction and
functioning than participants without SI. Themes from the qualitative analysis
among those with SI included current or prior adverse life situations, untreated
or partially treated complex depression, loss of a key relationship, experience
of illness and disability, and poor communication with providers. CONCLUSION: Our
findings suggest that current SI is common in COPD, may occur disproportionately
in women, can persist despite mental health treatment, and has complex
relationships with both health and life events. Adequate management of SI in COPD
may therefore require tailored, comprehensive treatment approaches that integrate
medical and mental health objectives.
PMID- 25587223
TI - Ponseti clubfoot management: Experience with the Steenbeek foot abduction brace.
PMID- 25587225
TI - Case 1: Hyperpigmented swirly patches in a toddler.
PMID- 25587224
TI - A novel MC4R mutation associated with childhood-onset obesity: A case report.
AB - The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis,
food intake and body weight. MC4R gene mutations are associated with early-onset
severe obesity. Most patients are heterozygotes, with some reports of homozygotes
and compound heterozygotes. The authors report a case involving an eight-year-old
girl with progressive weight gain from infancy, body mass index 44 kg/m(2) (>97th
percentile), hyperphagia, hyperinsulinemia and increased linear growth. There was
no phenotype of morbid obesity in the parents or sibling. Coding regions and
intron-exon boundaries of the genes encoding leptin, leptin receptor, pro
opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in the
MCR4 gene (S94N and C293R) were detected, of which the second has not been
previously reported. The mutations were on opposite chromosomes, confirming
compound heterozygosity. The molecular findings and clinical features associated
with this novel MC4R mutation are described. The authors emphasize that rare
mutations can be found in some patients with severe childhood-onset obesity.
PMID- 25587221
TI - Long-term efficacy and safety of human papillomavirus vaccination.
AB - In this paper, we review the published evidence about the long-term efficacy of
the available human papillomavirus (HPV) vaccines and their safety profile. Two
prophylactic HPV vaccines - bivalent (bHPV) and quadrivalent (qHPV) - are now
available, and vaccination programs are being widely implemented, primarily
targeting adolescent girls. Efficacy has been widely demonstrated for both
vaccines. Since the risk of HPV exposure potentially persists throughout a
woman's sexual life, vaccine duration of protection is critical to overall
effectiveness. Interpreting the results of long-term efficacy studies for the two
HPV vaccines can be puzzling, due to the heterogeneity of studies, different
methods used in the assessment of immunogenicity, histopathological and
virological end points, and statistical power issues. Moreover, an immunologic
correlate of protection has not yet been established, and it is unknown whether
higher antibody levels will really result in a longer duration of protection.
Disease prevention remains the most important measure of long-term duration of
vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4
years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8
years. The vaccine continues to be immunogenic and well tolerated up to 9 years
following vaccination. All randomized controlled clinical trials of the bHPV and
the qHPV vaccines provide evidence of an excellent safety profile. The most
common complaint reported is pain in the injection site, which is self-limiting
and spontaneously resolved. The incidence of systemic adverse events (AEs),
serious AEs, and discontinuations due to a serious AE reported in clinical
studies are similar between the two vaccines and their control groups. In
particular, no increased risk of autoimmune disease has been shown among HPV
vaccinated subjects in long-term observation studies. As these are crucial topics
in HPV vaccination, it is important to establish systems for continued monitoring
of vaccine immunogenicity, efficacy, and safety over time.
PMID- 25587226
TI - Case 2: An 11-year-old girl with aggressive behaviour and intellectual
impairment.
PMID- 25587227
TI - Case 3: Stridor and cough in a young child.
PMID- 25587228
TI - Case 4: Recurrent bacterial meningitis in an adolescent female.
PMID- 25587229
TI - Cyberbullying: Hiding behind the screen.
PMID- 25587230
TI - Lactose avoidance for young children with acute diarrhea.
PMID- 25587231
TI - Combined and alternating acetaminophen and ibuprofen therapy for febrile
children.
PMID- 25587232
TI - Children who 'grow up' in hospital: Inpatient stays of six months or longer.
AB - OBJECTIVE: To describe the clinical course of all infants and children
hospitalized for six consecutive months (180 days) or longer at a
tertiary/quaternary children's hospital in Western Canada. METHODS: A
retrospective review of medical records for all eligible patients from January 1,
2007 to December 31, 2012 at Stollery Children's Hospital (Edmonton, Alberta) was
performed. RESULTS: A total of 61 patients experienced 64 eligible
hospitalizations. The mean length of stay was 326 days, corresponding to a
cumulative 20,892 hospital days (57.2 patient-years). Prevalent procedures
resulting in long hospitalization were long-term tracheostomy +/- ventilation in
32 (52%) patients, need for organ transplantation in 24 (39%) with completed
transplantation in 15 (25%), and ventricular-assist devices (VADs) in seven
(11%). Sixteen (26%) patients in the study group died, and 16 (26%) were placed
in long-term care or out-of-home care at the end of their long hospitalization.
Of children displaced from their family home, 14 (88%) were Aboriginal.
CONCLUSION: Infants and children who experience very long hospitalizations have
complex illnesses, with substantial risk for mortality and a high rate of
displacement from their families after discharge. Aboriginal children appear to
be particularly vulnerable to displacement and problem solving for this
population must be undertaken, involving a variety of stakeholders.
PMID- 25587233
TI - Paediatric patient family engagement with clinical research at a tertiary care
paediatric hospital.
AB - BACKGROUND: Subject recruitment is essential for conducting clinical research;
however, there are very few studies evaluating research uptake by families in a
paediatric setting. OBJECTIVES: To determine how frequently paediatric patients
and their families receiving care at a tertiary paediatric hospital participated
in research. The secondary objectives were to explore factors that influence
patient families' decisions to participate in research and how they perceived
their experiences. METHODS: A cross-sectional study surveying families of
children receiving care in a sample of clinical areas at a tertiary care
paediatric hospital in British Columbia was conducted. A self-administered
questionnaire was used, and was facilitated by trained interviewers. Descriptive
statistics were used to report the proportion of patient families that have
previously been invited to participate in research and, among these, the
proportion who had agreed to participate. Patient families' perceptions of
research and their past experiences therein were also reported. RESULTS: A total
of 657 families were approached, of which 543 were enrolled (82.6% response
rate). Among the 439 families that had visited the hospital previously, 114
(26.0%) had been invited to participate in research and 99 (87%) had consented to
participate. Of these 99 families, only one had a negative experience, and 84
(85%) of these participant families were at least somewhat likely to participate
in research again in the future. CONCLUSIONS: Only one-quarter of families that
had previously visited the hospital had been invited to participate in a research
project. Of the families approached previously, there was a high rate of
participation and willingness to participate in future research.
PMID- 25587234
TI - A population-based study of paediatric emergency department and office visits for
concussions from 2003 to 2010.
AB - BACKGROUND: There is a paucity of information regarding descriptive epidemiology
of paediatric concussions over time, and few studies include both emergency
department (ED) and physician office visits. OBJECTIVE: To describe trends in
visits for paediatric concussions in both EDs and physician offices according to
age and sex. A secondary objective was to describe the cause of concussion for
children treated in EDs. METHODS: A retrospective, population-based study using
linked health administrative data from all concussion-related visits to the ED or
a physician office by school-age children and youth (three to 18 years of age) in
Ontario between April 1, 2003 and March 3, 2011 was conducted. RESULTS: The
number of children evaluated in both EDs and a physician offices increased
between 2003 and 2010, and this linear trend was statistically significant
(P=0.002 for ED visits and P=0.001 for office visits). The rate per 100,000
increased from 466.7 to 754.3 for boys and from 208.6 to 440.7 for girls during
the study period. Falls accounted for approximately one-third of the paediatric
concussions. Hockey/skating was the most common specific cause of paediatric
sports-related concussions. CONCLUSIONS: The increasing use of health care
services for concussions is likely related to changes in incidence over time and
increased awareness of concussion as a health issue. Evidence-based prevention
initiatives to help reduce the incidence of concussion are warranted,
particularly in sports and recreation programs.
PMID- 25587235
TI - Nutrition for healthy term infants, six to 24 months: An overview.
AB - Nutrition for Healthy Term Infants is a joint statement by Health Canada, the
Canadian Paediatric Society, Dietitians of Canada and the Breastfeeding Committee
for Canada. It was republished in September 2012, with recommendations on infant
feeding from birth to six months of age. The statement was most recently updated
in April 2014, with recommendations for feeding older infants and young children
from six to 24 months of age. The present practice point outlines the statement
development process and principles of feeding, with specific recommendations for
clinicians. Health professionals who counsel families on nutrition in infants and
young children are advised to read the statement in its entirety because
discussion in the longer document expands on and clarifies advice summarized in
the principles and recommendations given here. The complete statement is
available on Health Canada's website: www.hc-sc.gc.ca/fn-an/nutrition/infant
nourisson/index-eng.php.
PMID- 25587236
TI - Increasing the use of influenza vaccines in children with egg allergy.
AB - Administration of inactivated trivalent or quadrivalent influenza vaccines is now
believed to be safe for individuals with egg allergy. Unless children have
experienced an anaphylactic reaction to a previous dose of influenza vaccine,
they can and should be immunized with a full dose of trivalent or quadrivalent
inactivated vaccine.
PMID- 25587237
TI - The benefits of influenza vaccine in pregnancy for the fetus and the infant
younger than six months of age.
AB - Influenza is a serious problem for infants <6 months of age, whose
hospitalization rates for influenza and associated illness are comparable with
rates in the elderly. Because influenza vaccines are not effective in this age
group, the optimal evidence-based strategy is to administer trivalent inactivated
influenza vaccines during pregnancy. Immunizing with trivalent inactivated
influenza vaccines in the second and third trimester is well studied and safe,
not only providing protection for the pregnant woman and her infant <6 months of
age, but also for the fetus by decreasing the risk for low birth weight.
PMID- 25587238
TI - Evaluation of delivery of enteral nutrition in mechanically ventilated Malaysian
ICU patients.
AB - BACKGROUND: There are numerous challenges in providing nutrition to the
mechanically ventilated critically ill ICU patient. Understanding the level of
nutritional support and the barriers to enteral feeding interruption in
mechanically ventilated patients are important to maximise the nutritional
benefits to the critically ill patients. Thus, this study aims to evaluate
enteral nutrition delivery and identify the reasons for interruptions in
mechanically ventilated Malaysian patients receiving enteral feeding. METHODS: A
cross sectional prospective study of 77 consecutive patients who required
mechanical ventilation and were receiving enteral nutrition was done in an open
14-bed intensive care unit of a tertiary hospital. Data were collected
prospectively over a 3 month period. Descriptive statistical analysis were made
with respect to demographical data, time taken to initiate feeds, type of feeds,
quantification of feeds attainment, and reasons for feed interruptions. There are
no set feeding protocols in the ICU. The usual initial rate of enteral nutrition
observed in ICU was 20 ml/hour, assessed every 6 hours and the decision was made
thereafter to increase feeds. The target calorie for each patient was determined
by the clinician alongside the dietitian. The use of prokinetic agents was also
prescribed at the discretion of the attending clinician and is commonly IV
metoclopramide 10 mg three times a day. RESULTS: About 66% of patients achieved
80% of caloric requirements within 3 days of which 46.8% achieved full feeds in
less than 12 hours. The time to initiate feeds for patients admitted into the ICU
ranged from 0 - 110 hours with a median time to start feeds of 15 hours and the
interquartile range (IQR) of 6-59 hours. The mean time to achieve at least 80% of
nutritional target was 1.8 days +/- 1.5 days. About 79% of patients experienced
multiple feeding interruptions. The most prevalent reason for interruption was
for procedures (45.1%) followed by high gastric residual volume (38.0%),
diarrhoea (8.4%), difficulty in nasogastric tube placement (5.6%) and vomiting
(2.9%). CONCLUSION: Nutritional inadequacy in mechanically ventilated Malaysian
patients receiving enteral nutrition was not as common as expected. However,
there is still room for improvement with regards to decreasing the number of
patients who did not achieve their caloric requirement throughout their stay in
the ICU.
PMID- 25587239
TI - Music therapy to promote psychological and physiological relaxation in palliative
care patients: protocol of a randomized controlled trial.
AB - BACKGROUND: Music therapy is one of the most frequently used complementary
therapies in different palliative care settings. Despite its long tradition and
high acceptance by other health-care professionals, evidence on the effectiveness
of music therapy interventions for terminally ill patients is rare. Recent
reviews and health-care reports consistently point out the need of music
therapists to provide an evidence-based rationale for their clinical treatments
in this field. Therefore, the present study evaluates the psychological and
physiological response of palliative care patients to a standardized music
therapy relaxation intervention in a randomized controlled trial. METHODS/DESIGN:
A sample of 84 participants from a palliative care unit in Heidelberg is
randomized to either two sessions of music therapy or two sessions of a verbal
relaxation exercise, each lasting 30 minutes. The music therapy sessions consist
of live played monochord music and a vocal improvisation, the control group uses
a prerecorded excerpt from the mindfulness-based stress reduction program
containing no musical elements. Outcome measures include self-report data on
subjective relaxation, well-being, pain intensity, and quality of life, as well
as continuous recording of heart rate variability and blood volume pulse as
indicators of autonomous nervous system functioning. DISCUSSION: To our
knowledge, this study is the first clinical trial in Europe and one of very few
randomized controlled trials worldwide to systematically examine the effects of
music therapy in palliative care. TRIAL REGISTRATION: German Clinical Trials
Register - DRKS00006137.
PMID- 25587241
TI - PRIORITIZATION OF PEDIATRIC CBRNE DISASTER PREPAREDNESS EDUCATION AND TRAINING
NEEDS.
AB - Children are the members of our population who are most vulnerable to the effects
of a chemical, biological, radiological, nuclear or explosive (CBRNE) attack. It
has been over 12 years since 9/11 and the majority of clinicians who would be
providing care to children in the event of another attack still lack the
requisite disaster preparedness training. The purpose of this report is to
provide an overview of the recent developments that will enable the affordable
creation of key CBRNE educational and just in time material. In 2011, the
National Center for Disaster Medicine and Public Health (NCDMPH) convened a
pediatric disaster preparedness conference. Much of the initial groundwork for
development of a pediatric disaster preparedness curriculum, including the
identification of target audiences and requisite role specific CBRNE curriculum
content, was the product of this conference. Much of the needed pediatric
education and training content for the diagnosis and treatment of the injurious
effects of CBRNE has recently been both developed and well vetted. Bringing
together these efforts in an educational program will result in a workforce that
is better trained and prepared to address the needs of children impacted by these
types of disasters.
PMID- 25587240
TI - Unbearable suffering and requests for euthanasia prospectively studied in end-of
life cancer patients in primary care.
AB - BACKGROUND: An international discussion about whether or not to legally permit
euthanasia and (or) physician assisted suicide (EAS) is ongoing. Unbearable
suffering in patients may result in a request for EAS. In the Netherlands EAS is
legally permitted, and unbearable suffering is one of the central compulsory
criteria. The majority of EAS is performed in cancer patients in the primary care
practice. In around one in every seven end-of-life cancer patients dying in the
primary care setting EAS is performed. The prevalence of unbearable symptoms and
overall unbearable suffering in relationship to explicit requests for EAS was
studied in a cohort of end-of-life cancer patients in primary care. METHODS: A
prospective study in primary care cancer patients estimated to die within six
months was performed. Every two months suffering was assessed with the State-of
Suffering V (SOS-V). The SOS-V is a comprehensive instrument for quantitative and
qualitative assessment of unbearable suffering related to 69 physical,
psychological and social symptoms in five domains. RESULTS: Out of 148 patients
who were asked to participate 76 (51%) entered the study. The studied population
were 64 patients who were followed up until death; 27% explicitly requested EAS,
which was performed in 8% of the patients. The final interview per patient was
analyzed; in four patients the SOS-V was missing. Unbearable symptoms were
present in 94% of patients with an explicit request for EAS and in 87% of
patients without an explicit request. No differences were found in the prevalence
of unbearable suffering for physical, psychological, social and existential
symptoms, nor for overall unbearable suffering, between patients who did or who
did not explicitly request EAS. CONCLUSIONS: In a population of end-of-life
cancer patients cared for in primary care no differences in unbearable suffering
were found between patients with and without explicit requests for EAS. The study
raises the question whether unbearable suffering is the dominant motive to
request for EAS. Most patients suffered from unbearable symptoms, indicating that
the compulsory criterion of unbearable suffering may be met a priori in most end
of-life cancer patients dying at home, whether they request EAS or not.
PMID- 25587242
TI - Trauma-Induced Coagulopathy.
AB - Trauma is the leading cause of death among people under the age of 44. Hemorrhage
is a major contributor to deaths related to trauma in the first 48 h.
Accordingly, the management of these patients is a time-sensitive and critical
affair that anesthesiologists responsible for surgical resuscitation will face.
Coagulopathy associated with trauma exists in one-third of all severely injured
patients upon presentation to the hospital. Trauma patients presenting with
coagulopathy have significantly higher mortality. This trauma-induced
coagulopathy (TIC) must be managed adroitly in the resuscitation of these
patients. Recent advancements in our understanding of TIC have led to new
protocols and therapy guidelines. Anesthesiologists must be aware of these to
effectively manage this form of shock. TIC driven by a combination of endogenous
biological processes, as well as iatrogenic causes, can ultimately lead to the
lethal triad of hypothermia, acidemia, and coagulopathy. Providers should
understand how to promptly diagnose TIC and be aware of the early indicators of
massive transfusion. The use of common laboratory studies and patient vital signs
serve as our current guide, but the importance of each is still under debate.
Thromboelastography is a tool used often in the diagnosis of TIC and can be used
to guide blood product transfusion. Certain pharmaceutical strategies and non
transfusion strategies also exist, which aid in the management of hemorrhagic
shock. Damage control surgery, rewarming, tranexamic acid, and 1:1:1 transfusion
protocols are promising methods used to treat the critically wounded. Though
protocols have been developed, controversies still exist on the optimal
resuscitation strategy.
PMID- 25587244
TI - CHRONIC NEONATAL DIAZOXIDE THERAPY IS NOT ASSOCIATED WITH ADVERSE EFFECTS.
AB - Diazoxide is an ATP-sensitive potassium channel (KATP) agonist that has been
shown to neuroprotective effects. These observations raise the possibility that
diazoxide may have potential as a therapeutic agent for other applications. This
study investigated (1) the long term effects of chronic neonatal administration
of diazoxide and (2) the role of KATP on murin behavior and neurohistology.
C57B/6J pups were injected daily with diazoxide (10, 20 or 50 mg kg-1) or vehicle
from Postnatal days 2 (P2) through P12. Pups were allow to mature and underwent
behavioral testing at 5-7 months of age. After behavioral testing, animals were
euthanized and morphology of the brains was assessed. No long term adverse
effects of neonatal diazoxide therapy on physical characteristics, visual acuity,
sensori-motor reflexes, spontaneous locomotor activity, motor
coordination/balance or motor learning and memory were observed. In addition, no
morphological changes were observed on brains. However, we did observe that
diazoxide therapy causes depressive-like phenotypes in female murine mice.
Chronic neonatal diazoxide therapy does not cause deficits or enhancements in
mice behavior. Diazoxide does not cause abnormal morphological changes in brain
anatomy. However, diazoxide does cause gender specific depressive-like phenotype
in mice.
PMID- 25587243
TI - Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a
review of literature.
AB - Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often
have skin and oral lesions as part of their presentation. These mucocutaneous
lesions, as defined by the American College of Rheumatology (ACR) in 1997,
include malar rash, discoid rash, photosensitivity and oral ulcers. It is
therefore essential to recognize mucocutaneous lesions to accurately diagnose
JSLE. The mucocutaneous lesions can be divided into those with classical
histological features (LE specific) and those strongly associated with and
forming part of the diagnostic spectrum, but without the classical histological
changes of lupus (LE nonspecific). A malar rash is the most commonly associated
LE specific dermatological presentation. This skin manifestation is an acute form
and also correlates with disease activity. Subacute (polycyclic or papulosquamous
lesions) and chronic (discoid lesions) forms, whilst showing classical
histological changes supportive of lupus, are less commonly associated with
systemic lupus and do not correlate with disease activity. The most commonly
associated skin lesions without classical lupus changes are cutaneous vasculitis,
oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to
disease activity. An understanding of cutaneous signs and symptoms of lupus in
children is important to avoid delay in diagnosis. They will often improve as
lupus is adequately controlled and their reappearance is often the first
indicator of a disease flare.
PMID- 25587245
TI - Voluntary peer review as innovative tool for quality improvement in the intensive
care unit--a retrospective descriptive cohort study in German intensive care
units.
AB - INTRODUCTION: Quality improvement and safety in intensive care are rapidly
evolving topics. However, there is no gold standard for assessing quality
improvement in intensive care medicine yet. In 2007 a pilot project in German
intensive care units (ICUs) started using voluntary peer reviews as an innovative
tool for quality assessment and improvement. We describe the method of voluntary
peer review and assessed its feasibility by evaluating anonymized peer review
reports and analysed the thematic clusters highlighted in these reports. METHODS:
Retrospective data analysis from 22 anonymous reports of peer reviews. All ICUs -
representing over 300 patient beds - had undergone voluntary peer review. Data
were retrieved from reports of peers of the review teams and representatives of
visited ICUs. Data were analysed with regard to number of topics addressed and
results of assessment questionnaires. Reports of strengths, weaknesses,
opportunities and threats (SWOT reports) of these ICUs are presented. RESULTS:
External assessment of structure, process and outcome indicators revealed high
percentages of adherence to predefined quality goals. In the SWOT reports 11 main
thematic clusters were identified representative for common ICUs. 58.1% of
mentioned topics covered personnel issues, team and communication issues as well
as organisation and treatment standards. The most mentioned weaknesses were
observed in the issues documentation/reporting, hygiene and ethics. We identified
several unique patterns regarding quality in the ICU of which long-term personnel
problems und lack of good reporting methods were most interesting Conclusion:
Voluntary peer review could be established as a feasible and valuable tool for
quality improvement. Peer reports addressed common areas of interest in intensive
care medicine in more detail compared to other methods like measurement of
quality indicators.
PMID- 25587246
TI - Soy and phytoestrogens: possible side effects.
AB - Phytoestrogens are present in certain edible plants being most abundant in soy;
they are structurally and functionally analogous to the estrogens. Phytoestrogens
have been applied for compensation of hormone deficiency in the menopause. At the
same time, soy products are used in infant food and other foodstuffs.
Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and
their active metabolites such as equol can remain in meat and influence the
hormonal balance of the consumers. There have been only singular reports on
modified gender-related behavior or feminization in humans in consequence of soy
consumption. In animals, the intake of phytoestrogens was reported to impact
fertility, sexual development and behavior. Feminizing effects in humans can be
subtle and identifiable only statistically in large populations.
PMID- 25587247
TI - GMS German Medical Science: Best paper award 2013.
PMID- 25587248
TI - Seroepidemiological analysis of toxoplasmosis in college students.
AB - BACKGROUND: Toxoplasmosis is a zoonosis caused by an obligate intracellular
parasite, Toxoplasma gondii, which affects warm-blooded animals including humans.
Its prevalence rates usually vary in different regions of the planet. METHODS: In
this study, an analysis of the seroprevalence of toxoplasmosis among Brazilian
students was proposed by means of IgG specific antibodies detection. The presence
of anti-Toxoplasma gondii antibodies by indirect fluorescent antibody test (IFAT)
was also evaluated in order to compare it with enzyme-linked immunosorbent assay
(ELISA) and to assess the use of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
acid) and o-phenylenediamine dihydrochloride chromogens. RESULTS: The IFAT method
showed a seroprevalence of 22.3%. These results were similar to those obtained by
ELISA (24.1%). The seroprevalence was directly estimated from the IgG avidity,
which showed that in a sample of 112 students, three of them had acute infection,
an incidence of 1.6% in the studied population. CONCLUSION: In this study, the
use of different chromogenic substrates in immunoenzymatic ELISA assays did not
display different sensitivity in the detection of T. gondii-reagent serum. The
extrapolation of results to this population must be carefully considered, since
the investigation was conducted on a reduced sample. However, it allows us to
emphasize the importance of careful and well prepared studies to identify risk
factors for toxoplasmosis, to adopt preventive measures and to offer guidance to
at-risk populations about the disease.
PMID- 25587249
TI - Antioxidants and infertility treatment, the role of Satureja Khuzestanica: A mini
systematic review.
AB - BACKGROUND: The use of antioxidants in the treatment of infertility has been
suggested and recent studies have indicated that oral administration of Satureja
Khuzestanica essential oil (SKEO) to rats induces significant antioxidative
effects. OBJECTIVE: This systematic review was conducted to evaluate the
effectiveness of antioxidants in infertility and also to assess the effectiveness
of Satureja Khuzestanica in infertility management. MATERIALS AND METHODS:
Pubmed, Scopus, and Cochrane Library were searched for relevant trials published
from respective database inception dates to August 2010. Study selection, and
data extraction were performed by authors. RESULTS: Fifteen trials on evaluation
of antioxidants in infertility and seven studies on the effectiveness of Satureja
Khuzestanica were identified. Only 4 of the 15 trials were with application of
allocation concealment and three studies were done in in-vitro environment.
Despite the methodological and clinical heterogeneity of the trials, 14 of the 15
(93.33%) trials showed an improvement in either sperm quality or pregnancy rate
after antioxidant therapy. The human and animal studies of Satureja Khuzestanica
showed a significant antioxidative potential of the plant and its effectiveness
for infertility improvement. CONCLUSION: The use of oral antioxidants in
infertility could improve sperm quality and pregnancy rates. Improved fertility
observed by SKEO in rats might be due to its antioxidative effect. Further
studies and clinical trials in humans are necessary to evaluate SKEO
effectiveness in fertility disturbances.
PMID- 25587250
TI - The effect of morphine consumption on plasma corticosteron concentration and
placenta development in pregnant rats.
AB - BACKGROUND: Previous studies have shown that morphine consumption during
pregnancy may delay embryo development or cause abnormal nervous system function.
OBJECTIVE: The present study focused on the effect of maternal morphine
consumption on development of placenta and blood corticosteron concentration in
addictive pregnant mothers. MATERIALS AND METHODS: 24 female rats, 170-200g
weight, were used. The experimental groups after pregnancy received an oral dose
of 0.05 mg/ml of morphine by tap water while the control group received only tap
water. On 10(th) and 14(th) day of pregnancy, rats were anesthetized and placenta
removed surgically, 1ml blood was collected from each pregnant mother from retro
orbital sinus, the concentration of blood corticosteron was determined by
corticosteron Elisa kit after centrifugation. The fixed tissue was processed,
sectioned and stained with hematoxylin and eosin. Placenta was studied
microscopically according to the thickness of layers, area of blood cisterns, and
the number of cells. RESULTS: Comparing the plasma corticosteron concentration of
the treatment and the control groups, not only a severe increase in the treatment
group was detected, but also the thickness of maternal and embryonic portions of
the placenta at day 10(th) and 14(th) of gestation was different significantly
(p<=0.05). Furthermore, an increase in number of cells in maternal and embryonic
portion of placenta and a decrease in blood cistern area were demonstrated in
both the experimental and the control groups. CONCLUSION: The effects of
morphine, including an increase in blood concentration of corticosteron, in
dependent pregnant mothers were seen. Development of placenta in the experimental
group was delayed.
PMID- 25587251
TI - Observing principles of medical ethics during family planning services at Tehran
urban healthcare centers in 2007.
AB - BACKGROUND: Family planning has been defined in the framework of mothers and
children plan as one of Primary Healthcare (PHC) details. Besides quantity, the
quality of services, particularly in terms of ethics, such as observing
individuals' privacy, is of great importance in offering family planning
services. OBJECTIVE: A preliminary study to gather information about the degree
of medical ethics offered during family planning services at Tehran urban
healthcare centers. MATERIALS AND METHODS: A questionnaire was designed for
study. In the first question regarding informed consent, 47 clients who were
advised about various contraception methods were asked whether advantages and
disadvantages of the contraceptive methods have been discussed by the service
provider. Then a certain rank was measured for either client or method in 2007.
Finally, average value of advantage and disadvantage for each method was
measured. In questions about autonomy, justice and beneficence, yes/no answers
have been expected and measured accordingly. RESULTS: Health care providers have
stressed more on the advantages of pills and disadvantages of tubectomy and have
paid less attention to advantages of injection ampoules and disadvantages of
pills in first time clients. While they have stressed more on the advantages and
disadvantages of tubectomy and less attention to advantages of condom and
disadvantages of vasectomy in second time clients. Clients divulged their 100%
satisfaction in terms of observing turns and free charges services. Observance
degree of autonomy was 64.7% and 77.3% for first time and second- time clients
respectively. CONCLUSION: Applying the consultant's personal viewpoint for
selecting a method will breach an informed consent for first and second time
clients. System has good consideration to justice and no malfeasance.
PMID- 25587252
TI - Semen characteristics and sperm morphological studies of the West African Dwarf
Buck treated with Aloe vera gel extract.
AB - BACKGROUND: Aloe vera (Aloe barbadensis miller) is an evergreen perennial plant
widely used in modern herbal practice and is often available in proprietary
herbal preparations. OBJECTIVE: This study was designed to investigate the semen
picture and spermatozoa morphology of West African Dwarf (WAD) bucks treated with
Aloe vera extract. MATERIALS AND METHODS: Twelve sexually matured WAD bucks,
weighing between 11 and 15 kg, were used for the study. The bucks were first used
as control (pre-treatment) and later as two groups of six animals each. The first
six bucks received 10 mls of the 3% extract while the other six received 10 mls
of the 4% of the extract for a 7 day period. Semen was collected from both the 3
and 4% extract treated bucks for the control (pre-treatment), on days eight
(first week post-treatment) and fifteen (second week post-treatment) in each case
using the electroejaculation method. The spermiogram of the bucks were
investigated using standard procedures. Data obtained were analyzed using two way
ANOVA and significance reported at p<0.05. RESULTS: The continuous administration
of Aloe vera extract significantly (p<0.05) reduced sperm concentration, motility
and percentage livability and resulted in increased sperm abnormalities in the
WAD buck. CONCLUSION: Aloe vera adversely affected the spermiogram of bucks. The
plant can reduce fertility in male animals and is therefore not recommended for
medicinal purpose in male animals especially those used for breeding.
PMID- 25587253
TI - Incidence of sexual dysfunction in men after cardiac surgery in Afshar hospital,
Yazd.
AB - BACKGROUND: Successful rehabilitation of cardiac surgery patients should include
consideration of their sexual activity, but there is paucity of data regarding
this matter. OBJECTIVE: This study determined the incidence and type of sexual
dysfunction in our patients. MATERIALS AND METHODS: Two hundred-seventy nine men
with age under 70 years old who had coronary artery bypass graft (CABG),
valvular, or other types of cardiac surgery from Dec. 2006 until Dec. 2007 were
enrolled in this descriptive-analytical study. They were interviewed before and
12 weeks after the operation in regard to the impact of surgery on their
sexuality. The statistical methods used included analysis of variance, Kappa
test, and chi-square analysis. RESULTS: The mean age of the patients was 55.7 +/-
10.66 (25-69) years. The incidence of sexual dysfunction was 20.1% before,
and76.4%, 12 weeks after the operation. P-valueas tested by Kappa test was
0.0001, which means that cardiac surgery had adverse effect on sexual activity of
the patients. Types of sexual dysfunction were impotence, premature ejaculation,
and decreased or loss of libido in 6.5%, 4.3% and 9.3%, respectively before
operation, and 34.8%, 21.5% and 20.1%, respectively 12 weeks after the operation.
Concurrence of more than one dysfunction was not reported. CONCLUSION: Sexual
dysfunction is common after cardiac surgery, and sexual counseling is still not
being addressed adequately. The role and responsibility of the physician and the
rehabilitation nurse becomes evident, together with the need for the patient's
partner to participate in counseling.
PMID- 25587254
TI - The effects of laser assisted hatching on pregnancy rates.
AB - BACKGROUND: For infertile women aged over 35 years, failure of the ZP (zona
pellucida) to rupture is believed to be associated with a decreased implantation
rate in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI).
OBJECTIVE: In this research, laser assisted hatching (LAH) was offered to
patients with advanced maternal age to evaluate a possible benefit. MATERIALS AND
METHODS: Nine hundred thirty two cycles of IVF/ICSI in females were analyzed.
Women included in this study were allocated in 4 groups. In group I and II,
embryos were cultured and transferred with and without LAH in women aged <=35,
whereas embryos of group III and IV were examined with and without LAH in women
aged >= 35. Laser manipulations were performed using a suturn-Tm3 system using 2
3 pulses of 0.8 millisecond with 400 voltage duration. The size of the hole made
in the zona was measured to be 5-10 um, depending on the zona thickness of each
individual embryo. RESULTS: The performance of LAH significantly increased
clinical pregnancy rates in all patients. In group I and II, the chemical (50.99%
and 31.61% respectively), clinical (50% and 30.69% respectively) and multiple
pregnancies (22.27% and 5.94% respectively) significantly differ between these
groups. In the patients with advanced female age >=35 the performance of LAH
significantly increased chemical (30.12%) and clinical pregnancy (27.71%) rates
compared to whom without LAH (18.96% and 16.37% respectively). CONCLUSION: Our
data demonstrate in the patients who were less than 35 years old, multiple
pregnancy rates were significantly increased compared to other groups who aged
over 35 years old. In addition benefit of LAH in improving pregnancy rates after
IVF or ICSI in women of advanced age (>=35) was shown.
PMID- 25587255
TI - The status of depression and anxiety in infertile Turkish couples.
AB - BACKGROUND: Infertility is a major psychosocial crisis as well as being a medical
problem. The factors that predict psychosocial consequences of infertility may
vary in different gender and different infertile populations. OBJECTIVE: The
primary purpose of this study was to investigate whether Turkish infertile
couples had higher levels of depression and anxiety when compared to non
infertile couples. Our secondary aim was to evaluate the relationship between
sociodemographic characteristics and levels of depression and anxiety in Turkish
infertile couples. MATERIALS AND METHODS: We designed a descriptive cross
sectional study of 248 infertile women and 96 infertile men with no psychiatric
disturbance and 51 women and 40 men who have children to evaluate the depression
and anxiety levels between infertile couples and fertile couples. A gynecologist
evaluated participants for demographic data and then they were visited by a
psychologist to perform questionnaire scales which were The Beck Depression
Inventory and the State-Trait Anxiety Inventory for the evaluation of the degree
of psychopathology. The data were statistically analyzed, with p<0.05 as the
level of statistical significance. RESULTS: We observed significant differences
between the infertile couples and fertile couples with respect to state and trait
anxiety (p<0.0001) while no difference was regarding with depression, both of
women and men. Anxiety and depression were observed as independent from gender
when infertile women and men were compared (p=0.213). CONCLUSION: We believed
that the psychological management at infertile couples must be individualized
with cultural, religious, and class related aspects.
PMID- 25587256
TI - Analysis of 232 total fertilization failure cycles during intracytoplasmic sperm
injection.
AB - BACKGROUND: The intracytoplasmic sperm injection procedure ending with total
fertilization failure is very distressfull event for both the clinician and the
patient. OBJECTIVE: The aim of this study was to identify independent factors
which could be used to identify total fertilization failure before the day of
intracytoplasmic sperm injection. MATERIALS AND METHODS: This was a retrospective
study of 232 patients who were admitted to a tertiary-care hospital IVF Unit and
showed total fertilization failure during intracytoplasmic sperm injection
cycles. To sort out the interwined effects of female age, basal FSH, sperm
quality, antral follicle count, starting dose of gonadotrophine, sperm extraction
technique, cycle length, >14 mm follicle number, oocyte number after oocyte pick
up, estradiol and progesterone level on the day of hCG and the MI, MII and GV
oocyte number on the fertilization, multiple logistic regression analysis was
used. RESULTS: The total fertilization failure rate was 6% and the recurrance
rate was 23%. The original model illustrated that the presence of GV oocytes,
total oocyte number less than six, <2000 pg/mL E2 concentration on the day of hCG
and testicular sperm extraction increases the total fertilization failure risk.
CONCLUSION: It is very difficult to predict total fertilization failure.
Sometimes even with one good quality oocyte and sperm and in the case of
globozoospermia fertilization can be achieved. Not only azoospermia but also low
oocyte numbers increase the chance of total fertilization failure even after
intracytoplasmic sperm injection.
PMID- 25587257
TI - Lipid peroxidation is not associated with adipocytokines in preeclamptic women.
AB - BACKGROUND: The association between lipid peroxidation biomarkers and
adipocytokines is hypothesized in preeclampsia but little is known about it.
OBJECTIVE: he present study was undertaken to determine the association of lipid
peroxidation biomarkers measured by the levels of 8-isoprostane and
malondialdehyde with adipocytokines leptin and adiponectin in maternal serum of
preeclamptic women. MATERIALS AND METHODS: A cross-sectional study was designed.
The study population consisted of 30 preeclamptic patients and 30 healthy
pregnant women. Serum levels of 8-Isoprostane, total leptin and total adiponectin
were assessed using commercially available enzyme-linked immunosorbent assay
methods. The amount of malondialdehyde was determined by the thiobarbituric acid
assay. Mann-Whitney U test and Spearman's correlation coefficient were used for
statistical analysis. RESULTS: Both 8-Isoprostane and malondialdehyde were
significantly higher in preeclamptic group than those in normal pregnant women.
Serum levels of leptin were significantly increased in preeclamptic patients
compared with normal group, while adiponectin levels were decreased. Serum levels
of 8-Isoprostane and malondialdehyde did not show any significant correlation
with leptin and adiponectin. CONCLUSION: In preeclamptic women, maternal serum
levels of leptin and adiponectin were not correlated with lipid peroxidation.
PMID- 25587258
TI - Comparing intramuscular progesterone, vaginal progesterone and 17
hydroxyprogestrone caproate in IVF and ICSI cycle.
AB - BACKGROUND: Supplementation of luteal phase with progesterone is prescribed for
women undergoing routine IVF treatment. OBJECTIVE: The objective of this study
was to compare the efficacy of three types of progesterone on biochemical,
clinical and ongoing pregnancy rates and abortion and live birth rates. MATERIALS
AND METHODS: A prospective randomized study was performed at Royan Institute
between March 2008 and March 2009 in women under 40 years old, who use GnRH
analog down-regulation. One hundred eighty six patients in three groups were
received progesterone in oil (100 mg, IM daily), intravaginal progesterone (400
mg, twice daily) and 17-alpha hydroxyprogestrone caproate (375mg, every three
days), respectively. RESULTS: Final statistical analysis after withdrawal of some
patients was performed in 50, 50 and 53 patients in group 1, 2 and 3
respectively. No differences between the groups were found in baseline
characteristics. No statistical significance different was discovered for
biochemical, clinical and ongoing pregnancies. Although the abortion rate was
statistically higher in group 1 (p=0.025) the live birth rate was not
statistically significant between the three groups. CONCLUSION: The effects of
three types of progesterone were similar on pregnancies rate. We suggest the use
of intravaginal progesterone during the luteal phase in patients undergoing an
IVF-ET program because of the low numbers of abortions, and high ongoing
pregnancy rates.
PMID- 25587259
TI - Effects of sera taken from women with recurrent spontaneous abortion on sperm
motility and apoptosis.
AB - BACKGROUND: Recurrent spontaneous abortion impacts almost 1% of couples. The sera
from women with unexplained recurrent spontaneous abortion (URSA) have toxic
effects on embryos that grow in the uterus. Therefore, the abnormal condition of
the uterus may also affect sperm qualities. OBJECTIVE: The objectives of this
study were to search if these sera could induce DNA denaturation in sperm nuclei
and also it could reduce sperm motility. MATERIALS AND METHODS: Sera of 20 women
with URSA history and sera from 20 women with at least two healthy children were
added to the sperms samples from 20 healthy men for 2 hours. The sperm motility
was assessed after incubation with sera. The samples were stained with Tdt
mediated dUTP nick end labeling (TUNEL) assay for DNA fragmentation. The samples
were analyzed with flow cytometry and the percentage of the TUNEL positive sperms
were calculated. The data were analyzed by t-test. RESULTS: The incubation of the
sperm samples in sera with URSA lead to a decrease in the percentage of the
motile sperm from 55% in control to 41% in the treated group, significantly
(p=0.038). The percentage of the sperm with abnormal fragmented DNA increased
after incubation with URSA (26.6%) compare to the control (21.2%); however, it
was not significant. CONCLUSION: It seems that sera from URSA patients could not
induce a significant increase in the percentage of the sperms with nuclei contain
DNA fragmentation. However, the sera of women with URSA could affect the
fertility rate by reduction of the sperm motility.
PMID- 25587260
TI - Comparison of maternal and neonatal serum leptin levels in preeclampsia and
normal pregnancy.
AB - BACKGROUND: Leptin is a protein product of obesity gene and is synthesized mainly
by adipose tissue. OBJECTIVE: The aim of this study was to determine maternal and
neonatal serum leptin levels in term preeclamptic and normal pregnancies.
MATERIALS AND METHODS: This cross sectional study was performed on 37
preeclamptic and 40 normotensive term pregnant women without other disease. Serum
level of leptin was measured in all of pregnant mothers and after delivery, their
neonates. This study was performed in Babol Yahyanejad Hospital from March 2006
to December 2006. RESULTS: Infants with preeclamptic mothers had significantly
lower leptin level than control group (p=0.02). There was no significant
difference in serum leptin levels between normal and preeclamptic women
(p=0.749). CONCLUSION: According to the results, it would be concluded that
leptin level in infants of preeclamptic mothers is lower than infants of normal
mothers. This can only confirm the diagnosis of disease after birth but it cannot
predict the preeclampsia.
PMID- 25587262
TI - Reconstructive metroplastic myomectomy of an infertile woman.
AB - BACKGROUND: While myoma is the most common pelvic mass of women, most women do
not seek screening tests for uterine myoma and if they have any fibroid they are
not volunteer for its surgical removal. CASE: We present here a novel technique
of vascular skeletonization to preserve uterus, making pregnancy possible for an
infertile woman with a large uterine myoma, situated in the uterine lower
segment. CONCLUSION: Vascular skeletonization to preserve vessels for a case of
myomectomy helped preserve the patient's ability to conceive.
PMID- 25587261
TI - Unexplained infertility as primary presentation of celiac disease, a case report
and literature review.
AB - BACKGROUND: Celiac sprue (gluten sensitive enteropathy) is an autoimmune disease
which is hereditary and its pathology mainly bases on immunologic intolerance to
gluten. It has a vast variety of signs and symptoms and its clinical features
range from a silent disease to a typical gastrointestinal disorder. In this study
we reviewed and summarized some other related issues about this disease and its
relation with infertility. CASE: The case is a 26 years old lady who had referred
to a gynecologist because of infertility for 2 years and later it revealed that
she has celiac sprue. CONCLUSION: Screening for its silent or subtle types
especially among suspicious cases such as unexplained infertility seems to be a
cost effective action. Meanwhile, in time administration of a gluten-free diet
can lead to an almost complete cure.
PMID- 25587263
TI - Semen banking: consideration on viral contamination in the era of new emerging
viral infection.
PMID- 25587264
TI - Computer-assisted segmentation of videocapsule images using alpha-divergence
based active contour in the framework of intestinal pathologies detection.
AB - Visualization of the entire length of the gastrointestinal tract through natural
orifices is a challenge for endoscopists. Videoendoscopy is currently the "gold
standard" technique for diagnosis of different pathologies of the intestinal
tract. Wireless capsule endoscopy (WCE) has been developed in the 1990s as an
alternative to videoendoscopy to allow direct examination of the gastrointestinal
tract without any need for sedation. Nevertheless, the systematic postexamination
by the specialist of the 50,000 (for the small bowel) to 150,000 images (for the
colon) of a complete acquisition using WCE remains time-consuming and challenging
due to the poor quality of WCE images. In this paper, a semiautomatic
segmentation for analysis of WCE images is proposed. Based on active contour
segmentation, the proposed method introduces alpha-divergences, a flexible
statistical similarity measure that gives a real flexibility to different types
of gastrointestinal pathologies. Results of segmentation using the proposed
approach are shown on different types of real-case examinations, from
(multi)polyp(s) segmentation, to radiation enteritis delineation.
PMID- 25587265
TI - Improvement of adaptive GAs and back propagation ANNs performance in condition
diagnosis of multiple bearing system using grey relational analysis.
AB - Condition diagnosis of multiple bearings system is one of the requirements in
industry field, because bearings are used in many equipment and their failure can
result in total breakdown. Conditions of bearings commonly are reflected by
vibration signals data. In multiple bearing condition diagnosis, it will involve
many types of vibration signals data; thus, consequently, it will involve many
features extraction to obtain precise condition diagnosis. However, large number
of features extraction will increase the complexity of the diagnosis system.
Therefore, in this paper, we presented a diagnosis method which is hybridization
of adaptive genetic algorithms (AGAs), back propagation neural networks (BPNNs),
and grey relational analysis (GRA) to diagnose the condition of multiple bearings
system. AGAs are used in the diagnosis algorithm to determine the best initial
weights of BPNNs in order to improve the diagnosis accuracy. In addition, GRA is
applied to determine and select the dominant features from the vibration signal
data which will provide good diagnosis of multiple bearings system in less
features extraction. The experiments results show that AGAs-BPNNs with GRA
approaches can increase the accuracy of diagnosis in shorter processing time,
compared with the AGAs-BPNNs without the GRA.
PMID- 25587266
TI - Application of wireless intelligent control system for HPS lamps and LEDs
combined illumination in road tunnel.
AB - Because of the particularity of the environment in the tunnel, the rational
tunnel illumination system should be developed, so as to optimize the tunnel
environment. Considering the high cost of traditional tunnel illumination system
with high-pressure sodium (HPS) lamps as well as the effect of a single light
source on tunnel entrance, the energy-saving illumination system with HPS lamps
and LEDs combined illumination in road tunnel, which could make full use of these
two kinds of lamps, was proposed. The wireless intelligent control system based
on HPS lamps and LEDs combined illumination and microcontrol unit (MCU) Si1000
wireless communication technology was designed. And the remote monitoring,
wireless communication, and PWM dimming module of this system were designed
emphatically. Intensity detector and vehicle flow detector can be configured in
wireless intelligent control system, which gather the information to the master
control unit, and then the information is sent to the monitoring center through
the Ethernet. The control strategies are got by the monitoring center according
to the calculated results, and the control unit wirelessly sends parameters to
lamps, which adjust the luminance of each segment of the tunnel and realize the
wireless intelligent control of combined illumination in road tunnel.
PMID- 25587267
TI - A study on urban road traffic safety based on matter element analysis.
AB - This paper examines a new evaluation of urban road traffic safety based on a
matter element analysis, avoiding the difficulties found in other traffic safety
evaluations. The issue of urban road traffic safety has been investigated through
the matter element analysis theory. The chief aim of the present work is to
investigate the features of urban road traffic safety. Emphasis was placed on the
construction of a criterion function by which traffic safety achieved a
hierarchical system of objectives to be evaluated. The matter element analysis
theory was used to create the comprehensive appraisal model of urban road traffic
safety. The technique was used to employ a newly developed and versatile matter
element analysis algorithm. The matter element matrix solves the uncertainty and
incompatibility of the evaluated factors used to assess urban road traffic
safety. The application results showed the superiority of the evaluation model
and a didactic example was included to illustrate the computational procedure.
PMID- 25587268
TI - Metabolic changes and serum ghrelin level in patients with psoriasis.
AB - Background. Serum ghrelin levels may be related to metabolic and clinical changes
in patients with psoriasis. Objective. This study was performed to determine the
possible effects of serum ghrelin in patients with psoriasis. Methods. The study
population consisted of 25 patients with plaque psoriasis. The patients were
questioned with regard to age, gender, age of onset, duration of disease, height,
weight, and body mass index (BMI). In addition, fasting blood sugar,
triglyceride, cholesterol levels, insulin, and ghrelin levels were measured.
Results. The mean serum ghrelin level was 45.41 +/- 22.41 in the psoriasis group
and 29.92 +/- 14.65 in the healthy control group. Serum ghrelin level was
significantly higher in the psoriasis group compared with the controls (P =
0.01). The mean ghrelin level in patients with a lower PASI score was
significantly higher than in those with a higher PASI score (P = 0.02).
Conclusion. The present study was performed to determine the effects of ghrelin
in psoriasis patients. We found a negative correlation between severity of
psoriasis and ghrelin level. Larger and especially experimental studies focusing
on correlation of immune system-ghrelin levels and severity of psoriasis may be
valuable to clarify the etiopathogenesis of the disease.
PMID- 25587269
TI - Prognostic Value of AIMS65 Score in Cirrhotic Patients with Upper
Gastrointestinal Bleeding.
AB - Introduction. Unlike Rockall scoring system, AIMS65 is based only on clinical and
laboratory features. In this study we investigated the correlation between the
AIMS65 score and Endoscopic Rockall score, in cirrhotic and noncirrhotic
patients. Methods. This is a retrospective study of patients admitted with overt
UGIB and undergoing esophagogastroduodenoscopy (EGD). AIMS65 and Rockall scores
were calculated at the time of admission. We investigated the correlation between
both scores along with stigmata of bleed seen on endoscopy. Results. A total of
1255 patients were studied. 152 patients were cirrhotic while 1103 patients were
noncirrhotic. There was significant correlation between AIMS65 and Total Rockall
scores in patients of both groups. There was significant correlation between
AIMS65 score and Endoscopic Rockall score in noncirrhotics but not cirrhotics.
AIMS65 scores in both cirrhotic and noncirrhotic groups were significantly higher
in patients who died from UGIB than in patients who did not. Conclusion. We
observed statistically significant correlation between AIMS65 score and length of
hospitalization and mortality in noncirrhotic patients. We found that AIMS65
score paralleled the endoscopic grading of lesion causing UGIB in noncirrhotics.
AIMS65 score correlated only with mortality but not the length of hospitalization
or endoscopic stigmata of bleed in cirrhotics.
PMID- 25587270
TI - Factors Associated with Insomnia among Elderly Patients Attending a Geriatric
Centre in Nigeria.
AB - Background. Insomnia is a form of chronic sleep problem of public health
importance which impacts the life of elderly people negatively. Methods. Cross
sectional study of 843 elderly patients aged 60 years and above who presented
consecutively at Geriatric Centre, University College Hospital, Ibadan, Nigeria.
The World Health Organization Composite International Diagnostic Interview was
used to diagnose insomnia. We assessed the following candidate variables which
may be associated with insomnia such as socidemographic characteristics,
morbidities, and lifestyle habits. Statistical analysis was done with SPSS 17.
Results. The point prevalence of insomnia was 27.5%. Insomnia was significantly
associated with being female, not being currently married, having formal
education, living below the poverty line, and not being physically active. Health
complaints of abdominal pain, generalized body pain, and persistent headaches
were significantly associated with insomnia. Conclusion. The high prevalence of
insomnia among elderly patients in this setting calls for concerted effort by
healthcare workers to educate the elderly on lifestyle modification.
PMID- 25587271
TI - Serum leptin levels in polycystic ovary syndrome and its relationship with
metabolic and hormonal profile in pakistani females.
AB - The study aimed to investigate the levels of serum leptin in PCOS females and to
correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety
normal cycling (NC) females with matched age and body mass index (BMI) were
recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free
testosterone, progesterone, thyroid profile, and FBG levels were measured. The
mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL
+/- 1.49 vs 41.78 +/- 1.31 ng/mL, P > 0.05); however, leptin levels showed a
strong correlation with BMI in PCOS and NC group (r = 0.77, P < 0.0001; r = 0.82,
P < 0.0001, resp.). High E2 levels in NC had a significant correlation with
leptin whereas FBG correlated with leptin in PCOS (r = 0.51, P = 0.005). TSH had
a substantial correlation (r = 0.49, P < 0.005; r = 0.69, P < 0.005) in PCOS and
NC, respectively. There was no significant difference found in circulating leptin
concentration between PCOS and NC subjects. Leptin levels in PCOS were related
with metabolic impairments manifested by disturbance in FBG levels and impairment
of reproductive functions in terms of reduced E2 secretion.
PMID- 25587272
TI - Regulation of UCP1 in the Browning of Epididymal Adipose Tissue by beta3
Adrenergic Agonist: A Role for MicroRNAs.
AB - Background. White adipose tissue browning may be a promising strategy to combat
obesity. UCP1 is strongly induced in White adipose tissue with beta3-adrenergic
agonist treatment, but the causes of this increase have not been fully
elucidated. This study aims to explore more miRNAs involved in the process of
browning of visceral adipose tissue. Methods. Total of fourteen mice were
randomly divided into control and study group. Study group mice were injected
intraperitoneally with CL316243 once daily for seven days; meanwhile the control
group were treated with 0.9% NaCl. After a 7-day period, the expression of genes
involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues
was analyzed by qPCR. Results. qPCR analysis revealed that UCP1, DIO2, CIDEA, and
CPT1B in epididymal adipose tissue were overexpressed in CL316243 group.
Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose
tissue were significantly decreased in CL316243 group. Conclusion. This suggests
that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the
browning of epididymal adipose tissue by regulating UCP1 gene expression. In this
study, we demonstrated that this increase of UCP1 is due, at least in part, to
the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose
tissue compared to control.
PMID- 25587273
TI - Reevaluation of Acromegalic Patients in Long-Term Remission according to Newly
Proposed Consensus Criteria for Control of Disease.
AB - Acromegaly guidelines updated in 2010 revisited criteria of disease control: if
applied, it is likely that a percentage of patients previously considered as
cured might present postglucose GH nadir levels not adequately suppressed, with
potential implications on management. This study explored GH secretion, as well
as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a
cohort of 40 acromegalic patients considered cured on the basis of the previous
guidelines after a mean follow-up period of 17.2 years from remission, in order
to assess the impact of the current criteria. At the last follow-up visit, in the
presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 MUg/L
in 11 patients (Group A) and below 0.4 MUg/L in 29 patients (Group B); moreover,
Group A showed higher basal GH levels than Group B, whereas a significant decline
of both GH and postglucose GH nadir levels during the follow-up was observed in
Group B only. No differences in other evaluated parameters were found. These
results seem to suggest that acromegalic patients considered cured on the basis
of previous guidelines do not need a more intensive monitoring than patients who
met the current criteria of disease control, supporting instead that the cut-off
of 0.4 mcg/L might be too low for the currently used GH assay.
PMID- 25587274
TI - Interpreting the consequences of metformin accumulation in an emergency context:
impact of the time frame on the blood metformin levels.
AB - Objective. To clarify the link between metformin accumulation and its metabolic
consequences by taking the time frame for metformin measurement into account.
Research Design and Methods. Our database was studied for cases of metformin
accumulation and lactic acidosis status available on admission, and then we
selected patients in whom arterial pH, blood lactate, and plasma and erythrocyte
metformin levels had been determined at the same time point. Results. Seventeen
reports were studied on 16 patients, of whom 10 presented lactic acidosis. The
time interval between admission and comprehensive testing ranged from 0 to 52
hours. The study parameters were determined simultaneously on admission in only 4
patients. In the 9 patients with lactic acidosis on admission and a delayed
metformin assay, lactic acidosis persisted in 6 cases and had resolved in 3 cases
by the time the blood sampling for metformin assay was performed. Conversely,
lactic acidosis developed after admission in one case. Conclusions. Caution must
be taken when interpreting the consequences of metformin accumulation in an
emergency context: the patient's lactic acidosis status will have changed by the
time the metformin assay is performed, even though metformin accumulation may
still be present.
PMID- 25587276
TI - Accelerated Tooth Movement and Temporary Skeletal Anchorage Devices (TSADs).
PMID- 25587275
TI - Systematic Review of Surgical Approaches for Adrenal Tumors: Lateral
Transperitoneal versus Posterior Retroperitoneal and Laparoscopic versus Robotic
Adrenalectomy.
AB - Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the
standard method for resecting benign adrenal gland tumors. Recently, however,
laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular
as an alternative method. This systematic review evaluates current evidence on
adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic
adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of
Knowledge databases were searched systematically for studies comparing surgical
outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic
adrenalectomy. The studies were evaluated according to the PRISMA statement.
Results. Eight studies comparing laparoscopic PRA and LTA showed that
laparoscopic PRA was superior or at least comparable to laparoscopic LTA in
operation time, blood loss, pain score, hospital stay, and return to normal
activity. Conversion rates and complication rates were similar. Six studies
comparing robotic and laparoscopic adrenalectomy found that outcomes and
complications were similar. Conclusion. Laparoscopic PRA was more effective than
LTA, especially in reducing operation time and hospital stay, but there was no
evidence showing that robotic adrenalectomy was superior to laparoscopic
adrenalectomy. Cost reductions and further technical advances are needed for
wider application of robotic adrenalectomy.
PMID- 25587277
TI - Current controversies in classification, management, and prevention of
bisphosphonate-related osteonecrosis of the jaw.
PMID- 25587278
TI - Ciprofloxacin release using natural rubber latex membranes as carrier.
AB - Natural rubber latex (NRL) from Hevea brasiliensis is easily manipulated, low
cost, is of can stimulate natural angiogenesis and cellular adhesion, is a
biocompatible, material and presents high mechanical resistance. Ciprofloxacin
(CIP) is a synthetic antibiotic (fluoroquinolone) used in the treatment of
infection at external fixation screws sites and remote infections, and this use
is increasingly frequent in medical practice. The aim of this study was to
develop a novel sustained delivery system for CIP based on NRL membranes and to
study its delivery system behavior. CIP was found to be adsorbed on the NRL
membrane, according to results of energy dispersive X-ray spectroscopy. Results
show that the membrane can release CIP for up to 59.08% in 312 hours and the
mechanism is due to super case II (non-Fickian). The kinetics of the drug release
could be fitted with double exponential function X-ray diffraction and Fourier
transform infrared (FTIR) spectroscopy shows some interaction by hydrogen bound,
which influences its mechanical behavior.
PMID- 25587280
TI - Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance
Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium
perfringens Strains.
AB - Fluoroquinolone resistance affects toxin production of Clostridium perfringens
strains differently. To investigate the effect of fluoroquinolone resistance
selection on global changes in metabolic activities and drug susceptibilities,
four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and
gatifloxacin-resistant mutants were compared in nearly 2000 assays, using
phenotype microarray plates. Variations among mutant strains resulting from
resistance selection were observed in all aspects of metabolism. Carbon
utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant
strains were affected differently in the resistant mutants depending on both the
bacterial genotype and the fluoroquinolone to which the bacterium was resistant.
The susceptibilities to gentamicin and erythromycin of all resistant mutants
except one increased, but some resistant strains were less susceptible to
amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than
their wild types. Sensitivity to ethidium bromide decreased in some resistant
mutants and increased in others. Microarray analysis of two gatifloxacin
resistant mutants showed changes in metabolic activities that were correlated
with altered expression of various genes. Both the chemical structures of
fluoroquinolones and the genomic makeup of the wild types influenced the changes
found in resistant mutants, which may explain some inconsistent reports of the
effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria.
PMID- 25587279
TI - Determination of oxidative stress related toxicity on repeated dermal exposure of
hydroxyapatite nanoparticles in rats.
AB - Hydroxyapatite nanoparticles (HANPs) have numerous applications, such as
substitute for bone grafting, bone fillers, bioceramic coating, and dental
fillings. The toxicity of these nanomaterials is of growing concern despite their
significant scientific interest and promising potential in many applications. In
this study, an in-house synthesized, characterized HANP of size <50 nm was
investigated for the dermal toxicity. A paste of HANPs was prepared in water and
applied on the dorsal side of the rats for 28 days. At the end of 28 days, blood
was subjected to haematological and biochemical analysis. Gross necropsy was
conducted and major organs were collected for histopathological observations.
Liver from the animals was evaluated for lipid peroxidation, reduced glutathione,
and antioxidant enzymes activity. It was observed that none of the animals showed
any abnormality during the experimental period. Gross examination of carcasses
did not reveal any abnormality in the organs examined. The results also
demonstrated that there was no significant fluctuation in the level of
antioxidant defense mechanisms, lipid peroxidation, and haematological and
biochemical parameters. There was no histopathological lesion observed in any of
the organs. Hence, it can be concluded that the synthesized HANPs were nontoxic
at cellular level, when exposed dermally to rats.
PMID- 25587281
TI - Chronic pulmonary aspergillosis complicating bronchial atresia.
AB - Bronchial atresia is a rare pulmonary developmental anomaly characterized by the
presence of a focal obliteration of a segmental or lobar bronchial lumen. The
lung distal to the atretic bronchus is typically emphysematous along with the
presence of mucus filled ectatic bronchi (mucoceles). BA is usually asymptomatic
but pulmonary infections can rarely develop in the emphysematous lung distal to
the atretic bronchus. We present a unique case of chronic pulmonary aspergillosis
(CPA) in a patient with BA with no evidence of immune dysfunction. The patient
was treated initially with voriconazole and subsequently underwent surgical
excision of the involved area. On follow-up, she has done extremely well with no
evidence for recurrence. In summary, we describe the first case of chronic
pulmonary aspergillosis in an immunocompetent patient with bronchial atresia.
PMID- 25587282
TI - Maraviroc Failed to Control Progressive Multifocal Leukoencephalopathy-Associated
IRIS in a Patient with Advanced HIV Infection.
AB - Due to the lack of therapeutic options for patients with progressive multifocal
leukoencephalopathy-associated immune reconstitution inflammatory syndrome (PML
associated IRIS), maraviroc has generated expectations among the medical
community. However, we report a patient with advanced HIV infection, who
developed PML-associated IRIS and had a fatal outcome despite the addition of
maraviroc to suppressive ART. Future studies are required to define the
therapeutic role of maraviroc in PML-associated IRIS and differentiate
individuals who may benefit from maraviroc from those who may develop
neurological deterioration.
PMID- 25587284
TI - Efficient and cost-effective alternative treatment for recurrent urinary tract
infections and interstitial cystitis in women: a two-case report.
AB - Urinary tract infections (UTIs) are among the most common bacterial infections
affecting women. UTIs are primarily caused by Escherichia coli, which increases
the likelihood of a recurrent infection. We encountered two cases of recurrent
UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due
to the development of antibiotic resistance. An alternative therapeutic regimen
based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has
been given. This regimen showed a significant health improvement and symptoms
relief without recurrence for more than 12 months. In conclusion, the case
supports the concept of using alternative medicine in treating rUTI and as a
prophylaxis or in patients who had developed antibiotic resistance.
PMID- 25587283
TI - Metastasis to sartorius muscle from a muscle invasive bladder cancer.
AB - Bladder cancer constitutes the ninth most common cancer worldwide and
approximately only 30% of cases are muscle invasive at initial diagnosis.
Regional lymph nodes, bones, lung, and liver are the most common metastases from
bladder cancer and generally from genitourinary malignancies. Muscles constitute
a rare site of metastases from distant primary lesions even though they represent
50% of total body mass and receive a large blood flow. Skeletal muscles from
urothelial carcinoma are very rare and up to date only few cases have been
reported in the literature. We present a rare case of 51-year-old patient with
metastases to sartorius muscle 8 months after the radical cystectomy performed
for a muscle invasive bladder cancer.
PMID- 25587285
TI - A giant left atrial myxoma.
AB - Atrial myxomas are the most common primary cardiac tumors. Patients with left
atrial myxomas generally present with mechanical obstruction of blood flow,
systemic embolization, and constitutional symptoms. We present a case of an
unusually large left atrial myxoma discovered incidentally in a patient with
longstanding dyspnea being managed as bronchial asthma.
PMID- 25587288
TI - Nonpharmacological treatment of rhinoconjunctivitis and rhinosinusitis.
PMID- 25587286
TI - Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly
Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model.
AB - We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient
receptor potential cation channel (TRPC) 1 protein expression can suppress
hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6
mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and
group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure
(RVSP), number of muscularized arteries, right ventricle (RV), and lung weights
were increased in group 2 than in group 1 and reduced in group 3 compared with
group 2. Pulmonary crowded score showed similar pattern, whereas number of
alveolar sacs exhibited an opposite pattern compared to that of RVSP in all
groups. Protein expressions of TRPCs, HIF-1alpha, Ku-70, apoptosis, and fibrosis
and pulmonary mRNA expressions of inflammatory markers were similar pattern,
whereas protein expressions of antifibrosis and VEGF were opposite to the pattern
of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle
proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions
of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas
sarcomere length showed an opposite pattern compared to that of RVSP in all
groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression,
thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.
PMID- 25587287
TI - Directing parthenogenetic stem cells differentiate into adipocytes for
engineering injectable adipose tissue.
AB - The selection of appropriate seed cells is crucial for adipose tissue
engineering. Here, we reported the stepwise induction of parthenogenetic
embryonic stem cells (pESCs) to differentiate into adipogenic cells and its
application in engineering injectable adipose tissue with Pluronic F-127. pESCs
had pluripotent differentiation capacity and could form teratomas that include
the three primary germ layers. Cells that migrated from the embryoid bodies (EBs)
were selectively separated and expanded to obtain embryonic mesenchymal stem
cells (eMSCs). The eMSCs exhibited similar cell surface marker expression
profiles with bone morrow mesenchymal stem cells (BMSCs) and had multipotent
differentiation capacity. Under the induction of dexamethasone, indomethacin, and
insulin, eMSCs could differentiate into adipogenic cells with increased
expression of adipose-specific genes and oil droplet depositions within the
cytoplasm. To evaluate their suitability as seed cells for adipose tissue
engineering, the CM-Dil labelled adipogenic cells derived from eMSCs were seeded
into Pluronic F-127 hydrogel and injected subcutaneously into nude mice. Four
weeks after injection, glistering and semitransparent constructs formed in the
subcutaneous site. Histological observations demonstrated that new adipose tissue
was successfully fabricated in the specimen by the labelled cells. The results of
the current study indicated that pESCs have great potential in the fabrication of
injectable adipose tissue.
PMID- 25587289
TI - A microbiological explanation for the obesity pandemic?
PMID- 25587290
TI - That other EVD: Enterovirus-D68 - what's it all about?
PMID- 25587291
TI - Micafungin compared with caspofungin for the treatment of febrile episodes in
neutropenic patients with hematological malignancies: A retrospective study.
AB - BACKGROUND: Invasive fungal infections are associated with morbidity and
mortality in neutropenia secondary to hematological malignancies. Empirical
antifungal agents are used to reduce their consequences. Caspofungin is the only
echinocandin approved for this indication. Micafungin was compared with
caspofungin for the treatment of patients with hematological malignancies and
prolonged neutropenia. METHODS: A retrospective cohort study was conducted
involving patients who had hematological malignancies with profound neutropenia
for a minimum of 10 days, and received empirical micafungin or caspofungin for a
minimum of five days, between April 2005 and November 2009. Successful outcome
was based on a composite end point: survival for a minimum of seven days
following antifungal cessation, successful treatment of baseline fungal
infection, absence of adverse events and absence of breakthrough fungal
infection. Fungal infections were defined according to revised definitions of
invasive fungal disease from the European Organization for Research and Treatment
of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute
of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria, with
modification of the diagnostic imaging criteria. RESULTS: Micafungin had similar
overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82],
respectively; P=0.729). Survival was higher in the micafungin group compared with
the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No
baseline invasive fungal infections were identified in the micafungin group,
compared with three proven infections treated successfully with caspofungin
(3.7%; P=0.18). Three proven breakthrough infections were observed in the
micafungin group (three of 48 [27.3%]) compared with none in the caspofungin
group (zero of 82; P=0.02). CONCLUSION: Micafungin has similar efficacy to
caspofungin as empirical antifungal therapy in febrile neutropenic patients with
hematological malignancies. Verification of these results in a prospective trial
is warranted.
PMID- 25587292
TI - Triage and protocol recommendations for the parasitology laboratory based on an
epidemiological investigation of parasite diagnostics in Ontario laboratories.
AB - OBJECTIVES: A study was performed using a subset of Ontario laboratory
parasitology data, with three objectives: to describe parasitic infections in
Ontario; to identify risk factors for acquiring a parasitic infection using
routinely collected information; and to use this information to assess current
protocols for parasite testing in laboratories and, in turn, to propose
alternatives to optimize the allocation of laboratory resources. METHODS: All
parasitology records from January 4, 2010 to September 14, 2010 were reviewed
descriptively and risk factor analyses were performed using information collected
from requisitions. These results were used to develop preliminary alternative
protocols, which considered high-throughput screening tests and
inclusion/exclusion criteria for ova and parasite testing; these were then
retrospectively analyzed with the dataset to determine appropriateness. RESULTS:
Of the 29,260 records analyzed, 10% were multiple samples from single patients
submitted on the same day, of which 98% had the same result. Three percent of all
parasite tests were positive, with the most prevalent parasites being (in
ascending order) Dientamoeba fragilis, Giardia lamblia, Cryptosporidium species
and Entamoeba histolytica/dispar. Age and sex were found to be weak risk factors,
while rural living was found to be a moderate risk factor for D fragilis, G
lamblia and Cryptosporidium infections. The strongest risk factor was travel
history, especially for nonendemic parasites. The retrospective analysis of six
alternative protocols identified four that may be more efficient than current
procedures. CONCLUSIONS: The present study demonstrated that current protocols
may be redundant and can be optimized to target prevalent parasites and
populations with high risk factors.
PMID- 25587293
TI - CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core:
Updated Canadian guidelines for the treatment of hepatitis C infection in HIV
hepatitis C coinfected adults.
AB - BACKGROUND: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians
living with HIV and is responsible for a heavy burden of morbidity and mortality.
Management of HIV-HCV coinfection is more complex due to the accelerated
progression of liver disease, the timing and nature of antiretroviral and HCV
therapy, mental health and addictions management, socioeconomic obstacles and
drug-drug interactions between new HCV direct-acting antiviral therapies and
antiretroviral regimens. OBJECTIVE: To update national standards for the
management of HCV-HIV coinfected adults in the Canadian context. METHODS: A
standing working group with specific clinical expertise in HIV-HCV coinfection
was convened by The Canadian Institute of Health Research HIV Trials Network to
review recently published data regarding HCV antiviral treatments and to update
the Canadian HIV-HCV coinfection guidelines. RESULTS: Recent data suggest that
the gap in sustained virological response rates between HCV monoinfection and HIV
HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV
HCV coinfected individuals should be assessed for HCV therapy. First-line
treatment for genotypes 1 through 6 includes pegylated interferon and weight
based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in
combination with the protease inhibitor simeprevir is another first-line
consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks
(genotype 2) and 24 weeks (genotype 3) is also recommended as first-line
treatment. DISCUSSION: Recommendations may not supersede individual clinical
judgement.
PMID- 25587294
TI - A 71-year-old woman with recurrent falls and confusion.
PMID- 25587295
TI - Aches and pains with a shocking rash.
PMID- 25587298
TI - Parallel import: is it worth?
PMID- 25587297
TI - The first case of locally acquired tick-borne Babesia microti infection in
Canada.
AB - A child with a complicated medical history that included asplenia acquired an
infection with Babesia microti in the summer of 2013 and had not travelled
outside of Manitoba. Although the clinical findings were subtle, astute
laboratory work helped to reach a preliminary identification of Babesia species,
while reference laboratory testing confirmed the diagnosis. Blacklegged ticks
(Ixodes scapularis) are known to transmit Borrelia burgdorferi and Anaplasma
phagocytophilum in the province; however, the present case represents the first
known instance of tick-borne B microti, both in Manitoba and in Canada. The
expanding territory of the blacklegged tick increases the relevance of this
emerging infection. Clinicians, laboratory medical practitioners and public
health officials should be aware of B microti as a potential locally acquired
infection in Canada.
PMID- 25587299
TI - Preparation, Physicochemical Characterization and I n - vitro Dissolution Studies
of Diosmin-cyclodextrin Inclusion Complexes.
AB - Diosmin, a vascular-protecting agent, is practically insoluble in water, and its
oral absorption is limited by its extremely low dissolution rate. In this study,
beta-cyclodextrin (betaCD) and 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) were
obtained to improve the solubility and dissolution rate of diosmin. Phase
solubility studies of diosmin with betaCD and HPbetaCD in distilled water were
conducted to characterize the complexes in liquid state. The solid-state
characterization of the complexes prepared with different methods was performed
by fourier transform-infra red spectroscopy (FTIR), optical microscopy analyses,
and differential scanning calorimetry (DSC). Dissolution studies were carried out
in distilled water using US pharmacopeia dissolution rate testing equipment. The
complexation of diosmin with betaCD and HPbetaCD both indicated an AL type of
phase-solubility diagrams, and the apparent stability constants (Kc) was found to
be 222.13 and 200.08 M(-1), respectively. The Kc values indicated the betaCD and
HPbetaCD showed the similar equal complexation ability with diosmin, HPbetaCD
provided higher solubility for diosmin due to its higher water solubility. The
dissolution studies suggest that the inclusion complexes provide higher
dissolution rate compared with the physical mixtures and the drug alone.
Furthermore, the inclusion complex prepared by freeze drying method presented
higher dissolution rate than kneading method.
PMID- 25587300
TI - Preparation, characterization and stability study of dutasteride loaded
nanoemulsion for treatment of benign prostatic hypertrophy.
AB - Benign prostatic hyperplasia (BPH)is the most common condition in aging men,
associated with lower urinary tract symptoms. It is caused due to the augmented
levels of the androgen dihydrotestosterone. Dutasteride, a 5alpha-Reductase
inhibitor has been recommended for the treatment of BPH upon oral administration.
However, long term oral administration of dutasteride may cause sexual problem in
man. Therefore the main objective of this study was to develop transdermal patch
having nanoemulsion gel of dutasteride in order to enhance physical and chemical
stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was
prepared by aqueous phase-titration method and characterized by droplet size,
viscosity and refractive index. In-vitro skin permeation of dutasteride through
rat abdominal skin was determined by the Franz diffusion cell.Significant
increase in the steady state flux (J ss), permeability coefficient (K p) and
enhancement ratio (E r) was observed in optimized nanoemulsion formulation A1 (p
< 0.05). The Er of optimized nanoemulsion A1 was found to be 1.52 times with
respect to control which indicates transdermal delivery may be better approach
for BPH. Stability studies were performed for the period of 3 months. It was
found that droplet size, viscosity and refractive index were slightly increased
at refrigerator and room temperature in 3 months period. However, the changes in
these parameters were not statistically significant (p >= 0.05). The shelf-life
of optimized nanoemulsion A1 was found to be 2.18 years at room temperature.
These results indicated that both physical as well as chemical stability of
dutasteride in nanoemulsion formulation.
PMID- 25587301
TI - Effect of zirconium dioxide nanoparticles on glutathione peroxidase enzyme in
PC12 and n2a cell lines.
AB - Today, special attention is paid to the use of zirconium dioxide nanoparticle
(nano-ZrO2), a neutral bioceramic metal, particularly for drug and gene delivery
in medicine. However, there are some reports implying that use of nano-ZrO2 is
associated with cytotoxic effects like inhibiting the cell proliferation, DNA
damage and apoptosis. In the present study, we examined whether nano-ZrO2 alters
cell viability and glutathione peroxidase (GPx) activity in two neuronal cell
lines. The PC12 and N2a cells were cultured in the absence or presence of varying
concentrations (31.25-2000 ug/mL) of nano-ZrO2 for 12, 24 or 48 h. The cell
viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-(3
carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and GPx
activity was determined by quantifying the rate of oxidation of the reduced
glutathione to the oxidized glutathione. Nano-ZrO2 caused a significant reduction
in cell viability and GPx activity after 12, 24 and 48 h, as compared with
control group. These effects were concentration dependent and started from 250
ug/mL. The present study demonstrated that nano-ZrO2, at concentrations of > 250
ug/mL, has antiproliferative effects via reducing the cell defense mechanism
against oxidative stress.
PMID- 25587302
TI - Evaluation of Lipid-based Drug Delivery System (Phytosolve) on Oral
Bioavailability of Dibudipine.
AB - The objective of present study was to evaluate pharmacokinetic parameters of
dibudipine Phytosolve after oral administration in rats. The solubility test was
carried out to select suitable oily solvent for dibudipine. Phytosolve
formulation was prepared with a medium chain triglyceride (MCT) oil (20%),
soybean phospholipids (5%) and a 70% fructose solution (75%). The effect of
polyol content on the mean globule size of Phytosolve formulation was studied.
The optimized formulation was evaluated for robustness toward dilution,
transparency, droplet size, zeta potential and transmission electron microscopic
analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 +/-
4.3 nm and surface charge -18.36 +/- 0.37 mv was administered orally to rats. The
average relative bioavalabilities of dibudipine in the plasma with Phytosolve
were 170.4% and 211.2% as compared to the oily solution and aqueous suspension
respectively. So this formulation could be offered as a useful technique to
improve the oral delivery of the poorly water soluble drugs such as dibudipine.
PMID- 25587303
TI - Preparation of Pluronic/Bile salt/Phospholipid Mixed Micelles as Drug Solubility
Enhancer and Study the Effect of the PPO Block Size on the Solubility of Pyrene.
AB - Pluronic/bile salt/phospholipid mixed micelles (Pluronic/BS/PS-MM) drug carrier
system for solubilization hydrophobic drugs was developed. A typical hydrophobic
compound, pyrene, was selected as a representative hydrophobic compound to model
the hydrophobic drugs. Five Pluronics, F68, F88, F98, F108, and F127 with
different PPO chain length were studied. CMC data and solubilization capacities
were obtained from a pyrene solubilization method. A closed association model was
used to obtain the thermodynamic parameters: Gibbs free energy (DeltaG degrees ),
enthalpy, (DeltaH degrees ) and entropy (DeltaS degrees ) of micellization. The
results obtained from these experiments suggest that the mixed micelles was more
stable and solubilize more pyrene than single one; and the solubilization of
pyrene was strong effected by the PPO block size, thus accentuating synergistic
interaction mechanism in Pluronic/BS/PS-MM. The study generated an important
dataset so as to compare the effect of different Pluronics on solubility capacity
of Pluronic/BS/PS-MM.
PMID- 25587296
TI - Therapeutic drug monitoring for triazoles: A needs assessment review and
recommendations from a Canadian perspective.
AB - Invasive fungal infections cause significant morbidity and mortality in patients
with concomitant underlying immunosuppressive diseases. The recent addition of
new triazoles to the antifungal armamentarium has allowed for extended-spectrum
activity and flexibility of administration. Over the years, clinical use has
raised concerns about the degree of drug exposure following standard approved
drug dosing, questioning the need for therapeutic drug monitoring (TDM).
Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A
review of the rationale for triazole TDM, the targeted patient populations and
available laboratory methods, as well as practical recommendations based on
current evidence from an extended literature review are provided in the present
document.
PMID- 25587304
TI - Search for the pharmacophore of histone deacetylase inhibitors using
pharmacophore query and docking study.
AB - Histone deacetylase inhibitors have gained a great deal of attention recently for
the treatment of cancers and inflammatory diseases. So design of new inhibitors
is of great importance in pharmaceutical industries and labs. Creating
pharmacophor models in order to design new molecules or search a library for
finding lead compounds is of great interest. This approach reduces the overall
cost associated with the discovery and development of a new drug. Here we
elaborated an exact pharmacophore model for histone deacetylase inhibitors by
using pharmacophore query and docking study. The data set used for the modelling
exercise comprised of 383 molecules collated from the original literature. These
molecules were used to crating the model and docking study was held with Zolinza,
the recently FDA approved drug as potent histone deacetylase inhibitor. Our model
consists of 5 features: Hydrogen bond donors, Hydrogen bond acceptors, H-bond
donor/acceptors, Aromatic ring centers, and hydrophobic centers. With the aid of
this pharmacophore model and docking result, 3D searches in large databases can
be performed, leading to a significant enrichment of active analogs.
PMID- 25587305
TI - Synthesis and Biological Evaluation of Novel Mono Acid Esters Derived from the
Constituents of Urtica pilulifera.
AB - New mono acid esters have been synthesized from the reaction of benzoic acid and
mono-hydroxybenzoic acids with 2-phenoxyethanol separated from Urtica pilulifera,
characterized, and screened for possible antioxidant, antifungal, antimicrobial
and anticancer activities. These phenolic acid esters gave various degrees of
free radical scavenging, but the values were lower than that of alpha-tocopherol.
The concentrations of the tested compounds needed to reduce DPPH absorption by
50% at 517 nm were nearly in the range of 900-1100 ug/mL. While for alpha
tocopherol was 40 ug /mL. The compounds were tested in-vitro against six
bacterial species which are known to cause dermic and mucosal infections in
human. 2-phenoxyethyl benzoate showed significant activity in the range of 30%
against P. aeruginosa to 70% against E. coli compared with the activity of
Streptomycin. On the other hand 2-phenoxyethyl 2-hydroxybenzoate reveals 70% of
gentamicin against K. pneumoniae. The tested compounds also showed complete
inhibition at a concentration less than 37.5 ug/mL against M. canis and less than
50 ug/mL against T. rubrum. 2-phenoxyethyl 4-hydroxybenzoate showed considerable
activity against MCF-7 with IC50 is less than 62.5 ug/mL.
PMID- 25587306
TI - Synthesis of three rimantadine schiff bases and their biological effects on serum
albumin.
AB - Three new rimantadine Schiff bases (RSBs) were prepared, and then the interaction
of RSBs with bovine serum albumin (BSA) was investigated using fluorescence,
synchronous fluorescence, UV-vis absorption spectroscopy under physiological
conditions. The results showed that the three RSBs effectively quenched the
intrinsic fluorescence of BSA via static quenching. Binding constant (K a),
number of binding sites (n), and the binding distance (r) between three RSBs and
BSA were calculated by Stern-Volmer equation and Forster's theory in this study.
According to the results of displacement experiments of site probes, it was
considered that the binding sites were located in hydrophobic cavities in sub
domains IIA of BSA. What is more, synchronous fluorescence studies indicated that
the hydrophobicity around tryptophan residues was increased with the addition of
rimantadine-o-vanillin (ROV) and rimantadine-4-methoxy-salicylaldehyde (RMS),
while there was no apparent change with the addition of rimantadine
salicylaldehyde (RS).
PMID- 25587307
TI - Study on the Multi-marker Components Quantitative HPLC Fingerprint of the
Compound Chinese Medicine Wuwei Changyanning Granule.
AB - The aim of this paper is to develop a rapid and highly sensitive quantitative
HPLC fingerprint method with multiple indicators by using the Compound Chinese
Medicine Wuwei Changyanning granule and 5 herbs in the prescription. The
quantitative fingerprint chromatogram with multiple indicators was investigated.
i)6 compositions included rutin, gallic acid, chlorogenic acid, atractylenolide
I, pachymic acid and apigenin, which originated from 5 herbs respectively, were
selected as quantitative compositions, and their contents were determined using
HPLC from 11 batches granules and the corresponding 5 medicinal materials. ii)
The precision, stability and repeatability of fingerprinting were investigated.
In addition, common peaks number, the percentage of non-common peaks and
similarity were also studied. Among them, 21 common peaks in the granule could
find the source of peaks from the 5 herbs, among of 10 peaks from Niuerfeng, 9
peaks from Laliao, 3 peaks from Baishu, 3 peaks from Fuling and 5 peaks from
Guanghuoxiang. The results showed that the identification method of
fingerprinting was reliable.
PMID- 25587308
TI - RP-HPTLC Retention Data in Correlation with the In-silico ADME Properties of a
Series of s-triazine Derivatives.
AB - The properties relevant to pharmacokinetics and pharmacodynamics of four series
of synthesized s-triazine derivatives have been studied by Quantitative structure
retention relationship (QSRR) approach. The chromatographic behavior of these
compounds was investigated by using reversed-phase high performance thin-layer
chromatography (RP-HPTLC). Chromatographic retention (R M (0)) was correlated
with selected physicochemical parameters relevant to pharmacokinetics, i.e. ADME
(absorption, distribution, metabolism and excretion). In addition, the ability to
act as kinase inhibitors and protease inhibitors was predicted for all
investigated triazine classes. Also, in order to confirm
similarities/dissimilarities between series of examined compounds, principal
component analysis (PCA) based on calculated ADME properties was conducted. The R
M (0) values of the s-triazine derivatives have been recommended for description
and evaluation of pharmacokinetic properties. According to results of this study,
the synthesized s-triazine derivatives meet pharmacokinetic criteria of
preselection for drug candidates.
PMID- 25587309
TI - Meta-analysis of Selective Serotonin Reuptake Inhibitors (SSRIs) Compared to
Tricyclic Antidepressants (TCAs) in the Efficacy and Safety of Anti-depression
Therapy in Parkinson's Disease(PD) Patients.
AB - To assess the efficacy and safety of selective serotonin reuptake
inhibitors(SSRIs) and tricyclic antidepressants(TCAs) in treatment of
Parkinsonian depression. A computer-based search was conducted in the databases
of PUBMED, MEDLINE, EMBASE and CochraneControlled Trails Register up to December
2011. The random controlled clinic trials about SSRIs and TCAs in treatment of
Parkinsonian depression were collected. Statistical analysis was completed using
Review Manager, version 5.0. Five clinic controlled trials were identified for
this meta-analysis. There was no significant statistical difference in the
response rate of treatment [RR 0.95, 95%CI (0.78, 1.16)] and Hamilton depression
score [RR -2.54, 95%CI (-5.35, 0.26)] between two groups. In term of
complications, no statistical difference was observed in the insomnia rate
between two groups [RR 0.82, 95%CI (0.24, 2.84)]. Moreover, the incidence rate of
xerostomia [RR 0.21, 95%CI (0.07, 0.65)] and constipation [RR 0.12, 95%CI(0.02,
0.63)] was lower in SSRIs group rather than those in TCAs group. In general,
SSRIs and TCAs have comparable efficacy and equal acceptability in treatment of
Parkinson's disease-induced depression. However, SSRIs are superior to TCAs in
the terms of xerostomia and constipation.
PMID- 25587310
TI - Effect of a Combination of Omeprazole Plus Sustained Release Baclofen Versus
Omeprazole Alone on Symptoms of Patients with Gastroesophageal Reflux Disease
(GERD).
AB - Previous studies have reported the efficacy of baclofen in the treatment of
Gastroesophageal Reflux Diseases (GERD). The objective of present study is to
evaluate the effect of co-administration of omeprazole 20 mg/d plus sustained
Release baclofen (SR baclofen) vs. omeprazole 20 mg/d plus placebo on alleviation
of symptoms in patients with a diagnosis of GERD. A prospective, double blind,
placebo controlled trial included 60 patients with diagnosis of GERD have been
done. Patients were randomly selected to receive either SR baclofen or a placebo
in addition to omeprazole 20 mg/d for a period of 2 weeks. Patients were
questioned regarding heartburn, regurgitation, chest pain and hoarseness at the
base line and after 2 weeks. All patients tolerated the medications and no
patients failed to complete the study due to adverse drug reactions. A total of
53 patients completed the study, 25 in SR baclofen and 28 in placebo group. After
2 weeks, 1 patient (4%) in SR baclofen group reported heartburn and
regurgitation. However 13(46.4%) and 15 (53.6%) of patients in the placebo group
had heartburn and regurgitation respectively. The analysis of the data shows that
there is a significant difference between the two groups in heartburn and
regurgitation (p < 0.0001, p < 0.0001 respectively). Statistical analysis
revealed a significant difference in two groups regarding total GERD score (p
<0.0001). The results of the present study suggest that a combination of SR
baclofen and omeprazole may be a more effective treatment for heartburn and
regurgitation than omeprazole alone.
PMID- 25587311
TI - The effects of bupropion on negative symptoms in schizophrenia.
AB - This study was designed determine the efficacy of bupropion versus placebo in
subjects with negative symptoms of schizophrenia. A convenience sample of 40
patients of both genders aged 18-60 years who were living in psychiatric care
centers were randomly treated with bupropion (started with 75 mg twice a day;
increased to 100 mg thrice daily) or placebo. The diagnosis of schizophrenia was
confirmed by a psychiatrist based on Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. Before and after
the intervention, severity of negative symptoms was determined using a reliable
and valid Persian version of Scales for the Assessment of Negative Symptoms
(SANS). Comparison of post-treatment total SANS score and subscale scores between
bupropion treated patients and placebo group demonstrated no significant
difference. Moreover, comparison of pre- treatment and post-treatment total SANS
score and subscales within 2 groups revealed that nor bupropion neither placebo
improved the severity of negative symptoms significantly. Present study
demonstrated that bupropion has no significant effect on SANS score of patients
with severe negative symptoms. However, further studies with larger sample size
are recommended to achieve more accurate results.
PMID- 25587312
TI - Magnesium Sulfate in Exacerbations of COPD in Patients Admitted to Internal
Medicine Ward.
AB - The purpose of this study was to examine the effect of intravenous magnesium
sulfate on patients with COPD exacerbation requiring hospitalization. In this
randomized clinical trial 30 patients with COPD exacerbation were studied.
Patients were randomly assigned to group A (case) who concurrent with standard
therapy received 2 g magnesium sulfate in normal saline infused in 20 minutes on
days one to three and group B (control) who received standard medications and
placebo. PEFR and FEV1 were measured by before, 45 minutes and third day of
entering the study. Vital signs HR, BP, RR, temperature and SpO2 were monitored
during hospitalization. 21 males and 9 females patients with mean age of 68 +/- 9
years, case 67 +/- 10 and control 70 +/- 8 were studied (15 patients in each arm
of study). The mean pretreatment FEV1 was 26% +/- 12, and 35% +/- 18 in case and
control groups respectively (P=0.137). FEV1 after 45 minutes in case group was
27% +/- 9 and control group 36% +/- 20 (p=0.122). FEV1 after 3 days of study was
32% +/- 17 in case and 41% +/- 22 in control groups (P=0.205). The mean
pretreatment PEFR was 126 +/- 76 l/min in case and 142 +/- 62 l/min in control
groups (P=0.46). Changes in PEFR were not significant 45 min (p=0.540) and 3 days
(p=0.733) of the administration of intravenous magnesium sulfate. Duration of
hospital stay between the two groups did not show any significant difference.
This study showed that administration of intravenous magnesium sulfate in
hospitalized patients with COPD exacerbation neither revealed any significant
bronchodilating effect nor reduced duration of hospital stay.
PMID- 25587313
TI - Elevated Vancomycin Trough Concentration: Increased Efficacy and/or Toxicity?
AB - Vancomycin susceptibility of methicillin-resistant Staphylococcus aureus has been
changed over time and its average minimum inhibitory concentration increased from
1.5 to 1.75 mg/L.A recently published guideline by the American Society of Health
Pharmacist recommended a daily dose of 15-20 mg/Kg every 8 to 12 hours of
vancomycin to achieve a trough concentration between 15-20 mg/L for treatment of
severe infections. Medical records of 69 patients from infectious ward of Imam
Khomeini hospital, with suspected or confirmed gram-positive infection who had at
least one trough level of vancomycin, were evaluated regarding vancomycin
therapeutic goal; efficacy and renal safety. Most of patients (60.6%) with severe
infections did not achieve the recommended vancomycin trough level during
treatment course. Time to normalization of the signs and symptoms of infection
did not correlate with the patients' serum vancomycin trough levels. At the end
of treatment course, there was no significant correlation between patients'
creatinine clearance and vancomycin trough levels (P=0.32). However,
patients'cratinine clearance showed a negatively significant correlation with
trough level of vancomycin (P=0.01). Vancomycin induced nephrotoxicity was
detected in 4.3% of the patients. These data showed that vancomycin trough level
may not necessarily assure treatment success, and also it would not essentially
predict the risk of vancomycin induced nephrotoxicity. However, more well
designed studies with larger sample size needed for better clinical and practical
judgment.
PMID- 25587314
TI - The Effect of Sumac (Rhus coriaria L.)Powder on Serum Glycemic Status, ApoB, ApoA
I and Total Antioxidant Capacity in Type 2 Diabetic Patients.
AB - Sumac (Rhus coriaria L.) is used as an herbal remedy in traditional medicine. The
aim of this study was to determine the effects of sumac (R. coriaria) on serum
glycemic status, apolipoprotein (apo) B, apoA-I and total antioxidant capacity
(TAC) in type 2 diabetic patients. This double blind randomized controlled
clinical trial was conducted on 41type 2 diabetic volunteers randomly assigned
into 3g/day sumac powder (n=22) or placebo (n=19) groups over 3 months. Blood
samples were collected before and after the intervention. Serum glucose and HbA1c
were measured using enzymatic and turbidimetric inhibition immunoassay methods,
respectively. ApoB, apoA-I and TAC were determined using turbidimetric
immunoassay and spectrophotometric methods, respectively. There were significant
decreases in serum glucose and HbA1c and also apoB levels at the end of study
compared with initial values (P< 0.0001, P= 0.002 and P< 0.0001,respectively).
Also, there was a significant difference in HbA1c and TAC levels between placebo
and sumac groups at the end of study (P< 0.05).In sumac group, there were
significant increase in apoA-I and TAC(P< 0.0001) compared with initial values.
The mean of differences of serum glucose, HbA1c, apoB, apoA-I, apoB/apoA-I ratio
and TAC between groups were significant (P< 0.05). In conclusion, these results
showed the favorite effect of sumac consumption on serum glycemic status, apoB,
apoA-I and TAC levels in in type 2 diabetic patients.
PMID- 25587315
TI - Effects of Inhalation of Lavender Essential Oil on Open-heart Surgery Pain.
AB - This study evaluated the effects of inhalation of lavender essential oil on the
pain of open-heart surgery. The main complaint of patients after open-heart
surgery is chest pain. Due to the side effects of opioids, it is important to use
a non-invasive way to effectively relieve pain including aromatherapy with
analgesics. This study was a clinical single-blind trial and was conducted on 40
patients who had open-heart surgery in the cardiac ICU of 2 Hospitals of Tehran
University of Medical Sciences, 2012. Criteria included: full consciousness,
spontaneous breathing ability and not using synthetic opioids within 2 hours
before extubation. After extubation, the patients were asked to mark the
intensity of their pain using the visual analogue scale. Then, a cotton swab
which was impregnated with 2 drops of lavender essential oil 2% was placed in
their oxygen mask, and they got breath for 10 minutes. 30 minutes after
aromatherapy, they were asked to re-mark their pain intensity. The level of
patient's pain before and after aroma therapy were compared. The pain mean level
before and after inhaling lavender essential oil was 5.60 (SD = 2.262) and 4.98
(SD = 2.293), respectively (p-value>0.05). Therefore, there is no significant
difference and the result of study proves that lavender essential oil inhalation
has no effect on reducing the pain of open-heart surgery.
PMID- 25587317
TI - The Effects of Extending of Co-planarity in a Series of Structurally Relative
Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties.
AB - In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA)
and a series of four structurally relative palladium(II) complexes
[Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB)
is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline
(dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These
studies have been investigated by utilizing the electronic absorption
spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and
gel filtration techniques. a-d complexes cooperatively bind and denature the DNA
at low concentrations. Their concentration at midpoint of transition, L1/2,
follows the order a >> b > c > d. Also the g, the number of binding sites per
1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments
for a-d complexes suggest efficient intercalative binding affinity to CT-DNA
giving the order: d > c > b > a. Several binding and thermodynamic parameters are
also described. The biological activity of these cationic and water soluble
palladium complexes were tested against chronic myelogenous leukemia cell line,
K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower
than cisplatin.
PMID- 25587318
TI - Effect of Dietary Ethanolic Extract of Lavandula officinalis on Serum Lipids
Profile in Rats.
AB - Antioxidants are effective in prevention and treatment of cardiovascular
diseases. Lavandula officinalis possesses antioxidant activity, therefore, in
this study; the effects of Lavandula officinalis extract were investigated on
serum lipids levels of rats. Experimental mature male Wistar rats were treated
with 100, 200 or 400 mg/Kg/day of lavender ethanolic extract or distilled water
for 25 days via gastric gavage (n=8 each group). At the end of 25(th) day, the
serum cholesterol, triglyceride, HDL, LDL and VLDL levels, as well as atherogenic
indices were determined in rats' serum. The ethanolic extract of lavender
decreased serum cholesterol, triglyceride, LDL and VLDL levels in 100 mg/Kg group
(p=0.03, p=0.001, p=0.001, p=0.001, respectively). Serum HDL level increased in
100 mg/Kg/day group (p=0.01). Lavender extract decreased LDL/HDL level at doses
of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). The TG/HDL levels
decreased in experimental groups with doses of 100 and 200 mg/Kg/day (p=0.001,
p=0.001, respectively). Lavandula officinalis extract exerts hypolipidemic effect
in rats and might be beneficial in hyperlipidemic patients.
PMID- 25587316
TI - Cytoprotective Effects of Hydrophilic and Lipophilic Extracts of Pistacia vera
against Oxidative Versus Carbonyl Stress in Rat Hepatocytes.
AB - This study was conducted to evaluate the cytoprotection of various extracts and
bioactive compounds found in Pistacia vera againts cytotoxicity, ROS formation,
lipid peroxidation, protein carbonylation, mitochondrial and lysosomal membrane
damages in cell toxicity models of diabetes related carbonyl (glyoxal) and
oxidative stress (hydroperoxide). Methanol, water and ethyl acetate were used to
prepare crude pistachios extracts, which were then used to screen for in-vitro
cytoprotection of freshly isolated rat hepatocytes against these toxins. The
order of protection by Pistacia vera extracts against both hydroperoxide induced
oxidative stress (ROS formation) and glyoxal induced protein carbonylation was:
pistachio methanolic extract >pistachio water extract, gallic acid, catechin>
alpha-tochoferol and pistachio ethyl acetate extract. Finally due to higher
protection achieved by methanolic extract even compared to sole pretreatment of
gallic acid, catechin or alpha-tochoferol, we suggest that cytoprotection depends
on the variety of polar and non-polar compounds found in methanolic extract, it
is likely that multiple cytoprotective mechanisms are acting against oxidative
and carbonyl induced cytotoxicity. To our knowledge, we are the first to report
the cytoprotective activity of Pistacia vera extracts against oxidative and
carbonyl stress seen in type 2 diabetes hepatocytes model.
PMID- 25587319
TI - Role of Fructose as a Potent Antiarrhythmic and Anti-infarct agent in Isolated
Rat Heart.
AB - In the current study, effects of acute short term administration of fructose on
cardiac arrhythmias and myocardial infarction size following ischemia/reperfusion
were investigated in isolated rat heart. The hearts were subjected to 30 min zero
flow global ischemia followed by 120 min reperfusion. In the control group, the
hearts were perfused by normal drug free Krebs-Henseleit (K/H) solution
throughout the experiments, while in the treated groups (2-4), they were perfused
with fructose containing K/H solution at 12, 24 and 48 mM concentrations during
stabilization and reperfusion time, respectively. Cardiac arrhythmias were
determined based on the Lambeth conventions and the infarct size was measured by
computerized planimetry. Myocardial infarction size was 22 +/- 3% in the control
group, however administration of fructose (12, 24 and 48 mM) reduced it to 15 +/-
3 (P<0.05), 7+/-2 (P<0.001) and 4 +/- 2% (P<0.001), respectively. A direct linear
correlation between fructose concentrations and infarction size reduction was
observed (R(2)=0.970). In addition, total number of ventricular ectopic beats
were significantly decreased by all used concentrations of fructose (P<0.01 for
group 2, P<0.001 for groups 3 and 4, respectively). Fructose also produced
significant decrease in the number, incidence and duration of ventricular
tachycardia compared to the control (P<0.05). The data showed that acute short
term administration of fructose can protect isolated rat heart against
ischemia/reperfusion injuries as reduction of infarct size and cardiac
arrhythmias. Alterations in glycogen storage and/or glycolytic efficiency may
probably involve in these cardioprotective effects. Also it is possible that
fructose can act as a pharmacological preconditioning agent.
PMID- 25587320
TI - Antihyperglycemic and Antihyperlipidemic Effects of Fruit Aqueous Extract of
Berberis integerrima Bge. in Streptozotocin-induced Diabetic Rats.
AB - Use of medicinal plants for attenuation of hyperglycemia and restoration of
lipids disorder to normal level is clinically very important. The aim of present
study was to evaluate the effects of Berberis integerrima Bge. fruit aqueous
extract (BIFAE) on blood glucose and lipid profile in streptozotocin (STZ) -
induced diabetic rats. The STZ-induced diabetic rats were treated by fruit
aqueous extract of Berberis integerrima Bge. at doses (250 and 500 mg/Kg bw) and
glibenclamide (0.6 mg/Kg bw) for 42 days by gavage. Blood glucose levels and body
weights of rats were measured on weeks 0, 2, 4 and 6. Total lipid levels were
determined in normal and STZ-induced diabetic rats after administration of the
BIFAE and glibenclamide for 42 days. STZ-induced diabetic rats showed a
significant (P<0.001) increases in the levels of blood glucose, triglycerides
(TG), total cholesterol (TC), low density lipoprotein LDL-cholesterol (LDL-C)
while body weight and high density lipoprotein HDL-cholesterolan (HDL-C) were
significantly(P<0.001) decreased compared to normal rats. Daily administration of
BIFAE did not possess the hypoglycemic and hypolipidaemic activity in STZ-
diabetic rats during 6-week treatment period. Results indicate the usage of BIFAE
in traditional medicine for the treatment of diabetes may need more
investigation.
PMID- 25587321
TI - Anethole, a Medicinal Plant Compound, Decreases the Production of Pro
Inflammatory TNF-alpha and IL-1beta in a Rat Model of LPS-Induced Periodontitis.
AB - Periodontitis (PD) is known to be one of most prevalent worldwide chronic
inflammatory diseases. There are several treatments including antibiotics for PD;
however, since drug resistance is an increasing problem, new drugs particularly
derived from plants with fewer side effects are required. The effects of trans
anethole on IL-1 beta and TNF-alpha level in a rat model of PD were investigated
and compared to ketoprofen. Eschericia coli lipopolysaccharide (LPS, 30 ug) was
injected bilaterally into the palatal gingiva (3 uL/site) between the upper first
and second molars every two days for 10 days in anesthetized rats. Administration
of either trans-anethole (10 or 50 mg/Kg, i.p.) or ketoprofen (10 mg/Kg, i.p.)
was started 20 minute before LPS injection and continued for 10 days. Then, IL
1beta and TNF-alpha levels were measured in blood samples by ELISA at day 0
(control) and at day 10. Anethole at both concentrations significantly suppressed
IL-1beta and TNF-alpha production when compared to LPS-treated rats. The
suppressive effects of anethole on LPS-induced pro-inflammatory cytokines were
almost similar as seen with ketoprofen. In conclusion, the present results
suggest that anethole may have a potent inhibitory effect on PD through
suppression of pro-inflammatory molecules; therefore it could be a novel
therapeutic strategy for PD.
PMID- 25587322
TI - Econazole Nitrate Induces Apoptosis in MCF-7 Cells via Mitochondrial and Caspase
Pathways.
AB - Econazole nitrate (EN), a synthetic compound, is now in use as a routine
antifungal drug. EN was shown to have antitumor effect, the tumor cell killing
mechanisms, however, remain unclear. In this research, the apoptosis-inducing
effect of EN on MCF-7 cells was investigated. The results showed that EN
inhibited the proliferation of MCF-7 cells in a time- and dose-dependent manner
by MTT method and colony forming assay. MCF-7 cells treated with EN showed
typical characteristics of apoptosis including the morphological changes and DNA
fragmentation. Meanwhile, the loss of mitochondrial membrane potential was showed
by flow cytometry. In addition, western blot analysis showed that EN resulted in
the decrease expression of procaspase-3, procaspase-9 and bcl-2. In conclusion,
these findings suggest that EN may be an effective way for treating human breast
cancer. The anti-tumor mechanisms of EN might involve mitochondrial and caspase
pathways.
PMID- 25587323
TI - Anti-tumor Activity of Ferulago angulata Boiss. Extract in Gastric Cancer Cell
Line via Induction of Apoptosis.
AB - Ferulago angulata Boiss. known in Iran as Chavir, has some bioactive compounds
having antioxidant activity. Because of its antioxidant activities, it sounded
Chavir extract can be a good candidate for finding chemopreventive agents having
inductive apoptosis properties on cancer cells. In this study, the cytotoxic
effects and proapoptotic activities of Chavir's leaf and flower extracts were
investigated on human adenocarcinoma gastric cell line (AGS). The ferric reducing
antioxidant power (FRAP) assay was used to determine antioxidant activity of the
extract. Cytotoxic effects of the extract were performed by trypan blue and
neutral red assays. For apoptosis detection, we used Annexin V staining, flow
cytometry and DNA fragmentation assays. The FRAP assay results showed that
antioxidant activity of leaf extract was higher than flower extract. Cytotoxicity
and apoptosis-inducing activity of flower and leaf extracts changed coordinately,
indicating the cytotoxicity of chavir extracts is due probably to induce
apoptosis. Our results revealed that the cytotoxic effects of F. angulate Boiss.
extracts on AGS cell line is close to some other plant extracts such as Rhus
verniciflua Stokes (RVS) and Scutellaria litwinowii. This is the first study on
cytotoxic and apoptosis-inducing effects of chavir leaf and flower extracts
against AGS cell line. The Further investigation can be identification of the
agent(s) by which these effects is observed.
PMID- 25587324
TI - Buckwheat Rutin Inhibits AngII-induced Cardiomyocyte Hypertrophy via Blockade of
CaN-dependent Signal Pathway.
AB - Buckwheat rutin has been found to be able to inhibit angiotensin II (AngII) -
induced hypertrophy in cultured neonatal rat cardiomyocytes, but the mechanism
remains uncertain. In this study, myocardial hypertrophy model was made by adding
AngII to the medium of cardiac myocytes of neonatal rats; meanwhile, different
concentrations of buckwheat rutin were applied to observe their effects.
Intracellular Ca(2+) level was detected by Hitachi - 850 fluorospectrophotometer,
calcineurin (CaN) activity was measured by colorimetric method, the expression of
CaN protein was observed with immunocytochemistry, and the proto - oncogene c -
fos mRNA expression was assessed with reverse transcription polymerase chain
reaction (RT - PCR). Compared with control group, AngII could greatly stimulate
the increase of intracellular Ca(2+) level, the activities and protein expression
of cardiomyocytes CaN, and the expression of proto - oncogene c - fos mRNA in
cultured neonatal rat cardiomyocytes, which could be effectively decreased by
buckwheat rutin. Our results demonstrated that buckwheat rutin exhibited
inhibitory effect on AngII - induced hypertrophy in cultured neonatal rat
cardiomyocytes via Ca(2+) antagonism action thus block the CaN - dependent signal
pathway.
PMID- 25587325
TI - Evaluation of a Novel Herbal Immunomodulator Drug (IMOD) in Treatment of
Experimental Canine Visceral leishmaniasis.
AB - Toxicity and drug resistance against pentavalent antimonials, medications of
choice in treatment of leishmaniasis for more than 5 decades, have become
important subjects globally. This study was a randomized, open labeled trial that
was designed to determine efficacy and safety of IMOD as a novel herbal
immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty
healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes
and randomly divided to 5 groups with four animals for each included on: I:
negative control (non-infected) II: Glucantime(r) III: Glucantime(r) plus IMOD
(immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical
examination, hematological, biochemical, serological, parasitological,
pathological and imaging evaluations were performed pre-/post- interventions
every month for 3 months. Comparing with control groups (I&V), immune
chemotherapy group (Glucantime(r) plus IMOD) showed significantly higher efficacy
in resolving the clinical signs and hematobiochemistry factors. Based on our
results, using IMOD in combination with meglumine antimoniate (Glucantime(r)) has
significantly improved CVL than the latter drug alone. So, it seems this new
herbal medicine is useful as adjuvant therapy for canine visceral leishmaniasis.
PMID- 25587326
TI - Protective Effects of Lindera coreana on UVB-induced Oxidative Stress in Human
HaCaT Keratinocytes.
AB - The present study was designed to investigate the protective effect of ethanol
extracts from Lindera coreana leaves (LCE) on UVB-induced oxidative stress in
HaCaT keratinocytes. The HaCaT cells were pretreated with LCE for 24 h and then
exposed to UVB (20 mJ/cm(2)) for 2 h. UVB significantly decreased the cell
viability (p<0.05). LCE did not exhibit significantly cytotoxic effects and
increased the viability of the HaCaT cells in a concentration-dependent manner.
To further investigate the protective effects of LCE on UVB-induced oxidative
stress in HaCaT cells, the cellular levels of reactive oxygen species (ROS),
lipid peroxidation and endogenous antioxidant enzymes, including catalase (CAT),
superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were analyzed.
LCE decreased the intracellular levels of ROS and lipid peroxidation and
increased the activity of antioxidant enzymes. These results suggest that LCE
exerted cytoprotective activity against UVB-induced oxidative stress in HaCaT
cells through the inhibition of lipid peroxidation, reduction of ROS levels and
stimulation of antioxidant enzymes activities. In addition, LCE also decreased
the TNF-alpha, IL-1beta and IL-6 levels in UVB-irradiated HaCaT cells.
PMID- 25587328
TI - Mcl-1 is up regulated by prenylated coumarin, umbelliprenin in jurkat cells.
AB - Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the
western world and exists as subtypes with very different clinical courses.
Myeloid cell leukemia 1 (Mcl-1) is one member of Bcl-2 family proteins that has
been shown to be expressed in various tissues and malignant cells, including CLL,
where its expression is significantly associated with a failure to achieve
complete remission following cytotoxic therapy. Induction of apoptosis by
prenylated coumarin, umbelliprenin, in Jurkat cells was previously shown. We
examined whether umbelliprenin can down-regulate Mcl-1 gene and protein in Jurkat
cells. In this regard cells were incubated by umbelliprenin, and then down-
regulation of Mcl-1 gene was studied by Real Time PCR method. Moreover, down
regulation of Mcl-1 protein was studied by western blot analysis. We showed that,
expression of Mcl-1 mRNA was increased from 1 hour to 3 hours incubation, but
this increase has a scale down pattern. Moreover umbelliprenin could inhibit Mcl
1 protein. In conclusion umbelliprenin treatment modulates Mcl-1 expression at
both the transcriptional and posttranslational levels.
PMID- 25587327
TI - Use of artificial neural networks to examine parameters affecting the
immobilization of streptokinase in chitosan.
AB - Streptokinase is a potent fibrinolytic agent which is widely used in treatment of
deep vein thrombosis (DVT), pulmonary embolism (PE) and acute myocardial
infarction (MI). Major limitation of this enzyme is its short biological half
life in the blood stream. Our previous report showed that complexing
streptokinase with chitosan could be a solution to overcome this limitation. The
aim of this research was to establish an artificial neural networks (ANNs) model
for identifying main factors influencing the loading efficiency of streptokinase,
as an essential parameter determining efficacy of the enzyme. Three variables,
namely, chitosan concentration, buffer pH and enzyme concentration were
considered as input values and the loading efficiency was used as output.
Subsequently, the experimental data were modeled and the model was validated
against a set of unseen data. The developed model indicated chitosan
concentration as probably the most important factor, having reverse effect on the
loading efficiency.
PMID- 25587329
TI - Celecoxib Up Regulates the Expression of Drug Efflux Transporter ABCG2 in Breast
Cancer Cell Lines.
AB - Elevated expression of the drug efflux transporter ABCG2 seems to correlate with
multidrug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been
shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify
whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we
investigated whether the expression of ABCG2 in breast cancer cell lines, could
be modulated by celecoxib. The expression of the multidrug resistant gene (ABCG2)
at mRNA and protein level was detected by real-time quantitative reverse
transcription-polymerase chain reaction and flow cytometry analysis,
respectively. Among three human breast cancer cell lines ABCG2 and COX-2 were
highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2
inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7
MX cells, which was accompanied by increased ABCG2 protein expression. While
celecoxib was able to block the 12-O-tetradecanoylphorbol-13-acetate (TPA)
mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the
expression of ABCG2 up to 4.27 times to the control level at mRNA level and with
less intensity at protein level. Our findings provide evidence that celecoxib up
regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2
is not involved in chemosensitizing effects of celecoxib.
PMID- 25587330
TI - Structural characterisation of a polysaccharide from radix ranunculus ternati.
AB - A water soluble polysaccharide, HB-1, with a molecular weight of 23,930, was
isolated from radix Ranunculi ternati. by hot water extraction, ethanol
precipitation, deproteination,ultrafiltration and gel-filtration column
chromatography. Its sugar composition was determined by GLC as Glc, Ara, and Gal
in a molar ration of 16.071: 2.722: 1. And the absolute configuration of Glc was
identified as D. Smith degradation and methylation reaction showed the proportion
of -(1)Glc (A) was about 16%, -(1)Glc(4)- (B) about 62%, (C) about 14%, and
(1)Gal(6)- (D) about 8%. The repetitive unit was likely composed of 3 As, 3 Cs,
13 Bs and 1 D. Together with the average molecular weight, it was predictable
that HB-1 consisted of about seven of the repetitive unit. The inhibition
activity of HB-1 on human glioma cell line SF188 was also measured, only to find
it inactive.
PMID- 25587331
TI - Antioxidant, Metal Chelating, Anti-glucosidase Activities and Phytochemical
Analysis of Selected Tropical Medicinal Plants.
AB - The purpose of this investigation was to determine the antioxidant potentials and
anti-glucosidase activities of six tropical medicinal plants. The levels of
phenolic constituents in these medicinal plants were also quantified and
compared. Antioxidation potentials were determined colorimetrically for
scavenging activities against DPPH and NO radicals. Metal chelating assay was
based on the measurement of iron-ferrozine absorbance at 562 nm. Anti-diabetic
potentials were measured by using alpha-glucosidase as target enzyme. Medicinal
plants' total phenolic, total flavonoid and hydroxycinnamic acid contents were
determined using spectrophotometric methods, by comparison to standard plots
prepared using gallic acid, quercetin and caffeic acid standards, respectively.
Radical scavenging and metal chelating activities were detected in all medicinal
plants, in concentration-dependent manners. Among the six plants tested, C.
nutans, C. formosana and H. diffusa were found to possess alpha-glucosidase
inhibitory activities. Spectrophotometric analysis indicated that the total
phenolic, total flavonoid and hydroxycinnamic acid contents ranged from 12.13
21.39 mg GAE per g of dry sample, 1.83-9.86 mg QE per g of dry sample, and 0.91
2.74 mg CAE per g of dry sample, respectively. Our results suggested that C.
nutans and C. formosana could potentially be used for the isolation of potent
antioxidants and anti-diabetic compounds. To the best of our knowledge, this
study represents the first time that C. nutans (Acanthaceae family) was reported
in literature with glucosidase inhibition activity.
PMID- 25587332
TI - Chemical Composition and Antibacterial Activity of Essential Oil of Cosmos
bipinnatus Cav. Leaves from South Africa.
AB - The chemical composition of essential oils isolated from the leaves of Cosmos
bipinnatus and its antibacterial activity were analyzed by GC-MS and microbroth
dilution assay respectively. The essential oil extracted from this plant was
predominantly composed of monoterpenes (69.62%) and sesquiterpenes (22.73%). The
antibacterial assay showed that the oil had significant inhibitory effects
against both Gram-negative and Gram-positive bacteria isolates. The MIC of Gram
positive strains ranged between 0.16 and 0.31 mg/mL while those of Gram-negative
bacteria ranged between 0.31 and 0.63 mg/mL. The Gram-positive bacteria were more
susceptible to the essential oil than the Gram-negative bacteria. Most of the
major components of this oil in other plants have been reported for antimicrobial
activities. The antibacterial activity can be attributed to effects of the
combination of several components of the oil. The results indicate that the C.
bipinnatus might be exploited as natural antibacterial agent and have application
in the treatment of several infectious diseases caused by these bacteria. Since
this species is endemic to the eastern Free State, the plant could be collected
during its bloom and used efficiently in the management of bacterial infections
in South Africa.
PMID- 25587333
TI - Procerenone: a Fatty Acid Triterpenoid from the Fruit Pericarp of Omphalocarpum
procerum (Sapotaceae).
AB - Phytochemical investigation of a dichloromethane-methanol (1:1) extract of the
fruit pericarp of Omphalocarpum procerum which exhibited antiplasmodial activity
during preliminary screening led to the isolation of the new fatty ester
triterpenoid 3beta-hexadecanoyloxy-28-hydroxyolean-12-en-11-one (1), together
with five known compounds 2-6. The structure of the new compound as well as those
of the known compounds was established by means of spectroscopic methods and by
comparison with previously reported data. Compounds 1- 4 were evaluated in-vitro
for their cytotoxicity against L6 cell lines and antiprotozoal activities against
Plasmodium falciparum, Leishmania donovani, Trypanosoma brucei rhodesiense and
Trypanosoma cruzi (species responsible for human malaria, visceral leishmaniasis,
African trypanosomiasis and Chagas disease, respectively). The tested compounds
showed weak to moderate antiprotozoal activity and, no significant effect was
detected regarding their cytotoxic potency.
PMID- 25587334
TI - Improvement of Lidocaine Local Anesthetic Action Using Lallemantia royleana Seed
Mucilage as an Excipient.
AB - Lallemantia royleana (Balangu) is a well known Iranian medicinal plant that its
seed mucilage has many applications in modern pharmacology. Plant mucilage
traditionally was used as a gel supplement, and natural matrix for sustained
release of drugs. But it seems that these compounds are not a simple additive and
also have many undiscovered pharmacological properties. In this research, the
anesthetic action of gel prepared from Balangu mucilage alone and its mixture
with lidocaine hydrochloride are compared with the effect of commercial 2%
lidocaine gel by rat tail flick test. Mucilage of Balangu seed alone showed
analgesic effect. Duration and potency of anesthesia induced by gel containing
mucilage alone (0.01 g/mL) were identical to commercial 2% lidocaine gel. But,
local anesthetic potency and duration of gel made from 2% lidocaine-mucilage gel
mixture was significantly higher than commercial 2% lidocaine gel. The gel
prepared from mucilage causes a good analgesia with unknown mechanism. Besides,
mixture of Balangu mucilage prepared gel with lidocaine improves lidocaine
anesthesia. The increase in potency of lidocaine action results from mucilage
dermal penetration enhancing effects; and longer anesthetic duration of this
mixture are related to the capability of mucilage based gel for sustained drug
release.
PMID- 25587335
TI - Determination of some B Vitamins in Sour Cherry Juice Using Dispersive Liquid
liquid Microextraction Followed by High-performance Liquid Chromatography.
AB - Dispersive liquid-liquid microextraction method (DLLME) combined with high
performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to
determine thiamine (B1), nicotinamide (B3) and pyridoxine (B6) in sour cherry
juice. This method was rapid, simple and sensitive. Separation was accomplished
using a C18 column. The optimum chromatographic conditions were found to be:
mobile phase consisted of 8% methanol and 92% aqueous phase (1% (V/V) acetic acid
water solution); flow rate, 0.7 mL/min; detection wavelength, 260 nm and pH, 3.3.
The extraction efficiency of thiamine, nicotinamide and pyridoxine was influenced
by factors such as: additional salt effect, the kind and volume of disperser and
extraction solvents. In this research, the limit of detection (LOD) and
quantification (LOQ) were 0.9 and 3 ng/mL for thiamine, 1.5 and 5 ng/mL for
nicotinamide, 0.9 and 3 ng/mL for pyridoxine. The relative standard deviations
(RSDs) were less than 2.87% (n=3). An appropriate linear behavior over the
observed concentration range was obtained with the value of R2>0.996 for the
target vitamins. This method was successfully applied to the sour cherry juice
samples. Sour cherry var. Gise (Prunus cerasus var. Gise), which was used in this
research, was a local variety of the sour cherry with large stone, double
flowers, double fruits, dark red skin and dark red juice. This variety was
identified in high altitude areas of Isfahan province after five years of study,
since 2005, by Agricultural and Natural Resources Research Center of Isfahan.
PMID- 25587336
TI - In-vitro Callus Induction and Rosmarinic Acid Quantification in Callus Culture of
Satureja khuzistanica Jamzad (Lamiaceae).
AB - In the present study, an efficient protocol has been developed for callus
induction and production of RA in callus culture of Satureja khuzistanica for the
first time. In-vitro callus induction was achieved from young shoot tip explants
cultured on MS and B5 media supplemented with different concentrations of IBA
(0.1, 1.0, 2.0 and 5.0 mgL(-1)) solely or in combination with cytokinins BAP and
KIN (1.0, 2.0 and 5.0 mgL(-1)). B5 medium supplemented with 1.0 mgL(-1) IBA plus
5.0 mgL(-1) BAP and MS medium fortified with 2.0 mgL(-1) IBA and 2.0 mgL(-1) BAP
were the most favorable media for callus formation with the highest induction
rate (96%). Maximum growth index (2.89 and 2.63) and maximum callus biomass (2.34
and 2.33 g fresh weight) were obtained from the callus cultured on B5 medium
supplemented with 1.0 mgL(-1) IBA plus 5.0 mgL(-1) BAP and MS medium fortified
with 1.0 mgL(-1) IBA plus 1.0 mgL(-1) KIN, respectively. Determination and
quantification of RA in cultured calli were performed by HPLC UV/MS analysis.
Calli induced from the plant and maintained on supplements of IBA and BAP in the
absence of light produced RA 7.5% based on dry weight (DW). No differentiation
was observed in any callus during the course of this study.
PMID- 25587337
TI - Knowledge, Attitude and Practice of Pharmacists regarding Dietary Supplements : A
Community Pharmacy- based survey in Tehran.
AB - The present study aimed to evaluate pharmacy practice regarding dietary
supplements in Tehran (I.R. Iran). So, the factors affecting on pharmacists'
practice including their knowledge, attitude, and some underlying factors were
evaluated. This is an observational knowledge; attitude and practice (KAP) study.
The unit of analysis include pharmacies practice located in Tehran. The data was
collected in 2013 via an anonymous, self-administered; postal questionnaire
consisted of demographic information, knowledge (subjective and objective
questions), attitude, and practice evaluation part. Descriptive and inferential
statistics were performed using SPSS. This study showed that although the
knowledge has a significant effect on attitude and practice, the attention should
be paid on other underlying factors such as experience, pharmacy ownership
situation and academic degree which might have positive impact on pharmacists'
practice. According to this study, although many underlying factors such as
experience, university and pharmacy ownership have impact on pharmacy practice
regarding dietary supplements, the most attention should paid to knowledge as the
main factor and more attention should be paid to training on dietary supplement
could be recommended.
PMID- 25587338
TI - Effects of Oils and Essential Oils from Seeds of Zanthoxylum schinifolium against
Foodborne Viral Surrogates.
AB - Human noroviruses are the most frequent cause of foodborne viral disease and are
responsible for the vast majority of nonbacterial gastroenteritis. However, no
specific therapies are available for the efficient control or prevention of
foodborne viral disease. Here, we determined the antiviral activities of oils
from seeds of Zanthoxylum schinifolium (ZSO) against foodborne viral surrogates,
feline calicivirus-F9 (FCV-F9), and murine norovirus-1 (MNV-1), using plaque
assay. Time-of-addition experiments were designed to determine the antiviral
mechanism of action of ZSO against the surrogates. Maximal antiviral effect was
observed upon pretreatment of FCV-F9 or MNV-1 with ZSO, which comprised oleic
acid, linoleic acid, palmitic acid, and linolenic acid as the major fatty acids.
FCV-F9 was more sensitive to ZSO than MNV-1, and the 50% effective concentration
of ZSO against pretreatment of FCV-F9 was 0.0007%. However, essential oils from
Z. schinifolium (ZSE), which comprised 42% estragole, showed no inhibitory
effects against FCV-F9 and MNV-1. These results suggest that the inhibitory
activities of ZSO were exerted by direct interaction of FCV-F9 or MNV-1 virion
with ZSO, which may be a food material candidate for control of foodborne viral
disease.
PMID- 25587339
TI - Chemical Assessment and Antimicrobial and Antioxidant Activities of Endophytic
Fungi Extracts Isolated from Costus spiralis (Jacq.) Roscoe (Costaceae).
AB - Costus spiralis (Costaceae) is a species native to the Amazon region and is used
in traditional medicine. The endophytic fungi used in this study were obtained
from leaves of this plant. 13 strains were selected to obtain hydroethanolic
extracts and were submitted to hydroalcoholic extraction and evaluated for
antioxidant activity by DPPH (2,2-difenil-1-picrilhidrazil) and FRAP (ferric
reducing antioxidant power), and all of the fungi had positive results. The
antimicrobial action of crude extracts had a good range of activities. All
extracts had inhibitory activities against the yeasts of Candida albicans and C.
parapsilosis, with 125 to 500 MUg/mL MIC. Eight extracts had antimicrobial
activities against Bacillus subtilis (MIC from 62.4 to 125 MUg/mL), 5 against
Pseudomonas aeruginosa (MIC from 125 to 500 MUg/mL), 2 against Salmonella
enterica (MIC from 125 to 62.5 MUg/mL), and 2 against Enterococcus faecalis (MIC
from 500 to 125 MUg/mL). The presence of secondary metabolites, including
coumarins, was observed during chemical evaluation by thin layer chromatography.
Total phenol content was estimated, and a strong positive correlation to
antioxidant activity was observed, according to its Pearson coefficient. This is
the first report of the bioactive potential of endophytic fungi isolated from the
Costaceae family in Brazilian ecosystems.
PMID- 25587340
TI - Shenfu injection for intradialytic hypotension: a systematic review and meta
analysis.
AB - Objective. To evaluate the effectiveness and safety of Shenfu injection (SFI) for
intradialytic hypotension (IDH). Methods. A systematic review of data sources
published as of April 2014 was conducted. These included the Cochrane Central
Register of Controlled Trials (2014 issue 4), Pubmed, Embase, CBM, CNKI, VIP, and
Wangfang Data. Randomized controlled trials (RCTs) involving SFI for treatment
and prevention of IDH were identified. Two researchers independently selected
articles, extracted data, assessed quality, and cross checked the results. Revman
5.2 was used to analyze the results. Results. Eight RCTs were included. The meta
analysis indicated that compared with conventional therapies alone, SFI could
elevate systolic blood pressure (SBP), increase the clinical effective rate,
decrease the incidence of hypotension, increase serum albumin (ALB) levels, and
reduce C-reactive protein (CRP) levels without serious adverse effects. GRADE
Quality of Evidence. the quality of SBP, the effective rate, ALB, and CRP were
low, and hypotension incidence and DBP were very low. Conclusions. SFI is more
effective than conventional therapies for prevention and treatment of IDH.
However, a clinical recommendation is not warranted due to the small number of
studies included and low methodology quality. Multi-center and high-quality RCTs
with large sample sizes are needed to provide stronger evidence.
PMID- 25587341
TI - Use of angong niuhuang in treating central nervous system diseases and related
research.
AB - In Chinese medicine-based therapeutics, Angong Niuhuang pill (ANP) is one of the
three most effective formulas for febrile diseases, and it is also used to treat
other diseases. This paper reviews current knowledge regarding the clinical and
pharmacological effects of ANP for treating different central nervous system
(CNS) diseases to confirm its validity and efficacy. These diseases are like
centric fever, coma, stroke, and viral encephalitis. This review reveals that
various diseases could be treated using the same agent, which is one of the most
important principles of traditional Chinese medicine (TCM). According to the
"Same Treatment for Different Diseases" principle, ANP might be efficacious in
other CNS diseases.
PMID- 25587342
TI - Antidepressant-like effects of cordycepin in a mice model of chronic
unpredictable mild stress.
AB - Cordycepin (3'-deoxyadenosine), a major bioactive component isolated from
Cordyceps militaris, has multiple pharmacological activities. This study is
attempted to investigate whether cordycepin (COR) possesses beneficial effects on
chronic unpredictable mild stress- (CUMS-) induced behavioral deficits
(depression-like behaviors) and explore the possible mechanisms. ICR mice were
subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR
and fluoxetine (FLU, positive control drug) were administered for 21 consecutive
days at the last three weeks of CUMS procedure. The classical behavioral tests,
open field test (OFT), sucrose preference test (SPT), tail suspension test (TST),
and forced swimming test (FST), were applied to evaluate the antidepressant
effects of COR. Then the serotonin (5-HT) and noradrenaline (NE) concentrations
in hippocampal were evaluated by HPLC; tumor necrosis factor-alpha (TNF-alpha)
and interleukin-6 (IL-6) in hippocampal were evaluated, and the proteins of TNF
alpha, IL-6, NF-kappaBP65 5-HT2A receptor (5-HT2AR), and brain-derived
neurotrophic factor (BDNF) in hippocampal were evaluated by Western blot. Our
results indicated that 6 weeks of CUMS exposure induced significant depression
like behavior, with low 5-HT and NE levels, high TNF-alpha and IL-6 in brain and
high hippocampal TNF-alpha, IL-6, P-NF-kappaBP65, and 5-HT2AR levels, and low
BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg) treatments reversed
the behavioral deficiency induced by CUMS exposure, treatment with COR normalized
the change of TNF-alpha, IL-6, 5-HT, and NE levels, which demonstrated that COR
could partially restore CUMS-induced 5-HT receptor impairments and inflammation.
Besides, hippocampal BDNF expressions were also upregulated after COR treatments.
In conclusion, COR remarkably improved depression-like behavior in CUMS mice and
its antidepressant activity is mediated, at least in part, by the upregulating
BDNF and downregulating 5-HT2AR levels and inflammation in hippocampus.
PMID- 25587343
TI - Coptis chinensis and Myrobalan (Terminalia chebula) Can Synergistically Inhibit
Inflammatory Response In Vitro and In Vivo.
AB - Objectives. To investigate the anti-inflammatory effect of Coptis chinensis plus
myrobalan (CM) in vitro and in vivo. Methods. The inflammation in mouse
peritoneal macrophages was induced by lipopolysaccharide (LPS). Animal models
were established by using ear swelling and paw edema of mouse induced by xylene
and formaldehyde, respectively. In vitro, cytotoxicity, the phagocytosis of
macrophages, the levels of nitric oxide (NO), induced nitric oxide synthase
(iNOS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in cell
supernatant were detected. In vivo, swelling rate and edema inhibitory rate of
ear and paw were observed using CM-treated mice. Results. At 150-18.75 MUg.mL(
1), CM had no cytotoxicity and could significantly promote the growth and the
phagocytosis of macrophages and inhibit the overproduction of NO, iNOS, TNF
alpha, and IL-6 in macrophages induced by LPS. In vivo, pretreatment with CM, the
ear swelling, and paw edema of mice could be significantly inhibited in a dose
dependent manner, and the antiedema effect of CM at high dose was better than
dexamethasone. Conclusion. Our results demonstrated that Coptis chinensis and
myrobalan possessed synergistically anti-inflammatory activities in vitro and in
vivo, which indicated that CM had therapeutic potential for the prevention and
treatment of inflammation-mediated diseases.
PMID- 25587345
TI - Improving research on the efficacy, effectiveness, and harms of traditional
chinese medicine.
PMID- 25587344
TI - The effect of massage therapy on autonomic activity in critically ill children.
AB - Objectives. Our main objective was to describe the effect of foot and hand (F&H)
massage on the autonomic nervous system (ANS) activity in children hospitalized
in a pediatric intensive care unit (PICU); the secondary objectives were to
assess the relationship between ANS function and the clinical severity and to
explore the effects of repeated massage sessions on the ANS. Methods. Design was
a descriptive experimental study. Intervention was single or six session(s) of
F&H massage. ANS function was assessed through the frequency-domain analysis of
heart rate variability. Main metrics included high and low frequency power (HF
and LF), HF + LF, and LF/HF ratio. Results. Eighteen children participated in the
study. A strong Spearman's correlation (rho = -0.77) was observed between HF + LF
and clinical severity. During massage, the parasympathetic activity (measured by
HF) increased significantly from baseline (P = 0.04) with a mean percentage
increase of 75% (95% CI: 20%~130%). LF increased by 56% (95% CI: 20%~92%) (P =
0.026). Repeated sessions were associated with a persistent effect on HF and LF
which peaked at the second session and remained stable thereafter. Conclusions.
HF + LF is positively correlated with clinical severity. F&H massage can improve
the ANS activity and the effect persists when repeated sessions are offered.
PMID- 25587346
TI - Phenolic Profiling and Evaluation of Contraceptive Effect of the Ethanolic
Extract of Salsola imbricata Forssk. in Male Albino Rats.
AB - Reported researches dealing with either composition or bioactivity of Salsola
imbricata are limited. This study was conducted aiming to investigate the
phenolic composition of the plant and evaluate its efficacy as male
contraceptive. Polyphenols, namely, phenolic acids and flavonoids, were
qualitatively and quantitatively analysed by RP-HPLC in the hydrolysed methanol
extract using two different wavelengths, 280 and 330 nm. The efficiency of
different solvents in extracting the plant phenolics was assessed via
spectrophotometric determination of the total phenolic and flavonoid contents.
Acute toxicity study was carried out on the ethanolic extract to ascertain its
safety prior to biological evaluation. The contraceptive effect was assessed, in
male rats, by oral administration of the extract at two doses (250 and 500 mg/kg
b. wt.), over a period of 65 days. HPLC analyses allowed the identification and
quantification of a total of 13 and 8 components in the hydrolysed-methanol
extract; the overall phenolic composition was dominated by quercitrin (12.692%)
followed by coumaric acid (4.251%). Prolonged oral administration of the
ethanolic extract caused slight reduction in the testis weight only. A
significant decrease in the sperm count was observed (P < 0.01) in the two
treated groups while significant decrease in the epididymal sperm motility was
only observed in the high dose group. Morphological abnormalities were observed
in sperms of treated animals. No distinct change in serum FSH, LH, and
testosterone concentration was recorded. The histopathological findings supported
to a high extent these results. The male contraceptive activity of Salsola
imbricata could be ascribed to its phenolic components, especially quercitrin.
PMID- 25587349
TI - Automatic segmentation of anatomical structures from CT scans of thorax for RTP.
AB - Modern radiotherapy techniques are vulnerable to delineation inaccuracies owing
to the steep dose gradient around the target. In this aspect, accurate contouring
comprises an indispensable part of optimal radiation treatment planning (RTP). We
suggest a fully automated method to segment the lungs, trachea/main bronchi, and
spinal canal accurately from computed tomography (CT) scans of patients with lung
cancer to use for RTP. For this purpose, we developed a new algorithm for
inclusion of excluded pathological areas into the segmented lungs and a modified
version of the fuzzy segmentation by morphological reconstruction for spinal
canal segmentation and implemented some image processing algorithms along with
them. To assess the accuracy, we performed two comparisons between the
automatically obtained results and the results obtained manually by an expert.
The average volume overlap ratio values range between 94.30 +/- 3.93% and 99.11
+/- 0.26% on the two different datasets. We obtained the average symmetric
surface distance values between the ranges of 0.28 +/- 0.21 mm and 0.89 +/- 0.32
mm by using the same datasets. Our method provides favorable results in the
segmentation of CT scans of patients with lung cancer and can avoid heavy
computational load and might offer expedited segmentation that can be used in
RTP.
PMID- 25587348
TI - Human atrial cell models to analyse haemodialysis-related effects on cardiac
electrophysiology: work in progress.
AB - During haemodialysis (HD) sessions, patients undergo alterations in the
extracellular environment, mostly concerning plasma electrolyte concentrations,
pH, and volume, together with a modification of sympathovagal balance. All these
changes affect cardiac electrophysiology, possibly leading to an increased
arrhythmic risk. Computational modeling may help to investigate the impact of HD
related changes on atrial electrophysiology. However, many different human atrial
action potential (AP) models are currently available, all validated only with the
standard electrolyte concentrations used in experiments. Therefore, they may
respond in different ways to the same environmental changes. After an overview on
how the computational approach has been used in the past to investigate the
effect of HD therapy on cardiac electrophysiology, the aim of this work has been
to assess the current state of the art in human atrial AP models, with respect to
the HD context. All the published human atrial AP models have been considered and
tested for electrolytes, volume changes, and different acetylcholine
concentrations. Most of them proved to be reliable for single modifications, but
all of them showed some drawbacks. Therefore, there is room for a new human
atrial AP model, hopefully able to physiologically reproduce all the HD-related
effects. At the moment, work is still in progress in this specific field.
PMID- 25587347
TI - A review of hepatoprotective plants used in saudi traditional medicine.
AB - Liver disease is one of the major causes of morbidity and mortality across the
world. According to WHO estimates, about 500 million people are living with
chronic hepatitis infections resulting in the death of over one million people
annually. Medicinal plants serve as a vital source of potentially useful new
compounds for the development of effective therapy to combat liver problems.
Moreover herbal products have the advantage of better affordability and
acceptability, better compatibility with the human body, and minimal side effects
and is easier to store. In this review attempt has been made to summarize the
scientific data published on hepatoprotective plants used in Saudi Arabian
traditional medicine. The information includes medicinal uses of the plants,
distribution in Saudi Arabia, ethnopharmacological profile, possible mechanism of
action, chemical constituents, and toxicity data. Comprehensive scientific
studies on safety and efficacy of these plants can revitalise the treatment of
liver diseases.
PMID- 25587350
TI - Mathematical analysis of non-Newtonian blood flow in stenosis narrow arteries.
AB - The flow of blood in narrow arteries with bell-shaped mild stenosis is
investigated that treats blood as non-Newtonian fluid by using the K-L model.
When skin friction and resistance of blood flow are normalized with respect to
non-Newtonian blood in normal artery, the results present the effect of stenosis
length. When skin friction and resistance of blood flow are normalized with
respect to Newtonian blood in stenosis artery, the results present the effect of
non-Newtonian blood. The effect of stenosis length and effect of non-Newtonian
fluid on skin friction are consistent with the Casson model in which the skin
friction increases with the increase of either stenosis length or the yield
stress but the skin friction decreases with the increase of plasma viscosity
coefficient. The effect of stenosis length and effect of non-Newtonian fluid on
resistance of blood flow are contradictory. The resistance of blood flow (when
normalized by non-Newtonian blood in normal artery) increases when either the
plasma viscosity coefficient or the yield stress increases, but it decreases with
the increase of stenosis length. The resistance of blood flow (when normalized by
Newtonian blood in stenosis artery) decreases when either the plasma viscosity
coefficient or the yield stress increases, but it decreases with the increase of
stenosis length.
PMID- 25587351
TI - Mathematical modeling of radiofrequency ablation for varicose veins.
AB - We present a three-dimensional mathematical model for the study of radiofrequency
ablation (RFA) with blood flow for varicose vein. The model designed to analyze
temperature distribution heated by radiofrequency energy and cooled by blood flow
includes a cylindrically symmetric blood vessel with a homogeneous vein wall. The
simulated blood velocity conditions are U = 0, 1, 2.5, 5, 10, 20, and 40 mm/s.
The lower the blood velocity, the higher the temperature in the vein wall and the
greater the tissue damage. The region that is influenced by temperature in the
case of the stagnant flow occupies approximately 28.5% of the whole geometry,
while the region that is influenced by temperature in the case of continuously
moving electrode against the flow direction is about 50%. The generated RF energy
induces a temperature rise of the blood in the lumen and leads to an occlusion of
the blood vessel. The result of the study demonstrated that higher blood velocity
led to smaller thermal region and lower ablation efficiency. Since the peak
temperature along the venous wall depends on the blood velocity and pullback
velocity, the temperature distribution in the model influences ablation
efficiency. The vein wall absorbs more energy in the low pullback velocity than
in the high one.
PMID- 25587352
TI - Important CT findings for prediction of severe appendicitis: involvement of
retroperitoneal space.
AB - BACKGROUND: Determination of the severity of appendicitis and differentiation
between complicated and uncomplicated appendicitis are clinically important.
Severe appendicitis frequently affects extraperitoneal spaces. We have
investigated CT findings of retroperitoneal space (RPS) in patients with
appendicitis to create a model for identification of complicated appendicitis.
METHOD: CT images of 223 patients with pathologically proven appendicitis were
reviewed. The total number of the segments in RPS where inflammatory changes were
located (RPS count) was obtained as well as appendiceal diameter,
appendicolithiasis, WBC count, and CRP level. Data were analyzed to identify
factors indicating complicated appendicitis. Univariate analysis was conducted to
identify statistically significant variables. A multivariable logistic regression
analysis was performed in order to find independent predictors of complicated
appendicitis. RESULTS: Patients with complicated appendicitis were more likely to
have higher RPS count (P < 0.001), appendicolithiasis (P = 0.002), higher CRP
level (P < 0.001), and greater appendix diameter (P < 0.001) than patients with
uncomplicated appendicitis. Statistical analysis showed RPS count was the most
helpful predictor of complicated appendicitis. CONCLUSION: Radiologists and
surgeons should be aware of the importance of CT findings in RPS when treating
patients with appendicitis. Complicated appendicitis can be predicted by RPS
count, diameter of the appendix, appendicolithiasis, and CRP level.
PMID- 25587354
TI - Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune
thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre.
AB - INTRODUCTION: The cyclooxygenases are a group of enzymes catalyzing the formation
of prostaglandins from arachidonic acid. Cyclooxygenase-1 (COX-1) is a
constitutive form, thought to be a "housekeeping gene", with constant levels of
expression in most tissues. COX-1 expression in the thyroid gland, except for
medullary thyroid carcinoma, has not been a subject of much interest.
Cyclooxygenase-2 (COX-2) can be expressed in response to various stimuli, such as
mitogens, hormones, cytokines, growth factors. The product of COX-2 activity has
been implicated in carcinogenesis. Recent studies have shown that up-regulation
of COX-2 is associated with numerous neoplasms. Hereby, we present a study
analysing COX-1 and COX-2 expression in papillary thyroid carcinoma (PTC),
Hashimoto thyroiditis (HT) and nontoxic nodular goitre (NNG) in fine needle
aspiration biopsy (FNAB) washouts and in postoperative tissue. MATERIAL AND
METHODS: Cytological specimens from 120 patients (105 females and 15 males) have
been studied, including patients with HT, PTC and NNG. Moreover, we have examined
postoperative tissue specimens from 51 patients with PTC and NNG. The methods of
molecular analysis have included extraction of total RNA from FNAB cytological
material and postoperative tissues, spectrophotometric assessment of the RNA
purity, cDNA synthesis in reverse transcription reaction and an analysis of genes
expression data by real-time PCR. RESULTS: The performed analysis has revealed
statistically significant higher expression level of the COX-2 gene in PTC group,
in comparison with HT and NNG groups (in both cytological and postoperative
material). In PTC patients, COX-2 gene expression levels in the material obtained
by FNAB were similar to those in the postoperative thyroid tissue. No
correlations between COX-2 gene expression level and TNM staging in PTC samples
have been observed. There were no correlations between COX-2 expression and anti
TPO antibodies level, or patient's sex or age in the studied groups. Also, there
were no correlations of COX-1 gene expression level among PTC, HT and NNG groups.
CONCLUSIONS: Our results suggest that COX-2 gene does not participate in the
mechanisms involved in molecular association of HT with PTC. However, in case of
PTC itself, it may play some role in neoplastic transformation.
PMID- 25587353
TI - Correlates of psychological functioning of homeless youth in Accra, Ghana: a
cross-sectional study.
AB - BACKGROUND: Research on homeless youth has shown that this population is at high
risk for various mental health problems. Previous studies conducted among
homeless young adults in Ghana have focused primarily on economic, social and
cultural causes of homelessness, their engagement in risky sexual behaviours and
the prevalence of STI including HIV/AIDS. We are therefore not fully informed of
the prevalence of psychological symptoms and their associated factors. The aim of
the study was to determine the association between psychological functioning and
social and health risk behaviours among a sample of homeless youth in Ghana.
METHODS: A cross-sectional survey of a convenience sample of 227 (122 male and
105 female) homeless youth was conducted in Ghana in 2013. An interviewer
administered questionnaire was used to collect data due to low level of literacy
among the study population. Pearson-moment correlation coefficient (r) and
multiple standard regression models were fitted to analyse the data. RESULTS:
Approximately 87% of the participants in this study exhibited moderate to severe
psychosocial symptoms. Specifically, emotional, conduct, hyperactivity and peer
relationship problems among the participants were 69%, 74%, 54% and 89%
respectively. Overall psychosocial functioning was predicted by stigma (self
stigma and experienced stigma), violent behaviours and suicidal ideation.
Substance use and perceived resilience were significantly associated with
emotional problems. CONCLUSION: There is a need for holistic interventions to
help improve the psychological and social functioning of homeless youth. Such
programmes should strengthen socio-emotional coping strategies in street youth as
well as address contextual risk factors such as stigma and discrimination by the
public.
PMID- 25587355
TI - HP1beta-dependent recruitment of UBF1 to irradiated chromatin occurs
simultaneously with CPDs.
AB - BACKGROUND: The repair of spontaneous and induced DNA lesions is a multistep
process. Depending on the type of injury, damaged DNA is recognized by many
proteins specifically involved in distinct DNA repair pathways. RESULTS: We
analyzed the DNA-damage response after ultraviolet A (UVA) and gamma irradiation
of mouse embryonic fibroblasts and focused on upstream binding factor 1 (UBF1), a
key protein in the regulation of ribosomal gene transcription. We found that
UBF1, but not nucleolar proteins RPA194, TCOF, or fibrillarin, was recruited to
UVA-irradiated chromatin concurrently with an increase in heterochromatin protein
1beta (HP1beta) level. Moreover, Forster Resonance Energy Transfer (FRET)
confirmed interaction between UBF1 and HP1beta that was dependent on a functional
chromo shadow domain of HP1beta. Thus, overexpression of HP1beta with a deleted
chromo shadow domain had a dominant-negative effect on UBF1 recruitment to UVA
damaged chromatin. Transcription factor UBF1 also interacted directly with DNA
inside the nucleolus but no interaction of UBF1 and DNA was confirmed outside the
nucleolus, where UBF1 recruitment to DNA lesions appeared simultaneously with
cyclobutane pyrimidine dimers; this occurrence was cell-cycle-independent.
CONCLUSIONS: We propose that the simultaneous presence and interaction of UBF1
and HP1beta at DNA lesions is activated by the presence of cyclobutane pyrimidine
dimers and mediated by the chromo shadow domain of HP1beta. This might have
functional significance for nucleotide excision repair.
PMID- 25587356
TI - Next generation sequencing analysis of nine Corynebacterium ulcerans isolates
reveals zoonotic transmission and a novel putative diphtheria toxin-encoding
pathogenicity island.
AB - BACKGROUND: Toxigenic Corynebacterium ulcerans can cause a diphtheria-like
illness in humans and have been found in domestic animals, which were suspected
to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic C.
ulcerans were reported to take over the leading role in causing diphtheria in the
last years in many industrialized countries. METHODS: To gain deeper insights
into the tox gene locus and to understand the transmission pathway in detail, we
analyzed nine isolates derived from human patients and their domestic animals
applying next generation sequencing and comparative genomics. RESULTS: We provide
molecular evidence for zoonotic transmission of C. ulcerans in four cases and
demonstrate the superior resolution of next generation sequencing compared to
multi-locus sequence typing for epidemiologic research. Additionally, we provide
evidence that the virulence of C. ulcerans can change rapidly by acquisition of
novel virulence genes. This mechanism is exemplified by an isolate which acquired
a prophage not present in the corresponding isolate from the domestic animal.
This prophage contains a putative novel virulence factor, which shares high
identity with the RhuM virulence factor from Salmonella enterica but which is
unknown in Corynebacteria so far. Furthermore, we identified a putative
pathogenicity island for C. ulcerans bearing a diphtheria toxin gene. CONCLUSION:
The novel putative diphtheria toxin pathogenicity island could provide a new and
alternative pathway for Corynebacteria to acquire a functional diphtheria toxin
encoding gene by horizontal gene transfer, distinct from the previously well
characterized phage infection model. The novel transmission pathway might explain
the unexpectedly high number of toxigenic C. ulcerans.
PMID- 25587357
TI - A multi-gene signature predicts outcome in patients with pancreatic ductal
adenocarcinoma.
AB - BACKGROUND: Improved usage of the repertoires of pancreatic ductal adenocarcinoma
(PDAC) profiles is crucially needed to guide the development of predictive and
prognostic tools that could inform the selection of treatment options. METHODS:
Using publicly available mRNA abundance datasets, we performed a large
retrospective meta-analysis on 466 PDAC patients to discover prognostic gene
signatures. These signatures were trained on two clinical cohorts (n = 70), and
validated on four independent clinical cohorts (n = 246). Further validation of
the identified gene signature was performed using quantitative real-time RT-PCR.
RESULTS: We identified 225 candidate prognostic genes. Using these, a 36-gene
signature was discovered and validated on fully independent clinical cohorts
(hazard ratio (HR) = 2.06, 95% confidence interval (CI) = 1.51 to 2.81, P = 3.62
* 10(-6), n = 246). This signature serves as a good alternative prognostic
stratification marker compared to tumour grade (HR = 2.05, 95% CI = 1.45 to 2.88,
P = 3.18 * 10(-5)) and tumour node metastasis (TNM) stage (HR = 1.13, 95% CI =
0.66 to 1.94, P = 0.67). Upon multivariate analysis with adjustment for TNM stage
and tumour grade, the 36-gene signature remained an independent prognostic
predictor of clinical outcome (HR = 2.21, 95% CI = 1.17 to 4.16, P = 0.01).
Univariate assessment revealed higher expression of ITGA5, SEMA3A, KIF4A, IL20RB,
SLC20A1, CDC45, PXN, SSX3 and TMEM26 was correlated with shorter survival while
B3GNT1, NOSTRIN and CADPS down-regulation was associated with poor outcome.
CONCLUSIONS: Our 36-gene classifier is able to prognosticate PDAC independent of
patient cohort and microarray platforms. Further work on the functional roles,
downstream events and interactions of the signature genes is likely to reveal
true molecular candidates for PDAC therapeutics.
PMID- 25587358
TI - Complex host genetics influence the microbiome in inflammatory bowel disease.
AB - BACKGROUND: Human genetics and host-associated microbial communities have been
associated independently with a wide range of chronic diseases. One of the
strongest associations in each case is inflammatory bowel disease (IBD), but
disease risk cannot be explained fully by either factor individually. Recent
findings point to interactions between host genetics and microbial exposures as
important contributors to disease risk in IBD. These include evidence of the
partial heritability of the gut microbiota and the conferral of gut mucosal
inflammation by microbiome transplant even when the dysbiosis was initially
genetically derived. Although there have been several tests for association of
individual genetic loci with bacterial taxa, there has been no direct comparison
of complex genome-microbiome associations in large cohorts of patients with an
immunity-related disease. METHODS: We obtained 16S ribosomal RNA (rRNA) gene
sequences from intestinal biopsies as well as host genotype via Immunochip in
three independent cohorts totaling 474 individuals. We tested for correlation
between relative abundance of bacterial taxa and number of minor alleles at known
IBD risk loci, including fine mapping of multiple risk alleles in the Nucleotide
binding oligomerization domain-containing protein 2 (NOD2) gene exon. We
identified host polymorphisms whose associations with bacterial taxa were
conserved across two or more cohorts, and we tested related genes for enrichment
of host functional pathways. RESULTS: We identified and confirmed in two cohorts
a significant association between NOD2 risk allele count and increased relative
abundance of Enterobacteriaceae, with directionality of the effect conserved in
the third cohort. Forty-eight additional IBD-related SNPs have directionality of
their associations with bacterial taxa significantly conserved across two or
three cohorts, implicating genes enriched for regulation of innate immune
response, the JAK-STAT cascade, and other immunity-related pathways. CONCLUSIONS:
These results suggest complex interactions between genetically altered host
functional pathways and the structure of the microbiome. Our findings demonstrate
the ability to uncover novel associations from paired genome-microbiome data, and
they suggest a complex link between host genetics and microbial dysbiosis in
subjects with IBD across independent cohorts.
PMID- 25587359
TI - Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for
cancer epigenomics.
AB - BACKGROUND: The use of tumour xenografts is a well-established research tool in
cancer genomics but has not yet been comprehensively evaluated for cancer
epigenomics. METHODS: In this study, we assessed the suitability of patient
derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K
Beadchips and MeDIP-seq. RESULTS: Controlled for confounding host (mouse)
sequences, comparison of primary PDXs and matching patient tumours in a rare
(osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the
assayed CpG sites undergo major (Deltabeta >= 0.51) methylation changes in a
cancer-specific manner as a result of the xenografting procedure. No significant
subsequent methylation changes were observed after a second round of xenografting
between primary and secondary PDXs. Based on computational simulation using
publically available methylation data, we additionally show that future studies
comparing two groups of PDXs should use 15 or more samples in each group to
minimise the impact of xenografting-associated changes in methylation on
comparison results. CONCLUSIONS: Our results from rare and common cancers
indicate that PDXs are a suitable discovery tool for cancer epigenomics and we
provide guidance on how to overcome the observed limitations.
PMID- 25587360
TI - Visceral adiposity index score indicated the severity of coronary heart disease
in Chinese adults.
AB - BACKGROUND: Visceral adiposity contributes to cardiometabolic risk, and visceral
adiposity index (VAI) had significant correlation with visceral adiposity. We
aimed to explore whether VAI was associated with cardiac structure and function
and assess the impact of the cut-off points of VAI defining visceral adipose
dysfunction (VAD) on the severity of coronary heart disease (CHD). METHODS: A
total of 95 patients with CHD were divided into Control (nondiabetic CHD
patients) and DM group (diabetic CHD patients). Then the two groups were
respectively divided into VAD absent and VAD groups. Clinical, echocardiographic
and coronary artery angiographic indexes were acquired to examine in relation to
VAI. RESULTS: A significant increasing trend among the four groups of patients
(Control + VAD absent, Control +VAD, DM + VAD absent and DM +VAD groups) were
observed for waist circumference (WC), body mass index (BMI), systolic blood
pressure (SBP), glucose, VAI and Gensini score (P<0.05 for all). The following
variables were associated with VAI: total cholesterol, nonesterified fatty acid,
Waist-Hip ratio and SBP. VAI was independently associated with Gensini score.
CONCLUSIONS: The extent of CHD was more severe in diabetes, and VAI as a simple
indicator of visceral adipose mass was strongly associated with the severity of
CHD. The cut-off points of VAI used for defining VAD were more useful in diabetic
CHD patients in identifying the severity of CHD.
PMID- 25587361
TI - Malformation and plastic surgery in childhood.
AB - Malformations of the head and neck show a huge variety of clinical symptoms with
functional and esthetic consequences. Often times its rehabilitation requires
multi-staged and multi-disciplinary procedures and concepts. These must consider
eating, speech, mimic expression, hearing and "esthetics" or at least
"normality". A survey of the most common head and neck malformations and their
treatment options are presented here.
PMID- 25587363
TI - Pediatric radiology in oto-rhino-laryngology.
AB - Head and neck diseases in children and adolescents present special diagnostic and
differential diagnostic challenges to ENT surgeons as well as to radiologists.
Both disciplines have to adapt the latest radiological and interventional
technologies to the needs of the pediatric patient in order to enable a minimally
invasive but successful diagnostic procedure. High quality sonography by an
experienced examiner is often the only imaging technique that is necessary in
children and adolescents. Radiographs are rarely indicated in pediatric head and
neck diseases. MRI, compared to computed tomography, has the advantage of absent
radiation exposure. Additionally, due to current advances in high resolution
techniques to delineate very small details or in visualization of different
tissue characteristics, it has become an integral part of pre- and postoperative
imaging. However, children should not be denied an adequate diagnostic procedure
even if it includes sedation, intervention, or exposure to radiation. The
responsible use of the diagnostic options under consideration of the therapeutic
consequences is essential. It is most likely to be successful in a close
interdisciplinary cooperation of pediatric ENT specialists and radiologists as
well as pediatric anesthesiologists in selected cases. Although benign diseases
predominate in children and adolescents, the possibility of malignancy has to be
considered in cases of atypical clinical and radiological findings. In many of
these young patients, the outcome and the probability of survival are directly
associated with the initial diagnostic and therapeutic strategies, which should
therefore be in accordance with the current guidelines of pediatric oncology
therapy studies. Our collection of clinical cases consists of representative
examples of useful diagnostic approaches in common and age specific diagnoses as
well as in rare diseases and malformations. It shows the significance of a
special knowledge in embryology and normal postnatal development for the
differentiation of normal variants from pathological findings. Only in
considering the results of imaging studies in their clinical context, it is
possible to succeed in detecting a syndrome behind a single malformation or
adequately caring for patients with a chronic disease such as cystic fibrosis.
PMID- 25587362
TI - Extracranial vascular malformations (hemangiomas and vascular malformations) in
children and adolescents - diagnosis, clinic, and therapy.
AB - The field of extracranial vascular anomalies is considered as special focus of
pediatric otolaryngology and it has shown a rapid development during the last
years. The reason for this interest is finally also due to the global acceptance
of the classification introduced by the ISSVA (International Society for the
Study of Vascular Anomalies). Hemangiomas are the most frequently observed
vascular tumors. Today the systemic propranolol therapy is mostly used for
therapy of hemangiomas requiring treatment. Increasingly, the topical application
of beta blocker is discussed while the benefit in the head and neck seems to be
limited. Vascular malformations are classified according to the morphology of the
affected part of the vascular system in arterial, venous, arterio-venous,
lymphatic, capillary, and combined vascular malformations. Conventional surgery,
sclerosing therapy, and laser treatment are invasive options for the treatment of
lymphatic malformations. The options for the treatment of venous malformations
could be significantly improved during the last years. In this context, the use
of Nd:YAG laser, the conservative treatment of the localized disseminated
intravascular coagulation with low-molecular weight heparin, the re-discovery of
bleomycin as effective sclerosing agent, and the improvement of alcohol-based
embolization agents must be mentioned. Today the treatment with dye laser is the
preferred therapy for capillary malformations and it is superior to other
therapeutic options as for example photodynamic therapy. Arterio-venous
malformations as representatives for high-flow lesions are the high-risk lesions.
Frequently they are compared to malignant head and neck tumors, in particular
when a curative treatment can no longer be assured because of diffuse or
multifocal extent and when the disease shows a progressive course. The combined
treatment of embolization and surgical resection and if necessary consecutive
defect reconstruction have turned out to be appropriate for arterio-venous
malformations. Incurable findings are still a major challenge. Despite the
introduction of antiangiogenetic drugs in oncology, the medicamentous therapeutic
approach could not be established for arterio-venous malformations up to now.
PMID- 25587364
TI - Anesthesia for ORL surgery in children.
AB - ORL procedures are the most common operations in children - an optimal anesthetic
management provides an uncomplicated, safe perioperative process with as little
discomfort for the child as possible. Children at risk must already be identified
preoperatively: the combination of ORL surgery, airway susceptibility and age
below 3 years can increase the risk of perioperative respiratory adverse events.
Postoperatively, it is important to prevent complications such as pain and PONV
by dedicated prevention and treatment strategies, as well as to recognize and
treat respiratory or circulatory complications competently. Interdisciplinary
guidelines and agreements as well as the overall competence of the team have the
potential to improve patient safety and outcome in children.
PMID- 25587365
TI - Hearing impairment and language delay in infants: Diagnostics and genetics.
AB - This overview study provides information on important phoniatric and audiological
aspects of early childhood hearing and language development with the aim of
presenting diagnostic and therapeutic approaches. The article first addresses the
universal newborn hearing screening that has been implemented in Germany for all
infants since January 2009. The process of newborn hearing screening from the
maternity ward to confirmation diagnostics is presented in accordance with a
decision by the Federal Joint Committee (G-BA). The second topic is pediatric
audiology diagnostics. Following confirmation of a permanent early childhood
hearing disorder, the search for the cause plays an important role. Hereditary
hearing disorders and intrauterine cytomegalovirus (CMV) infection, probably the
most common cause of an acquired hearing disorder, are discussed and compared
with the most common temporary hearing disorder, otitis media with effusion,
which in some cases is severe enough to be relevant for hearing and language
development and therefore requires treatment. The third topic covered in this
article is speech and language development in the first 3 years of life, which is
known today to be crucial for later language development and learning to read and
write. There is a short overview and introduction to modern terminology, followed
by the abnormalities and diagnostics of early speech and language development.
Only some aspects of early hearing and language development are addressed here.
Important areas such as the indication for a cochlear implant in the first year
of life or because of unilateral deafness are not included due to their
complexity.
PMID- 25587366
TI - Salivary gland diseases in children.
AB - Salivary gland diseases in children are rare, apart from viral-induced diseases.
Nevertheless, it is essential for the otolaryngologist to recognize these
uncommon findings in children and adolescents and to diagnose and initiate the
proper treatment. The present work provides an overview of the entire spectrum of
congenital and acquired diseases of the salivary glands in childhood and
adolescence. The current literature was reviewed and the results discussed and
summarized. Besides congenital diseases of the salivary glands in children, the
main etiologies of viral and bacterial infections, autoimmune diseases and tumors
of the salivary glands were considered. In addition to the known facts, new
developments in diagnostics, imaging and therapy, including sialendoscopy in
obstructive diseases and chronic recurrent juvenile sialadenitis were taken into
account. In addition, systemic causes of salivary gland swelling and the
treatment of sialorrhoea were discussed. Although salivary gland diseases in
children are usually included in the pathology of the adult, they differ in their
incidence and some-times in their symptoms. Clinical diagnostics and especially
the surgical treatment are influenced by a stringent indications and a less
invasive strategy. Due to the rarity of tumors of the salivary glands in
children, it is recommended to treat them in a specialized center with greater
surgical experience. Altogether the knowledge of the differential diagnoses in
salivary gland diseases in children is important for otolaryngologists, to
indicate the proper therapeutic approach.
PMID- 25587369
TI - Pathologies of the larynx and trachea in childhood.
AB - Pathologies in the larynx and trachea in the pediatric age can be characterized
in 4 main groups: airway stenosis, acute infections, benign neoplasia and foreign
body aspiration. In this review main diagnostic strategies and therapeutic
options are presented. Laryngomalazia is the most frequent condition of
supraglottic stenosis. The term supraglottoplasty summarizes all different
techniques used for it's repair using an endoscopic approach. Glottic stenosis is
rare in children. Usually a compromise between voice preservation and airway
restoration has to be sought. Type of reconstruction and timing are varying
considerably in individual cases, endoscopic approaches should be preferred.
Subglottic stenosis remains the largest group in paediatric airway pathology,
with cicatrial stenosis being predominant. Today, cricotracheal resection is the
most successful treatment option, followed by the classical laryngotracheal
reconstruction with autologous cartilage. In early infancy subglottic stenosis is
particularly demanding. Endoscopic treatment is possible in selected patients,
but open reconstruction is superior in more severe cases. Tracheostomy is not a
safe airway in early infancy, it's indication should be strict. Foreign body
aspiration needs to be managed according to a clear algorhythm. Recurrent
respiratory papillomatosis should be treated with emphasis on function
preservation. The role of adjuvant medication remains unclear. Infectious
diseases can be managed conservatively by a pediatrician in the majority of
cases.
PMID- 25587368
TI - Cervical lymph node diseases in children.
AB - The lymph nodes are an essential part of the body's immune system and as such are
affected in many infectious, autoimmune, metabolic and malignant diseases. The
cervical lymph nodes are particularly important because they are the first
drainage stations for key points of contact with the outside world
(mouth/throat/nose/eyes/ears/respiratory system) - a critical aspect especially
among children - and can represent an early clinical sign in their exposed
position on a child's slim neck. Involvement of the lymph nodes in multiple
conditions is accompanied by a correspondingly large number of available
diagnostic procedures. In the interests of time, patient wellbeing and cost, a
careful choice of these must be made to permit appropriate treatment. The basis
of diagnostic decisions is a detailed anamnesis and clinical examination.
Sonography also plays an important role in differential diagnosis of lymph node
swelling in children and is useful in answering one of the critical diagnostic
questions: is there a suspicion of malignancy? If so, full dissection of the most
conspicuous lymph node may be necessary to obtain histological confirmation.
Diagnosis and treatment of childhood cervical lymph node disorders present the
attending pediatric and ENT physicians with some particular challenges. The
spectrum of differential diagnoses and the varying degrees of clinical relevance
from banal infections to malignant diseases - demand a clear and considered
approach to the child's individual clinical presentation. Such an approach is
described in the following paper.
PMID- 25587367
TI - Tonsillitis and sore throat in children.
AB - Surgery of the tonsils is still one of the most frequent procedures during
childhood. Due to a series of fatal outcomes after hemorrhage in children in
Austria in 2006, the standards and indications for tonsillectomy have slowly
changed in Germany. However, no national guidelines exist and the frequency of
tonsil surgery varies across the country. In some districts eight times more
children were tonsillectomized than in others. A tonsillectomy in children under
six years should only be done if the child suffers from recurrent acute
bacterially tonsillitis. In all other cases (i.e. hyperplasia of the tonsils) the
low risk partial tonsillectomy should be the first line therapy. Postoperative
pain and the risk of hemorrhage are much lower in partial tonsillectomy
(=tonsillotomy). No matter whether the tonsillotomy is done by laser,
radiofrequency, shaver, coblation, bipolar scissor or Colorado needle, as long as
the crypts are kept open and some tonsil tissue is left behind. Total
extracapsular tonsillectomy is still indicated in severely affected children with
recurrent infections of the tonsils, allergy to antibiotics, PFAPA syndrome
(periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) and
peritonsillar abscess. With regard to the frequency and seriousness of the
recurrent tonsillitis the indication for tonsillectomy in children is justified
if 7 or more well-documented, clinically important, adequately treated episodes
of throat infection occur in the preceding year, or 5 or more of such episodes
occur in each of the 2 preceding years (according to the paradise criteria).
Diagnosis of acute tonsillitis is clinical, but sometimes it is hard to
distinguish viral from bacterial infections. Rapid antigen testing has a very low
sensitivity in the diagnosis of bacterial tonsillitis and swabs are highly
sensitive but take a long time. In all microbiological tests the treating
physician has to keep in mind, that most of the bacterials, viruses and fungi
belong to the healthy flora and do no harm. Ten percent of healthy children even
bear strepptococcus pyogenes all the time in the tonsils with no clinical signs.
In these children decolonization is not necessary. Therefore, microbiological
screening tests in children without symptoms are senseless and do not justify an
antibiotic treatment (which is sometimes postulated by the kindergartens). The
acute tonsillitis should be treated with steroids (e.g. dexamethasone), NSAIDs
(e.g. ibuprofene) and betalactam antibiotics (e.g. penicillin or cefuroxime).
With respect to the symptom reduction and primary healing the short-term late
generation antibiotic therapy (azithromycin, clarithromycin or cephalosporine for
three to five days) is comparable to the long-term penicilline therapy. There is
no difference in the course of healing, recurrence or microbiological resistance
between the short-term penicilline therapy and the standard ten days therapy. On
the other hand, only the ten days antibiotic therapy has proven to be effective
in the prevention of rheumatic fever and glomerulonephritic diseases. The
incidence of rheumatic heart disease is currently 0.5 per 100,000 children of
school age. The main morbidity after tonsillectomy is pain and the late
haemorrhage. Posttonsillectomy bleeding can occur till the whole wound is
completely healed, which is normally after three weeks. Life-threatening
haemorrhages occur often after smaller bleedings, which can spontaneously cease.
That is why every haemorrhage, even the smallest, has to be treated properly and
in ward. Patients and parents have to be informed about the correct behaviour in
case of haemorrhage with a written consent before the surgery. The handout should
contain important addresses, phone numbers and contact persons. Almost all cases
of fatal outcome after tonsillectomy were due to false management of haemorrhage.
Haemorrhage in small children can be especially life-threatening because of the
lower blood volume and the danger of aspiration with asphyxia. A massive
haemorrhage is an extreme challenge for every paramedic or emergency doctor
because of the difficult airway management. Intubation is only possible with
appropriate inflexible suction tubes. All different surgical techniques have the
risk of haemorrhage and even the best surgeon will experience a postoperative
haemorrhage. The lowest risk of haemorrhage is after cold dissection with
ligature or suturing. All "hot" techniques with laser, radiofrequency, coblation,
mono- or bipolar forceps have a higher risk of late haemorrhage. Children with a
hereditary coagulopathy have a higher risk of haemorrhage. It is possible, that
these children were not identified before surgery. Therefore it is recommended by
the Society of paediatrics, anaesthesia and ENT, that a standardised
questionnaire should be answered by the parents before tonsillectomy and
adenoidectomy. This 17-point-checklist questionnaire is more sensitive and easier
to perform than a screening with blood tests (e.g. INR and PTT). Unfortunately, a
lot of surgeons still screen the children preoperatively by coagulative blood
tests, although these tests are inappropriate and incapable of detecting the von
Willebrand disease, which is the most frequent coagulopathy in Europe. The
preoperative information about the surgery should be done with the child and the
parents in a calm and objective atmosphere with a written consent. A copy of the
consent with the signature of the surgeon and both custodial parents has to be
handed out to the parents.
PMID- 25587372
TI - Making a hydrophoretic focuser tunable using a diaphragm.
AB - Microfluidic diagnostic devices often require handling particles or cells with
different sizes. In this investigation, a tunable hydrophoretic device was
developed which consists of a polydimethylsiloxane (PDMS) slab with hydrophoretic
channel, a PDMS diaphragm with pressure channel, and a glass slide. The height of
the hydrophoretic channel can be tuned simply and reliably by deforming the
elastomeric diaphragm with pressure applied on the pressure channel. This
operation allows the device to have a large operating range where different
particles and complex biological samples can be processed. The focusing
performance of this device was tested using blood cells that varied in shape and
size. The hydrophoretic channel had a large cross section which enabled a
throughput capability for cell focusing of ~15 000 cells s(-1), which was more
than the conventional hydrophoretic focusing and dielectrophoresis (DEP)-active
hydrophoretic methods. This tunable hydrophoretic focuser can potentially be
integrated into advanced lab-on-a-chip bioanalysis devices.
PMID- 25587373
TI - A large-area hemispherical perforated bead microarray for monitoring bead based
aptamer and target protein interaction.
AB - Herein, we present a large-area 3D hemispherical perforated microwell structure
for a bead based bioassay. Such a unique microstructure enables us to perform the
rapid and stable localization of the beads at the single bead level and the
facile manipulation of the bead capture and retrieval with high speed and
efficiency. The fabrication process mainly consisted of three steps: the convex
micropatterned nickel (Ni) mold production from the concave micropatterned
silicon (Si) wafer, hot embossing on the polymer matrix to generate the concave
micropattened acrylate sheet, and reactive ion etching to make the bottom holes.
The large-area hemispherical perforated micropatterned acrylate sheet was
sandwiched between two polydimethylsiloxane (PDMS) microchannel layers. The bead
solution was injected and recovered in the top PDMS microchannel, while the
bottom PDMS microchannel was connected with control lines to exert the
hydrodynamic force in order to alter the flow direction of the bead solution for
the bead capture and release operation. The streptavidin-coated microbead capture
was achieved with almost 100% yield within 1 min, and all the beads were
retrieved in 10 s. Lysozyme or thrombin binding aptamer labelled microbeads were
trapped on the proposed bead microarray, and the in situ fluorescence signal of
the bead array was monitored after aptamer-target protein interaction. The
protein-aptamer conjugated microbeads were recovered, and the aptamer was
isolated for matrix assisted laser desorption/ionization time-of-flight mass
spectrometry analysis to confirm the identity of the aptamer.
PMID- 25587370
TI - Diseases of the nose and paranasal sinuses in child.
AB - Diseases of the pediatric nose and nasal sinuses as well as neighboring
anatomical structures encompass a variety of pathologies, especially of
inflammatory nature. Congenital disease, such as malformations and structural
deviations of the nasal septum, as well as systemic metabolic pathologies
affecting the nose and sinuses, rarely require medical therapy from an
Otolaryngologist. The immunological function of the mucosa and genetic factors
play a role in the development of disease in the pediatric upper airway tract,
especially due to the constantly changing anatomy in this growth phase. Disease
description of the nose and nasal sinuses due to mid-facial growth must also take
developmental age differences (infant, toddler, preschool, and school age) into
account. Epidemiological examinations and evidence based studies are often
lacking in the pediatric population. The wide range of inflammatory diseases of
the nose and paranasal sinuses, such as the acute and chronic rhinosinusitis, the
allergic rhinitis, and adenoid disease, play a role in the susceptibility of a
child to infection. The susceptibility to infection depends on the pediatric age
structure (infant, young child) and has yet to be well defined. The acute
rhinosinusitis in children develops after a viral infection of the upper airways,
also referred to as the "common cold" in the literature. It usually spontaneously
heals within ten days without any medical therapy. Antibiotic therapy is prudent
in complicated episodes of ARS. The antibiotic therapy is reserved for children
with complications or associated disease, such as bronchial asthma and/or chronic
bronchitis. A chronic rhinosinusitis is defined as the inflammatory change in the
nasal mucosa and nasal sinus mucosa, in which the corresponding symptoms persist
for over 12 weeks. The indication for CT-imaging of the nasal sinuses is reserved
for cases of chronic rhinosinusitis that have been successfully treated with
medication. A staged therapeutic concept is followed in CRS based on conservative
and surgical methods. Nasal sinus surgery is considered nowadays as effective and
safe in children. Based on the assumption that adenoids are a reservoir for
bacteria, from which recurrent infections of the nose and nasal sinus originate,
the adenoidectomy is still defined as a cleansing procedure in rhinosinusitis.
69.3% of the children had benefit from adenoidectomy. Comorbidities, such as
pediatric bronchial asthma, presently play an even more important role in the
therapy of rhinosinusitis; therefore, it is often wise to have the support of
pediatricians. In western European countries 40% of children presently suffer
from allergic rhinitis, in which pronounced nasal obstruction can cause disturbed
growth in facial bones. An early therapy with SIT may prevent the development of
bronchial asthma and secondary sensitization to other allergens. Therefore, SIT
is recommended in treatment of allergic rhinitis whenever, if possible. The
assessment of diagnostic tools is for the examiner not often possible due to the
lack of evidence. Rhinosurgical approaches are often described in study reports;
however, they lack the standard prospective randomized long-term study design
required nowadays and can only be evaluated with caution in the literature.
PMID- 25587375
TI - Protein and cell patterning in closed polymer channels by photoimmobilizing
proteins on photografted poly(ethylene glycol) diacrylate.
AB - Definable surface chemistry is essential for many applications of microfluidic
polymer systems. However, small cross-section channels with a high surface to
volume ratio enhance passive adsorption of molecules that depletes active
molecules in solution and contaminates the channel surface. Here, we present a
one-step photochemical process to coat the inner surfaces of closed microfluidic
channels with a nanometer thick layer of poly(ethylene glycol) (PEG), well known
to strongly reduce non-specific adsorption, using only commercially available
reagents in an aqueous environment. The coating consists of PEG diacrylate
(PEGDA) covalently grafted to polymer surfaces via UV light activation of the
water soluble photoinitiator benzoyl benzylamine, a benzophenone derivative. The
PEGDA coating was shown to efficiently limit the adsorption of antibodies and
other proteins to <5% of the adsorbed amount on uncoated polymer surfaces. The
coating could also efficiently suppress the adhesion of mammalian cells as
demonstrated using the HT-29 cancer cell line. In a subsequent equivalent process
step, protein in aqueous solution could be anchored onto the PEGDA coating in
spatially defined patterns with a resolution of <15 MUm using an inverted
microscope as a projection lithography system. Surface patterns of the cell
binding protein fibronectin were photochemically defined inside a closed
microfluidic device that was initially homogeneously coated by PEGDA. The
resulting fibronectin patterns were shown to greatly improve cell adhesion
compared to unexposed areas. This method opens for easy surface modification of
closed microfluidic systems through combining a low protein binding PEG-based
coating with spatially defined protein patterns of interest.
PMID- 25587371
TI - Diseases of the middle ear in childhood.
AB - Middle ear diseases in childhood play an important role in daily ENT practice due
to their high incidence. Some of these like acute otitis media or otitis media
with effusion have been studied extensively within the last decades. In this
article, we present a selection of important childhood middle ear diseases and
discuss the actual literature concerning their treatment, management of
complications and outcome. Another main topic of this paper deals with the
possibilities of surgical hearing rehabilitation in childhood. The bone-anchored
hearing aid BAHA((r)) and the active partially implantable device Vibrant
Soundbridge((r)) could successfully be applied for children. In this manuscript,
we discuss the actual literature concerning clinical outcomes of these
implantable hearing aids.
PMID- 25587374
TI - Inducing chemotactic and haptotactic cues in microfluidic devices for three
dimensional in vitro assays.
AB - Microfluidic devices allow for the production of physiologically relevant
cellular microenvironments by including biomimetic hydrogels and generating
controlled chemical gradients. During transport, the biomolecules interact in
distinct ways with the fibrillar networks: as purely diffusive factors in the
soluble fluid or bound to the matrix proteins. These two main mechanisms may
regulate distinct cell responses in order to guide their directional migration:
caused by the substrate-bound chemoattractant gradient (haptotaxis) or by the
gradient established within the soluble fluid (chemotaxis). In this work 3D
diffusion experiments, in combination with ELISA assays, are performed using
microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF
beta1 across collagen and fibrin gels. Furthermore, to gain a deeper
understanding of the fundamental processes, the experiments are reproduced by
computer simulations based on a reaction-diffusion transport model. This model
yields an accurate prediction of the experimental results, confirming that
diffusion and binding phenomena are established within the microdevice.
PMID- 25587376
TI - A microfluidic manifold with a single pump system to generate highly mono
disperse alginate beads for cell encapsulation.
AB - Cell encapsulation technology is a promising strategy applicable to tissue
engineering and cell therapy. Many advanced microencapsulation chips that
function via multiple syringe pumps have been developed to generate mono-disperse
hydrogel beads encapsulating cells. However, their operation is difficult and
only trained microfluidic engineers can use them with dexterity. Hence, we
propose a microfluidic manifold system, driven by a single syringe pump, which
can enable the setup of automated flow sequences and generate highly mono
disperse alginate beads by minimizing disturbances to the pump pressure. The
encapsulation of P19 mouse embryonic carcinoma cells and embryonic body formation
are demonstrated to prove the efficiency of the proposed system.
PMID- 25587377
TI - Erratum: Publisher's Note: "Inducing chemotactic and haptotactic cues in
microfluidicdevices for three-dimensional in vitro assays" [Biomicrofluidics 8,
064122 (2014)].
PMID- 25587378
TI - Correlation between serum RANTES levels and the severity of Parkinson's disease.
AB - Inflammatory mediators may reflect a role of systemic inflammation in the
neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and
chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal
T cell expressed and secreted), have been implicated in neurodegenerative
diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD
patients and age-matched 80 controls were measured. Patients with PD had higher
RANTES and IL-6 levels compared with the controls. We found that serum RANTES
levels strongly correlated with Hoehn-Yahr score and disease duration in PD
patients. This study indicated that patients with PD have an on-going systemic
inflammatory profile where the elevated peripheral production of RANTES may play
a role in the neurodegenerative process.
PMID- 25587379
TI - Efficacy of Connective Tissue with and without Periosteum in Regeneration of
Intrabony Defects.
AB - Background and aims. Connective tissue grafts with and without periosteum is used
in regenerative treatments of bone and has demonstrated successful outcomes in
previous investigations. The aim of present study was to evaluate the
effectiveness of connective tissue graft with and without periosteum in
regeneration of intrabony defects. Materials and methods. In this single-blind
randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15
patients with moderate to advanced periodontitis were treated by periosteal
connective tissue graft + ABBM (test group) or non-periosteal connective tissue
graft + ABBM (control group). Probing pocket depth, clinical attachment level,
free gingival margin position, bone crestal position, crest defect depth and
defect depth to stent were measured at baseline and after six months by surgical
re-entry. Data was analyzed by Student's t-test and paired t-tests (alpha=0.05).
Results. Changes in clinical parameters after 6 months in the test and control
groups were as follows: mean of PPD reduction: 3.1+/-0.6 (P<0.0001); 2.5+/-1.0 mm
(P<0.0001), CAL gain: 2.3+/-0.9 (P<0.0001); 2.2+/-1.0 mm (P<0.0001), bone fill:
2.2+/-0.7 mm (P<0.0001); 2.2+/-0.7 mm (P<0.0001), respectively. No significant
differences in the position of free gingival margin were observed during 6 months
compared to baseline in both groups. Conclusion. Combinations of periosteal
connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM
were similarly effective in treating intrabony defects without any favor for any
group. Connective tissue and perio-steum can be equally effective in regeneration
of intrabony defects.
PMID- 25587380
TI - Effect of TiO2 Nanoparticles on Tensile Strength of Dental Acrylic Resins.
AB - Background and aims. Adding further fillers to dental resins may enhance their
physical characteristics. The aim of this study was to evaluate the tensile
strength of heat-curing acrylic resin reinforced by TiO2nanoparticles added into
the resin matrix. Materials and methods. Commercially available TiO2
nanoparticles were obtained and characterized using X-ray diffrac-tion (XRD) and
scanning electron microscopy (SEM) to determine their crystalline structure,
particle size and morphology. TiO2-acrylic resin nanocomposite was prepared by
mixing 0.5, 1 and 2 (wt%) of surface modified TiO2 nanoparticles in an
amalgamator providing three groups of samples. Before curing, the obtained paste
was packed into steel molds. After cur-ing, the specimens were removed from the
molds. The tensile strength test samples were prepared according to ISO 1567.
Results. Two crystalline phases were found in TiO2 nanoparticles including: (i)
anatase as the major one, and (ii) rutile. The average particle size calculated
according to the Scherrer equation was 20.4 nm, showing a normal size
distribution. According to SEM images, the nanocomposite with 1wt% TiO2
nanoparticles had a better distribution compared to other groups. In addition,
the group by 1wt% TiO2 exhibited higher tensile strength with a significant
difference compared to other groups. ANOVA showed significant differences between
the contents of TiO2 particles in acrylic resin (F = 22.19; P < 0.001).
Conclusion. A considerable increase in tensile strength was observed with titania
NPs reinforcement agents in 1wt% by weight. Further increase of TiO2
nanoparticles decreased the tensile strength.
PMID- 25587381
TI - In Vitro Comparison of Compressive and Tensile Strengths ofAcrylic Resins
Reinforced by Silver Nanoparticles at 2% and0.2% Concentrations.
AB - Background and aims. Polymethyl methacrylate, PMMA, is widely used in
prosthodontics for fabrication of removable prostheses. This study was undertaken
to investigate the effect of adding silver nanoparticles (AgNPs) to PMMA at 2%
and 0.2% concentrations on compressive and tensile strengths of PMMA. Materials
and methods. The silver nanoparticles were mixed with heat-cured acrylic resin in
an amalgamator in two groups at 0.2 and 2 wt% of AgNPs. Eighteen 2*20*200-mm
samples were prepared for tensile strength test, 12 samples containing silver
nanoparticle and 6 samples for the control group. Another 18 cylindrical 25*38-mm
samples were prepared for compressive strength test. Scanning electron microscopy
was used to verify homogeneous distribution of particles. The powder was manually
mixed with a resin monomer and then the mixture was properly blended. Before
curing, the paste was packed into steel molds. After curing, the specimens were
removed from the molds. One-way ANOVA was used for statistical analysis, followed
by multiple comparison test (Scheffe's test). Results. This study showed that the
mean compressive strength of PMMA reinforced with AgNPs was significantly higher
than that of the unmodified PMMA (P<0.05). It was not statistically different
between the two groups reinforced with AgNPs. The tensile strength was not
significantly different between the 0.2% group and unmodified PMMA and it de
creased significantly after incorporation of 2% AgNPs (P<0.05). Conclusion. Based
on the results and the desirable effect of nanoparticles of silver on improvement
of compressive strength of PMMA, use of this material with proper concentration
in the palatal area of maxillary acrylic resin dentures is recommended.
PMID- 25587382
TI - Effect of Sodium Ascorbate and Delayed Bonding on the Bond Strength of Silorane
and Two-step Self-etch Adhesive Systems in Bleached Enamel.
AB - Background and aims. Studies have shown decreased bond strength of composite
resin to human and bovine bleached enamel. This study evaluated the effect of
sodium ascorbate and delayed bonding on the bond strength of two adhesive systems
to bleached enamel. Materials and methods. The labial surfaces of 150 sound
bovine incisor teeth were abraded with abrasive paper. The teeth were randomly
divided into 8 groups: A: control; B: bleached with 35% hydrogen peroxide; C:
bleached with 35% hydrogen peroxide + sodium ascorbate gel; and D: bleached with
35% hydrogen peroxide + delayed bonding. In groups A-D, silorane adhesive system
and Filtek silorane composite resin were used. In groups E-H, the same
preparation methods of groups A-D were used. Two-step self-etch Clearfil SE Bond
adhesive systems and AP-X composite resin were administered. Shear bond strength
of each group was measured. Two samples were prepared for each surface
preparation for ultra-structural evaluation. Two-way ANOVA and Tukey test were
used for data analysis at P<0.05. Results. The interaction between the adhesive
system type and surface preparation protocol was significant (P=0.014),
withsignificant differences in shear bond strengths in terms of the adhesive
systems (P<0.01). There were significant differences in shear bond strength in
terms of surface preparation techniques irrespective of the adhesive system
(P<0.01). Conclusion. The results showed that bleaching with 35% hydrogen
peroxide decreased the shear bond strength values with both adhesive systems, and
a one-week delay in bonding and 10% sodium ascorbate for10 minutes restored the
bond strength in both adhesive systems.
PMID- 25587383
TI - In vitro investigation of heat transfer phenomenon in human immature teeth.
AB - Background and aims. Heat generated within tooth during clinical dentistry can
cause thermally induced damage to hard and soft components of the tooth (enamel,
dentin and pulp). Geometrical characteristics of immature teeth are different
from those of mature teeth. The purpose of this experimental and theoretical
study was to investigate thermal changes in immature permanent teeth during the
use of LED light-curing units (LCU). Materials and methods. This study was
performed on the second mandibular premolars. This experimental investiga-tion
was carried out for recording temperature variations of different sites of tooth
and two dimensional finite element models were used for heat transfer phenomenon
in immature teeth. Sensitivity analysis and local tests were included in the
model validation phase. Results. Overall, thermal stimulation for 30 seconds with
a low-intensity LED LCU increased the temperature from 28 degrees C to 38 degrees
C in IIT (intact immature tooth) and PIT (cavity-prepared immature tooth). When a
high-intensity LED LCU was used, tooth temperature increased from 28 degrees C to
48 degrees C. The results of the experimental tests and mathematical modeling
illustrated that using LED LCU on immature teeth did not have any detrimental
effect on the pulp temperature. Conclusion. Using LED LCU in immature teeth had
no effect on pulp temperature in this study. Sensitivity analysis showed that
variations of heat conductivity might affect heat transfer in immature teeth;
therefore, further studies are required to determine thermal conductivity of
immature teeth.
PMID- 25587384
TI - Antibacterial Effect of All-in-one Self-etch Adhesives on Enterococcus faecalis.
AB - Background and aims. The aim of this study was to evaluate the antibacterial
activity of one-step self-etch adhesives on Enterococcus faecalis on days 1, 7
and 14 with the use of modified direct contact test. Materials and methods. The
modified directcontact test was used to evaluate the antibacterial effect of
Adper Easy One, Bond Force, Clearfil S3 Bond, Futurabond M, G-Bond, iBond and
OptiBond All-in-one adhesives on Enterococcus faecalis after aging the samples in
phosphate-buffered saline for one, seven and fourteen days. Data were analyzed
using one-way ANOVA and post hoc Tukey tests. Aging effect of each adhesive was
evaluated by paired-sample test. In this study, P<0.05 was considered
significant. Results. All the tested adhesives exhibited antibacterial activity
after one day and had significant differences with the positive control group
(P<0.05). After one week, OptiBond All-in-one, iBond and Futurabond M exhibited
significant differences in bacterial growth from other groups (P<0.05). There
were no significant differences between the groups in two weeks (P>0.05).
Conclusion. iBond exhibited the highest antibacterial effect on E. faecalis after
one week. Futurabond and OptiBond All-in-one exhibited antibacterial effects
against E. faecalis for one week.
PMID- 25587385
TI - Oral health related quality of life in diabetic patients.
AB - Background and aims. Diabetic patients display an increased risk of oral
disorders, and oral health related quality of life (OHRQL) might affect their
management and treatment modalities. The aim of the present study was to
determine OHRQL and associated parameters in patients with diabetes. Materials
and methods. In this study two hundred patients were recruited from the diabetes
clinic in Mustafa Khomeini Hospital in Tehran, Iran. OHRQL was assessed using
Oral Health Impact Profile Questionnaire (OHIP-20). Also, another questionnaire
was designed which contained questions regarding participants' knowledge about
oral complications of diabetes and oral health behavior. OHRQL was categorized as
low and good. Data were analyzed using logistic regression at P = 0.05. Results.
Of the diabetic patients assessed, 77.5% were in good and 22.5% were in low
categories of OHRQL. This quality was significantly associated with age (OR =
4.03, 95% CI = 1.63-11.29), knowledge about diabetes oral complications (OR =
18.17 95% CI = 4.42-158.6), educational level (OR = 26.31 95% CI = 4.2-1080.3),
referred for dental visit by physician (OR = 3.16 95% CI = 1.48-6.69), frequency
of brushing (OR = 10.29 95% CI = 3.96-31.2) and length of time diagnosed with
diabetes (OR = 6.21 95% CI = 2.86-13.63). Conclusion. Oral health related quality
of life was not negatively affected by diabetes mellitus in the assessed sample.
PMID- 25587387
TI - CD56 Expression in Odontogenic Cysts and Tumors.
AB - Background and aims. Odontogenic cysts and tumors have a wide spectrum of
clinical characteristics that lead to the different management strategies. Since
definite diagnosis is difficult in some cases, it has been suggested that CD56
may be a candidate marker for definitive diagnosis of some odontogenic tumors.
The present study was designed to examine CD56 expression in lesions with
histopathological similarities. Materials and methods. In this cross-sectional,
analytical study the subjects were 22 ameloblastomas, 13 dentigerous cysts, 10
keratocystic odontogenic tumors (KCOT), 4 adenomatoid odontogenic tumors (AOT), 3
orthokeratinized odonto-genic cysts, 3 calcifying odontogenic cysts (COC) and one
glandular odontogenic cyst (GOC). All the samples were examined for CD56
immunoreactivity. Data were analyzed using chi-square test. Results. Twenty cases
(91%) of ameloblastomas, 3 (75%) AOT, 4 (40%) KCOT and one case of GOC were
positive for CD56. None of the dentigerous cysts, COC and orthokeratinized
odontogenic cysts was CD56-positive. There was a significant difference in the
CD56 expression between ameloblastoma and dentigerous cyst, as well as COC. Also,
KCOT showed significantly higher expression than orthokeratinized odontogenic
cyst. Conclusion. In this study CD56 expression was limited to the odontogenic
tumors and more aggressive cystic lesions. This marker can be a useful aid for
distinguishing cysts and tumors from similar lesions.
PMID- 25587386
TI - Effect of Iranian Propolis on Salivary Total Antioxidant Capacity in Gamma
irradiated Rats.
AB - Background and aims. The antioxidant and anti-inflammatory properties of propolis
were studied. Since saliva containsantioxidants and radiotherapy of the head and
neck mainly affects the saliva, salivary antioxidant defensive mechanism
iscompromised with oxidative stress produced by radiation therapy. Therefore, the
aim of the present study was to investigatethe effect of propolis on salivary
total antioxidant capacity in irradiated rats. Materials and methods. The study
was conducted on 28 rats, 7-11 weeks of age (160+/-20 g), divided into four
groups:saline with no radiation (S), saline and radiation (SR), propolis with no
radiation (P) [400 mg/kg IP], propolis and radiation(PR) [400 mg/kg IP]. SP and
PR were exposed to 15 Gy of gamma irradiation for 7 minutes and 39 seconds. The
rats received intraperitoneal injections each day for 10 days, and their tongues
and lips were daily examined for mucositis; salivasample were also taken three
times on days 0, 6, and 10. Results. Mucositis incidence appeared to be delayed
in the PR compared to the SR, and the severity was significantlyhigher in the SR
compared to the PR. No significant alterations were observed in salivary
antioxidant levels during the ex-periment, except the SR group in which a
significant reduction was found. Conclusion. Propolis might reduce and delay
radiation-induced mucositis in animal models; it might be able to prevent
thereduction in salivary antioxidant levels in irradiated rats as well.
PMID- 25587388
TI - The efficacy of magnetic resonance imaging and color Doppler ultrasonography in
diagnosis of salivary gland tumors.
AB - Background and aims. Although salivary gland tumors are not very common, early
diagnosis and treatment is crucial because of their proximity to vital organs,
and therefore, determining the efficacy of new imaging procedures becomes
important. This study aimed to evaluate the efficacy of magnetic resonance
imaging (MRI) and color doppler ultrasonography parameters in the diagnosis and
differentiation of benign and malignant salivary gland tumors. Materials and
methods. In this cross-sectional study, color doppler ultrasonography and MRI
were performed for 22 patients with salivary gland tumor. Demographic data as
well as MRI, color doppler ultrasonography, and surgical parameters including
tumor site, signal in MRI images, ultrasound echo, tumor border, lymphadenopathy,
invasion, perfusion, vascular resistance index (RI), vascular pulse index (PI)
were analyzed using Chi-square test, Fisher's exact test, and independent t-test.
Results. The mean age of patients was 46.59+/-13.97 years (8 males and
14females). Patients with malignant tumors were older (P < 0.01). The most common
tumors were pleomorphic adenoma (36.4%), metastasis (36.4%), and mucoepidermoid
carcinoma (9%). Nine tumors (40.9%) were benign and 13 (59.1%) were malignant.
The overall accuracy of MRI and color doppler ultrasonography in determining
tumor site was 100% and 95%, respectively. No significant difference observed
between RI and PI and the diagnosis of tumor. Conclusion. Both MRI and
ultrasonography have high accuracy in the localization of tumors. Well-identified
border was a sign of benign tumors. Also, invasion to adjacent structures was a
predictive factor for malignancy.
PMID- 25587389
TI - Micro-leakage of a Fissure Sealant Cured Using Quartz-tungsten-halogen and Plasma
Arc Light Curing Units.
AB - Background and aims. Newer curing units such as plasma arc can polymerize the
sealants in much shorter curing times. The aim of this study was to compare the
effect of two different curing units on the micro-leakage of a fissure sealant
material. Materials and methods. Sixty two extracted premolars without caries
were randomly divided into two groups of 31 samples. Occlusal surfaces of all
teeth were cleansed. Then, teeth surfaces were etched by 37% phosphoric acid.
After rinsing and drying, occlusal surfaces of teeth were sealed by a fissure
sealant. The sealant was then cured using either a halogen light curing unit or a
plasma arc curing light. After sealing, the teeth were thermocycled for 500
cycles. The teeth were then sectioned and examined for micro-leakage. Statistical
analyses were performed with Mann-Whitney test. Results. There was no significant
difference between two groups regarding micro-leakage (P = 0.42). Conclusion.
Results showed that there was no significant difference between two different
curing units. Therefore, plasma arc unit might be a useful alternative for
sealant polymerization.
PMID- 25587390
TI - Rehabilitation of a partial nasal defect with facial prosthesis: a case report.
AB - >Malignancies of the midface result in cosmetic deformities that make
maxillofacial prosthesis as an integral part of the treatment plan. Facial
defects can be devastating in their impact on physical structure and function of
the affected individual, leading to potentional compromises in quality of life.
Reconstruction of nasal defects is a challenge for the prosthodontist because of
esthetic and retention problems associated with the facial prosthesis. This paper
reports the rehabilitation of a partial nasal defect caused by basal cell
carcinoma treatment using a nasal prosthesis made with silicone elastomers and
mechanical and anatomical retentive aids. The patient had no problem with the
prosthesis, except for a partial loss of extrinsic coloration in the two-year
follow-up.
PMID- 25580220
TI - The second touch hypothesis: T cell activation, homing and polarization.
AB - The second touch hypothesis states that T cell activation, proliferation,
induction of homing receptors and polarization are distinguishable and, at least
in part, sequential. The second touch hypothesis maintains that full T cell
polarization requires T cell interaction with antigen-presenting cells (DCs,
macrophages, B cells and certain activated stromal cells) in the non-lymphoid
tissue where the antigen resides. Upon initial antigen encounter in peripheral
lymph nodes (PLN), T cells become activated, proliferate and express homing
receptors that enable them to recirculate to the (inflamed) tissue that contains
the antigen. Differentiation into the T helper lineages Th1, Th2, Th17 and
induced regulatory T cells (iTreg) requires additional antigen presentation by
tissue macrophages and other antigen presenting cells (APCs) in the inflamed
tissue. Here, I present a conceptual framework for the importance of peripheral
(non-lymphoid) antigen presentation to antigen-experienced T cells.
PMID- 25587392
TI - Preclinical screening for acute toxicity of therapeutic monoclonal antibodies in
a hu-SCID model.
AB - Monoclonal antibodies (mAbs) have been a spectacular clinical and commercial
success in the treatment of cancer and autoimmune diseases. Many of these mAbs
(for example, OKT3, Campath-1H, rituximab and infliximab) are against surface or
secreted products of lymphocytes. However, mAbs can have a variety of adverse
effects including fever, chills and nausea. This is probably a result of cytokine
release, which is most seriously manifested as a 'cytokine storm' as highlighted
by the TGN1412 (anti-CD28) trial. Prediction of adverse effects of mAbs would be
clinically advantageous and numerous in vitro assays attempting to predict
adverse effects have been reported. Here, we report an in vivo humanized mouse
model to detect adverse effects in response to OKT3, Campath-1H or the polyclonal
Ab preparation anti-thymocyte globulin. We found that the administration of each
of these Abs to humanized mice led to acute clinical symptoms such as
piloerection, hypomotility and hypothermia, particularly when delivered via the
intravenous route. A cytokine storm occurred in the humanized mice receiving
OKT3. This model system is a potentially useful tool to predict adverse effects
and select initial doses for first-in-human trials. We would advocate this in
vivo model, in addition to current in vitro preclinical testing, as a more
representative and robust means of assessing potential adverse effects of mAb
before their human use.
PMID- 25587393
TI - Performance evaluation of a scoria-compost biofilter treating xylene vapors.
AB - The removal of xylene vapors was studied in a biofilter packed with a new hybrid
(scoria/compost) packing material at various inlet loads (IL) and empty bed
residence times (EBRT) of 90, 60, and 40s. The best performance was observed for
EBRT of 90s, where a removal efficiency of 98% was obtained under steady state
condition for inlet xylene concentration of 1.34 g m(-3), while a maximum
elimination capacity of 97.5 g m(-3) h(-1) was observed for IL of 199.5 g m(-3)
h(-1). Carbon dioxide production rates and the microbial counts for xylene
degraders followed xylene elimination capacities. Overall look to the results of
this study indicates that the scoria/compost mixture could be considered as a
potential biofilter carrier, with low pressure drop (here <4 mm H2O), to treat
air streams containing VOCs.
PMID- 25587395
TI - Welcome to biosensors: a new open-access journal.
AB - The journal Biosensors has been started as a peer-reviewed, open access journal.
As editors, we believe that it will fulfill an important role in the community of
researchers and developers in the field of biosensors. The addition of a "free
access" journal to the existing, high quality publications in this field is
something that we believe is very important in a field which is now so entwined
with commercial activity and where researchers aim, not only at academic
research, but on the development of products at a potentially massive scale. For
these researchers, it is important that they can publish their results in a
journal that guarantees quality that comes from peer-review, but that at the same
time breaks the traditional boundaries of academic journals which need a
subscription or a pay-per-view option to access the published data.
PMID- 25587394
TI - Fast Pure R Implementation of GEE: Application of the Matrix Package.
AB - Generalized estimating equation solvers in R only allow for a few pre-determined
options for the link and variance functions. We provide a package, geeM, which is
implemented entirely in R and allows for user specified link and variance
functions. The sparse matrix representations provided in the Matrix package
enable a fast implementation. To gain speed, we make use of analytic inverses of
the working correlation when possible and a trick to find quick numeric inverses
when an analytic inverse is not available. Through three examples, we demonstrate
the speed of geeM, which is not much worse than C implementations like geepack
and gee on small data sets and faster on large data sets.
PMID- 25587396
TI - Application of paper-supported printed gold electrodes for impedimetric
immunosensor development.
AB - In this article, we report on the formation and mode-of-operation of an affinity
biosensor, where alternate layers of biotin/streptavidin/biotinylated-CRP
antigen/anti-CRP antibody are grown on printed gold electrodes on disposable
paper-substrates. We have successfully demonstrated and detected the formation of
consecutive layers of supra-molecular protein assembly using an electrical
(impedimetric) technique. The formation process is also supplemented and verified
using conventional surface plasmon resonance (SPR) measurements and surface
sensitive characterization techniques, such as X-ray photoelectron spectroscopy
(XPS) and atomic force microscopy (AFM). The article provides a possible
biosensor development scheme, where-(1) fabrication of paper substrate (2)
synthesis of gold nanoparticle inks (3) inkjet printing of gold electrodes on
paper (4) formation of the biorecognition layers on the gold electrodes and (5)
electrical (impedimetric) analysis of growth-all are coupled together to form a
test-structure for a recyclable and inexpensive point-of-care diagnostic
platform.
PMID- 25587398
TI - Quinone-based polymers for label-free and reagentless electrochemical
immunosensors: application to proteins, antibodies and pesticides detection.
AB - Polyquinone derivatives are widely recognized in the literature for their
remarkable properties, their biocompatibility, simple synthesis, and easy bio
functionalization. We have shown that polyquinones present very stable
electroactivity in neutral aqueous medium within the cathodic potential domain
avoiding side oxidation of interfering species. Besides, they can act as
immobilized redox transducers for probing biomolecular interactions in sensors.
Our group has been working on devices based on such modified electrodes with a
view to applications for proteins, antibodies and organic pollutants using a
reagentless label-free electrochemical immunosensor format. Herein, these
developments are briefly reviewed and put into perspective.
PMID- 25587399
TI - Single step nanoplasmonic immunoassay for the measurement of protein biomarkers.
AB - A nanoplasmonic biosensor for highly-sensitive, single-step detection of protein
biomarkers is presented. The principle is based on the utilization of the optical
scattering properties of gold nanorods (GNRs) conjugated to bio-recognition
molecules. The nanoplasmonic properties of the GNRs were utilized to detect
proteins using near-infrared light interferometry. We show that the antibody
conjugated GNRs can specifically bind to our model analyte, Glucose Transporter-1
(Glut-1). The signal intensity of back-scattered light from the GNRs bound after
incubation, correlated well to the Glut-1 concentration as per the calibration
curve. The detection range using this nanoplasmonic immunoassay ranges from 10
ng/mL to 1 ug/mL for Glut-1. The minimal detectable concentration based on the
lowest discernable concentration from zero is 10 ng/mL. This nanoplasmonic
immunoassay can act as a simple, selective, sensitive strategy for effective
disease diagnosis. It offers advantages such as wide detection range, increased
speed of analysis (due to fewer incubation/washing steps), and no label
development as compared to traditional immunoassay techniques. Our future goal is
to incorporate this detection strategy onto a microfluidic platform to be used as
a point-of-care diagnostic tool.
PMID- 25587397
TI - Isothermal amplification methods for the detection of nucleic acids in
microfluidic devices.
AB - Diagnostic tools for biomolecular detection need to fulfill specific requirements
in terms of sensitivity, selectivity and high-throughput in order to widen their
applicability and to minimize the cost of the assay. The nucleic acid
amplification is a key step in DNA detection assays. It contributes to improving
the assay sensitivity by enabling the detection of a limited number of target
molecules. The use of microfluidic devices to miniaturize amplification protocols
reduces the required sample volume and the analysis times and offers new
possibilities for the process automation and integration in one single device.
The vast majority of miniaturized systems for nucleic acid analysis exploit the
polymerase chain reaction (PCR) amplification method, which requires repeated
cycles of three or two temperature-dependent steps during the amplification of
the nucleic acid target sequence. In contrast, low temperature isothermal
amplification methods have no need for thermal cycling thus requiring simplified
microfluidic device features. Here, the use of miniaturized analysis systems
using isothermal amplification reactions for the nucleic acid amplification will
be discussed.
PMID- 25587400
TI - Biomimetic strategies for sensing biological species.
AB - The starting point of modern biosensing was the application of actual biological
species for recognition. Increasing understanding of the principles underlying
such recognition (and biofunctionality in general), however, has triggered a
dynamic field in chemistry and materials sciences that aims at joining the best
of two worlds by combining concepts derived from nature with the processability
of manmade materials, e.g., sensitivity and ruggedness. This review covers
different biomimetic strategies leading to highly selective (bio)chemical
sensors: the first section covers molecularly imprinted polymers (MIP) that
attempt to generate a fully artificial, macromolecular mold of a species in order
to detect it selectively. A different strategy comprises of devising polymer
coatings to change the biocompatibility of surfaces that can also be used to
immobilized natural receptors/ligands and thus stabilize them. Rationally
speaking, this leads to self-assembled monolayers closely resembling cell
membranes, sometimes also including bioreceptors. Finally, this review will
highlight some approaches to generate artificial analogs of natural recognition
materials and biomimetic approaches in nanotechnology. It mainly focuses on the
literature published since 2005.
PMID- 25587401
TI - Fast and Sensitive Interferon-gamma Assay Using Supercritical Angle Fluorescence.
AB - We present an immunoassay for Interferon-gamma (IFN-gamma) with a limit of
detection of 1.9 pM (30 pg/mL) and a linear concentration range spanning three
orders of magnitude. The developed one-step assay takes only 12 min and can
replace the time-consuming and labor-intensive enzyme-linked immunosorbent assay
(ELISA). The solid-phase sandwich assay is performed on a new measurement system
comprising single-use test tubes and a compact fluorescence reader. The polymer
tubes contain an optical configuration for the detection of supercritical angle
fluorescence, allowing for highly sensitive real-time binding measurements.
PMID- 25587402
TI - Special issue on organic electronic bio-devices.
AB - The aim of the present editorial is to briefly summarize the current scientific
and technological accomplishments in the field of organic electronic biosensors
as described in the articles published in this Special Issue. By definition, a
biosensor is a robust analytical device that combines a biological recognition
element (e.g., antibodies, enzymes, cells) with a transducer. Organic electronic
bio-devices are considered as potentially reliable substitutes of conventional
and rather expensive analytical techniques employed for several applications such
as medical diagnosis, food safety and environment pollution monitoring. Some
insights into the selection and immobilization of recognition elements, signal
amplification, fabrication techniques and analytical performance of biosensing
devices will be presented.
PMID- 25587403
TI - Fiber-Optic Fluoroimmunoassay System with a Flow-Through Cell for Rapid On-Site
Determination of Escherichia coli O157:H7 by Monitoring Fluorescence Dynamics.
AB - Dynamic fluoroimmunoassay with a flow-through system using optical fiber probes
consisting of polystyrene was developed and applied to a quantitative detection
of E. coli O157:H7. The system measures E. coli as fluorescence of sandwich-type
immune complexes formed by capture antibodies immobilized on the surface of the
probe, E. coli cells, and fluorescently labeled detection antibodies. Excitation
was carried out using an evanescent wave from the probe. Resulting fluorescence
recoupled into the probe was detected by a photodiode. The assay system was
constructed with a flow cell which was available for sequential injection of
experimental reagents. In vitro characterization was performed using the flow
cell, and the calibration range of E. coli O157:H7 was from 10(3) to 10(7)
cells/mL. The measurement for each sample was completed within 12 min.
Furthermore, it was also possible to estimate the concentrations of E. coli
O157:H7 by the increasing rate of fluorescence during binding reaction of
detection antibodies to antigens. This minimized the time for measurement down to
6 min. The system is suitable for rapid and direct determination for
microorganisms or bacteria in food, clinical, and environmental sources.
PMID- 25587404
TI - Evaluation of impedance-based label-free technology as a tool for pharmacology
and toxicology investigations.
AB - The use of label-free technologies based on electrical impedance is becoming more
and more popular in drug discovery. Indeed, such a methodology allows the
continuous monitoring of diverse cellular processes, including proliferation,
migration, cytotoxicity and receptor-mediated signaling. The objective of the
present study was to further assess the usefulness of the real-time cell analyzer
(RTCA) and, in particular, the xCELLigence platform, in the context of early drug
development for pharmacology and toxicology investigations. In the present
manuscript, four cellular models were exposed to 50 compounds to compare the cell
index generated by RTCA and cell viability measured with a traditional viability
assay. The data revealed an acceptable correlation (ca. 80%) for both cell lines
(i.e., HepG2 and HepaRG), but a lack of correlation (ca. 55%) for the primary
human and rat hepatocytes. In addition, specific RTCA profiles (signatures) were
generated when HepG2 and HepaRG cells were exposed to calcium modulators,
antimitotics, DNA damaging and nuclear receptor agents, with a percentage of
prediction close to 80% for both cellular models. In a subsequent experiment,
HepG2 cells were exposed to 81 proprietary UCB compounds known to be genotoxic or
not. Based on the DNA damaging signatures, the RTCA technology allowed the
detection of ca. 50% of the genotoxic compounds (n = 29) and nearly 100% of the
non-genotoxic compounds (n = 52). Overall, despite some limitations, the
xCELLigence platform is a powerful and reliable tool that can be used in drug
discovery for toxicity and pharmacology studies.
PMID- 25587405
TI - Study of Immobilization Procedure on Silver Nanolayers and Detection of Estrone
with Diverged Beam Surface Plasmon Resonance (SPR) Imaging.
AB - An immobilization protocol was developed to attach receptors on smooth silver
thin films. Dense and packed 11-mercaptoundecanoic acid (11-MUA) was used to
avoid uncontrolled sulfidization and harmful oxidation of silver nanolayers. N,N'
dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) were added to make
the silver surfaces reactive. A comparative study was carried out with different
immersion times of silver samples in 11-MUA solutions with different
concentrations to find the optimum conditions for immobilization. The signals,
during each step of the protocol, were analyzed with a refractometer based on the
surface plasmon resonance (SPR) effect and luminescence techniques. Molecular
interactions at the surfaces between the probe and target at the surface
nanolayer shift the SPR signal, thus indicating the presence of the substance. To
demonstrate specific biosensing, rabbit anti-estrone polyclonal immunoglobulin G
(IgG) antibody was immobilized through a linker on 47 nm silver layer deposited
on SF11 glass. At the final stage, the representative endocrine disruptor-estrone
was attached and detected in deionized water with a diverging beam SPR imaging
sensor.
PMID- 25587406
TI - Development of a Fluorescence Resonance Energy Transfer (FRET)-Based DNA
Biosensor for Detection of Synthetic Oligonucleotide of Ganoderma boninense.
AB - An optical DNA biosensor based on fluorescence resonance energy transfer (FRET)
utilizing synthesized quantum dot (QD) has been developed for the detection of
specific-sequence of DNA for Ganoderma boninense, an oil palm pathogen. Modified
QD that contained carboxylic groups was conjugated with a single-stranded DNA
probe (ssDNA) via amide-linkage. Hybridization of the target DNA with conjugated
QD-ssDNA and reporter probe labeled with Cy5 allows for the detection of related
synthetic DNA sequence of Ganoderma boninense gene based on FRET signals.
Detection of FRET emission before and after hybridization was confirmed through
the capability of the system to produce FRET at 680 nm for hybridized sandwich
with complementary target DNA. No FRET emission was observed for non
complementary system. Hybridization time, temperature and effect of different
concentration of target DNA were studied in order to optimize the developed
system. The developed biosensor has shown high sensitivity with detection limit
of 3.55 * 10(-9) M. TEM results show that the particle size of QD varies in the
range between 5 to 8 nm after ligand modification and conjugation with ssDNA.
This approach is capable of providing a simple, rapid and sensitive method for
detection of related synthetic DNA sequence of Ganoderma boninense.
PMID- 25587408
TI - Microfluidic platform for the elastic characterization of mouse submandibular
glands by atomic force microscopy.
AB - The ability to characterize the microscale mechanical properties of biological
materials has the potential for great utility in the field of tissue engineering.
The development and morphogenesis of mammalian tissues are known to be guided in
part by mechanical stimuli received from the local environment, and tissues
frequently develop to match the physical characteristics (i.e., elasticity) of
their environment. Quantification of these material properties at the microscale
may provide valuable information to guide researchers. Presented here is a
microfluidic platform for the non-destructive ex vivo microscale mechanical
characterization of mammalian tissue samples by atomic force microscopy (AFM).
The device was designed to physically hold a tissue sample in a dynamically
controllable fluid environment while allowing access by an AFM probe operating in
force spectroscopy mode to perform mechanical testing. Results of measurements
performed on mouse submandibular gland samples demonstrate the ability of the
analysis platform to quantify sample elasticity at the microscale, and observe
chemically-induced changes in elasticity.
PMID- 25587410
TI - Microstructured block copolymer surfaces for control of microbe adhesion and
aggregation.
AB - The attachment and arrangement of microbes onto a substrate is influenced by both
the biochemical and physical surface properties. In this report, we develop
lectin-functionalized substrates containing patterned, three-dimensional
polymeric structures of varied shapes and densities and use these to investigate
the effects of topology and spatial confinement on lectin-mediated microbe
immobilization. Films of poly(glycidyl methacrylate)-block-4,4-dimethyl-2
vinylazlactone (PGMA-b-PVDMA) were patterned on silicon surfaces into line arrays
or square grid patterns with 5 MUm wide features and varied pitch. The patterned
films had three-dimensional geometries with 900 nm film thickness. After surface
functionalization with wheat germ agglutinin, the size of Pseudomonas fluorescens
aggregates immobilized was dependent on the pattern dimensions. Films patterned
as parallel lines or square grids with a pitch of 10 MUm or less led to the
immobilization of individual microbes with minimal formation of aggregates. Both
geometries allowed for incremental increases in aggregate size distribution with
each increase in pitch. These engineered surfaces combine spatial confinement
with affinity-based capture to control the extent of microbe adhesion and
aggregation, and can also be used as a platform to investigate intercellular
interactions and biofilm formation in microbial populations of controlled sizes.
PMID- 25587407
TI - Application of a nitric oxide sensor in biomedicine.
AB - In the present study, we describe the biochemical properties and effects of
nitric oxide (NO) in intact and dysfunctional arterial and venous endothelium.
Application of the NO electrochemical sensor in vivo and in vitro in erythrocytes
of healthy subjects and patients with vascular disease are reviewed. The
electrochemical NO sensor device applied to human umbilical venous endothelial
cells (HUVECs) and the description of others NO types of sensors are also
mentioned.
PMID- 25587411
TI - Asynchronous Magnetic Bead Rotation (AMBR) Microviscometer for Label-Free DNA
Analysis.
AB - We have developed a label-free viscosity-based DNA detection system, using
paramagnetic beads as an asynchronous magnetic bead rotation (AMBR)
microviscometer. We have demonstrated experimentally that the bead rotation
period is linearly proportional to the viscosity of a DNA solution surrounding
the paramagnetic bead, as expected theoretically. Simple optical measurement of
asynchronous microbead motion determines solution viscosity precisely in
microscale volumes, thus allowing an estimate of DNA concentration or average
fragment length. The response of the AMBR microviscometer yields reproducible
measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at
template concentrations across a 5000-fold range. The results demonstrate the
feasibility of viscosity-based DNA detection using AMBR in microscale aqueous
volumes.
PMID- 25587412
TI - Hierarchical thin film architectures for enhanced sensor performance: liquid
crystal-mediated electrochemical synthesis of nanostructured imprinted polymer
films for the selective recognition of bupivacaine.
AB - Nanostructured bupivacaine-selective molecularly imprinted 3-aminophenylboronic
acid-p-phenylenediamine co-polymer (MIP) films have been prepared on gold-coated
quartz (Au/quartz) resonators by electrochemical synthesis under cyclic
voltammetric conditions in a liquid crystalline (LC) medium (triton X-100/water).
Films prepared in water and in the absence of template were used for control
studies. Infrared spectroscopic studies demonstrated comparable chemical
compositions for LC and control polymer films. SEM studies revealed that the
topologies of the molecularly imprinted polymer films prepared in the LC medium
(LC-MIP) exhibit discernible 40 nm thick nano-fiber structures, quite unlike the
polymers prepared in the absence of the LC-phase. The sensitivity of the LC-MIP
in a quartz crystal microbalance (QCM) sensor platform was 67.6 +/- 4.9 Hz/mM
under flow injection analysis (FIA) conditions, which was ~250% higher than for
the sensor prepared using the aqueous medium. Detection was possible at 100 nM
(30 ng/mL), and discrimination of bupivacaine from closely related structural
analogs was readily achieved as reflected in the corresponding stability
constants of the MIP-analyte complexes. The facile fabrication and significant
enhancement in sensor sensitivity together highlight the potential of this LC
based imprinting strategy for fabrication of polymeric materials with
hierarchical architectures, in particular for use in surface-dependent
application areas, e.g., biomaterials or sensing.
PMID- 25587414
TI - A phage display screening derived Peptide with affinity for the adeninyl moiety.
AB - Phage display screening of a surface-immobilized adenine derivative led to the
identification of a heptameric peptide with selectivity for adenine as
demonstrated through quartz crystal microbalance (QCM) studies. The peptide
demonstrated a concentration dependent affinity for an adeninyl moiety decorated
surface (K D of 968 +/- 53.3 MUM), which highlights the power of piezoelectric
sensing in the study of weak interactions.
PMID- 25587415
TI - Use of a parasitic wasp as a biosensor.
AB - Screening cargo for illicit substances is in need of rapid high-throughput
inspection systems that accurately identify suspicious cargo. Here we investigate
the ability of a parasitic wasp, Microplitis croceipes to detect and respond to
methyl benzoate, the volatile component of cocaine, by examining their response
to training concentrations, their sensitivity at low concentrations, and their
ability to detect methyl benzoate when two concealment substances (green tea and
ground coffee) are added to the testing arena. Utilizing classical associative
learning techniques with sucrose as reward, we found that M. croceipes learns
individual concentrations of methyl benzoate, and they can generalize this
learning to concentrations 100* lower than the training concentration. Their
sensitivity to methyl benzoate is very low at an estimated 3 ppb. They are also
able to detect methyl benzoate when covered completely by green tea, but were not
able to detect methyl benzoate when covered completely by coffee grounds.
Habituation to the tea and coffee odors prior to testing improves their
responses, resulting in effective detection of methyl benzoate covered by the
coffee grounds. With the aid of the portable device called 'the wasp hound', the
wasps appear to have potential to be effective on-site biosensors for the
detection of cocaine.
PMID- 25587416
TI - Polymerization Parameters Influencing the QCM Response Characteristics of BSA
MIP.
AB - Designing Molecularly Imprinted Polymers for sensing proteins is still a somewhat
empirical process due to the inherent complexity of protein imprinting. Based on
Bovine Serum Albumin as a model analyte, we explored the influence of a range of
experimental parameters on the final sensor responses. The optimized polymer
contains 70% cross linker. Lower amounts lead to higher sensitivity, but also
sensor response times substantially increase (to up to 10 h) at constant
imprinting effect (signal ratio MIP/NIP on quartz crystal microbalance-QCM).
However, by shifting the polymer properties to more hydrophilic by replacing
methacrylic acid by acrylic acid, part of the decreased sensitivity can be
recovered leading to appreciable sensor responses. Changing polymer morphology by
bulk imprinting and nanoparticle approaches has much lower influence on
sensitivity.
PMID- 25587413
TI - Recent advances in bioprinting and applications for biosensing.
AB - Future biosensing applications will require high performance, including real-time
monitoring of physiological events, incorporation of biosensors into feedback
based devices, detection of toxins, and advanced diagnostics. Such functionality
will necessitate biosensors with increased sensitivity, specificity, and
throughput, as well as the ability to simultaneously detect multiple analytes.
While these demands have yet to be fully realized, recent advances in
biofabrication may allow sensors to achieve the high spatial sensitivity
required, and bring us closer to achieving devices with these capabilities. To
this end, we review recent advances in biofabrication techniques that may enable
cutting-edge biosensors. In particular, we focus on bioprinting techniques (e.g.,
microcontact printing, inkjet printing, and laser direct-write) that may prove
pivotal to biosensor fabrication and scaling. Recent biosensors have employed
these fabrication techniques with success, and further development may enable
higher performance, including multiplexing multiple analytes or cell types within
a single biosensor. We also review recent advances in 3D bioprinting, and explore
their potential to create biosensors with live cells encapsulated in 3D
microenvironments. Such advances in biofabrication will expand biosensor utility
and availability, with impact realized in many interdisciplinary fields, as well
as in the clinic.
PMID- 25587418
TI - Magnetic Properties of FeNi-Based Thin Film Materials with Different Additives.
AB - This paper presents a study of FeNi-based thin film materials deposited with Mo,
Al and B using a co-sputtering process. The existence of soft magnetic properties
in combination with strong magneto-mechanical coupling makes these materials
attractive for sensor applications. Our findings show that FeNi deposited with Mo
or Al yields magnetically soft materials and that depositing with B further
increases the softness. The out-of-plane magnetic anisotropy of FeNi thin films
is reduced by depositing with Al and completely removed by depositing with B. The
effect of depositing with Mo is dependent on the Mo concentration. The coercivity
of FeNiMo and FeNiAl is reduced to less than a half of that of FeNi, and a value
as low as 40 A/m is obtained for FeNiB. The surfaces of the obtained FeNiMo,
FeNiAl and FeNiB thin films reveal very different morphologies. The surface of
FeNiMo shows nano-cracks, while the FeNiAl films show large clusters and fewer
nano-cracks. When FeNi is deposited with B, a very smooth morphology is obtained.
The crystal structure of FeNiMo strongly depends on the depositant concentration
and changes into an amorphous structure at a higher Mo level. FeNiAl thin films
remain polycrystalline, even at a very high concentration of Al, and FeNiB films
are amorphous, even at a very low concentration of B.
PMID- 25587417
TI - Localized surface plasmon resonance as a biosensing platform for developing
countries.
AB - The discovery of the phenomena known as localized surface plasmon resonance
(LSPR) has provided the basis for many research areas, ranging from materials
science to biosensing. LSPR has since been viewed as a transduction platform that
could yield affordable, portable devices for a multitude of applications. This
review aims to outline the potential applications within developing countries and
the challenges that are likely to be faced before the technology can be
effectively employed.
PMID- 25587419
TI - An inexpensive, fast and sensitive quantitative lateral flow magneto-immunoassay
for total prostate specific antigen.
AB - We describe the detection characteristics of a device the Resonant Coil
Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in
immunochromatographic (lateral flow) assays. Lateral flow assays were developed
using PMPs for the measurement of total prostate specific antigen (PSA) in serum
samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM
and is at clinically significant concentrations. Comparison of data obtained in a
pilot study from the analysis of serum samples with commercially available
immunoassays shows good agreement. The development of a quantitative magneto
immunoassay in lateral flow format for total PSA suggests the potential of the
RCM to operate with many immunoassay formats. The RCM has the potential to be
modified to quantify multiple analytes in this format. This research shows
promise for the development of an inexpensive device capable of quantifying
multiple analytes at the point-of-care using a magneto-immunoassay in lateral
flow format.
PMID- 25587421
TI - Electrochemical biosensors based on ferroceneboronic Acid and its derivatives: a
review.
AB - We review recent progress in the development of electrochemical biosensors based
on ferroceneboronic acid (FcBA) and ferrocene (Fc)-modified boronic acids. These
compounds can be used to construct electrochemical biosensors because they
consist of a binding site (i.e., a boronic acid moiety) and an electrochemically
active part (i.e., an Fc residue). By taking advantage of the unique properties
of FcBA and its derivatives, electrochemical sensors sensitive to sugars,
glycated hemoglobin (HbA1c), fluoride (F(-)) ions, and so forth have been widely
studied. FcBA-based sugar sensors rely on the selective binding of FcBA to 1,2-
or 1,3-diol residues of sugars through the formation of cyclic boronate ester
bonds. The redox properties of FcBA-sugar adduct differ from those of free FcBA,
which forms the basis of the electrochemical determination of sugars. Thus, non
enzymatic glucose sensors are now being actively studied using FcBA and Fc
modified boronic acids as redox markers. Using a similar principle, HbA1c can be
detected by FcBA-based electrochemical systems because it contains hydrocarbon
chains on the polypeptide chain. HbA1c sensors are useful for monitoring blood
glucose levels over the preceding 8-12 weeks. In addition, FcBA and Fc-modified
boronic acids have been used for the detection of F(-) ions due to the selective
binding of boronic acid to F(-) ions. F(-)-ion sensors may be useful alternatives
to conventional ion-selective electrodes sensitive to F(-) ion. Furthermore, FcBA
derivatives have been studied to construct lectin; steroids; nucleotides;
salicylic acid; and bacteria sensors. One of the limitations of FcBA-based
sensors comes from the fact that FcBA derivatives are added in sample solutions
as reagents. FcBA derivatives should be immobilized on the surface of electrodes
for developing reagentless sensors.
PMID- 25587422
TI - Study of Paclitaxel-Treated HeLa Cells by Differential Electrical Impedance Flow
Cytometry.
AB - This work describes the electrical investigation of paclitaxel-treated HeLa cells
using a custom-made microfluidic biosensor for whole cell analysis in continuous
flow. We apply the method of differential electrical impedance spectroscopy to
treated HeLa cells in order to elucidate the changes in electrical properties
compared with non-treated cells. We found that our microfluidic system was able
to distinguish between treated and non-treated cells. Furthermore, we utilize a
model for electrical impedance spectroscopy in order to perform a theoretical
study to clarify our results. This study focuses on investigating the changes in
the electrical properties of the cell membrane caused by the effect of
paclitaxel. We observe good agreement between the model and the obtained results.
This establishes the proof-of-concept for the application in cell drug therapy.
PMID- 25587420
TI - Sensing magnetic directions in birds: radical pair processes involving
cryptochrome.
AB - Birds can use the geomagnetic field for compass orientation. Behavioral
experiments, mostly with migrating passerines, revealed three characteristics of
the avian magnetic compass: (1) it works spontaneously only in a narrow
functional window around the intensity of the ambient magnetic field, but can
adapt to other intensities, (2) it is an "inclination compass", not based on the
polarity of the magnetic field, but the axial course of the field lines, and (3)
it requires short-wavelength light from UV to 565 nm Green. The Radical Pair
Model of magnetoreception can explain these properties by proposing spin-chemical
processes in photopigments as underlying mechanism. Applying radio frequency
fields, a diagnostic tool for radical pair processes, supports an involvement of
a radical pair mechanism in avian magnetoreception: added to the geomagnetic
field, they disrupted orientation, presumably by interfering with the receptive
processes. Cryptochromes have been suggested as receptor molecules. Cry1a is
found in the eyes of birds, where it is located at the membranes of the disks in
the outer segments of the UV-cones in chickens and robins. Immuno-histochemical
studies show that it is activated by the wavelengths of light that allow magnetic
compass orientation in birds.
PMID- 25587424
TI - Piezoelectric biosensors for organophosphate and carbamate pesticides: a review.
AB - Due to the great amount of pesticides currently being used, there is an increased
interest for developing biosensors for their detection. Among all the physical
transducers, piezoelectric systems have emerged as the most attractive due to
their simplicity, low instrumentation costs, possibility for real-time and label
free detection and generally high sensitivity. This paper presents an overview of
biosensors based on the quartz crystal microbalance, which have been reported in
the literature for organophosphate and carbamate pesticide analysis.
PMID- 25587423
TI - Biosensors with built-in biomolecular logic gates for practical applications.
AB - Molecular logic gates, designs constructed with biological and chemical
molecules, have emerged as an alternative computing approach to silicon-based
logic operations. These molecular computers are capable of receiving and
integrating multiple stimuli of biochemical significance to generate a definitive
output, opening a new research avenue to advanced diagnostics and therapeutics
which demand handling of complex factors and precise control. In molecularly
gated devices, Boolean logic computations can be activated by specific inputs and
accurately processed via bio-recognition, bio-catalysis, and selective chemical
reactions. In this review, we survey recent advances of the molecular logic
approaches to practical applications of biosensors, including designs constructed
with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as
well as the research avenues for future development of digitally operating "sense
and act" schemes that logically process biochemical signals through networked
circuits to implement intelligent control systems.
PMID- 25587425
TI - Microelectrode Arrays and the Use of PEG-Functionalized Diblock Copolymer
Coatings.
AB - PEG-modified diblock copolymer surfaces have been examined for their
compatibility with microelectrode array based analytical methods. The use of PEG
modified polymer surfaces on the arrays was initially problematic because the
redox couples used in the experiments were adsorbed by the polymer. This led the
current measured by cyclic voltammetry for the redox couple to be unstable and
increase with time. However, two key findings allow the experiments to be
successful. First, after multiple cyclic voltammograms the current associated
with the redox couple does stabilize so that a good baseline current can be
established. Second, the rate at which the current stabilizes is consistent every
time a particular coated array is used. Hence, multiple analytical experiments
can be conducted on an array coated with a PEG-modified diblock copolymer and the
data obtained is comparable as long as the data for each experiment is collected
at a consistent time point.
PMID- 25587426
TI - Biosensor Applications of MAPLE Deposited Lipase.
AB - Matrix Assisted Pulsed Laser Evaporation (MAPLE) is a thin film deposition
technique derived from Pulsed Laser Deposition (PLD) for deposition of delicate
(polymers, complex biological molecules, etc.) materials in undamaged form. The
main difference of MAPLE technique with respect to PLD is the target: it is a
frozen solution or suspension of the (guest) molecules to be deposited in a
volatile substance (matrix). Since laser beam energy is mainly absorbed by the
matrix, damages to the delicate guest molecules are avoided, or at least reduced.
Lipase, an enzyme catalyzing reactions borne by triglycerides, has been used in
biosensors for detection of beta-hydroxyacid esters and triglycerides in blood
serum. Enzymes immobilization on a substrate is therefore required. In this paper
we show that it is possible, using MAPLE technique, to deposit lipase on a
substrate, as shown by AFM observation, preserving its conformational structure,
as shown by FTIR analysis.
PMID- 25587427
TI - Detection of the inflammation biomarker C-reactive protein in serum samples:
towards an optimal biosensor formula.
AB - The development of an electrochemical immunosensor for the biomarker, C-reactive
protein (CRP), is reported in this work. CRP has been used to assess inflammation
and is also used in a multi-biomarker system as a predictive biomarker for
cardiovascular disease risk. A gold-based working electrode sensor was developed,
and the types of electrode printing inks and ink curing techniques were then
optimized. The electrodes with the best performance parameters were then employed
for the construction of an immunosensor for CRP by immobilizing anti-human CRP
antibody on the working electrode surface. A sandwich enzyme-linked immunosorbent
assay (ELISA) was then constructed after sample addition by using anti-human CRP
antibody labelled with horseradish peroxidase (HRP). The signal was generated by
the addition of a mediator/substrate system comprised of 3,3,5',5'
Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H2O2).
Measurements were conducted using chronoamperometry at -200 mV against an
integrated Ag/AgCl reference electrode. A CRP limit of detection (LOD) of 2.2
ng.mL(-1) was achieved in spiked serum samples, and performance agreement was
obtained with reference to a commercial ELISA kit. The developed CRP immunosensor
was able to detect a diagnostically relevant range of the biomarker in serum
without the need for signal amplification using nanoparticles, paving the way for
future development on a cardiac panel electrochemical point-of-care diagnostic
device.
PMID- 25587428
TI - Evaluating the Equilibrium Association Constant between ArtinM Lectin and Myeloid
Leukemia Cells by Impedimetric and Piezoelectric Label Free Approaches.
AB - Label-free methods for evaluating lectin-cell binding have been developed to
determine the lectin-carbohydrate interactions in the context of cell-surface
oligosaccharides. In the present study, mass loading and electrochemical
transducer signals were compared to characterize the interaction between lectin
and cellular membranes by measuring the equilibrium association constant, Ka ,
between ArtinM lectin and the carbohydrate sites of NB4 leukemia cells. By
functionalizing sensor interfaces with ArtinM, it was possible to determine Ka
over a range of leukemia cell concentrations to construct analytical curves from
impedimetric and/or mass-associated frequency shifts with analytical signals
following a Langmuir pattern. Using the Langmuir isotherm-binding model, the Ka
obtained were (8.9 +/- 1.0) * 10(-5) mL/cell and (1.05 +/- 0.09) * 10(-6) mL/cell
with the electrochemical impedance spectroscopy (EIS) and quartz crystal
microbalance (QCM) methods, respectively. The observed differences were
attributed to the intrinsic characteristic sensitivity of each method in
following Langmuir isotherm premises.
PMID- 25587429
TI - Carboxylated or aminated polyaniline-multiwalled carbon nanotubes nanohybrids for
immobilization of cellobiose dehydrogenase on gold electrodes.
AB - Polymer-multiwalled carbon nanotube (MWCNT) nanohybrids, which differ in surface
charge have been synthesized to study the bioelectrocatalysis of adsorbed
cellobiose dehydrogenase (CDH) from Phanerochaete sordida on gold electrodes. To
obtain negatively charged nanohybrids, poly(3-amino-4-methoxybenzoic acid-co
aniline) (P(AMB-A)) was covalently linked to the surface of MWCNTs while
modification with p-phenylenediamine (PDA) converted the COOH-groups to
positively charged amino groups. Fourier transform infrared spectroscopy (FTIR)
measurements verified the p-phenylenediamine (PDA) modification of the polymer
CNT nanohybrids. The positively charged nanohybrid MWCNT-P(AMB-A)-PDA promoted
direct electron transfer (DET) of CDH to the electrode and bioelectrocatalysis of
lactose was observed. Amperometric measurements gave an electrochemical response
with KMapp = 8.89 mM and a current density of 410 nA/cm(2) (15 mM lactose). The
catalytic response was tested at pH 3.5 and 4.5. Interference by ascorbic acid
was not observed. The study proves that DET between the MWCNT-P(AMB-A)-PDA
nanohybrids and CDH is efficient and allows the sensorial detection of lactose.
PMID- 25587430
TI - Development of a Pseudomonas aeruginosa Agmatine Biosensor.
AB - Agmatine, decarboxylated arginine, is an important intermediary in polyamine
production for many prokaryotes, but serves higher functions in eukaryotes such
as nitric oxide inhibition and roles in neurotransmission. Pseudomonas aeruginosa
relies on the arginine decarboxylase and agmatine deiminase pathways to convert
arginine into putrescine. One of the two known agmatine deiminase operons, aguBA,
contains an agmatine sensitive TetR promoter controlled by AguR. We have
discovered that this promoter element can produce a titratable induction of its
gene products in response to agmatine, and utilized this discovery to make a
luminescent agmatine biosensor in P. aeruginosa. The genome of the P. aeruginosa
lab strain UCBPP-PA14 was altered to remove both its ability to synthesize or
destroy agmatine, and insertion of the luminescent reporter construct allows it
to produce light in proportion to the amount of exogenous agmatine applied from
~100 nM to 1mM. Furthermore it does not respond to related compounds including
arginine or putrescine. To demonstrate potential applications the biosensor was
used to detect agmatine in spent supernatants, to monitor the development of
arginine decarboxylase over time, and to detect agmatine in the spinal cords of
live mice.
PMID- 25587431
TI - Electrical Wiring of the Aldehyde Oxidoreductase PaoABC with a Polymer Containing
Osmium Redox Centers: Biosensors for Benzaldehyde and GABA.
AB - Biosensors for the detection of benzaldehyde and gamma-aminobutyric acid (GABA)
are reported using aldehyde oxidoreductase PaoABC from Escherichia coli
immobilized in a polymer containing bound low potential osmium redox complexes.
The electrically connected enzyme already electrooxidizes benzaldehyde at
potentials below -0.15 V (vs. Ag|AgCl, 1 M KCl). The pH-dependence of
benzaldehyde oxidation can be strongly influenced by the ionic strength. The
effect is similar with the soluble osmium redox complex and therefore indicates a
clear electrostatic effect on the bioelectrocatalytic efficiency of PaoABC in the
osmium containing redox polymer. At lower ionic strength, the pH-optimum is high
and can be switched to low pH-values at high ionic strength. This offers
biosensing at high and low pH-values. A "reagentless" biosensor has been formed
with enzyme wired onto a screen-printed electrode in a flow cell device. The
response time to addition of benzaldehyde is 30 s, and the measuring range is
between 10-150 uM and the detection limit of 5 uM (signal to noise ratio 3:1) of
benzaldehyde. The relative standard deviation in a series (n = 13) for 200 uM
benzaldehyde is 1.9%. For the biosensor, a response to succinic semialdehyde was
also identified. Based on this response and the ability to work at high pH a
biosensor for GABA is proposed by coimmobilizing GABA-aminotransferase (GABA-T)
and PaoABC in the osmium containing redox polymer.
PMID- 25587432
TI - Microfabricated tactile sensors for biomedical applications: a review.
AB - During the last decades, tactile sensors based on different sensing principles
have been developed due to the growing interest in robotics and, mainly, in
medical applications. Several technological solutions have been employed to
design tactile sensors; in particular, solutions based on microfabrication
present several attractive features. Microfabrication technologies allow for
developing miniaturized sensors with good performance in terms of metrological
properties (e.g., accuracy, sensitivity, low power consumption, and frequency
response). Small size and good metrological properties heighten the potential
role of tactile sensors in medicine, making them especially attractive to be
integrated in smart interfaces and microsurgical tools. This paper provides an
overview of microfabricated tactile sensors, focusing on the mean principles of
sensing, i.e., piezoresistive, piezoelectric and capacitive sensors. These
sensors are employed for measuring contact properties, in particular force and
pressure, in three main medical fields, i.e., prosthetics and artificial skin,
minimal access surgery and smart interfaces for biomechanical analysis. The
working principles and the metrological properties of the most promising tactile,
microfabricated sensors are analyzed, together with their application in
medicine. Finally, the new emerging technologies in these fields are briefly
described.
PMID- 25587433
TI - Fabrication of functionalized carbon nanotube buckypaper electrodes for
application in glucose biosensors.
AB - A highly sensitive glucose detection method was developed using functionalized
carbon nanotube buckypaper as a free standing electrode in an electrochemical
biosensor. Glucose oxidase was immobilized onto various buckypaper samples in
order to oxidize glucose resulting in a measureable current/voltage signal output
of the biosensor. Cyclic voltammetry (CV) and amperometry were utilized to
determine the sensitivity of these buckypaper electrodes. Sensors of three
different types of buckypaper were prepared and compared. These modified
buckypaper electrode-based sensors showed much higher sensitivity to glucose
compared to other electrochemical glucose sensors.
PMID- 25587434
TI - Trimetallic (aurod-pdshell-ptcluster) catalyst used as amperometric hydrogen
peroxide sensor.
AB - Bimetallic nanostructured core-shell structures are commonly used as catalysts in
a wide variety of reactions. We surmised that the addition of an additional metal
would potentially allow catalytic tailoring with the possibility of an increase
in activity. Here a tri-metallic catalytic structure, consisting of clustered
catalytic Pt on the surface of a Pd shell supported on a rod shaped Au core was
fabricated. The significance of the additional metallic component is shown by
comparative electrochemically active surface area (ECSA) analysis results for the
trimetallic Aurod-Pdshell-Ptcluster, bimetallic Aurod-Ptcluster and monometallic
JM-Pt (used as a reference), which have respective ECSA values (cm(2)/mgPt) of
1883.0, 1371.7 and 879. The potential utility of the trimetallic catalysts was
shown in a hydrogen peroxide sensing protocol, which showed the catalyst to have
a sensitivity of 604 iA/mMcm(2) within a linear range of 0.0013-6.191 mM.
PMID- 25587435
TI - Biosensors for the detection of antibiotics in poultry industry-a review.
AB - Antibiotic resistance is emerging as a potential threat in the next decades. This
is a global phenomenon whereby globalization is acting as a catalyst. Presently,
the most common techniques used for the detection of antibiotics are biosensors,
ELISA and liquid chromatography-mass spectrometry. Each of these techniques has
its benefits as well as drawbacks. This review aims to evaluate different
biosensing techniques and their working principles in order to accurately,
quickly and practically detect antibiotics in chicken muscle and blood serum. The
review is divided into three main sections, namely: a biosensors overview, a
section on biosensor recognition and a section on biosensor transducing elements.
The first segment provides a detailed overview on the different techniques
available and their respective advantages and disadvantages. The second section
consists of an evaluation of several analyte systems and their mechanisms. The
last section of this review studies the working principles of biosensing
transducing elements, focusing mainly on surface plasmon resonance (SPR)
technology and its applications in industries.
PMID- 25587437
TI - High-contrast fluorescence microscopy for a biomolecular analysis based on
polarization techniques using an optical interference mirror slide.
AB - Fluorescence microscopy with an improved contrast for fluorescence images is
developed using an optical interference mirror (OIM) slide, which can enhance the
fluorescence from a fluorophore as a result of the double interference of the
excitation light and emission light. To improve the contrast of a fluorescence
image using an OIM slide, a linearly-polarized excitation light was employed, and
the fluorescence emission polarized perpendicular to the polarization of the
excitation light was detected. The image contrast with this optical system was
improved 110-fold for rhodamine B spotted on the OIM, in comparison with a glass
slide using a general fluorescence microscopy optical system. Moreover, a 24-fold
improvement of the image contrast was achieved for the detection of Cy3-labeled
streptavidin bound to immobilize biotin.
PMID- 25587436
TI - Biosensors for inorganic and organic arsenicals.
AB - Arsenic is a natural environmental contaminant to which humans are routinely
exposed and is strongly associated with human health problems, including cancer,
cardiovascular and neurological diseases. To date, a number of biosensors for the
detection of arsenic involving the coupling of biological engineering and
electrochemical techniques has been developed. The properties of whole-cell
bacterial or cell-free biosensors are summarized in the present review with
emphasis on their sensitivity and selectivity. Their limitations and future
challenges are highlighted.
PMID- 25587439
TI - Mucocutaneous Manifestations of HIV and the Correlation with WHO Clinical Staging
in a Tertiary Hospital in Nigeria.
AB - Skin diseases are indicators of HIV/AIDS which correlates with WHO clinical
stages. In resource limited environment where CD4 count is not readily available,
they can be used in assessing HIV patients. The study aims to determine the
mucocutaneous manifestations in HIV positive patients and their correlation with
WHO clinical stages. A prospective cross-sectional study of mucocutaneous
conditions was done among 215 newly diagnosed HIV patients from June 2008 to May
2012 at adult ART clinic, Wesley Guild Hospital Unit, OAU Teaching Hospitals
Complex, Ilesha, Osun State, Nigeria. There were 156 dermatoses with
oral/oesophageal/vaginal candidiasis (41.1%), PPE (24.4%), dermatophytic
infections (8.9%), and herpes zoster (3.8%) as the most common dermatoses. The
proportions of dermatoses were 4.5%, 21.8%, 53.2%, and 20.5% in stages 1-4,
respectively. A significant relationship (using Pearson's Chi square with P value
<0.05) was obtained between dermatoses and WHO clinical stages. Pearson's
correlation coefficient showed a positive correlation between the number of
dermatoses and the WHO clinical stages. Dermatoses can therefore serve as
diagnostic and prognostic markers in resource limited settings to initiate HAART
in clinical stages 3 and 4.
PMID- 25587438
TI - A delphi study to detect deficiencies and propose actions in real life treatment
of neovascular age-related macular degeneration.
AB - Purpose. Spanish retina specialists were surveyed in order to propose actions to
decrease deficiencies in real-life neovascular age macular degeneration treatment
(nv-AMD). Methods. One hundred experts, members of the Spanish Vitreoretinal
Society (SERV), were invited to complete an online survey of 52 statements about
nv-AMD management with a modified Delphi methodology. Four rounds were performed
using a 5-point Linkert scale. Recommendations were developed after analyzing the
differences between the results and the SERV guidelines recommendations. Results.
Eighty-seven specialists completed all the Delphi rounds. Once major potential
deficiencies in real-life nv-AMD treatment were identified, 15 recommendations
were developed with a high level of agreement. Consensus statements to reduce the
burden of the disease included the use of treat and extend regimen and to reduce
the amount of diagnostic tests during the loading phase and training technical
staff to perform these tests and reduce the time between relapse detection and
reinjection, as well as establishing patient referral protocols to outside
general ophthalmology clinics. Conclusion. The level of agreement with the final
recommendations for nv-AMD treatment among Spanish retinal specialist was high
indicating that some actions could be applied in order to reduce the deficiencies
in real-life nv-AMD treatment.
PMID- 25587440
TI - A retrospective study investigating the incidence and predisposing factors of
hospital-acquired anemia.
AB - Hospitalized patients frequently have considerable volumes of blood removed for
diagnostic testing which could lead to the development of hospital-acquired
anemia. Low hemoglobin levels during hospitalization may result in significant
morbidity for patients with underlying cardiorespiratory and other illnesses. We
performed a retrospective study and data was collected using a chart review
facilitated through an electronic medical record. A total of 479 patients who
were not anemic during admission were included in analysis. In our study, we
investigated the incidence of HAA and found that, between admission and
discharge, 65% of patients dropped their hemoglobin by 1.0 g/dL or more, and 49%
of patients developed anemia. We also found that the decrease in hemoglobin
between admission and discharge did not differ significantly with smaller
phlebotomy tubes. In multivariate analysis, we found that patients with longer
hospitalization and those with lower BMI are at higher risk of developing HAA. In
conclusion, our study confirms that hospital-acquired anemia is common. More
aggressive strategies such as reducing the frequency of blood draws and expanding
the use of smaller volume tubes for other laboratory panels may be helpful in
reducing the incidence of HAA during hospitalization.
PMID- 25587441
TI - Freedom and confinement: patients' experiences of life with home haemodialysis.
AB - Patients with chronic end stage renal disease need dialysis to survive; however,
they also need a treatment that suits their life situation. It is important that
healthcare providers provide reliable, up-to-date information about different
dialysis treatment options. Since home haemodialysis is a relatively new
treatment, it is necessary to gather more knowledge about what the treatment
entails from the patient's perspective. The aim of this study was to describe
patients' experiences of having home haemodialysis. To gain access to the
patients' experiences, they were asked to write narratives, which describe both
their good and bad experiences of life with the treatment. The narratives were
analysed with a qualitative method. The results of this analysis are subdivided
into five themes: freedom to be at home and control their own treatment, feeling
of being alone with the responsibility, changes in the home environment, need for
support, and security and well-being with home haemodialysis. The conclusion is
that home haemodialysis provides a certain level of freedom, but the freedom is
limited as the treatment itself is restrictive. In order to improve patients'
experiences with home haemodialysis, more research based on patients' experiences
is needed and it is necessary to involve the patients in the development of the
care.
PMID- 25587442
TI - Surgical implications of asymmetric distribution of dermal collagen and elastic
fibres in two orientations of skin samples from extremities.
AB - Background. Clinically, scar related complications are observed to be dissimilar
in different regions of the body. Unequal distribution of dermal collagen and
elastic fibres in different orientations could be one of the multifocal causes of
scar related complications, for which this evaluating study has been taken up.
Materials and Method. 300 skin samples collected in horizontal and vertical
orientations were studied histomorphometrically. This study involved image
analysis of specially stained histological section using tissue-quant software.
The outcome result was termed as quantitative fraction. From the result, various
ratio values were also calculated for the ratio analysis. Results. The
differences in the quantitative fraction of dermal elastic content between 2
directions were statistically significant at joint areas (shoulder joint, wrist,
and ankle) (P < 0.001) but for collagen, significant difference was observed at
shoulder joint and wrist only. Dermis of the forearm and thigh did not show any
differences in their collagen content, but for elastic, thigh did show a
significant difference while forearm had no change between 2 directions.
Conclusion. Analysis of unequal content of dermal element in two directions under
the perspective of wound healing consequences is subjective depending upon the
anatomical position and functional status of the areas.
PMID- 25587444
TI - Premature calcifications of costal cartilages: a new perspective.
AB - Background. Calcifications of the costal cartilages occur, as a rule, not until
the age of 30 years. The knowledge of the clinical significance of early and
extensive calcifications is still incomplete. Materials and Methods. A search was
made to find patients below the age of 30 years who showed distinct
calcifications of their lower costal cartilages by viewing 360 random samples of
intravenous pyelograms and abdominal plain films. The histories, and clinical and
laboratory findings of these patients were analyzed. Results. Nineteen patients
fulfilled the criteria of premature calcifications of costal cartilages (CCCs).
The patients had in common that they were frequently referred to a hospital and
were treated by several medical disciplines. Nevertheless many complaints of the
patients remained unsolved. Premature CCCs were often associated with rare
endocrine disorders, inborn errors of metabolism, and abnormal hematologic
findings. Among the metabolic disorders there were 2 proven porphyrias and 7
patients with a suspected porphyria but with inconclusive laboratory findings.
Conclusion. Premature CCCs are unlikely to be a normal variant in skeletal
radiology. The findings in this small group of patients call for more intensive
studies, especially in regard to the putative role of a porphyria.
PMID- 25587443
TI - Sleep disordered breathing in children with mitochondrial disease.
AB - A retrospective chart review study was performed to determine the presence of
sleep disordered breathing (SDB) in children with primary mitochondrial disease
(MD). The symptoms, sleep-related breathing, and movement abnormalities are
described for 18 subjects (ages 1.5 to 18 years, 61% male) with MD who underwent
polysomnography in our pediatric sleep center from 2007 to 2012. Of the 18
subjects with MD, the common indications for polysomnography were excessive
somnolence or fatigue (61%, N = 11), snoring (44%, N = 8), and sleep movement
complaints (17%, N = 3). Polysomnographic measurements showed SDB in 56% (N = 10)
(obstructive sleep apnea in 60% (N = 6), hypoxemia in 40% (N = 4), and sleep
hypoventilation in 20% (N = 2)). There was a significant association between
decreased muscle tone and SDB (P: 0.043) as well as obese and overweight status
with SDB (P = 0.036). SDB is common in subjects with MD. Early detection of SDB,
utilizing polysomnography, should be considered to assist in identification of MD
patients who may benefit from sleep-related interventions.
PMID- 25587445
TI - Image guidance in radiation therapy: techniques and applications.
AB - In modern day radiotherapy, the emphasis on reduction on volume exposed to high
radiotherapy doses, improving treatment precision as well as reducing radiation
related normal tissue toxicity has increased, and thus there is greater
importance given to accurate position verification and correction before
delivering radiotherapy. At present, several techniques that accomplish these
goals impeccably have been developed, though all of them have their limitations.
There is no single method available that eliminates treatment-related
uncertainties without considerably adding to the cost. However, delivering "high
precision radiotherapy" without periodic image guidance would do more harm than
treating large volumes to compensate for setup errors. In the present review, we
discuss the concept of image guidance in radiotherapy, the current techniques
available, and their expected benefits and pitfalls.
PMID- 25587446
TI - Passive Posterior Tibial Subluxation on Routine Knee MRI as a Secondary Sign of
PCL Tear.
AB - The posterior drawer test is an accurate clinical test to diagnose posterior
cruciate ligament (PCL), indicating laxity of the PCL that allows posterior
tibial translation. This study aimed to determine whether posterior tibial
translation relative to the femur on routine MRI could serve as an additional
sign of PCL tear. Routine knee MRI in eleven patients (7 males, 4 females) with
arthroscopically confirmed isolated PCL tears were reviewed independently by two
musculoskeletal radiologists. Measurements of tibial translation were made in the
medial and lateral compartments of patients and controls (10 males, 12 females)
without clinical or MRI evidence of ligament injury. Significant medial
compartment posterior tibial translation was present in patients with PCL tear
compared to controls (+2.93 mm versus +0.03 mm, P = 0.002) with excellent
interobserver agreement (intraclass correlation coefficient (ICC) = 0.94). No
significant difference in lateral compartment tibial translation was observed
(+0.17 mm versus -0.57 mm, P = 0.366) despite excellent interobserver agreement
(ICC = 0.96). Posterior tibial translation in the midmedial compartment may be a
secondary sign of isolated PCL tear on routine knee MRI with passive extension
without manipulation or weight bearing. Additional work in a larger cohort may
better address the accuracy of this finding.
PMID- 25587447
TI - Annual decline in pentraxin 3 is a risk of vascular access troubles in
hemodialysis patients.
AB - Pentraxin 3 (PTX3), a multifunctional modulator of the innate immunoinflammatory
response, is higher in patients undergoing hemodialysis than healthy control. Our
study focused on annual change in PTX3 levels in patients with chronic
hemodialysis, because regularly undergoing hemodialysis for many years modifies
vascular inflammatory status. To demonstrate whether annual change in PTX3 is
associated with vascular events, we measured blood levels of pentraxins (PTX3 and
high-sensitivity C-reactive protein (hsCRP)) at baseline and in the next year in
76 hemodialysis patients and observed 20 patients with vascular access troubles
during follow-up years. The annual decline in PTX3, but not hsCRP, is a
significant risk of the incidence of vascular access trouble that is a critical
and specific complication for hemodialysis patients (hazard ratio; 0.732 per +1
ng/mL/year in PTX3, (*) P = 0.039). This study is the first to focus on the
annual change of pentraxins in a hemodialysis cohort.
PMID- 25587448
TI - Sustainability literacy of older people in retirement villages.
AB - With many developed countries experiencing the aging of the population, older
people play a large role in contributing to environmental problems but also to
environmental solutions. The purpose of this research is to understand the
awareness and behavior of current older people living in retirement villages
towards sustainability development. To achieve this, a sustainability literacy
survey was conducted with 65 older residents of a private retirement village
located 10 Km outside the Brisbane, Australia's central business district (CBD).
Most of residents recognized the importance of environment protection and would
like to lead a more environmentally friendly lifestyle. In addition, the majority
were willing to pay higher prices for a living environment with sustainable
features. The importance of positive social communications was emphasized with
most residents having established good relationships with others in the village.
The findings provide an important insight into consumer perspectives regarding
the sustainable features that should and can be incorporated into the village
planning and development.
PMID- 25587451
TI - Fatty Acid Composition of Egg Yolk from Chickens Fed a Diet including Marigold
(Tagetes erecta L.).
AB - The objective of this study was to determine the effects of diet supplemented
with marigold on egg yolk fatty acid composition and egg quality parameters.
Sixty hens were assigned into three groups and fed diets supplemented with 0
(control), 10 g kg(-1), or 20 g kg(-1) marigold for 42 days. Eggs collected at
the 6th week of the study were analyzed for fatty acid analysis. Laying
performance, egg quality parameters, and feed intake were also evaluated. Yolk
color scores in the group fed the 20 g kg(-1) marigold-supplemented diet were
found greater than control (10.77 versus 9.77). Inclusion of 20 g kg(-1) marigold
in diet influenced egg weights adversely compared to the control. Diet
supplemented with 10 g kg(-1) or 20 g kg(-1) marigold increased the levels of
C16:0 and C18:0 and decreased levels of C16:1 (n-7) and C18:1 (n-9) in the egg
yolk. Also, diet including marigold increased total saturated fatty acids (SFA)
and decreased monounsaturated fatty acids (MUFA) in the egg yolk.
PMID- 25587449
TI - A pilot study of an exercise-based patient education program in people with
multiple sclerosis.
AB - There is increasing evidence that physical exercise leads to numerous positive
effects in PwMS. However, long-term effects of exercise may only be achievable if
training is implemented in daily routine. Enabling patients to exercise
regularly, we developed a patient education program focused on evidence-based
information of training. PwMS were educated in neurophysiological effects of
physical exercise, exercise-induced benefits for PwMS, and risk factors (e.g.,
weather). Fifteen PwMS were analyzed before (T 0) and after (T 1) a 12-week
patient education. Afterwards, participants performed their exercises
autonomously for 32 weeks and were tested in sustainability tests (T 2). Guided
interviews were carried out, additionally. Significant improvements from T 0 to T
1 were found in 6MWT, gait velocity, TUG, fatigue, and quality of life.
Significant results of TUG and gait velocity from T 1 to T 2 demonstrated that
participants kept few effects after the 32-week training phase. Qualitative
analyses showed improved self-confidence and identified training strategies and
barriers. This pilot study provides evidence that PwMS are able to acquire good
knowledge about physical exercise and apply this knowledge successfully in
training management. One might conclude that this exercise-based patient
education seems to be a feasible option to maintain or improve patients' integral
constitution concerning physical and mental health.
PMID- 25587450
TI - Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.
AB - OBJECTIVES: The aim of this review was to identify clinically significant
ultrasound predictors of adverse neonatal outcome in fetal gastroschisis.
METHODS: A quasi-systematic review was conducted in PubMed and Ovid using the key
terms "gastroschisis," "predictors," "outcome," and "ultrasound." RESULTS: A
total of 18 papers were included. The most common sonographic predictors were
intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR),
and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were
consistently found to be statistically insignificant with respect to predicting
adverse outcome including abdominal circumference, stomach herniation and
dilatation, and extra-abdominal bowel dilatation (EABD). CONCLUSIONS:
Gastroschisis is associated with several comorbidities, yet there is much
discrepancy in the literature regarding which specific ultrasound markers best
predict adverse neonatal outcomes. Future research should include prospective
trials with larger sample sizes and use well-defined and consistent definitions
of the adverse outcomes investigated with consideration given to IABD.
PMID- 25587452
TI - Intraoperative full-dose of partial breast irradiation with electrons delivered
by standard linear accelerators for early breast cancer.
AB - Purpose. To assess feasibility, efficacy, toxicity, and cosmetic results of
intraoperative radiotherapy (IORT) with electrons delivered by standard linear
accelerators (Linacs) during breast conserving surgeries for early infiltrating
breast cancer (BC) treatment. Materials and Methods. A total of 152 patients with
invasive ductal carcinoma (T <= 3.0 cm) at low risk for local relapses were
treated. All had unicentric lesions by imaging methods and negative sentinel
node. After a wide local excision, 21 Gy were delivered on the parenchyma target
volume with electron beams. Local recurrences (LR), survival, toxicity, and
cosmetic outcomes were analyzed. Results. The median age was 58.3 years (range 40
85); median follow-up was 50.7 months (range 12-101.5). There were 5 cases with
LR, 2 cases with distant metastases, and 2 cases with deaths related to BC. The
cumulative incidence rates of LR, distant metastases, and BC death were 3.2%,
1.5%, and 1.5%, respectively. Complications were rare, and the cosmetic results
were excellent or good in most of the patients. Conclusions. IORT with electrons
delivered by standard Linacs is feasible, efficient, and well tolerated and seems
to be beneficial for selected patients with early infiltrating BC.
PMID- 25587453
TI - Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery:
Overview and Single Center Experiences.
AB - Breast-conserving surgery followed by whole-breast irradiation is the standard
local therapy for early breast cancer. The international discussion of reduced
importance of wider tumor-free resection margins than "tumor not touching ink"
leads to the development of five principles in targeted oncoplastic breast
surgery. IORT improves local recurrence risk and diminishes toxicity since there
is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT) can be
delivered in two settings: an IORT boost followed by a conventional regimen of
external beam radiotherapy or a single IORT dose. The data from TARGIT-A and
ELIOT reinforce the conviction that intraoperative radiotherapy during breast
conserving surgery is a reliable alternative to conventional postoperative
fractionated irradiation, but only in a carefully selected population at low risk
of local recurrence. We describe our experiences with IORT boost (50 kV energy X
rays; 20 Gy) in combination with targeted oncoplastic breast surgery in a routine
clinical setting. Our experiences demonstrate the applicability and reliability
of combining IORT boost with targeted oncoplastic breast surgery in breast
conserving therapy of early breast cancer.
PMID- 25587454
TI - Differences in the malariometric indices of asymptomatic carriers in three
communities in ibadan, Nigeria.
AB - This study was conducted to determine the malariometric indices of children in
three different settings in Ibadan, Nigeria. Children were recruited from an
urban slum (Oloomi) and a periurban (Sasa) and a rural community (Igbanda) in
Ibadan. Children aged between 2 and 10 years were randomly selected from primary
schools in the urban and periurban areas. In the rural community, children were
recruited from the centre of the village. A total of 670 (55.0%) out of 1218
children recruited were positive for malaria parasitaemia. The urban population
had the highest proportion of children with malaria parasitaemia. Splenomegaly
was present in 31.5%, hepatomegaly in 41.5%, hepatosplenomegaly in 27.5%, and
anaemia in 25.2% of the children. The parasite density was not significantly
different among children in the three communities. Children in the rural
community had the highest mean PCV of 34.2% and the lowest rates of splenomegaly
(6.1%), hepatomegaly (7.6%), and hepatosplenomegaly (4.6%). The spleen rates,
liver rates, and presence of hepatosplenomegaly and anaemia were similar in the
urban and periurban communities. The malariometric indices among the asymptomatic
carriers were high, especially in the urban slum. This stresses the need for
intensified efforts at controlling the disease in the study area.
PMID- 25587456
TI - The drop that spilled the cup: acute myocardial infarction in a young woman with
underlying thrombophilic polymorphisms and oral contraceptive use.
AB - We present the case of a 28-year-old woman who was admitted to our cardiology
unit for acute coronary syndrome. Her history was notable for cardiovascular
disease familiarity, active smoking, and oral contraceptive use. On further
analysis, she was noted to have thrombophilic polymorphisms involving the
plasminogen activator inhibitor (PAI), angiotensin-converting enzyme (ACE), and
methylenetetrahydrofolate reductase (MTHFR) genes. We discuss the implications
that these cofactors may have had in the genesis of the disease.
PMID- 25587457
TI - Octreotide for the Management of Gastrointestinal Bleeding in a Patient with a
HeartWare Left Ventricular Assist Device.
AB - HeartWare is a third generation left ventricular assist device (LVAD), widely
used for the management of advanced heart failure patients. These devices are
frequently associated with a significant risk of gastrointestinal (GI) bleeding.
The data for the management of patients with LVAD presenting with GI bleeding is
limited. We describe a 56-year-old lady, recipient of a HeartWare device, who
experienced recurrent GI bleeding and was successfully managed with subcutaneous
(SC) formulations of octreotide.
PMID- 25587455
TI - Auditory cortex tACS and tRNS for tinnitus: single versus multiple sessions.
AB - Tinnitus is the perception of a sound in the absence of an external acoustic
source, which often exerts a significant impact on the quality of life. Currently
there is evidence that neuroplastic changes in both neural pathways are involved
in the generation and maintaining of tinnitus. Neuromodulation has been suggested
to interfere with these neuroplastic alterations. In this study we aimed to
compare the effect of two upcoming forms of transcranial electrical
neuromodulation: alternating current stimulation (tACS) and random noise
stimulation (tRNS), both applied on the auditory cortex. A database with 228
patients with chronic tinnitus who underwent noninvasive neuromodulation was
retrospectively analyzed. The results of this study show that a single session of
tRNS induces a significant suppressive effect on tinnitus loudness and distress,
in contrast to tACS. Multiple sessions of tRNS augment the suppressive effect on
tinnitus loudness but have no effect on tinnitus distress. In conclusion this
preliminary study shows a possibly beneficial effect of tRNS on tinnitus and can
be a motivation for future randomized placebo-controlled clinical studies with
auditory tRNS for tinnitus. Auditory alpha-modulated tACS does not seem to be
contributing to the treatment of tinnitus.
PMID- 25587458
TI - Compound composite odontoma and its management.
AB - Odontomas are odontogenic benign tumors composed of dental tissue. Majority of
these lesions are asymptomatic and are often detected on routine radiographs.
They can be thought of as "tooth hamartomas" with the lesion consisting of
various tooth components. They are divided histologically into complex odontomas
and compound odontomas. This paper describes the case of a compound odontoma in a
13-year-old girl diagnosed due to the retention of the primary right mandibular
second molar. A surgical excision was performed without disturbing the unerupted
premolar. The results achieved indicate that early diagnosis of odontomas enables
adoption of less complex treatment, a better prognosis, and displacement or
devitalisation of adjacent tooth.
PMID- 25587459
TI - Cartilaginous choristoma of the gingiva: a rare clinical entity.
AB - Choristomas are rare entities which are aggregates of microscopically normal
cells or tissues in aberrant locations. They are a "heterotopic" rest of cells,
as they appear as a tumor-like mass. Herein we report a case of cartilaginous
choristoma in a 54-year-old male who presented with a swelling on right lower
gingiva. The histopathological examination revealed features of a well
circumscribed mass of mature cartilage in a dense fibrous connective tissue
stroma.
PMID- 25587460
TI - Fraser syndrome-oral manifestations and a dental care protocol.
AB - Fraser syndrome is a rare genetic malformation with an autosomal recessive
pattern of inheritance and an incidence of consanguinity ranging from 15% to 25%.
A 5-year-old male patient who is a carrier of Fraser syndrome initiated treatment
in the pediatric dentistry sector. The patient was fed parenterally since birth,
experienced recurring bouts of chronic lung disease, and was referred to the
pediatric dentistry sector by the medical team. Radiographic examination revealed
the presence of all permanent teeth. Supragingival dental calculus, halitosis,
and gingival inflammation were also observed. Dental calculus was removed by
manual scraping, and chemotherapeutic agents were used, chlorhexidine 0,12%,
chlorhexidine gel 2%, and PVP-I, to control the bacterial flora. The patient is
still being monitored after an 8-year follow-up period, the complications
associated with periodontal disease decreased, and since the initiation of
treatment, the patient has not needed to be hospitalized because of chronic lung
disease. This study reports the case of a patient diagnosed with Fraser syndrome
and describes the clinical manifestations (general and oral).
PMID- 25587461
TI - Craniodentofacial Manifestations in a Rare Syndrome: Orofaciodigital Type IV
(Mohr-Majewski Syndrome).
AB - Background. The orofaciodigital syndromes (OFDS) are a heterogeneous group of
syndromes that affect the face, oral cavity, and the digits. OFDS type IV (OMIM
%258860) is rare and characterized by broad nasal root and tip, orbital
hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set
ears. Oral symptoms may include cleft lip, cleft or highly arched palate, bifid
uvula, cleft or hypoplastic maxillary and mandibular alveolar ridge, oral
frenula, lingual hamartoma, and absent or hypoplastic epiglottis. Dental
anomalies are common and generally include disturbances in the number of teeth.
Case Report. This report presents a six-year-old girl, referred with the chief
complaint of missing teeth. She was diagnosed as having OFDS type IV based on
clinical findings. Her parents reported three deceased children and two fetuses
that had the same phenotype. She was the seventh child of consanguineous parents
who were first cousins. Conclusion. This is a very rare syndrome. Many reported
OFDS type IV cases have consanguineous parents, consistent with an autosomal
recessive trait. Manifestation of cleft palate in the healthy sibling may be mild
expression of the disorder or an unrelated isolated cleft.
PMID- 25587462
TI - Rare periodontal ligament drainage for periapical inflammation of an adjacent
tooth: a case report and review of the literature.
AB - Aim. To report a case with an unusual drainage route of periapical inflammation
exiting through the gingival sulcus of an adjacent vital tooth and review
probable factors determining the diversity of the discharge routes of periapical
inflammation. Summary. An 18-year-old male patient presented with periodontal
abscess of tooth 46, which was found to be caused by a periapical cyst with an
acute abscess of tooth 45. During endodontic surgery, a rarely reported drainage
route for periapical inflammation via the gingival sulcus of an adjacent vital
tooth was observed for the first time. Complete periodontal healing of the deep
pocket of tooth 46 and hiding of the periapical cyst of tooth 45 followed after
root canal treatment and periapical surgery with Bio-Oss Collagen implantation on
tooth 45. The drainage routes of periapical inflammation are multivariate and the
diversity of drainage pathways of periapical inflammation is mainly related to
factors such as gravity, barriers against inflammation, and the causative tooth
itself.
PMID- 25587463
TI - Unilateral fusion of maxillary lateral incisor: diagnosis using cone beam
computed tomography.
AB - Objective. The objective of this paper is to report a dental fusion case focusing
on clinical and radiographic features for the diagnosis. Method. To report a case
of right maxillary lateral incisor fusion and a supernumerary tooth, the anatomy
of the root canal and dental united portion were assessed by cone beam computed
tomography (CBCT). Results. The clinical examination showed dental juxtaposition
with the absence of interdental papilla and esthetic impairment in the right
maxillary lateral incisor region. The periapical radiography did not provide
enough information for the differential diagnosis due to the inherent limitations
of this technique. CBCT confirmed the presence of tooth fusion. Conclusion. CBCT
examination supports the diagnosis and provides both the identification of
changes in tooth development and the visualization of their extent and limits.
PMID- 25587464
TI - Angioedema due to Systemic Isotretinoin Therapy.
AB - Angioedema is the swelling of the mucosal membranes as a variant of urticaria
induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or
drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne
presenting with widespread facial angioedema on the 2nd day of systemic
isotretinoin treatment. The patient had taken no drugs other than isotretinoin in
the preceding days and had no known food allergy. Her angioedema was resolved
after the isotretinoin was discontinued. We want to draw the attention of
dermatologists to this rare adverse allergic effect of isotretinoin which is
frequently used in the treatment of acne vulgaris.
PMID- 25587465
TI - Paraneoplastic dermatomyositis with carcinoma cervix: a rare clinical
association.
AB - Dermatomyositis is an uncommon inflammatory myopathy associated with cutaneous
manifestations. It may also occur as paraneoplastic syndrome associated with
various malignancies, most common of which being lung, breast, stomach, rectum,
kidney, or testicular cancer. A postmenopausal woman presented to us with
generalized itching along with skin rash and proximal muscle weakness of 2 years'
duration. Examination revealed heliotrope rash and mechanic hands and muscle
power 2/5 in proximal muscle groups of both upper and lower limbs. A clinical
diagnosis of dermatomyositis was made which was supported by raised lactate
dehydrogenase levels and skin biopsy findings. Past history was significant for
vaginal discharge and bleeding per vagina. Further work-up revealed carcinoma
cervix and she was referred to oncology department for further management.
Temporal relationship and improvement of muscle weakness with treatment of
underlying neoplasm supported its paraneoplastic nature. So, final diagnosis of
keratinizing squamous cell carcinoma of cervix with paraneoplastic
dermatomyositis was made. A nationwide cohort study of 1,012 patients with
dermatomyositis in Taiwan revealed only 3 patients with cervical cancer. So this
case is being reported for its rare association with carcinoma cervix and to
highlight the need of detailed evaluation for underlying malignancies in patients
with dermatomyositis.
PMID- 25587466
TI - A vertebral artery dissection with basilar artery occlusion in a child.
AB - This paper presents the case report of an 11-year-old boy with an acute
dissection with thrombosis of the left vertebral artery and thrombosis of the
basilar artery. The patient was treated with acute systemic thrombolysis,
followed by intra-arterial thrombolysis, without any clinical improvement,
showing left hemiplegia, bilateral clonus, hyperreflexia, and impaired
consciousness. MRI indicated persistent thrombosis of the arteria basilaris with
edema and ischemia of the right brainstem. Heparinization for 72 hours, followed
by a two-week LMWH treatment and subsequent oral warfarin therapy, resulted in a
lasting improvement of the symptoms. Vertebral artery dissection after minor
trauma is rare in children. While acute basilar artery occlusion as a
complication is even more infrequent, it is potentially fatal, which means that
prompt diagnosis and treatment are imperative. The lack of class I recommendation
guidelines for children regarding treatment of vertebral artery dissection and
basilar artery occlusion means that initial and follow-up management both require
a multidisciplinary approach to coordinate emergency, critical care,
interventional radiology, and child neurology services.
PMID- 25587467
TI - Pediatric stroke presenting as a seizure.
AB - Background. Childhood arterial ischemic stroke (AIS) is rare and may be difficult
to diagnose. Management of acute stroke in any age group is time sensitive, so
awareness of the manifestations and appropriate diagnostic procedures for
pediatric AIS is vital to establishing care. We present a pediatric case of
arterial ischemic stroke that presented to the emergency department (ED) after
two seizures. Case Report. A five-year-old female with an existing seizure
disorder presented to a pediatric ED after having two seizures. Postictal upon
arrival, she underwent a computed tomography (CT) scan of her head. Family
reported that she had complained of a severe headache and vomited; her seizures
were described as different from those she had experienced in the past. Loss of
grey white matter differentiation on the CT warranted magnetic resonance imaging
(MRI), which demonstrated a right-sided stroke. After a complicated course in the
hospital, the patient was discharged to a rehabilitation hospital. Why Should an
Emergency Physician Be Aware of This? It is important that emergency physicians
recognize that a seizure may be the initial symptom of a pediatric stroke
regardless of an established seizure history. Pediatric seizures are relatively
common; however consideration of the diagnosis of pediatric stroke may prevent
unnecessary delays in treatment.
PMID- 25587468
TI - Spontaneous Regression of a Carcinoid Tumor following Pregnancy.
AB - We present a case of spontaneous regression of a neuroendocrine tumor following
pregnancy in the absence of chemotherapy, radiotherapy, or alternative medicine
(including herbal medicine). The diagnosis of a nonsecretory carcinoid tumor was
confirmed using CT imaging, octreotide scan, and histology. Furthermore, serial
imaging has demonstrated spontaneous regression of the carcinoid suggesting that
pregnancy did not worsen the course of the disease but instead may have
contributed to tumour regression. We discuss mechanisms underlying tumour
regression and the possible effect of pregnancy on these processes.
PMID- 25587469
TI - Metastatic hepatocellular carcinoma in a patient with Crohn's disease treated
with azathioprine and infliximab: a case report and literature review.
AB - Hepatocellular carcinoma most commonly occurs in patients with underlying liver
disease or cirrhosis. We describe a case of hepatocellular carcinoma in a 34-year
old man with Crohn's disease treated with azathioprine and infliximab. The
patient had no history of liver disease and a complete autoimmune and viral
workup was unremarkable. Unfortunately, the patient developed widespread
metastatic disease and passed away 5 months after his initial diagnosis. The
mechanism of hepatocellular carcinoma in patients' with Crohn's disease is poorly
understood and may include both autoimmunity and treatment-related complications.
Previous case reports suggest the possibility of a concerning association between
azathioprine therapy and the development of hepatocellular carcinoma in patients
with Crohn's disease. Clinicians may consider early imaging in patients with
Crohn's disease presenting with concerning symptomatology or abnormal liver
enzymes, especially in those being treated with azathioprine alone or in
combination with infliximab. Future research may help to uncover additional risk
factors for this exceedingly rare diagnosis in this patient population.
PMID- 25587470
TI - Adult T-cell lymphoma/leukemia presenting as isolated central nervous system T
cell lymphoma.
AB - Adult T-cell leukemia/lymphoma (ATLL) is a T-cell neoplasm, associated with
infection by the retrovirus human T-lymphotropic virus type 1 (HTLV-1). Central
nervous system (CNS) involved by ATLL is often occurred in advanced disease, such
as acute and lymphomatous variants. On the other hand, isolated CNS lymphoma is
rare. We repot a 50-year-old woman who presented with multiple infiltrative brain
lesions on the magnetic resonance (MR) imaging. Results of initial biopsy of
brain tumor indicated CNS vasculitis. The patient received one course of high
dose methotrexate and MR imaging of brain revealed remission of infiltrative
lesions. Two years later, new brain lesions were detected. Histopathologic
examination of specimens via craniotomy revealed T-cell lymphoma. The patient
responded poorly to subsequent chemotherapy, and salvage whole-brain irradiation
was performed. Six months later, the patient had hepatosplenomegaly,
hypercalcemia, and multiple lymphocytes with a cloverleaf appearance in
circulation. Results of flow cytometry analysis of peripheral blood indicated
ATLL and antibodies to human T-lymphotropic virus type 1 (HTLV-1) were detected.
Clinicians should screen HTLV-1 infection when patients are diagnosed with
peripheral T-cell lymphoma. Combined antiviral therapy and intensive chemotherapy
may improve the outcomes of ATLL.
PMID- 25587471
TI - Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury:
Literature Review and Case Report of a Successful Outcome.
AB - Hepatitis associated aplastic anemia (HAAA) is a rare syndrome in which severe
aplastic anemia (SAA) complicates the recovery of acute hepatitis (AH). HAAA is
described to occur with AH caused by viral infections and also with idiopathic
cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to
fulminant and transient to persistent and precedes the onset SAA. It is assumed
that immunologic dysregulation following AH leads to the development of SAA.
Several observations have been made to elucidate the immune mediated injury
mechanisms, ensuing from liver injury and progressing to trigger bone marrow
failure with the involvement of activated lymphocytes and severe T-cell
imbalance. HAAA has a very poor outcome and often requires bone marrow transplant
(BMT). The findings of immune related myeloid injury implied the use of
immunosuppressive therapy (IST) and led to improved survival from HAAA. We report
a case of young male who presented with AH resulting from the intake of muscle
building protein supplements and anabolic steroids. The liver injury slowly
resolved with supportive care and after 4 months of attack of AH, he developed
SAA. He was treated with IST with successful outcome without the need for a BMT.
PMID- 25587472
TI - Sudden Death by Pulmonary Thromboembolism due to a Large Uterine Leiomyoma with a
Parasitic Vein to the Mesentery.
AB - The pathophysiology of venous thrombosis is classically attributed to alterations
in one or more components of Virchow's triad: hypercoagulability, stasis, and
damage to the vascular endothelium. Deep vein thrombosis (DVT) may lead to
pulmonary thromboembolism (PE), and the latter is culpable for many deaths
annually in the United States; however, DVT as a complication of uterine
leiomyoma has rarely been reported. We report a case of a 57-year-old woman whose
death was due to a large pedunculated subserosal leiomyoma externally compressing
the pelvic veins resulting in stasis and venous thrombosis leading to fatal PE.
The association of large pelvic masses with venous thrombosis has clinical
implications, since prophylactic surgery could be life-saving.
PMID- 25587473
TI - Genital Schistosomiasis: A Report on Two Cases of Ovarian Carcinomas Containing
Viable Eggs of Schistosoma mansoni.
AB - Schistosomiasis is a parasitic infection that is highly prevalent worldwide, with
a variety of species being responsible for causing the disease. In Brazil,
however, the only identified species is Schistosoma mansoni. The adult parasites
inhabit the blood vessels of the hepatic portal system of the main host. The
disease may range from being asymptomatic to provoking liver damage or portal
hypertension. Furthermore, ectopic schistosomiasis may develop, and several
hypotheses have been raised to explain the occurrence of the disease. This paper
describes two cases, one in a 39-year-old woman and the other in a 47-year-old
woman. Both had similar symptoms of pain and abdominal distension caused by a
large abdominal/pelvic mass. Histopathology of the ovary showed a mucinous
cystadenocarcinoma of the intestinal type in the first patient and a papillary
serous carcinoma in the second, with both tumors containing viable eggs of
Schistosoma mansoni. The neoplasms probably serve as a migratory route for the
adult parasites and the embolization of eggs. Nevertheless, there is insufficient
evidence to confirm the malignization of a benign lesion due to the presence of
Schistosoma mansoni. Few cases have been reported in the international literature
on the association between ovarian schistosomiasis and neoplasms.
PMID- 25587474
TI - Unusual presentation of a rectovestibular fistula as gastrointestinal hemorrhage
in a postmenopausal woman.
AB - Background. Anorectal malformations (ARMs) are extremely rare and are usually
identified neonatally. It is unusual for these cases to present in the
postmenopausal period. This case report describes a postmenopausal patient with
ARM and rectovaginal hemorrhage. Case. An 86-year-old, gravida 11, para 9,
presented to the emergency department complaining of profuse postmenopausal
vaginal bleeding. Her gynecologic history was significant only for an unclear
history of an anal abnormality that was noted at birth. Speculum examination
revealed profuse rectal bleeding from a rectovestibular fistula exterior to her
hymenal ring. Colonoscopic examination revealed severe diverticular disease.
Conclusion. This patient was born with an imperforate anus which resolved as
rectovestibular fistula and ectopic anus. This case presents a rare clinical
circumstance which integrates the fields of obstetrics, gynecology,
gastroenterology, and embryology alike.
PMID- 25587475
TI - Adult alveolar soft part sarcoma of the head and neck: a report of two cases and
literature review.
AB - Background. Alveolar soft part sarcomas (ASPS) of the head and neck are rare,
aggressive soft-tissue malignancies. This study describes the clinical course and
management of two patients presenting with ASPS in very rare head and neck
locations, the larynx and parotid gland. Methods. We identified two patients
presenting with ASPS of the head and neck and treated at the University of North
Carolina. We compared our results to the literature from 1987 to 2013. Results.
Patient ages at diagnosis were 27 and 39 with presenting symptoms of hoarseness
and parotid swelling, respectively. Mean follow-up was 87 months. All patients
received surgical resection and adjuvant radiotherapy. There were no recurrences
or evidence of distant metastatic spread during the series. Disease-free survival
time for the patients was 4 months and 168 months, respectively. Conclusions. Our
study suggests that a combined-modality approach is important in the treatment of
ASPS of the head and neck even in these rare locations. Continued research into
new therapies is necessary to improve historically poor outcomes.
PMID- 25587476
TI - Compartment Syndrome following Open Femoral Fracture with an Isolated Femoral
Vein Injury Treated with Acute Repair.
AB - Acute compartment syndrome is a surgical emergency and its diagnosis is more
difficult in obtunded or insensate patients. We present the case of a 34-year-old
woman who sustained a Gustilo-Anderson grade III open midshaft femur fracture
with an isolated femoral vein injury treated with direct repair. She developed
lower leg compartment syndrome at 48 hours postoperatively, necessitating
fasciotomies. She was subsequently found to have a DVT in her femoral vein at the
level of the repair and was started on therapeutic anticoagulation. This case
highlights the importance of recognition of isolated venous injuries in a trauma
setting as a risk factor for developing compartment syndrome.
PMID- 25587478
TI - Osteoclastic giant cell rich squamous cell carcinoma of the uterine cervix: a
case report and review of the literature.
AB - Cervical carcinoma is the most common malignancy of the female genital tract and
represents the second most common malignancy in women worldwide. Histologically
85 to 90% of cervical cancers are squamous cell carcinoma. Osteoclastic giant
cell rich squamous cell carcinoma is an unusual histological variant of which
only 4 cases have been reported. We present the case of a 49-year-old woman with
a 6-month history of irregular vaginal bleeding. Examination revealed a 2.7 cm
polypoid mass in the anterior lip of the uterine cervix. The patient underwent
hysterectomy with bilateral salpingo-oophorectomy. Microscopically the tumor was
composed of infiltrative nests of poorly differentiated nonkeratinizing squamous
cell carcinoma. Interspersed in between these tumor cells were numerous
osteoclastic giant cells with abundant eosinophilic cytoplasm devoid of nuclear
atypia, hyperchromatism, or mitotic activity. Immunohistochemistry was performed;
CK and P63 were strongly positive in the squamous component and negative in the
osteoclastic giant cells, while CD68 and Vimentin were strongly positive in the
giant cell population and negative in the squamous component. The patient
received chemo- and radiotherapy for recurrent disease identified 3 months later
on a follow-up CT scan; 7 months after the surgical procedure the patient is
clinically and radiologically disease-free.
PMID- 25587477
TI - Carcinosarcoma of the ureter with a small cell component: report of a rare
pathologic entity and potential for diagnostic error on biopsy.
AB - Carcinosarcomas of the ureter are rare biphasic neoplasms, composed of both
malignant epithelial (carcinomatous) and malignant mesenchymal (sarcomatous)
components. Carcinosarcomas of the urinary tract are exceedingly rare. We report
a unique case of a carcinosarcoma of the ureter with a chondrosarcoma and small
cell tumor component arising in a 68-year-old male who presented with microscopic
hematuria. CT intravenous pyelogram revealed right-sided hydroureter and
hydronephrosis with thickening and narrowing of the right ureter. The patient
underwent robot-assisted ureterectomy with bladder cuff excision and subsequent
adjuvant chemotherapy. The patient is disease-free at 32 months after treatment.
We provide a brief synoptic review of carcinosarcoma of the ureter and bladder
with utilization of immunohistochemical (IHC) stains and potential diagnostic
pitfalls.
PMID- 25587479
TI - Unilateral heliotrope rash in juvenile dermatomyositis: an unusual presentation
of an underlying serious disease.
AB - Background. Heliotrope rash is one of the characteristic skin manifestations of
juvenile dermatomyositis. It is a reddish-purple rash on the upper eyelids that
is usually bilateral. Case Presentation. We report a boy who presented with
unilateral heliotrope rash, Gottron's papules, and muscle weakness. Muscle biopsy
was consistent with inflammatory myositis. Patient was started on prednisolone
and methotrexate with an excellent response in both the skin and muscles.
Conclusion. Unilateral heliotrope rash can occur in patients with juvenile
dermatomyositis. Being a paraneoplastic condition caution should be taken not to
miss any underlying malignancy.
PMID- 25587480
TI - Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy,
cavotomy, and thrombectomy.
AB - Up to 3.2% of patients with testicular germ cell tumours represent with late
relapsing disease. Aggressive surgical resection confers the greatest chance of
cure in this patient group. We present the case of a late and extensively
relapsed nonseminomatous germ cell tumour with thrombus present along the entire
length of the inferior vena cava, as well as in the right hepatic vein.
Techniques practised in liver transplantation were used to achieve complete
resection of the tumour thrombus. This case illustrates the enhanced potential
for tumour resection through a fusion of principles derived from surgical
oncology and liver transplantation.
PMID- 25587482
TI - Isolated bilateral renal mucormycosis masquerading as renal abscess in an
immunocompetent individual: a lesson learnt.
AB - Isolated renal mucormycosis is a rare entity in immunocompetent subjects. It is
usually a rapidly progressive disease with poor prognosis but it can mimic renal
abscess with a protracted course.
PMID- 25587481
TI - Bladder perforation secondary to primary systemic amyloidosis.
AB - Amyloidosis is a disorder of protein folding characterized by extracellular
aggregation and deposition of amyloid protein fibrils. Light-chain amyloidosis,
also known as primary systemic amyloidosis, is the most common form of the
disease. We present a case of an 84-year-old male with a history of systemic
primary amyloidosis causing genitourinary, cardiac, and autonomic dysfunction who
presented with hematuria and hypotension secondary to bladder perforation. He
underwent open repair of a large extraperitoneal bladder defect. He ultimately
died as a result of medical complications from his disease.
PMID- 25587483
TI - Bilateral double ureters with bladder neck diverticulum in a nigerian woman
masquerading as an obstetric fistula.
AB - A 43-year-old woman presented with 20-year history of leakage of urine per
vaginam. She had one failed repair attempt. Pelvic examination with dye test
showed leakage of clear urine suggestive of ureterovaginal fistula. The
preoperative intravenous urogram revealed duplex ureter and cystoscopy showed
normally cited ureteric orifices with two other ectopic ureteric openings and
bladder diverticula. The definitive surgery performed was ureteric reimplantation
(ureteroneocystostomy) of the two distal ureteric to 2 cm superiolateral to the
two normal orifices and diverticuloplasty. There was resolution of urinary
incontinence after surgery. Three months after surgery, she had urodynamic
testing done (cystometry), which showed 220 mLs with no signs of instability or
leakage during filling phase but leaked on coughing at maximal bladder capacity.
This is to showcase some diagnostic dilemma that could arise with obstetric
fistula, which is generally diagnosed by clinical assessment.
PMID- 25587484
TI - Distinct lysosome phenotypes influence inflammatory function in peritoneal and
bone marrow-derived macrophages.
AB - Lysosomes play a critical role in the degradation of both extracellular and
intracellular material. These dynamic organelles also contribute to nutrient
sensing and cell signaling pathways. Macrophages represent a heterogeneous group
of phagocytic cells that contribute to tissue homeostasis and inflammation.
Recently, there has been a renewed interest in understanding the role of
macrophage autophagy and lysosome function in health and disease. Thioglycollate
elicited peritoneal and bone marrow-derived macrophages are commonly used ex vivo
systems to study primary macrophage function. In this study, we reveal dramatic
baseline differences in the lysosome morphology and function between these
macrophage populations and provide evidence that these differences can be
functionally relevant. Our results provide important insights into the diversity
of lysosomes in primary macrophages and illustrate the importance of accounting
for this in data interpretation.
PMID- 25587485
TI - Treatment for Osteoporosis among Women in Japan: Associations with Patient
Characteristics and Patient-Reported Outcomes in the 2008-2011 Japan National
Health and Wellness Surveys.
AB - This study was conducted to identify characteristics associated with treatment
for osteoporosis among women aged 50 years and older in Japan and to explore
differences among patients according to treatment regimen. Data were provided by
a large annual survey representative of Japanese aged 18 and older; all measures
were by self-report. Women aged 50 and older who reported diagnosed osteoporosis
(N = 900) were compared based on current treatment status using bivariate
statistics and logistic regression. Approximately 1 in 3 women in this study
reporting diagnosed osteoporosis were currently untreated. Factors associated
with current treatment for osteoporosis included having >=1 physician visit in
the prior 6 months (OR = 5.4, P < 0.001), self-rated moderate or severe
osteoporosis (OR = 2.8, P < 0.001), completion of menopause (OR = 1.6, P < 0.05),
and family history of osteoporosis (OR = 1.5, P < 0.05), while longer duration of
osteoporosis diagnosis (OR = 0.9, P < 0.05) and arthritis (OR = 0.7, P < 0.05)
were associated with lower odds of treatment. These findings suggest that
diagnosed patients are not being actively managed in the longer term, and efforts
need to be made to ensure that patients stay engaged with their healthcare
providers.
PMID- 25587488
TI - Determination of beta -Cyano-L-alanine, gamma -Glutamyl- beta -cyano-L-alanine,
and Common Free Amino Acids in Vicia sativa (Fabaceae) Seeds by Reversed-Phase
High-Performance Liquid Chromatography.
AB - A method for determination of beta-cyano-L-alanine, gamma-glutamyl-beta-cyano-L
alanine and other free amino acids in Vicia sativa is presented. Seed extracts
were derivatized by reaction with diethyl ethoxymethylenemalonate and analyzed by
reverse-phase high-performance liquid chromatography. Calibration curves showed
very good linearity of the response. The limit of detection and quantification
was 0.15 and 0.50 MUM, respectively. The method has high intra- (RSD = 0.28
0.31%) and interrepeatability (RSD = 2.76-3.08%) and remarkable accuracy with a
99% recovery in spiked samples. The method is very easy to carry out and allows
for ready analysis of large number of samples using very basic HPLC equipment
because the derivatized samples are very stable and have very good
chromatographic properties. The method has been applied to the determination of
gamma-glutamyl-beta-cyano-L-alanine, beta-cyano-L-alanine, and common free amino
acids in eight wild populations of V. sativa from southwestern Spain.
PMID- 25587487
TI - Measuring hemoglobin levels in the optic disc of Parkinson's disease patients
using new colorimetric analysis software.
AB - Objective. To evaluate a new method of measuring hemoglobin (Hb) levels and
quantifying the color changes in the optic nerve head of Parkinson's disease (PD)
patients. We also compared differences in retinal nerve fiber layer (RNFL)
thicknesses obtained using spectral domain optical coherence tomography (OCT)
device between PD group and healthy group. Methods. One hundred and fifty-five PD
patients and 91 sex- and age-matched healthy subjects were included in this cross
sectional study. OCT examinations and one photograph of the optic disc were
performed. The Laguna ONhE ("optic nerve hemoglobin"; Insoft SL, Tenerife, Spain)
software was used to analyze the Hb level on the acquired optic disc photographs.
Results. PD patients exhibited significantly reduced mean optic disc Hb
percentages (57.56% in PD, 67.63% in healthy subjects; P = 0.001) as well as
reduced Hb in almost all analyzed sectors, with the largest differences detected
in the inferior and nasal sectors. RNFL parameters were significantly reduced in
PD patients compared with healthy subjects, especially in the inferior quadrant.
Conclusions. Measurements of optic disc Hb levels obtained with the Laguna ONhE
software had good ability to detect optic nerve color changes (more papillary
paleness and consequently this could suggest optic atrophy and axonal loss) in PD
patients.
PMID- 25587486
TI - Evidence of insulin resistance in adult uncomplicated malaria: result of a two
year prospective study.
AB - The study aimed at investigating the effects of adult uncomplicated malaria on
insulin resistance. Fasting levels of blood glucose (FBG), glycosylated
hemoglobin (HbA1c), and serum insulin were measured in 100 diabetics and 100 age
matched controls before and during Plasmodium falciparum malaria. Insulin
resistance and beta cell function were computed by homeostatic models assessment
of insulin resistance (HOMAIR) and beta cell function (HOMAB) formulae,
respectively. Body mass index (BMI) was computed. At baseline, diabetics had
significantly (P < 0.05) higher levels of BMI, FBG, HbA1c, and HOMAIR but lower
level of HOMAB than controls. Baseline insulin levels were comparable (P > 0.05)
between the two study groups. During malaria, diabetics maintained significantly
(P < 0.05) higher levels of BMI, FBG, and HbA1c but lower levels of insulin and
HOMAB than controls. Malaria-induced HOMAIR levels were comparable (P > 0.05)
between the two study groups but higher than baseline levels. Apart from BMI and
HOMAB, mean levels of all the remaining parameters increased in malaria-infected
controls. In malaria-infected diabetics, significant (P < 0.05) increase was only
observed for insulin and HOMAIR but not the other measured parameters.
Uncomplicated malaria increased insulin resistance in diabetics and controls
independent of BMI. This finding may have implications for the evolution of T2DM
in malaria-endemic regions.
PMID- 25587489
TI - Quantification of Caffeoylquinic Acids in Coffee Brews by HPLC-DAD.
AB - The influence of different brewing conditions on the concentration of the main
caffeoylquinic acids (3-caffeoylquinic acid (3-CQA), 4-caffeoylquinic acid (4
CQA), and 5-caffeoylquinic acid (5-CQA)) was investigated. For this purpose,
twenty-four coffee brews were extracted and analyzed using HPLC-DAD at 325 nm.
Our findings demonstrate the great impact of brewing techniques on the
caffeoylquinic acids (CQAs) content. The major isomer was 3-CQA, accounting for
about 50% of the total CQAs, followed by 5-CQA and 4-CQA, accounting for about 24
36% for each one. The total content of CQAs was in the range of 45.79 to 1662.01
mg/L, found in iced cappuccino and pod espresso, respectively. In conclusion,
this study demonstrates that coffee brews, in particular those prepared using
pressurized methods, can be considered as the potential sources of antioxidants
such as CQAs.
PMID- 25587490
TI - Primary injuries and secondary organ failures in trauma patients with acute
kidney injury treated with continuous renal replacement therapy.
AB - Background. Acute kidney injury (AKI) treated with continuous renal replacement
therapy (CRRT) is a severe complication in trauma patients. The aim of the study
was to assess primary traumatic injuries and secondary organ failures in severe
posttraumatic AKI. Methods. Retrospective review of adult trauma patients
admitted to the trauma centre at Oslo University Hospital Ulleval. Injury
severity score (ISS) was used to assess the severity of primary injuries, and
sequential organ failure assessment (SOFA) score was utilized to measure
secondary organ failures. Results. Forty-two (8%) of 506 trauma patients admitted
to intensive care unit developed AKI treated with CRRT, whereof 40 (95%) suffered
blunt trauma mechanisms. Patients had extensive primary organ injuries with
median (interquartile range) ISS 36 (27-49). The majority of the patients had
respiratory (93% intubated) and cardiovascular (67% with inotropic and/or
vasoactive medication) failure within 24 hours after admission. AKI was often
part of multiple organ failure, most frequently respiratory and cardiovascular
failure, affecting 33 (75%) and 30 (71%) of the patients, respectively.
Conclusion. Trauma patients with AKI undergoing CRRT often had severe primary
injuries due to blunt trauma. Most of them suffered from secondary multiple organ
failure concomitant to AKI.
PMID- 25587492
TI - Biodefense Oriented Genomic-Based Pathogen Classification Systems: Challenges and
Opportunities.
AB - Countermeasures that will effectively prevent or diminish the impact of a
biological attack will depend on the rapid and accurate generation and analysis
of genomic information. Because of their increasing level of sensitivity, rapidly
decreasing cost, and their ability to effectively interrogate the genomes of
previously unknown organisms, Next Generation Sequencing (NGS) technologies are
revolutionizing the biological sciences. However, the exponential accumulation
microbial data is equally outpacing the computational performance of existing
analytical tools in their ability to translate DNA information into reliable
detection, prophylactic and therapeutic countermeasures. It is now evident that
the bottleneck for next-generation sequence data analysis will not be solved
simply by scaling up our computational resources, but rather accomplished by
implementing novel biodefense-oriented algorithms that overcome exiting
vulnerabilities of speed, sensitivity and accuracy. Considering these
circumstances, this document highlights the challenges and opportunities that
biodefense stakeholders must consider in order to exploit more efficiently
genomic information and translate this data into integrated countermeasures. The
document overviews different genome analysis methods and explains concepts of DNA
fingerprints, motif fingerprints, genomic barcodes and genomic signatures. A
series of recommendations to promote genomics and bioinformatics as an effective
form of deterrence and a valuable scientific platform for rapid technological
insertion of detection, prophylactic, therapeutic countermeasures are discussed.
PMID- 25587493
TI - Use of non-benzodiazepine sedative hypnotics and risk of falls in older men.
AB - BACKGROUND: To ascertain whether use of non-benzodiazepine sedative-hypnotics is
associated with risk of falls and compare this to risk of falls associated with
use of benzodiazepines. METHODS: Among 4450 community-dwelling men, aged 71 years
and older, enrolled in the population-based prospective cohort study,
Osteoporotic Fractures in Men (MrOS), use of nonbenzodiazepine sedative-hypnotics
and benzodiazepines was assessed by interview and verified from medication
containers at the third annual visit of the MrOS study. Falls in the subsequent
one-year period were ascertained by tri-annual questionnaires and a computerized
dictionary used to categorize type of medication. RESULTS: In age-adjusted
models, non-benzodiazepine sedative hypnotic use was associated with an increased
risk of any falls (one or more falls) (RR 1.44, 95% CI 1.15, 1.81) and recurrent
falls (2 or more falls) (RR 1.51, 95% CI 1.07, 2.14). Use of benzodiazepines was
associated with a similar increase in age-adjusted risk of falling. Depressive
symptoms, inability to stand from a chair, and instrumental activities of daily
living (IADL) impairment modestly attenuated these associations. The association
between non-benzodiazepine sedative-hypnotic use and falls was most pronounced
among men without a history of falls in the previous year: in a multivariable
model controlling for multiple potential confounders, the RR of any falls was
1.74 (95% CI 1.13, 2.68) in this subgroup. CONCLUSIONS: Use of non-benzodiazepine
sedative-hypnotics is associated with an increased risk of falls. Non
pharmacologic approaches to sleep disturbances may represent the safest approach
to sleep difficulties in older adults.
PMID- 25587491
TI - Signaling Networks of Activated Oncogenic and Altered Tumor Suppressor Genes in
Head and Neck Cancer.
AB - Head and neck squamous cell carcinoma (HNSCC) arises from the upper aerodigestive
tract and is the six most common cancers worldwide. HNSCC is associated with high
morbidity and mortality, as standard surgery, radiation, and chemotherapy can
cause significant disfigurement and only provide 5-year survival rates of ~50
60%. The heterogeneity of HNSCC subsets with different potentials for recurrence
and metastasis challenges the traditional pathological classification system,
thereby increasing demand for the development of new diagnostic, prognostic, and
therapeutic tools based on global molecular signatures of HNSCC. Historically,
using classical biological techniques, it has been extremely difficult and time
consuming to survey hundreds or thousands of genes in a given disease. However,
the development of high throughput technologies and high-powered computation
throughout the last two decades has enabled us to investigate hundreds or
thousands of genes simultaneously. Using high throughput technologies, our
laboratory has identified the gene signatures and protein networks, which
significantly affect HNSCC malignant phenotypes, including TP53/p63/p73 family
members, IL-1/TNF-beta/NF-kappaB, PI3K/AKT/mTOR, IL-6/IL-6R/JAK/STAT3,
EGFR/MAPK/AP1, HGF/cMET/EGR1, and TGFbeta/TGFbetaR/TAK1/SMAD pathways. This
review summarizes the results from high-throughput technological assays conducted
on HNSCC samples, including microarray, DNA methylation, miRNA profiling, and
protein array, using primarily experimental data and conclusions generated in our
own laboratory. The use of bioinformatics and integrated analyses of data sets
from different platforms, as well as meta-analysis of large datasets pulled from
multiple publicly available studies, provided significantly higher statistical
power to extract biologically relevant information. The data suggested that the
heterogeneity of HNSCC genotype and phenotype are much more complex than we
previously thought. Understanding of global molecular signatures and disease
classification for specific subsets of HNSCC will be essential to provide
accurate diagnoses for targeted therapy and personalized treatment, which is an
important effort toward improving patient outcomes.
PMID- 25587495
TI - Persistent Reduced Pigmentation of Areola after Breast Reconstruction with Brava
assisted Autologeous Fat Grafting.
AB - SUMMARY: A 17-year-old healthy woman treated for unilateral hypoplastic breast
anomaly with Brava-assisted fat grafting experienced persistent reduced
pigmentation of the areola on the treated breast. The reduced pigmentation was
confirmed at 6-month postoperative follow-up and verified by histological
examination of comparable biopsies from both areolas.
PMID- 25587494
TI - Fat Graft Viability in the Subcutaneous Plane versus the Local Fat Pad.
AB - BACKGROUND: Fat grafting has been increasingly utilized in both aesthetic and
reconstructive surgical procedures, yet the basic scientific understanding of fat
grafting has lagged behind the pace of clinical innovation and utilization. This
lack of basic scientific understanding has perhaps manifested itself in the wide
range of graft viability reported across the literature. This study attempts to
further the underlying mechanisms of fat graft take and viability through the
comparison of the subcutaneous plane and the local fat pad in athymic rats.
METHODS: Lipoaspirate from a consenting patient was grafted into 2 locations in
the subcutaneous plane and into the 2 inguinal fat pads in each of 4 athymic
rats. Specimens were then collected after 47 days, and immunohistochemistry was
utilized to determine angiogenesis in the fat grafts as a measure of fat graft
take. Data were analyzed using the Student's t test and analysis of variance
followed by multiple comparisons. RESULTS: There was no statistically significant
difference (P = 0.2913) between the inguinal fat pad and the subcutaneous plane
when measuring neovascularization. Analysis of variance comparing the graft
locations also indicated no statistically significant difference when comparing
each of the rats. CONCLUSIONS: Investigation into fat graft injection location
indicates that there is no statistically significant difference in angiogenesis
signals between the subcutaneous plane and the local fat pad in the athymic rat
model. Further research should aim to continue to close the gap between clinical
practice and basic scientific understanding of fat grafting.
PMID- 25587496
TI - Wrist Tenosynovitis due to Mycobacterium bovis Infection: Case Series and Review
of the Literature.
AB - SUMMARY: Tuberculosis infections are still one of the most important public
health problems among developing countries. Musculoskeletal involvement
represents 10-15% of all extrapulmonary cases. Tuberculosis tenosynovitis is
usually misdiagnosed as nonspecific tenosynovitis. To avoid misdiagnosis and
mistreatment, it is important to be alert for mycobacterial infections. This
article presents 3 patients with wrist tenosynovitis, which was caused by
Mycobacterium bovis infection. The article also includes review of the
literature.
PMID- 25587497
TI - An Unusual Cause of Flexor Tenosynovitis: Streptococcus mitis.
AB - SUMMARY: Streptococcus mitis is a commensal organism of the human oropharynx that
rarely causes infection in healthy individuals. Herein, we describe a previously
healthy 35-year-old woman who presented with acute pyogenic flexor tenosynovitis
of the left index finger due to S. mitis infection. The patient's infection was
treated successfully via surgical and medical interventions, and during follow
up, it was determined that she was complement component C3 deficient.
Tenosynovitis is an emergent clinical syndrome that can result in permanent
disability or amputation. To the best of our knowledge, this case report is the
first to describe tenosynovitis due to S. mitis; in addition, it highlights the
importance of initiating therapy with antibiotics that are effective against this
rare pathogen.
PMID- 25587498
TI - A Case of Complex Facial Clefts Treated with Staged-tissue Expansion.
AB - SUMMARY: Craniofacial clefts involve all soft tissue and skeletal elements
throughout the cleft. Usefulness of tissue expansion in craniofacial clefts is
reported. Surgery for a complex type of facial clefts is more difficult and more
extensive than for a simple one. We experienced a primary case of complex facial
clefts (Tessier No. 2 and 12 on the right and 3, 11, and 5 on the left). Soft
tissue closure of all clefts could be completed by using 4 tissue expanders and 7
operations. Because multiple tissue deficiencies and abnormalities exist in
craniofacial clefts, especially complex type, a planned, staged, sequential
approach by tissue expansion is necessary to produce ideal results.
PMID- 25587499
TI - Inferior Turbinate Flap for Nasal-side Closure of Palatal Fistula in Cleft
Patients: Technical Note.
AB - SUMMARY: Residual palatal fistula after repair of palatal cleft is common. Repair
of residual oronasal fistula is not always successful. Two-layer closure
techniques that close these fistulas with soft tissue are a common practice.
Turnover flaps are the most used flaps and often the sole method for nasal-side
closure of fistula. Anteriorly based inferior turbinate flap can be used to
provide soft tissue for nasal-side closure when turnover flaps will not provide
sufficient tissue for this purpose. Under general anesthesia with nasotracheal
intubation, inferior turbinate was released from posterior attachment. After
removing the inferior conchal bone, mucoperiosteal flap was used for nasal-side
closure of anterior palatal fistula in patients with cleft. Anteriorly based
inferior turbinate flap was used for nasal-side closure of residual palatal
fistula in 3 patients with cleft. Age of the patients was 14, 16, and 18, and
recurrence of palatal fistula has not occurred. Anteriorly based inferior
turbinate flap is an axial pattern flap with appropriate surface of the paddle
and vicinity to the oral cavity roof. It can be used in large anterior, palatal
fistula for reconstruction of nasal floor. Considering appropriate another flap
for oral side coverage of such fistula is mandatory.
PMID- 25587501
TI - Muscular pedicled lateral chest composite flap-a new nonmicrosurgical option for
forearm salvage.
AB - SUMMARY: Posttraumatic upper or lower limb salvage is still challenging. Under
difficult situations in which only one vessel supplies the hand or foot, free
microvascular reconstruction might damage not only the transferred tissue but
also the terminal hand or foot. Two cases of incomplete amputation of the
unilateral forearm with large radius bone and soft tissue loss were reconstructed
using a newly-refined pedicled osteomyocutaneous flap including vascularized rib,
lateral part of the latissimus dorsi muscle, and skin as a lateral chest flap.
After insetting of the flap, the transferred limb is fixed with a soft bandage,
and the flap is divided no less than 4 weeks after the first operation. The flap
completely survived, and bone union between the rib and radius was observed.
Although our treatment needed a two-stage procedure, safe and secure
reconstruction with an appropriate amount of tissue for salvage was accomplished.
PMID- 25587500
TI - Exclusion of musculature from the submental flap: a contingency plan for facial
nerve palsy.
AB - SUMMARY: Submental flap surgery is a useful and versatile reconstructive
procedure. Currently, disagreement exists regarding the need to include the
anterior belly of the digastric muscle or mylohyoid in the submental flap. The
report outlines the value of excluding normal and variant anterior digastric and
mylohyoid musculature from the submental flap as a contingency plan for marginal
mandibular branch of facial nerve palsy. Also, the article addresses variant
anterior digastric musculature, a common anatomical finding, as it relates to the
submental flap. The question of whether or not to include the anterior digastric
musculature does not necessitate an all-or-none decision. In the case of multiple
anterior digastric bellies, some bellies may be included in the flap, whereas
others are not. The location of the submental vessels and the desired bulk or
contour of the flap should guide the decision of which anterior digastric
bellies, if any, are included in the flap.
PMID- 25587502
TI - Outcome studies in plastic surgery: knowing the objectives and avoiding pitfalls.
PMID- 25587503
TI - The pinking shears: a novel tool for improving skin graft cosmesis.
AB - SUMMARY: A significant aesthetic disadvantage to split skin grafts is the obvious
transition between the graft and the normal skin. We report on a novel method to
interrupt this transition point by using pinking shears, which are dressmaking
scissors with saw-toothed blades that create a chevron pattern instead of a
straight edge. We describe a case where the pinking shears were utilized on a
split skin graft and Integra for reconstruction of the skin on a volar forearm.
This technique allows for breaking-up of the transition point between the skin
graft and normal skin and gives rise to an improved aesthetic outcome as the
boundary is significantly less well-defined. This novel method shows promise and
further study is certainly warranted.
PMID- 25587504
TI - Severe Acute Radiodermatitis in a Keloid Patient with Takayasu's Arteritis.
AB - SUMMARY: Although combination therapy for keloid including postoperative
radiation therapy (RT) is common, the radiation toxicity of RT in a patient with
a history of collagen vascular disease has not been fully recognized. We
experienced a case of an acute radiodermatitis in a patient with keloid. This
patient had a chest keloid because of the bypass surgery for Takayasu's
arteritis. After we performed an excision and postoperative RT, severe
radiodermatitis occurred. We speculate that the higher single dose and the use of
electron beams may be related to the onset of severe acute radiodermatitis in
this case. It should be kept in mind that there is a risk of exacerbation of
radiation toxicity in patients with collagen vascular disease.
PMID- 25587505
TI - The modifications of the sagittal ramus split osteotomy: a literature review.
AB - BACKGROUND: In 1953, the sagittal ramus split osteotomy was introduced by
Obwegeser. For many years, and in some countries still, this technique has
defined the term oral and maxillofacial surgery. METHODS: The basic design of the
sagittal ramus split surgical procedure evolved very quickly. The original
operation technique by Obwegeser was shortly after improved by Dal Pont's
modification. The second major improvement of the basic technique was added by
Hunsuck in 1967. Since then, the technical and biological procedure has been well
defined. Resolution of the problems many surgeons encountered has, however, taken
longer. Some of these problems, such as the unfavorable split or the damage of
the inferior alveolar nerve, have not been satisfactorily resolved. RESULTS:
Further modifications, with or without the application of new instruments, have
been introduced by Epker and Wolford, whose modification was recently elaborated
by Bockmann. The addition of a fourth osteotomy at the inferior mandibular border
in an in vitro experiment led to a significant reduction of the torque forces
required for the mandibular split. CONCLUSIONS: The literature was reviewed, and
the last modifications of the successful traditional splitting procedure are
presented narrowly. It indicates the better the split is preformatted by
osteotomies, the less torque force is needed while splitting, giving more
controle, a better predictability of the lingual fracture and maybe less
neurosensory disturbances of the inferior alveolar nerve.
PMID- 25587506
TI - Nd:YAG Laser Treatment for Keloids and Hypertrophic Scars: An Analysis of 102
Cases.
AB - BACKGROUND: The present retrospective cohort study was performed to determine the
efficacy of contact-mode 1064 nm neodymium-yttrium-aluminum-garnet (Nd:YAG) laser
laser for keloids and hypertrophic scars. The indication and limitations of this
modality are discussed. METHODS: The cohort consisted of 102 consecutive Japanese
patients (23 males and 79 females) with keloids and hypertrophic scars for more
than 1 year. They were treated every 3-4 weeks for 1 year with a long-pulsed 1064
nm Nd:YAG laser (Cutera, Brisbane, Calif.) in contact mode. Thirty-eight patients
had hypertrophic scars and 64 had keloids. The scars were evaluated before the
treatment commenced and 1 month after the last session by using the Japan Scar
Workshop Scar Scale 2011. Recurrence was assessed at 6 months after the
termination of treatment. RESULTS: The average total Japan Scar Workshop score of
the keloid and hypertrophic scar region groups dropped significantly after 1 year
of treatment compared with before treatment (all P < 0.05). None of the
hypertrophic scars or keloids deteriorated. However, 3 of the 34 anterior chest
keloids (8.8%) did not respond. The following recurrence rates were observed 6
months after stopping laser treatment: 1 of the abdomen hypertrophic scars (4%),
18 of the anterior chest keloids (52.9%), 5 of the upper arm keloids (35.7%), and
4 of the scapula keloids (25%). CONCLUSIONS: Hypertrophic scars responded
significantly better to 1064 nm Nd:YAG laser treatment than keloids. However,
keloid recurrence occurred when there was remaining redness and induration, even
if only a small part of the scar was affected.
PMID- 25587507
TI - A rare complication of septorhinoplasty.
AB - SUMMARY: Septoplasty and septorhinoplasty are common procedures. A 28-year-old
woman underwent the procedure and presented postoperatively with headache and
vomiting and had developed a large pneumocephalus. We describe the case in detail
and analyze the possible causes and ways to prevent such a complication.
PMID- 25587508
TI - Innovative tactic in submandibular salivary gland partial resection.
AB - SUMMARY: Adequate neck contour is one of the goals in facial rejuvenation. In
some patients, treating the submandibular salivary gland (SMSG) ensures a
satisfying result. Hematoma, sialoma, and paralysis of the depressors of the
lower lip may occur when the deep neck is approached. The objective of this work
is to present a new tactic to prevent the aforementioned complications. Two
hundred forty consecutive neck lift patients with partial resection of the SMSG
were studied. The tactic consisted of placing sutures to facilitate the
retraction of the platysma muscle and the accompanying marginal mandibular and
cervical branches of the facial nerve during the resection of the SMSG. It also
included stitches that bring the platysma muscle in contact with the remaining
SMSG, sealing the dissected area. The first 25 (control) subjects did not undergo
the tactic; the remaining 215 (study group) did. The occurrence of paralysis of
the depressors of the lower lip and of hematoma and sialoma originating from the
SMSG resection was observed. When comparing the control group with the study
group, the rates of hematoma (8% vs 0%) and sialoma (24% vs 0%) were
significantly higher in the former. Paralysis of the depressors of the lower lip
also had a higher rate in the control group (4% vs 0.9%) although this difference
was not statistically significant. The surgical tactic described is efficient in
preventing the occurrence of hematoma, sialoma, and paralysis of the depressors
of the lower lip in neck lift with partial resection of the SMSG.
PMID- 25587510
TI - Incidental Internal Mammary Nodes during Recipient Vessel Dissection in Breast
Reconstruction: Are They Significant?
AB - SUMMARY: Internal mammary (IM) lymph nodes may be exposed during recipient vessel
preparation in free-flap breast reconstruction, and in rare cases, positivity of
these nodes may affect treatment in patients with breast cancer. This systematic
review examines the incidence and significance of IM nodes identified by plastic
surgeons. Eligibility criteria included free-flap breast reconstruction with
concurrent IM node biopsy. Data were analyzed for incidence of IM node biopsy and
nodal positivity. Ten studies met inclusion criteria, with a total of 2055
patients and 717 nodes submitted to pathology. Incidence of IM positivity ranged
approximately from 1% to 11%, for a calculated gross overall incidence of 2.9%.
Of 59 patients with a positive IM node, 50 patients received additional adjuvant
therapy, with insufficient data to determine the effect of treatment on survival.
PMID- 25587511
TI - Surgical Excision of Non-Melanoma Skin Cancer in an Elderly Veteran's Affairs
Population.
AB - BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common malignancy in the
United States. Recommended treatment for NMSC remains surgical excision following
a positive biopsy. Evidence of complete spontaneous regression of residual NMSC
exists in the case of small lesions macroscopically removed by shave biopsy, but
with a positive microscopic margin. The present study investigates the rate at
which residual tumor is present at subsequent excisional biopsy, with the aim to
assess if recommendation to forgo surgical excision can be made. METHODS: A total
of 233 shave biopsies of basal cell carcinoma (BCC) or squamous cell carcinoma
(SCC) were performed during a 5-year period. All specimens included in the study
were less than 2 cm in diameter, were macroscopically removed by shave biopsy,
and had a positive initial microscopic margin. RESULTS: On subsequent surgical
excisional biopsy, 42% of BCC specimens were negative for residual tumor, 38% had
residual tumor, but the tumor was completely contained in the excised specimen,
and 20% of the specimens had positive margin residual tumor. For SCC specimens,
73% were negative for residual tumor, 21% had residual tumor, but the tumor was
completely contained in the excised specimen, and 6% of the specimens had
positive margin residual tumor. CONCLUSIONS: Although reduction of residual tumor
at reexcision is noted with both BCC and even more so with SCC, the rate at which
this occurs is not sufficient that a general recommendation to forgo surgical
excision can be made.
PMID- 25587509
TI - Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing.
AB - BACKGROUND: Fibromodulin (FMOD) plays a critical role in the wound-healing
process. Our previous studies revealed that FMOD deficiency led to marked
alterations in adult wound healing characterized by delayed dermal cell
migration, postponed wound closure, and increased scar formation, all accompanied
by impeded angiogenesis. Therefore, the aim of this study was to reveal the
effect of FMOD on angiogenesis during the wound-healing process. METHODS: In vivo
angiogenic effects of FMOD were assessed by a chick embryo chorioallantoic
membrane assay, a Matrigel (BD Bioscience, Franklin Lakes, N.J.) plug implant
assay, and rodent primary closure wound models. In vitro angiogenic effects of
FMOD were recorded by cell invasion and dimensional and topological parameters of
human umbilical vein endothelial cells. RESULTS: We provided evidence that FMOD
significantly enhanced vascularization: first, FMOD boosted blood vessel
formation on the chorioallantoic membrane; second, FMOD markedly stimulated
capillary infiltration into Matrigel plugs subcutaneously implanted in adult
mice; and finally, FMOD robustly promoted angiogenesis in multiple adult rodent
cutaneous wound models. Furthermore, FMOD administration restored the vascularity
of fmod (-/-) mouse wounds. In support of this, FMOD endorsed an angiogenesis
favored microenvironment in adult rodent wounds not only by upregulating
angiogenic genes but also by downregulating angiostatic genes. In addition, FMOD
significantly enhanced human umbilical vein endothelial cell invasion and tube
like structure formation in vitro. CONCLUSIONS: Altogether, we demonstrated that
in addition to reducing scar formation, FMOD also promotes angiogenesis. As blood
vessels organize and regulate wound healing, its potent angiogenic properties
will further expand the clinical application of FMOD for cutaneous healing of
poorly vascularized wounds.
PMID- 25587512
TI - The Rationale for Treating the Nodule in Dupuytren's Disease.
AB - BACKGROUND: Dupuytren's disease encompasses a spectrum of fibroblastic disorders
from the presence of 1-2 nodules in the palm of a hand with no joint contracture
to grotesque, crippling and disabling deformities of hands. Over the last 50
years, many enlightening studies have been forthcoming, which, through techniques
of histopathology, biochemistry, tissue culture, and electron microscopy, have
shed pearls of light on various aspects of the disease process. METHODS: A
comprehensive review of the literature on Dupuytren's disease was undertaken,
stringing together results from numerous studies to establish a table of events
and their location in the development of the disease. RESULTS: What will be seen
is a credible scenario of events which will enable the clinician to be more
proactive in the earlier treatment of the disease and more aware of factors that
increase or decrease recurrence rates postoperatively. CONCLUSIONS: The most
effective management of Dupuytren's disease is early recognition and treatment of
the nodule, before the development of a joint contracture, particularly of a
proximal interphalangeal joint. As there is evidence of a significant
inflammatory role in the development of the nodule, the process of fibroplasia
can be minimized by altering the macrophage > fibroblast > collagen cascade by
the intralesional injection of a potent anti-inflammatory agent such as
triamcinolone, which also blocks tissue inhibitors of collagenase, thus enhancing
the action of native collagenase, and reduces the size and firmness of nodules
and, at least temporarily, arrests their progression.
PMID- 25587513
TI - Reply: the limitations of psychometric outcome studies in plastic surgery.
PMID- 25587514
TI - Psychometrics: Essential for Valid, Reliable, and Responsive Measurement in the
Development of Patient-reported Outcome Instruments in Plastic Surgery.
PMID- 25587515
TI - Breast Reduction versus Breast Reduction Plus Implants: A Comparative Study with
Measurements and Outcomes.
AB - BACKGROUND: Breast reduction is well-known to provide an improvement in physical
symptoms. However, measurements show that this procedure is less effective in
restoring upper-pole fullness. Breast implants effectively augment the upper
pole. This study was undertaken to determine the effectiveness and safety of this
treatment combination. METHODS: This retrospective study consists of 3 parts: (1)
a clinical study, (2) breast measurements, and (3) an outcome study. Eighty
consecutive women undergoing breast reduction (n = 56) or breast reduction plus
implants (n = 24) were evaluated. All breast implants were inserted
submuscularly. All patients were treated with the same vertical reduction
technique, using a medially based pedicle and intraoperative nipple positioning.
Measurements were compared between preoperative photographs and photographs taken
at least 3 months after surgery (n = 51). Patient surveys (n= 56) were evaluated.
RESULTS: There was no significant difference in complication or reoperation rates
between groups. Both procedures elevated the breast mound and lower-pole level
and increased the breast parenchymal ratio (upper-pole area/lower-pole area).
Breast implants significantly increased upper-pole projection (P < 0.01). All
surveyed patients who had simultaneous implants reported that they were pleased
with their decision. Physical symptoms were reduced in both groups. Patient
satisfaction was 92.5% for breast reduction and 93.8% for breast reduction plus
implants. Both groups reported an improvement in quality of life. CONCLUSIONS:
Vertical breast reduction with a medial pedicle may be combined safely and
effectively with breast implants in patients who desire upper-pole fullness.
PMID- 25587516
TI - Medial and lateral pectoral nerve block with liposomal bupivacaine for the
management of postsurgical pain after submuscular breast augmentation.
AB - SUMMARY: This report describes an ultrasound-guided medial and lateral pectoralis
nerve block using liposome bupivacaine, performed before the surgical incision,
in a patient undergoing submuscular breast augmentation. The anatomic basis and
technique are described. This procedure may be offered to patients undergoing
submuscular insertion of a breast implant or tissue expander. Advancements in
ultrasound guidance allow for more precise anatomic placement of local anesthetic
agents. The injection technique used for this procedure resulted in complete
relaxation of the pectoralis major, facilitating the surgical dissection and
markedly diminishing postsurgical pain and muscle spasms.
PMID- 25587517
TI - Gold Nanoparticle-assisted Selective Photothermolysis of Adipose Tissue
(NanoLipo).
AB - BACKGROUND: Conventional suction-assisted lipectomy (SAL) often results in
contour irregularity. Selective photothermal heating of adipose tissue by polymer
coated gold nanorods energized by an external near-infrared exposure at 800 nm is
introduced in this work to facilitate fat removal. METHODS: The effects of
NanoLipo were examined in food-grade porcine abdominal tissue (skin, fat, and
fascia) by histology. The efficacy of NanoLipo was compared with that of
conventional SAL in vivo in Yucatan mini pigs by quantification of removed
subcutaneous tissue and fatty acids and ultrasound measurement of adipose layer
thickness. RESULTS: NanoLipo led to the appearance of disruptions in adipose
tissue that were not apparent in control groups in ex vivo samples. NanoLipo
allowed removal of more subcutaneous tissue (~33% vs ~25% of removed material, P
< 0.05) and approximately twice as much free fatty acids (~60% vs ~30% of removed
tissue, P < 0.05) in comparison with conventional SAL. Most importantly, NanoLipo
led to a greater decrease in adipose layer thickness at 1 month post surgery (P <
0.001). CONCLUSIONS: NanoLipo facilitates removal of a greater quantity of fat
and requires less suction time (4 vs 10 minutes) than conventional SAL. As the
safety of poly(ethylene-glycol)-coated gold nanorods is well-established, a
clinical trial is currently being organized.
PMID- 25587518
TI - Models of Care in Geriatric Oncology.
AB - Cancer is common in older adults and the approach to cancer treatment and
supportive measures in this age group is continuously evolving. Incorporating
geriatric assessment (GA) into the care of the older patient with cancer has been
shown to be feasible and predictive of outcomes, and there are unique aspects of
the traditional geriatric domains that can be considered in this population.
Geriatric assessment-guided interventions can also be developed to support
patients during their treatment course. There are several existing models of
incorporating geriatrics into oncology care, including a consultative geriatric
assessment, geriatrician "embedded" within an oncology clinic and primary
management by a dual-trained geriatric oncologist. Although a geriatrician or
geriatric oncologist leads the geriatric assessment, is it truly a
multidisciplinary assessment, and often includes evaluation by a physical
therapist, occupational therapist, pharmacist, social worker and nutritionist.
PMID- 25587519
TI - Diets for constipation.
AB - Chronic constipation is a very common disease in children. Successful treatment
of constipation can be achieved not only with medication but also with lifestyle
changes, including a proper diet. Diets including fruits, fluids, and probiotics
are good for constipation. Some dietary components are helpful for constipation,
and some are harmful. In this study, we present diets related to constipation
from the literature, and propose some perspectives regarding diets related to
constipation.
PMID- 25587521
TI - Short-Term Complications of Percutaneous Endoscopic Gastrostomy according to the
Type of Technique.
AB - PURPOSE: The method of percutaneous endoscopic gastrostomy (PEG) tube placement
can be divided into the pull and introducer techniques. We compared short-term
complications and prognosis between patients who underwent the pull technique and
two other types of introducer techniques, the trocar introducer technique and T
fastener gastropexy technique. METHODS: Twenty-six patients who underwent PEG
were enrolled in this study. We retrospectively investigated the age, sex, body
weight, weight-for-age Z-score, underlying diseases, PEG indications,
complications, duration of NPO (nil per os), pain control frequency, and duration
of antibiotic therapy. The patients were classified into three groups according
to the PEG technique. The occurrence of complications was monitored for 10 weeks
after the procedure. RESULTS: The age, sex, body weight, and weight-for-age Z
score were not significantly between the three groups. Most patients had cerebral
palsy and seizure disorders. Dysphagia was the most common indication for PEG.
Major complications occurred in 5 (50%), 4 (66.7%), and 0 (0%) patients in group
I, II, and III, respectively (p=0.005). Further, peristomal infection requiring
systemic antibiotic therapy occurred in 2 (20%), 3 (50%), and 0 (0%) patients in
group I, II, and III, respectively (p=0.04). There was no significant difference
between the groups with respect to minor complications, duration of NPO, pain
control frequency, and duration of antibiotic therapy. CONCLUSION: The results
indicate that the T-fastener gastropexy technique was associated with the lowest
rate of major complications.
PMID- 25587520
TI - Clonazepam treatment of pathologic aerophagia in children with mental
retardation.
AB - PURPOSE: Pathologic aerophagia (PA) may lead to bowel perforation or volvulus in
mentally retarded patients. The authors investigated the effects of clonazepam on
the management of PA in children with severe to profound mental retardation (MR).
METHODS: This study was undertaken as a retrospective case analysis of 21 PA
patients with MR who were followed for over 12 months and diagnosed as having PA.
Patients were assigned to two management groups, that is, to a clonazepam
randomized open-labeled, treatment group or a reassurance group. The following
were recorded and analyzed; age, response, remission rate to clonazepam
treatment, and the side effect of clonazepam. It was defined positive response
(response+) as being symptom-free for a whole week within 1 month of commencing
treatment and remission(+) as being symptom-free for a whole month within 6
months of treatment. RESULTS: The average age of the 21 PA children with MR was
10 years and 13 patients were female. Symptom duration before diagnosis of PA was
7 months. Clinical features of the clonazepam-trial group (n=11) and the
reassurance group (n=10) were non-significantly different. Response(+) was
achieved by 2 patients (18.2%) in the clonazepam-trial group and by no patient in
the reassurance group. Remission(+) was achieved by 6 patients (54.5%) in the
clonazepam-trial group and by one patient (10%) in the reassurance group
(p=0.040). CONCLUSION: When PA children with MR with severe bowel distention are
considered for surgical treatment to prevent acute abdomen, a trial of clonazepam
could be recommended.
PMID- 25587522
TI - Systemic classification for a new diagnostic approach to acute abdominal pain in
children.
AB - PURPOSE: With previous methods based on only age and location, there are many
difficulties in identifying the etiology of acute abdominal pain in children. We
sought to develop a new systematic classification of acute abdominal pain and to
give some helps to physicians encountering difficulties in diagnoses. METHODS:
From March 2005 to May 2010, clinical data were collected retrospectively from
442 children hospitalized due to acute abdominal pain with no apparent underlying
disease. According to the final diagnoses, diseases that caused acute abdominal
pain were classified into nine groups. RESULTS: The nine groups were group I
"catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis
and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal
obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute
gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and
gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic
disease" (14 patients, 3.2%), group VII "febrile viral illness and
extraintestinal infection" (69 patients, 15.6%), group VIII "functional
gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group
IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were
enrolled in two disease groups each. CONCLUSION: Patients were distributed
unevenly across the nine groups of acute abdominal pain. In particular, the
"unclassified abdominal pain" only group was not uncommon. Considering a systemic
classification for acute abdominal pain may be helpful in the diagnostic approach
in children.
PMID- 25587523
TI - Clinical Characteristics of Symptomatic Clostridium difficile Infection in
Children: Conditions as Infection Risks and Whether Probiotics Is Effective.
AB - PURPOSE: This study investigated the clinical presentations of symptomatic
Clostridium difficile infection (CDI) in children. METHODS: We reviewed the
medical records of 43 children aged <20 years who showed either positive C.
difficile culture or C. difficile toxin test results between June 2010 and April
2014. RESULTS: Of the 43 patients (mean age 6.7 years), 22 were boys. Sixteen
patients (37.2%) showed both positive C. difficile culture and toxin test
results. Seventeen out of 43 children (39.5%) had preexisting gastrointestinal
diseases, and 26 children had other medical conditions that were risk factors for
CDI. Twenty-eight children had a history of antibiotic treatment for >3 days, and
the most frequently prescribed antibiotic was amoxicillin-clavulanate (35.7%).
Twenty-eight patients were diagnosed with CDI despite taking probiotic
supplements, most commonly Lactobacillus acidophilus (53.6%). The most common
symptom was diarrhea (72.1%) at the time CDI was diagnosed. C. difficile was
eradicated in 11 patients (25.6%) after treatment with oral metronidazole for 10
14 days, and in the two patients (4.6%) who required two courses of oral
metronidazole. Sixteen patients (37.2%) showed clinical improvement without any
treatment. CONCLUSION: This study showed the various clinical characteristics of
CDI in children and that preexisting clinical conditions favored the development
of CDI. In addition, CDI was found to occur in a number of patients even after
probiotic prophylaxis given in conjunction with antibiotic therapy.
PMID- 25587525
TI - The clinical significance of serum ferritin in pediatric non-alcoholic Fatty
liver disease.
AB - PURPOSE: Non-alcoholic fatty liver disease (NAFLD) in children has become an
important public health issue because of its high prevalence and severity.
Several noninvasive methods for estimating NAFLD are under investigation. We
aimed to evaluate the usefulness of serum ferritin as a biomarker of severity of
pediatric NAFLD patients. METHODS: A total of 64 NAFLD patient were enrolled from
Severance Children's Hospital from March 2010 to February 2013. Serum ferritin
levels, liver related laboratory tests, liver magnetic resonance imaging (MRI) (2
dimensional [2D] proton density-fat fraction) and NAFLD severity markers were
compared between obese group and overweight group. Correlation analyses were
performed between serum ferritin and laboratory values including NAFLD severity
markers. RESULTS: In obese group, serum ferritin, alanine aminotransferase (ALT),
total bilirubin, international normalized ratio (INR), MRI 2D proton density-fat
fraction, aspartate aminotransferase (AST) to platelet ratio index (APRI) and
fibrosis-4 (FIB-4) (an index score calculated from platelet count, ALT, AST and
age) were significantly higher than those of overweight group. NAFLD severity
markers, APRI and FIB-4, and liver specific important laboratory values, AST,
ALT, INR, cholesterol, triglyceride and low density lipoprotein show significant
correlation with serum ferritin in NAFLD patients. CONCLUSION: Serum ferritin
concentrations could be a candidate of useful severity marker in the pediatric
NAFLD patients.
PMID- 25587524
TI - Does type I truly dominate hepatic glycogen storage diseases in Korea?: a single
center study.
AB - PURPOSE: There are no studies of hepatic glycogen storage diseases (GSDs) other
than type I and III in Korea. We aimed on investigating the characteristics of
hepatic GSDs in Korea diagnosed and followed at a single center. METHODS: We
retrospectively analyzed patients who were diagnosed as GSD and followed at
Samsung Medical Center from January, 1997 to December, 2013. Clinical
manifestations, laboratory results, treatment, and prognosis were investigated.
RESULTS: Twenty-one patients were included in the study. The types of 17 patients
were confirmed by enzyme activity tests and/or gene analysis. GSD Ia was
diagnosed in 7 patients (33.3%), Ib in 1 patient (4.8%), III in 2 patients
(9.5%), IV in 1 patient (4.8%), and IX in 6 patients (28.6%). Types other than
GSD I constituted 52.9% (9/17) of the patients diagnosed with a specific type of
hepatic GSD. The median age at presentation was 2 years. Hepatomegaly was
observed in 95.2%, elevated liver transaminases in 90.5%, and hyperlactacidemia
in 81.0% of the patients. The duration for follow-up was 77+/-62.0 months.
Uncooked corn starch was initiated in all the patients. No mortality was observed
during the follow-up period, and liver transplantation was performed in 14.3%.
CONCLUSION: Types other than GSD I comprised more than half of the patients
diagnosed with a specific type of hepatic GSD. Clinical suspicion and thorough
evaluation of hepatic GSDs in Korea should be focused not only on GSD I, but also
on other types.
PMID- 25587526
TI - The complex surgical management of the first case of severe combined
immunodeficiency and multiple intestinal atresias surviving after the fourth year
of life.
AB - Severe combined immunodeficiency (SCID) is a life-threatening syndrome of
recurrent infections and gastrointestinal alterations due to severe compromise of
T cells and B cells. Clinically, most patients present symptoms before the age of
3 months and without intervention SCID usually results in severe infections and
death by the age of 2 years. Its association with intestinal anomalies as
multiple intestinal atresias (MIA) is rare and worsens the prognosis, resulting
lethal. We describe the case of a four year-old boy with SCID-MIA. He presented
at birth with meconium peritonitis, multiple ileal atresias and underwent several
intestinal resections. A targeted Sanger sequencing revealed a homozygous 4-bp
deletion (c.313DeltaTATC; p.Y105fs) in tetratricopeptide repeat domain 7A
(TTC7A). He experienced surgical procedures including resection and
stricturoplasty. Despite parenteral nutrition-associated liver disease, the
patient is surviving at the time of writing the report. Precocious immune system
assessment, scrutiny of TTC7A mutations and prompt surgical procedures are
crucial in the management.
PMID- 25587527
TI - A case of epiploic appendagitis with acute gastroenteritis.
AB - Epiploic appendagitis is an inflammation of the epiploic appendage in which the
small sacs projecting from the serosal layer of the colon are positioned
longitudinally from the caecum to the rectosigmoid area. Epiploic appendagitis is
rare and self-limiting; however, it can cause sudden abdominal pain in children.
Epiploic appendagitis does not typically accompany other gastrointestinal
diseases. Here, we report on a healthy eight-year-old girl who presented with
abdominal pain, fever, vomiting, and diarrhea. Based on these symptoms, she was
diagnosed with acute gastroenteritis, but epiploic appendagitis in the ascending
colon was revealed in contrast computed tomography (CT). The patient was treated
successfully with conservative management. CT is beneficial in diagnosis and
further assessment of epiploic appendagitis. Pediatricians need to be aware of
this self-limiting disease and consider it as a possible alternate diagnosis in
cases of acute abdominal pain.
PMID- 25587528
TI - Coexistence of gilbert syndrome and hereditary spherocytosis in a child
presenting with extreme jaundice.
AB - Gilbert syndrome is the most common inherited disorder of bilirubin
glucuronidation. It is characterized by intermittent episodes of jaundice in the
absence of hepatocellular disease or hemolysis. Hereditary spherocytosis is the
most common inherited hemolytic anemia and is characterized by spherical,
osmotically fragile erythrocytes that are selectively trapped by the spleen. The
patients have variable degrees of anemia, jaundice, and splenomegaly. Hereditary
spherocytosis usually leads to mild-to-moderate elevation of serum bilirubin
levels. Severe hyperbilirubinemia compared with the degree of hemolysis should be
lead to suspicion of additional clinical conditions such as Gilbert syndrome or
thalassemia. We present the case of a 12-year-old boy with extreme jaundice and
nausea. The diagnosis of hereditary spherocytosis was confirmed by osmotic
fragility test results and that of Gilbert syndrome by genetic analysis findings.
PMID- 25587530
TI - Peripheral nerve regeneration: mechanism, cell biology, and therapies.
PMID- 25587529
TI - The potential utility of pharmacogenetic testing in psychiatry.
AB - Over the last decade, pharmacogenetics has become increasingly significant to
clinical practice. Psychiatric patients, in particular, may benefit from
pharmacogenetic testing as many of the psychotropic medications prescribed in
practice lead to varied response rates and a wide range of side effects. The use
of pharmacogenetic testing can help tailor psychotropic treatment and inform
personalized treatment plans with the highest likelihood of success. Recently,
many studies have been published demonstrating improved patient outcomes and
decreased healthcare costs for psychiatric patients who utilize genetic testing.
This review will describe evidence supporting the clinical utility of genetic
testing in psychiatry, present several case studies to demonstrate use in
everyday practice, and explore current patient and clinician opinions of genetic
testing.
PMID- 25587531
TI - Proteoglycans/glycosaminoglycans: from basic research to clinical practice.
PMID- 25587533
TI - Performance analysis of extracted rule-base multivariable type-2 self-organizing
fuzzy logic controller applied to anesthesia.
AB - We compare type-1 and type-2 self-organizing fuzzy logic controller (SOFLC) using
expert initialized and pretrained extracted rule-bases applied to automatic
control of anaesthesia during surgery. We perform experimental simulations using
a nonfixed patient model and signal noise to account for environmental and
patient drug interaction uncertainties. The simulations evaluate the performance
of the SOFLCs in their ability to control anesthetic delivery rates for
maintaining desired physiological set points for muscle relaxation and blood
pressure during a multistage surgical procedure. The performances of the SOFLCs
are evaluated by measuring the steady state errors and control stabilities which
indicate the accuracy and precision of control task. Two sets of comparisons
based on using expert derived and extracted rule-bases are implemented as
Wilcoxon signed-rank tests. Results indicate that type-2 SOFLCs outperform type-1
SOFLC while handling the various sources of uncertainties. SOFLCs using the
extracted rules are also shown to outperform those using expert derived rules in
terms of improved control stability.
PMID- 25587534
TI - Imaging neurodegenerative diseases: mechanisms and interventions.
PMID- 25587535
TI - Radiopharmaceuticals in nuclear medicine: recent developments for SPECT and PET
studies.
PMID- 25587532
TI - Cysteine cathepsin activity regulation by glycosaminoglycans.
AB - Cysteine cathepsins are a group of enzymes normally found in the endolysosomes
where they are primarily involved in intracellular protein turnover but also have
a critical role in MHC II-mediated antigen processing and presentation. However,
in a number of pathologies cysteine cathepsins were found to be heavily
upregulated and secreted into extracellular milieu, where they were found to
degrade a number of extracellular proteins. A major role in modulating cathepsin
activities play glycosaminoglycans, which were found not only to facilitate their
autocatalytic activation including at neutral pH, but also to critically modulate
their activities such as in the case of the collagenolytic activity of cathepsin
K. The interaction between cathepsins and glycosaminoglycans will be discussed in
more detail.
PMID- 25587536
TI - Current and future novel treatments for glioblastoma multiforme.
PMID- 25587537
TI - The tumor microenvironment and cancer.
PMID- 25587538
TI - Advances in molecular pathway-directed cancer systems imaging and therapy.
PMID- 25587539
TI - Ovarian cancer.
PMID- 25587540
TI - Parasites: from source to vector and human.
PMID- 25587541
TI - Biomarkers of environmental pollutants.
PMID- 25587542
TI - High-performance computing and big data in omics-based medicine.
PMID- 25587543
TI - T-cell cytokine gene polymorphisms and vitamin D pathway gene polymorphisms in
end-stage renal disease due to type 2 diabetes mellitus nephropathy: comparisons
with health status and other main causes of end-stage renal disease.
AB - BACKGROUND: T-cell cytokine gene polymorphisms and vitamin D pathway gene
polymorphisms were evaluated as possibly associated with end-stage renal disease
(ESRD) resulting from type 2 diabetes mellitus (DM) nephropathy. METHODS: Studies
were conducted among hemodialysis (HD) patients with ESRD due to type 2 DM
nephropathy, chronic glomerulonephritis, chronic infective tubulointerstitial
nephritis, and hypertensive nephropathy as well as in healthy subjects. A
frequency distribution of T-cell-related interleukin (IL) genes (IL18 rs360719,
IL12A rs568408, IL12B rs3212227, IL4R rs1805015, IL13 rs20541, IL28B rs8099917,
IL28B, and rs12979860) and vitamin D pathway genes (GC genes: rs2298849, rs7041,
and rs1155563; VDR genes: rs2228570, rs1544410; and RXRA genes: rs10776909,
rs10881578, and rs749759) was compared between groups. RESULTS: No significant
differences in a frequency distribution of tested polymorphisms were shown
between type 2 DM nephropathy patients and controls. A difference was found in
IL18 rs360719 polymorphic distribution between the former group and chronic
infective tubulointerstitial nephritic patients (P trend = 0.033), which also
differed in this polymorphism from controls (P trend = 0.005). CONCLUSION: T-cell
cytokine and vitamin D pathway gene polymorphisms are not associated with ESRD
due to type 2 DM nephropathy in Polish HD patients. IL18 rs360719 is probably
associated with the pathogenesis of chronic infective tubulointerstitial
nephritis.
PMID- 25587544
TI - TNF-alpha and microalbuminuria in patients with type 2 diabetes mellitus.
AB - AIM: Recent evidence suggests that chronic subclinical inflammation plays a key
role in the pathogenesis and progression of diabetic nephropathy. Aim of the
present study was to investigate possible correlation between the presence and
degree of microalbuminuria and markers of inflammation in patients with type 2
diabetes mellitus (DM). PATIENTS-METHODS: Eighty patients were enrolled and
clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was
calculated in first-morning urine samples. Serum and urinary tumor necrosis
factor-alpha (TNF-alpha) levels were determined by ELISA. RESULTS: Forty-five
patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria.
Patients with microalbuminuria were older, with higher glycosylated hemoglobin
levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and
cardiovascular disease and were on treatment with angiotensin converting enzyme
inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was
significantly correlated with the presence of cardiovascular disease,
hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or
ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF
alpha levels but had a strong correlation with urinary TNF-alpha levels.
CONCLUSIONS: In patients with type 2 DM, urinary, but not serum, TNF-alpha levels
are associated with the presence and severity of microalbuminuria.
PMID- 25587545
TI - Generating and reversing chronic wounds in diabetic mice by manipulating wound
redox parameters.
AB - By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will
develop foot ulcer(s) and 20 M will undergo an amputation, creating a major
health problem. Understanding how these wounds become chronic will provide
insights to reverse chronicity. We hypothesized that oxidative stress (OS) in
wounds is a critical component for generation of chronicity. We used the db/db
mouse model of impaired healing and inhibited, at time of injury, two major
antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the
wounds. This was necessary and sufficient to trigger wounds to become chronic.
The wounds initially contained a polymicrobial community that with time selected
for specific biofilm-forming bacteria. To reverse chronicity we treated the
wounds with the antioxidants alpha-tocopherol and N-acetylcysteine and found that
OS was highly reduced, biofilms had increased sensitivity to antibiotics, and
granulation tissue was formed with proper collagen deposition and remodeling. We
show for the first time generation of chronic wounds in which biofilm develops
spontaneously, illustrating importance of early and continued redox imbalance
coupled with the presence of biofilm in development of wound chronicity. This
model will help decipher additional mechanisms and potentially better diagnosis
of chronicity and treatment of human chronic wounds.
PMID- 25587546
TI - ACE insertion/deletion polymorphism and diabetic nephropathy: clinical
implications of genetic information.
AB - Approximately 20-40% of diabetic patients develop nephropathy which is the
leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought
to be a marker for functional polymorphism which regulates circulating and tissue
ACE activity. While the initial study found a protective effect of the II
genotype on the development of nephropathy in IDDM patients, subsequent studies
have addressed the role of ACE I/D polymorphism in the development and
progression of diabetic nephropathy. RAAS blockers are the first line drugs for
the treatment hypertension associated with diabetes and have been widely used in
everyday clinical practice for the purpose of reducing proteinuria in patients
with various renal diseases. However, the antiproteinuric effect of RAAS blockers
is variable and the percentage of reducing proteinuria is in the range of 20-80%.
The antiproteinuric effect of RAAS blockers may be related to a number of
factors: the type or the dose of RAAS blockers, the duration of therapy, the
level of sodium intake, and the type of patient's ACE I/D genotype. Besides the
nongenetic factors, drug responses, can be influenced by ACE gene polymorphism.
In this review, we discuss the relationship between ACE I/D polymorphism and
diabetic nephropathy and therapeutic response of RAAS blockers.
PMID- 25587548
TI - Needs assessment and evaluation of a short course to improve faculties teaching
skills at a former World Health Organization regional teacher training center.
AB - INTRODUCTION: In the design of educational programs, much attention has been paid
to teaching methods, needs assessment, an important part of the development of
educational programs, generally is neglected. Another important aspect in
educational program design is assessing effectiveness. The aims of this study
were to design a formal needs assessment program to define the core contents of a
faculty development program, and to determine whether participation in the
faculty development program reinforced new teaching skills. METHODS: A teacher
training program was designed at Shiraz University of Medical Sciences to help
medical instructors boost their teaching skills. Needs assessment was done with
nominal group technique followed by a 5-point Likert scale questionnaire. The
program, imparted in workshop format, covered effective teaching methods,
feedback, assessing knowledge and time management. Instruction was in the form of
lectures, group discussions, case simulations, video presentations and role
plays. The program was evaluated in several phases using data triangulation and
multi-item assessments of overall program quality in three major dimensions:
Kirkpatrick program evaluation model, evaluation of the educational environment
and qualitative analysis with open-ended questions. All participants in the study
belonged to the academic staff of Shiraz University of Medical Sciences (n=396).
RESULTS: Seven main categories were derived from nominal group techniques and
questionnaires. After the program, participants rated the quality of the program
highly. They felt that the educational intervention was appropriate and had a
positive impact on their knowledge of effective teaching methods, feedback,
knowledge assessment and time management. Assessment of the effectiveness of the
program showed that participants reported significant improvements in their
teaching abilities. CONCLUSIONS: Our faculty development program have a
significant positive effect on medical university teaching staff members'
competencies. Further research is needed to investigate whether the faculty
development program actually results in improved teaching performance.
PMID- 25587547
TI - Relationship between levels of brain-derived neurotrophic factor and metabolic
parameters in patients with type 2 diabetes mellitus.
AB - BACKGROUND AND AIM: Studies have suggested that brain-derived neurotrophic factor
(BDNF) plays a role in glucose and lipid metabolism and inflammation. The aim of
this study was to evaluate the relationship between serum BDNF levels and various
metabolic parameters and inflammatory markers in patients with type 2 diabetes
mellitus (T2DM). MATERIALS AND METHODS: The study included 88 T2DM patients and
33 healthy controls. Fasting blood samples were obtained from the patients and
the control group. The serum levels of BDNF were measured with an ELISA kit. The
current paper introduces a receiver-operating characteristic (ROC) generalization
curve to identify cut-off for the BDNF values in type 2 diabetes patients.
RESULTS: The serum levels of BDNF were significantly higher in T2DM patients than
in the healthy controls (206.81 +/- 107.32 pg/mL versus 130.84 +/- 59.81 pg/mL; P
< 0.001). They showed a positive correlation with the homeostasis model
assessment of insulin resistance (HOMA-IR) (r = 0.28; P < 0.05), the triglyceride
level (r = 0.265; P < 0.05), and white blood cell (WBC) count (r = 0.35; P <
0.001). In logistic regression analysis, age (P < 0.05), body mass index (BMI) (P
< 0.05), C-reactive protein (CRP) (P < 0.05), and BDNF (P < 0.01) were
independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137.
CONCLUSION: The serum BDNF level was higher in patients with T2DM. The BDNF had a
cut-off value of 137. The findings suggest that BDNF may contribute to glucose
and lipid metabolism and inflammation.
PMID- 25587549
TI - Impact of media literacy education on knowledge and behavioral intention of
adolescents in dealing with media messages according to Stages of Change.
AB - INTRODUCTION: Mass media influence the health behaviors of adolescents. Evidence
shows that traditional strategies such as censorship or limitation are no longer
efficient; therefore, teaching media literacy is the best way to protect
adolescents from harmful effects. The aim of this pilot study was to evaluate the
effects of a media literacy training program on knowledge and behavioral
intention of a sample of female students according to the stages of change in
dealing with media messages. METHODS: The study was conducted based on a pre-test
and post-test control group design. Some 198 female students including 101 in the
intervention group and 97 in the control group participated in this study. The
educational program was run using interactive teaching-learning techniques. Data
collection was performed using a validated and reliable self-administered
questionnaire in three phases including a pre-test, post-test, 1 and post-test,
2. The research data was analyzed through SPSS statistical software, version 14
using both descriptive and inferential statistics. RESULTS: The results of the
study showed a significant increase (p=0.001) in the intervention group's
knowledge mean scores after the training program. On the other hand, the
difference was not significant in the control group (p=0.200). A considerable
percentage of the participants, in the intervention and control groups, were in
pre contemplation and contemplation stages in the pre-test (64 and 61,
respectively). After the intervention, however, a significant improvement
(p=0.001) was observed in the intervention group's stages of change compared to
that in the control group. The distribution of the control group students
regarding the stages of change was similar to that in the pre-test. CONCLUSION:
The study findings revealed that the planned education programs are efficient to
improve the adolescents' knowledge and behavioral intention in dealing with mass
media messages.
PMID- 25587550
TI - Academic training and clinical placement problems to achieve nursing competency.
AB - INTRODUCTION: High quality of care is one of the requirements of nursing which
depends on the nursing competency. In this connection, the aim of this research
was to determine the problems related to the academic training (nursing'
educational program) and clinical practice to achieve competency from the
viewpoint of nurses, faculty members, and nursing students. METHODS: the study
was an analytical cross-sectional one. The sample consisted of the academic
staff, the third and the fourth year nursing students and nurses in practice. The
instrument of the study was a two-part researcher-made questionnaire with 22
questions in the theoretical- clinical realm to assess problems related to the
theoretical and clinical teaching in nursing, and 23 questions to assess the
clinical functions. The questionnaire was validated in terms of both face and
content validity. Its reliability, using Cronbach's Alpha coefficient, was 0.72
in the theoretical-clinical and 0.73 in the clinical realm. Both descriptive and
analytical statistics were used to analyze the data, using SPSS software.
RESULTS: The results of this study indicated that from the participants'
viewpoints, the most important problems in the academic education for nursea to
acquire competency were as follows: lack of academic research the clinical period
(88.9%), no application of theoretical aspects of the nursing process in practice
(85.6%), insufficient knowledgeable and professional educators (81.1%), the use
of traditional routine-oriented methods on the wards (75.6%); also insufficient
time for performance based on knowledge in relation to the nurse's workload
(86.5%), weakness and usefulness of scientific function encouragement systems in
clinic (85.2%), and learnt theoretical subjects not coming into practice in
clinical fields after graduation (75.6%). CONCLUSION: Efforts to reduce the gap
between the theoretical and practical (clinical function) knowledge in
educational and work environment are required to improve the training of
qualified nurses.
PMID- 25587551
TI - Medical Students' and Physicians' Attitudes toward Patients' Consent to
Participate in Clinical Training.
AB - INTRODUCTION: The responsibility of the medical training team towards a patient
referring to an academic medical center has not been fully clarified. In this
article we have looked at current practice in Medical University of Isfahan and
evaluated the attitude of the medical team towards patients'consent to be
involved in medical students'education. METHODS: In this cross-sectional study,
conducted in 2012, we distributed self-administrated questionnaires among medical
mentors, residents and students of academic hospitals in Isfahan, Iran. This
researcher-made questionnaire consisted of several questions concerning
dimensions of informed consent. The data were analyzed, using independent t-tests
and ANOVA. RESULTS: Ninety-one medical students (51 females) and 61 members of
medical training team (25 females) completed the questionnaires. The overall
average attitude score was 36.53+/-5.89 out of 60, which is classified as fair.
The average attitude score for medical students and mentors were not
significantly different. The average attitude score of the female students was
classified as good, and was different from that of male students, significantly
(p<0.05). By categorizing subjects into those with>=5 years of managerial or
educational experience and those below 5, a significant difference in average
attitude score was documented (35.8+/-2.54 in>=5and 34.0+/-2.9 in>5group).
CONCLUSION: The attitude of the medical team is thoroughly far from what is
expected. Thus, the need to provide both medical students and medical mentors
with data on the importance of obtaining patients' consent to be involved in
medical education is highlighted.
PMID- 25587552
TI - Achievement motivation level in students of Shiraz University of Medical Sciences
and its influential factors.
AB - INTRODUCTION: Many studies have investigated the relationship between motivation
and educational outcomes. The present study was conducted to determine whether
the students' motivation in Shiraz University of Medical Sciences (SUMS)
decreases during educational years. METHODS: 770 students in SUMS were selected
by multi-stage stratified random sampling from each field and entrance year. The
first questionnaire contained 57 questions on the effect of economic, social,
educational, geographical and personality factors on the students' motivation.
The second one was based on 50 incomplete sentences. The validity and reliability
of these questionnaires were approved by the experts and Cronbach's Alpha
coefficients (85% and 90%, respectively). In this cross-sectional study, ANOVA, t
test and Chi-square tests were applied for data analysis at the 0.05 significance
level. RESULTS: Six factors with the most effect on academic motivation were
"family attitudes", "getting good jobs in future", "respect for themselves", "
the ability to learn", "believing their role in victory and defeat" and "the
tendency toward optimism about themselves". In addition, comparing professional
doctorate and basic sciences' results revealed no significant relationship
between academic motivation and educational years (F=0.819, p=0.397). But
comparing field by field showed that Dentistry and Hospital Management and
Medical Information (HMMI) had a significant decrease in motivation score by
increase in educational years (F=3.991, p=0.015). CONCLUSION: Achievement
motivation level in SUMS students was higher than average and did not decrease
during educational years. Also, the results showed that personal, social and
educational related factors affected motivation level more than economic and
environmental factors.
PMID- 25587553
TI - Medical ethics as practiced by students, nurses and faculty members in Shiraz
University of Medical Sciences.
AB - INTRODUCTION: Assuming any social role has obligations and fulfilling the related
responsibilities has ethical aspects that must be addressed carefully. Each role
requires extensive training, which usually takes place in university
institutions. Ethics is applied in at least three academic areas, including: a)
in education of students' personal growth, b) in patient care, and c) in
university communion in population-based health care. Given the importance of
this issue in the moral domain, this study examines the correlation among the
students, nurses and teacher's opinions regarding principles of medical ethics at
Shiraz University of Medical Sciences. METHODS: This is a descriptive-analytic
and cross-sectional study conducted in 2010. The participants of this research
consisted of all medical students, nurses in public hospitals, and faculty
members in Shiraz University of Medical Sciences. For validity evaluation, the
expert panel method and for reliability evaluation, test-retest method was used.
RESULTS: Based on the medical ethics' scores in these three groups, there was a
significant relationship between the mean scores of student-nurses and employed
nurses, but there was no significant relationship between those of student
faculties. Also the mean score of the students was the highest in medical ethics.
CONCLUSION: In this study, we presented a list of virtues and moral
characteristics of medical staff and found out the method of practicing medical
ethics in everyday life of students to improve the moral reasoning of teachers,
nurses and students. Moreover, medical ethics, with the presentation of specific
criteria for ethical behavior in various domains of human life, especially in
dealing with patients, can help practice ethical values in the medical community.
PMID- 25587554
TI - Nursing students' perspectives on clinical education.
AB - INTRODUCTION: The importance of optimal clinical nursing education in
professional skills development is undeniable. In clinical education, nursing
students are often faced with problems. Recognizing nursing students' perception
on clinical education is the first step to remove the barriers of this challenge.
Methods This descriptive cross-sectional study was conducted to determine the
nursing students' perspectives on clinical education. 150 nursing students were
selected randomly from nursing and midwifery schools (Tehran). Data collection
instrument was a researcher made questionnaire consisting of five domains:
objective and curricula, instructor, feedback to student in clinical field,
clinical environment, supervision and evaluation. Mean and standard deviation
were calculated for each item, using SPSS, ver.14. Chi- square test was used to
compare the nursing students' perspectives on clinical education based on age,
sex and the work experience. The significance level was considered 0.05. RESULTS:
Mean age of the students was 21.58+/-26.97 students (66%) were male. 44 students
(30.1%) had work experience (3.58+/-6.48 month). Male and female students had
different perceptions in domains of clinical education (p<0.05). Nursing student
had different perceptions as to objectives and curricula (p=0.039), how to deal
with students in the clinical environment (p=0.032), supervision, and evaluation
(p<0.001) with respect to their work experience duration. The most positive
responses were in clinical instructor (81.5%) and the most negative ones were the
clinical environment (33.66%), respectively. CONCLUSION: Providing an optimal
clinical environment and improving the supervision and evaluation of student
practice should prioritized in schools of nursing and midwifery.
PMID- 25587555
TI - Clinical characteristics and outcomes of pediatric oncology patients with
aggressive biology enrolled in phase I clinical trials designed for adults: the
university of Texas MD anderson cancer center experience.
AB - BACKGROUND: Children (patients <= 18 years of age) are not usually included on
pharmaceutical industry sponsored Phase I trials. METHODS: We reviewed the
medical records of 40 patients <= 18 years treated in >= 1 phase I trial at MD
Anderson. RESULTS: The median OS was 8.5 months (95% CI, 5.5-13.2 months). In the
multivariate analysis, age >=15 only predicted increased OS (P = 0.0065), and >3
prior therapies (P = 0.053) predicted decreased OS. The median PFS was 2.8 months
(95% CI, 2.3-4.1 months). In the multivariate analysis, independent factors that
predicted increased PFS were age >=15 years (P < 0.001) and prior radiation
therapy (P = 0.049); performance status >1 (P < 0.001) and >3 prior therapies (P
= 0.002) predicted decreased PFS. RMH score >= 2 and MDACC score >= 3 were
associated with decreased median OS (P = 0.029 and P = 0.031 respectively).
CONCLUSIONS: It is feasible to conduct phase I studies in pediatric patients
based on adult protocols. In the era of targeted therapy more trials should allow
pediatric patients earlier in the drug development especially if deemed safe in
adults in early phase trials. TRANSLATIONAL RELEVANCE: Most pharmaceutical
industry sponsored trials exclude patients less than 18 years in phase I clinical
trials. Even in the era of targeted therapy pediatric patients usually have to
wait for most phases of trials to be completed in adults before being allowed to
enroll in clinical trials of new therapies, even in the advanced metastatic and
relapsed setting. Some investigator initiated phase 1 trials of combinations of
US FDA approved agents allow patients less than 18 years. We report the
preliminary analyses of the outcomes of pediatric patients enrolled in phase I
studies initially designed for adults, but allowing for enrollment of patients
under 18.
PMID- 25587556
TI - Evolutionary behavioral genetics.
AB - We describe the scientific enterprise at the intersection of evolutionary
psychology and behavioral genetics-a field that could be termed Evolutionary
Behavioral Genetics-and how modern genetic data is revolutionizing our ability to
test questions in this field. We first explain how genetically informative data
and designs can be used to investigate questions about the evolution of human
behavior, and describe some of the findings arising from these approaches.
Second, we explain how evolutionary theory can be applied to the investigation of
behavioral genetic variation. We give examples of how new data and methods
provide insight into the genetic architecture of behavioral variation and what
this tells us about the evolutionary processes that acted on the underlying
causal genetic variants.
PMID- 25587558
TI - Dynamics of nonlinear systems.
PMID- 25587559
TI - Induced neurocysticercosis in rhesus monkeys (Macaca mulatta) produces clinical
signs and lesions similar to natural disease in man.
AB - Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of
seizure and epilepsy in humans. The genesis of clinical manifestations of the
disease through experimental animal models is poorly exploited. The monkeys may
prove useful for the purpose due to their behavior and cognitive responses
mimicking man. In this study, neurocysticercosis was induced in two rhesus
monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given
placebo. The monkeys given higher dose developed hyperexcitability, epileptic
seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of
limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed
delayed and milder clinical signs. On necropsy, all the infected monkeys showed
numerous cysticerci in the brain. Histopathologically, heavily infected monkeys
revealed liquefactive necrosis and formation of irregular cystic cavities lined
by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In
contrast, the monkeys infected with lower dose showed formation of typical
foreign body granulomas characterized by central liquefaction surrounded by
chronic inflammatory response. It was concluded that the inflammatory and immune
response exerted by the host against cysticerci, in turn, led to
histopathological lesions and the resultant clinical signs thereof.
PMID- 25587557
TI - Evaluation of the inhibition of carbohydrate hydrolyzing enzymes, the antioxidant
activity, and the polyphenolic content of Citrus limetta peel extract.
AB - Type 2 diabetes mellitus is one of the most frequent causes of death in Mexico,
characterized by chronic hyperglycemia. One alternative strategy for this
metabolic abnormality is inhibiting the enzymes responsible for the metabolism of
carbohydrates. We evaluated whether the aqueous Citrus limetta peel extract could
inhibit the metabolism of carbohydrates. We found that this extract inhibited
primarily the enzyme alpha-amylase by 49.6% at a concentration of 20 mg/mL and to
a lesser extent the enzyme alpha-glucosidase with an inhibition of 28.2% at the
same concentration. This inhibition is likely due to the high polyphenol content
in the Citrus limetta peel (19.1 mg GAE/g). Antioxidant activity of the Citrus
limetta peel demonstrated dose-dependent antioxidant activity, varying from 6.5%
at 1.125 mg/mL to 42.5% at 20 mg/mL. The study of these polyphenolic compounds
having both antihyperglycemic and antioxidant activities may provide a new
approach to the management of type 2 diabetes mellitus.
PMID- 25587560
TI - Development of robust behaviour recognition for an at-home biomonitoring robot
with assistance of subject localization and enhanced visual tracking.
AB - Our research is focused on the development of an at-home health care
biomonitoring mobile robot for the people in demand. Main task of the robot is to
detect and track a designated subject while recognizing his/her activity for
analysis and to provide warning in an emergency. In order to push forward the
system towards its real application, in this study, we tested the robustness of
the robot system with several major environment changes, control parameter
changes, and subject variation. First, an improved color tracker was analyzed to
find out the limitations and constraints of the robot visual tracking considering
the suitable illumination values and tracking distance intervals. Then, regarding
subject safety and continuous robot based subject tracking, various control
parameters were tested on different layouts in a room. Finally, the main
objective of the system is to find out walking activities for different patterns
for further analysis. Therefore, we proposed a fast, simple, and person specific
new activity recognition model by making full use of localization information,
which is robust to partial occlusion. The proposed activity recognition algorithm
was tested on different walking patterns with different subjects, and the results
showed high recognition accuracy.
PMID- 25587561
TI - Histological features of the gastrointestinal tract of wild Indonesian shortfin
eel, Anguilla bicolor bicolor (McClelland, 1844), captured in Peninsular
Malaysia.
AB - This study was conducted to record the histological features of the
gastrointestinal tract of wild Indonesian shortfin eel, Anguilla bicolor bicolor
(McClelland, 1844), captured in Peninsular Malaysia. The gastrointestinal tract
was segmented into the oesophagus, stomach, and intestine. Then, the oesophagus
was divided into five (first to fifth), the stomach into two (cardiac and
pyloric), and the intestine into four segments (anterior, intermediate,
posterior, and rectum) for histological examinations. The stomach had
significantly taller villi and thicker inner circular muscles compared to the
intestine and oesophagus. The lamina propria was thickest in stomach,
significantly when compared with oesophagus, but not with the intestine. However,
the intestine showed significantly thicker outer longitudinal muscle while
gastric glands were observed only in the stomach. The histological features were
closely associated with the functions of the different segments of the
gastrointestinal tract. In conclusion, the histological features of the
gastrointestinal tract of A. b. bicolor are consistent with the feeding habit of
a carnivorous fish.
PMID- 25587562
TI - Recent advances in communications and networking.
PMID- 25587563
TI - The filtering of the posturographic signals shows the age related features.
AB - OBJECTIVE: Lower frequencies of slow oscillations of the posturographic signals
can be removed using high-pass filtering. This procedure releases postural
reflexes possessing higher frequencies and lower amplitude range. Mutual
dependence between the x and y components of posturographic signals was analyzed
using principal component analysis (PCA). The posturographic signals of old
patients with idiopathic gait disturbance were compared with the control group of
similar age and with younger patients. There was also the analysis of the
influence of the eyes state (open versus closed) and the head position (normal or
bent back). The statistically significant differences in the mutual dependence
between x and y components between the groups of patients were analyzed using
MANOVA. The significant differences were observed mainly in the range of filter
frequencies f = 0.1-1.5 Hz and f = 2.2-5.5 Hz with a maximum effect at
approximately 4-5 Hz. A detailed post-hoc analysis is also presented. The
differences in the higher frequency range suggest the main disturbance to be
connected with the spinal reflexes. Visual and vestibular support appear
insufficient for postural stability control in the idiopathic gait disturbance
group. The results suggest that idiopathic gait disturbance is the final stage of
the aging process of postural system.
PMID- 25587564
TI - Seropositivity of dengue antibodies during pregnancy.
AB - PURPOSE: Malaysia a dengue endemic country with dengue infections in pregnancy on
the rise. The present study was aimed at determining dengue seroprevalence (IgG
or IgM) during pregnancy and its neonatal transmission in dengue seropositive
women. METHODS: Maternal with paired cord blood samples were tested for dengue
antibodies (IgG and IgM) using an enzyme-linked immunosorbent assay (ELISA).
Maternal age, parity, occupation, ethnic group, and gestational age were
recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive
Care Unit (NICU) were analyzed. RESULTS: Out of 358 women recruited, about 128
(35.8%) patients were seropositive. Twelve patients (3.4%) had recent infections
(IgM positive) and another 116 women (32.4%) were with past infections (IgG
positive). All babies born to seropositive mothers had positive IgG paired cord
blood; however, no IgM seropositivity was observed. All neonates had good Apgar
scores and did not require NICU admission. CONCLUSION: In this study, 35.8%
pregnant women were found to be dengue seropositive. However, transplacental
transfer of IgG antibodies had no detrimental effect on the neonatal outcomes.
PMID- 25587565
TI - Characterization of antibiotic producing rare actinomycete Nonomuraea sp. JAJ18
derived from an Indian coastal solar saltern.
AB - Rare actinomycete genera are accepted as a promising source of novel metabolites
having pharmaceutical importance. One such genus of rare actinomycete is
Nonomuraea. The present study was aimed at characterizing the antibiotic
producing Nonomuraea strain JAJ18 which was previously isolated from coastal
solar saltern. Strain JAJ18 was recognized as a member of genus Nonomuraea based
on its almost complete 16S rRNA gene sequence and phenotypic characteristics. The
strain JAJ18 was found to be closely related to Nonomuraea maheshkhaliensis 16-5
14(T) (98.90%), Nonomuraea candida HMC10(T) (98.58%), and Nonomuraea jabiensis
A4036(T) (98.43%). From cell-free culture broth of strain JAJ18, an antibiotic
was extracted and purified by silica column chromatography. The obtained
antibiotic was found to be active against a range of Gram-positive and Gram
negative bacteria including drug-resistant Staphylococcus, with minimal
inhibitory concentration (MIC) ranging from 0.5 to 16.0 ug mL(-1). The structural
characteristics of antibiotic were determined by FTIR and NMR spectroscopy. The
antibiotic was identified to be an aliphatic rich compound with significant
dissimilarity to known antibiotics reported from members of the genus,
Nonomuraea. As the trends to discover novel metabolites from Nonomuraea are
vibrant, further studies are needed to understand the structural and
biotechnological significance of antibiotic compound produced by Nonomuraea sp.
JAJ18.
PMID- 25587566
TI - Biomechanics of gait during pregnancy.
AB - INTRODUCTION: During pregnancy women experience several changes in the body's
physiology, morphology, and hormonal system. These changes may affect the balance
and body stability and can cause discomfort and pain. The adaptations of the
musculoskeletal system due to morphological changes during pregnancy are not
fully understood. Few studies clarify the biomechanical changes of gait that
occur during pregnancy and in postpartum period. PURPOSES: The purpose of this
review was to analyze the available evidence on the biomechanical adaptations of
gait that occur throughout pregnancy and in postpartum period, specifically with
regard to the temporal, spatial, kinematic, and kinetic parameters of gait.
METHODS: Three databases were searched and 9 studies with a follow-up design were
retrieved for analysis. RESULTS: Most studies performed temporal, spatial, and
kinematic analysis. Only three studies performed kinetic analysis. CONCLUSION.
The adaptation strategies to the anatomical and physiological changes throughout
pregnancy are still unclear, particularly in a longitudinal perspective and
regarding kinetic parameters.
PMID- 25587568
TI - Transcriptome sequencing in a Tibetan barley landrace with high resistance to
powdery mildew.
AB - Hulless barley is an important cereal crop worldwide, especially in Tibet of
China. However, this crop is usually susceptible to powdery mildew caused by
Blumeria graminis f. sp. hordei. In this study, we aimed to understand the
functions and pathways of genes involved in the disease resistance by
transcriptome sequencing of a Tibetan barley landrace with high resistance to
powdery mildew. A total of 831 significant differentially expressed genes were
found in the infected seedlings, covering 19 functions. Either "cell," "cell
part," and "extracellular region" in the cellular component category or "binding"
and "catalytic" in the category of molecular function as well as "metabolic
process" and "cellular process" in the biological process category together
demonstrated that these functions may be involved in the resistance to powdery
mildew of the hulless barley. In addition, 330 KEGG pathways were found using
BLASTx with an E-value cut-off of <10(-5). Among them, three pathways, namely,
"photosynthesis," "plant-pathogen interaction," and "photosynthesis-antenna
proteins" had significant matches in the database. Significant expressions of the
three pathways were detected at 24 h, 48 h, and 96 h after infection,
respectively. These results indicated a complex process of barley response to
powdery mildew infection.
PMID- 25587570
TI - Video multiple watermarking technique based on image interlacing using DWT.
AB - Digital watermarking is one of the important techniques to secure digital media
files in the domains of data authentication and copyright protection. In the
nonblind watermarking systems, the need of the original host file in the
watermark recovery operation makes an overhead over the system resources, doubles
memory capacity, and doubles communications bandwidth. In this paper, a robust
video multiple watermarking technique is proposed to solve this problem. This
technique is based on image interlacing. In this technique, three-level discrete
wavelet transform (DWT) is used as a watermark embedding/extracting domain,
Arnold transform is used as a watermark encryption/decryption method, and
different types of media (gray image, color image, and video) are used as
watermarks. The robustness of this technique is tested by applying different
types of attacks such as: geometric, noising, format-compression, and image
processing attacks. The simulation results show the effectiveness and good
performance of the proposed technique in saving system resources, memory
capacity, and communications bandwidth.
PMID- 25587567
TI - Role of melatonin in traumatic brain injury and spinal cord injury.
AB - Brain and spinal cord are implicated in incidences of two of the most severe
injuries of central nervous system (CNS). Traumatic brain injury (TBI) is a
devastating neurological deficit involving primary and secondary injury cascades.
The primary and secondary mechanisms include complex consequences of activation
of proinflammatory cytokines, cerebral edema, upregulation of NF-kappa beta,
disruption of blood-brain barrier (BBB), and oxidative stress. Spinal cord injury
(SCI) includes primary and secondary injury cascades. Primary injury leads to
secondary injury in which generation of free radicals and oxidative or nitrative
damage play an important pathophysiological role. The indoleamine melatonin is a
hormone secreted or synthesized by pineal gland in the brain which helps to
regulate sleep and wake cycle. Melatonin has been shown to be a versatile hormone
having antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory
properties. It has a special characteristic of crossing BBB. Melatonin has
neuroprotective role in the injured part of the CNS after TBI and SCI. A number
of studies have successfully shown its therapeutic value as a neuroprotective
agent in the treatment of neurodegenerative diseases. Here in this review we have
compiled the literature supporting consequences of CNS injuries, TBI and SCI, and
the protective role of melatonin in it.
PMID- 25587571
TI - Recent advances on internet of things.
PMID- 25587569
TI - Outer membrane proteome analysis of Indian strain of Pasteurella multocida
serotype B:2 by MALDI-TOF/MS analysis.
AB - Identification of outer membrane proteins (OMPs) is important to understand the
bacteria structure and function, host-pathogen interaction, development of novel
vaccine candidates, and diagnostic antigens. But till now the key antigens of P.
multocida B:2 isolate causing haemorrhagic septicaemia (HS) in animals are not
clearly defined. In this study, P52 strain of P. multocida serotype B:2 was grown
in vitro under iron-rich and iron-limited condition. The OMPs were extracted by
sarkosyl method followed by SDS-PAGE and the proteins were identified by MALDI
TOF/MS analysis. In total, 22 proteins were identified, of which 7 were observed
exclusively under iron-limited condition. Most of the high molecular weight
proteins (TbpA, HgbA, HgbB, HasR, IroA, and HemR) identified in this study were
involved in iron acquisition. Some hypothetical proteins (HP-KCU-10206, HP and
AAUPMB 08244, HP AAUPMB 21592, HP AAUPMB 19766, AAUPMB 11295) were observed for
the first time in this study which could be unique to serotype B:2. Further
functional in vivo study of the proteins identified are required to explore the
utility of these proteins in developing diagnostics and vaccine against HS.
PMID- 25587573
TI - The moss flora of Akdag Mountain (Amasya, Turkey).
AB - The moss flora of Akdag Mountain (Amasya, Turkey) was investigated. At the result
of identifications of 1500 moss specimens, collected from the research area, 178
taxa belonging to 69 genera and 26 families were determined. Among them, 94 taxa
are new for A3 grid square according to the Turkey grid system which was adopted
by Henderson. The location data of Grimmia crinitoleucophaea Cardot and Barbula
enderesii Garov. are the first records for Turkey, and Encalypta spathulata Mull.
Hal., Schistidium dupretii (Ther.) W. A. Weber, Weissia condensa var. armata
(Ther. & Trab.) M. J. Cano, Ros & J. Guerra, Tortella bambergeri (Schimp.),
Barbula enderesii Garov., Hedwigia ciliata var. leucophaea Bruch & Schimp., and
Campyliadelphus elodes (Lindb.) Kanda are recorded for the second time to the
byroflora of Turkey.
PMID- 25587572
TI - The meaning of collaboration, from the perspective of Iranian nurses: a
qualitative study.
AB - BACKGROUND: Interdisciplinary collaboration among nurses is a complex and
multifaceted process, an essential element in nursing, which is crucial to
maintain an efficient, safe, and viable medical setting. The aim of this study
was to explore the meaning of concept of collaboration through conducting a
qualitative research approach. METHOD: The present study is qualitatively
conducted in a content analysis approach. The data collection process included 18
unstructured and in-depth interviews with nurses during 2012-2013 in educational
medical centers of west and northwest of Iran. A purposive sampling method was
used. All the interviews were recorded, transcribed, and finally analyzed using a
qualitative content analysis with a conventional method. RESULT: Categories
obtained from analysis of the data to explain the meaning of collaboration
consist of (i) prerequisites of collaboration, (ii) actualization of
collaboration, and (iii) achievement of a common goal. CONCLUSION: The results of
the present study ended in the discovery of meaning of collaboration that confirm
results of other related studies, hence clarifying and disambiguating the concept
under study. These results also contribute to the development of collaboration
theories and the relevant measurement tools.
PMID- 25587574
TI - Cell hydration as a biomarker for estimation of biological effects of nonionizing
radiation on cells and organisms.
AB - "Changes in cell hydration" have been hypothesized as an input signal for
intracellular metabolic cascade responsible for biological effects of nonionizing
radiation (NIR). To test this hypothesis a comparative study on the impacts of
different temperature and NIR (infrasound frequency mechanical vibration (MV),
static magnetic field (SMF), extremely low frequency electromagnetic field (ELF
EMF), and microwave (MW)) pretreated water on the hydration of barley seeds in
its dormant and germination periods was performed. In dormant state temperature
sensitivity (Q 10) of seed hydration in distilled water (DW) was less than 2, and
it was nonsensitive to NIR treated DW, whereas during the germination period (48
72 hours) seeds hydration exhibited temperature sensitivity Q 10 > 2 and higher
sensitivity to NIR treated DW. Obtained data allow us to suggest that the
metabolic driving of intracellular water dynamics accompanied by hydrogen bonding
and breaking is more sensitive to NIR-induced water structure changes in seed
bathing aqua medium than the simple thermodynamic processes such as osmotic
gradient driven water absorption by seeds in dormant state. Therefore, cell
hydration is suggested to be a universal and extrasensitive biomarker for
detection of biological effects of NIR on cells and organisms.
PMID- 25587575
TI - Inheritance of nitrogen use efficiency in inbred progenies of tropical maize
based on multivariate diallel analysis.
AB - The objective of our study was to characterize and determine the patterns of
genetic control in relation to tolerance and efficiency of nitrogen use by means
of a complete diallel cross involving contrasting inbred progenies of tropical
maize based on a univariate approach within the perspective of a multivariate
mixed model. Eleven progenies, previously classified regarding the tolerance and
responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five
hybrids were obtained. The hybrids and the progenies were evaluated at two
different nitrogen levels, in two locations. The grain yield was measured as well
as its yield components. The heritability values between the higher and lower
nitrogen input environment did not differ among themselves. It was observed that
the general combining ability values were similar for both approaches univariate
and multivariate, when it was analyzed within each location and nitrogen level.
The estimate of variance of the specific combining ability was higher than
general combining ability estimate and the ratio between them was 0.54. The
univariate and multivariate approaches are equivalent in experiments with good
precision and high heritability. The nonadditive genetic effects exhibit greater
quantities than the additive genetic effects for the genetic control of nitrogen
use efficiency.
PMID- 25587577
TI - Characterization of core-shell MOF particles by depth profiling experiments using
on-line single particle mass spectrometry.
AB - Materials with core-shell structures have distinct properties that lend
themselves to a variety of potential applications. Characterization of small
particle core-shell materials presents a unique analytical challenge. Herein,
single particles of solid-state materials with core-shell structures were
measured using on-line aerosol time-of-flight mass spectrometry (ATOFMS). Laser
'depth profiling' experiments verified the core-shell nature of two known core
shell particle configurations (<2 MUm diameter) that possessed inverted,
complimentary core-shell compositions (ZrO2@SiO2 versus SiO2@ZrO2). The average
peak area ratios of Si and Zr ions were calculated to definitively show their
core-shell composition. These ratio curves acted as a calibrant for an
uncharacterized sample - a metal-organic framework (MOF) material surround by
silica (UiO-66(Zr)@SiO2; UiO = University of Oslo). ATOFMS depth profiling was
used to show that these particles did indeed exhibit a core-shell architecture.
The results presented here show that ATOFMS can provide unique insights into core
shell solid-state materials with particle diameters between 0.2-3 MUm.
PMID- 25587576
TI - Prescribing multiple neurostimulants during rehabilitation for severe brain
injury.
AB - BACKGROUND: Despite a lack of clear evidence, multiple neurostimulants are
commonly provided after severe brain injury (BI). The purpose of this study is to
determine if the number of neurostimulants received during rehabilitation was
associated with recovery of full consciousness or improved neurobehavioral
function after severe BI. METHOD: Data from 115 participants were extracted from
a neurobehavioral observational study database for this exploratory,
retrospective analysis. Univariate optimal data analysis was conducted to
determine if the number of neurostimulants influenced classification of four
outcomes: recovery of full consciousness during rehabilitation, recovery of full
consciousness within one year of injury, and meaningful neurobehavioral
improvement during rehabilitation defined as either at least a 4.7 unit (minimal
detectable change) or 2.58 unit (minimal clinically important difference) gain on
the Disorders of Consciousness Scale-25 (DOCS-25). RESULTS: Number of
neurostimulants was not significantly (P > 0.05) associated with recovery of full
consciousness during rehabilitation, within one year of injury, or meaningful
neurobehavioral improvement using the DOCS-25. CONCLUSIONS: Receiving multiple
neurostimulants during rehabilitation may not influence recovery of full
consciousness or meaningful neurobehavioral improvement. Given costs associated
with additional medication, future research is needed to guide physicians about
the merits of prescribing multiple neurostimulants during rehabilitation after
severe BI.
PMID- 25587580
TI - On Asylums: Essays on the social stituation of mental patients and other inmates,
by Irving Goffmann.
PMID- 25587579
TI - Assessing dimerisation degree and cooperativity in a biomimetic small-molecule
model by pulsed EPR.
AB - Pulsed electron paramagnetic resonance (EPR) spectroscopy is gaining increasing
importance as a complementary biophysical technique in structural biology. Here,
we describe the synthesis, optimisation, and EPR titration studies of a spin
labelled terpyridine Zn(II) complex serving as a small-molecule model system for
tuneable dimerisation.
PMID- 25587581
TI - In a coma.
PMID- 25587582
TI - New hopes for gene therapy.
PMID- 25587583
TI - Bernard Wood.
PMID- 25587584
TI - In memoriam: Dietrich Lehmann, 1929-2014.
PMID- 25587585
TI - Will the Nicaragua Canal connect or divide?
AB - A century after the opening of the Panama Canal, a second inter-oceanic passage
is set to be built in Central America, this time in Nicaragua. The ambitious and
astronomically expensive project promises to bring economic opportunity to a poor
country but it also carries risks to its tropical ecosystems. Will the new
waterway ultimately link two oceans or divide a continent? Michael Gross
investigates.
PMID- 25587586
TI - Ronald R. Hoy.
PMID- 25587587
TI - Standardization of terminology in stereotactic radiosurgery: Report from the
Standardization Committee of the International Leksell Gamma Knife Society:
special topic.
AB - OBJECT: This report has been prepared to ensure more uniform reporting of Gamma
Knife radiosurgery treatment parameters by identifying areas of controversy,
confusion, or imprecision in terminology and recommending standards. METHODS:
Several working group discussions supplemented by clarification via email allowed
the elaboration of a series of provisional recommendations. These were also
discussed in open session at the 16th International Leksell Gamma Knife Society
Meeting in Sydney, Australia, in March 2012 and approved subject to certain
revisions and the performance of an Internet vote for approval from the whole
Society. This ballot was undertaken in September 2012. RESULTS: The
recommendations in relation to volumes are that Gross Target Volume (GTV) should
replace Target Volume (TV); Prescription Isodose Volume (PIV) should generally be
used; the term Treated Target Volume (TTV) should replace TVPIV, GTV in PIV, and
so forth; and the Volume of Accepted Tolerance Dose (VATD) should be used in
place of irradiated volume. For dose prescription and measurement, the
prescription dose should be supplemented by the Absorbed Dose, or DV% (for
example, D95%), the maximum and minimum dose should be related to a specific
tissue volume (for example, D2% or preferably D1 mm3), and the median dose (D50%)
should be recorded routinely. The Integral Dose becomes the Total Absorbed Energy
(TAE). In the assessment of planning quality, the use of the Target Coverage
Ratio (TTV/ GTV), Paddick Conformity Index (PCI = TTV2/[GTV . PIV]), New
Conformity Index (NCI = [GTV . PIV]/TTV2), Selectivity Index (TTV/PIV),
Homogeneity Index (HI = [D2% -D98%]/D50%), and Gradient Index (GI = PIV0.5/PIV)
are reemphasized. In relation to the dose to Organs at Risk (OARs), the emphasis
is on dose volume recording of the VATD or the dose/volume limit (for example,
V10) in most cases, with the additional use of a Maximum Dose to a small volume
(such as 1 mm3) and/or a Point Dose and Mean Point Dose in certain circumstances,
particularly when referring to serial organs. The recommendations were accepted
by the International Leksell Gamma Knife Society by a vote of 92% to 8%.
CONCLUSIONS: An agreed-upon and uniform terminology and subsequent
standardization of certain methods and procedures will advance the clinical
science of stereotactic radiosurgery.
PMID- 25587589
TI - The Anatomische Gesellschaft mourns an honorary fellow, Joachim-Hermann Scharf.
PMID- 25587588
TI - Design, synthesis and biological evaluation of metronidazole-thiazole derivatives
as antibacterial inhibitors.
AB - A series of metronidazole-thiazole derivatives has been designed, synthesized and
evaluated as potential antibacterial inhibitors. All the synthesized compounds
were determined by elemental analysis, (1)H NMR and MS. They were also tested for
antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus
subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The
results showed that compound 5 e exhibited the most potent inhibitory activity
against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies
were performed in order to predict the biological activity of proposed compounds.
Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were
noncytotoxic against human macrophage. The results revealed that these compounds
offered remarkable viability.
PMID- 25587590
TI - Introduction: atherosclerosis.
PMID- 25587591
TI - Words of wisdom. Re: Radical prostatectomy or watchful waiting in early prostate
cancer.
PMID- 25587592
TI - Words of wisdom. Re: Screening and prostate cancer mortality: results of the
European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of
follow-up.
PMID- 25587593
TI - Words of wisdom. Re: Coadministration of anastrozole sustains therapeutic
testosterone levels in hypogonadal men undergoing testosterone pellet insertion.
PMID- 25587594
TI - Words of wisdom. Re: Rapid induction of androgen receptor splice variants by
androgen deprivation in prostate cancer.
PMID- 25587595
TI - Words of wisdom. Re: Antibody-drug conjugates targeting prostate-specific
membrane antigen.
PMID- 25587596
TI - Retraction notice to: 'Reply from authors re: Declan G. Murphy, Anthony J.
Costello. How can the autonomic nervous system contribute to urinary continence
following radical prostatectomy? A ''Boson-like'' conundrum. Eur urol 2013;63:445
7: Sparing of the neurovascular bundle leads to improved rates of continence'
[Eur urol 2013;63:447-9].
PMID- 25587597
TI - With this issue of Transfusion and Apheresis Science, we mark the passing, last
year, of one of the most important early figures in apheresis. Introduction.
PMID- 25587598
TI - Measurement characteristics and clinical utility of the high-level mobility
assessment tool among individuals with traumatic brain injury.
PMID- 25587599
TI - Words of wisdom. Re: Vasectomy and risk of aggressive prostate cancer: a 24-year
follow-up study.
PMID- 25587611
TI - A 66-year-old patient with progressive left hemiparesis: question.
PMID- 25587612
TI - An unusual cause of chronic headaches: question.
PMID- 25587613
TI - Cystic fibrosis: An update for clinicians. Part 1: Nutrition and
gastrointestinal complications.
PMID- 25587614
TI - Decreased density of CD3+ tumor-infiltrating lymphocytes during gastric cancer
progression.
PMID- 25587615
TI - Autofluorescence imaging endoscopy for predicting acid reflux in patients with
gastroesophageal reflux disease.
PMID- 25587616
TI - Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in
chronic hepatitis C genotype 1 infection.
AB - Background and Aim: While genetic polymorphisms upstream of the interleukin
28B(IL28B) gene are associated with necroinflammatory activity grade in chronic
hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is
less definitive. Pretreatment liver biopsies in a cohort of treatment-naive
patients with HCV-1 were analyzed to evaluate associations between liver
histology, and the rs12979860 and rs8099917 IL28B single nucleotide
polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and
pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single
nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high
activity grade (A2/3) were identified using multivariable logistic regression
analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141
patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype
was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower
in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P =
0.03), with an increasing number of Talleles associated with a higher frequency
of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of
advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR]
0.98, 95% confidence interval [CI] 0.97-0.99; P < 0.0001), high activity grade
(OR 5.68, 95% CI% 1.86-17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36,
95% CI 0.14-0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00
1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and
liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be
independently associated with a lower prevalence of advanced fibrosis stage in
HCV-1 infection. This association warrants further evaluation.
PMID- 25587617
TI - Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e
antigen-positive, lamivudine-resistant chronic hepatitis B.
PMID- 25587618
TI - Clinicopathologic analysis of the simple nodular type of well-differentiated
hepatocellular carcinoma with extensive peliotic change.
PMID- 25587620
TI - Regulation of T cell recruitment and inflammation in the human immunodeficiency
virus/hepatitis C virus coinfected liver.
PMID- 25587619
TI - Markers of endothelial dysfunction in patients with non-alcoholic fatty liver
disease and coronary artery disease.
PMID- 25587621
TI - Colorado ASC reaches out to community with annual free surgery day.
PMID- 25587622
TI - You can't say that: using social media in the healthcare setting requires sound
judgment.
PMID- 25587623
TI - Sharpen coding skills and reimbursement strategies during ICD-10 delay.
PMID- 25587624
TI - Vibrational signatures of cation-anion hydrogen bonding in ionic liquids: a
periodic density functional theory and molecular dynamics study.
AB - Hydrogen bonding in alkylammonium based protic ionic liquids was studied using
density functional theory (DFT) and ab initio molecular dynamics (AIMD)
simulations. Normal-mode analysis within the harmonic approximation and power
spectra of velocity autocorrelation functions were used as tools to obtain the
vibrational spectra in both the gas phase and the crystalline phases of these
protic ionic liquids. The hydrogen bond vibrational modes were identified in the
150-240 cm(-1) region of the far-infrared (far-IR) spectra. A blue shift in the
far-IR mode was observed with an increasing number of hydrogen-bonding sites on
the cation; the exact peak position is modulated by the cation-anion hydrogen
bond strength. Sub-100 cm(-1) bands in the far-IR spectrum are assigned to the
rattling motion of the anions. Calculated NMR chemical shifts of the acidic
protons in the crystalline phase of these salts also exhibit the signature of
cation-anion hydrogen bonding.
PMID- 25587625
TI - NADH->NAD+ Transhydrogenation in Adult Ascaris suum Mitochondria.
AB - Although lacking an NADPH->NAD(+) transhydrogenase system, the essentially
energetically anaerobic mitochondria of the adult intestinal nematode Ascaris
suum display an inner membrane-associated NADH->NAD(+) transhydrogenation
reaction. This reaction is considered to be reflective of a mechanism(s) that
acts in catalyzing a transmembrane translocation of reducing equivalents from
NADH in the intermembrane space to matrix NAD(+), thereby forming matrix NADH
that would serve in electron transport. Ascarid mitochondrial lipoamide
dehydrogenase rather than an NADH->NAD(+) transhydrogenase system has been viewed
as the predominant source of inner membrane-associated NADH->NAD(+)
transhydrogenation activity. However, the present study made apparent yet another
source of mitochondrial, inner membrane-associated NADH->NAD(+) activity in A.
suum , viz., NADH dehydrogenase. This was made evident via comparisons of the A.
suum mitochondrial NADH->NAD(+) transhydrogenation, NADH dehydrogenase, and
lipoamide dehydrogenase activities in terms of pH effects, thermal labilities,
the involvement of NADH dehydrogenase in the activities of mitochondrial,
membrane-associated rotenone-insensitive and rotenone-sensitive NADH-dependent
cytochrome c reductases, and mitochondrial membrane versus mitochondrial soluble
localizations. Studies of the responses of the NADH->NAD(+) transhydrogenation,
rotenone-insensitive and rotenone-sensitive cytochrome c reductases, and
lipoamide dehydrogenase activities to inhibition by copper and cadmium lent
additional support to the catalysis of an NADH->NAD(+) transhydrogenation
activity by NADH dehydrogenase. Collectively, the data presented are consistent
with an additional physiological catalysis of an NADH->NAD(+) transhydrogenation
in A. suum mitochondria by an inner membrane NADH dehydrogenase component of the
rotenone-sensitive cytochrome c reductase system, i.e., the NADH dehydrogenase
component of the electron transport system. Comparisons of the A. suum data with
those from other essentially anaerobic helminth parasites as well as free-living
eukaryotic mitochondrial systems are noted.
PMID- 25587626
TI - Tuning mechanical properties of pharmaceutical crystals with multicomponent
crystals: voriconazole as a case study.
AB - Crystals of voriconazole, an antifungal drug, are soft in nature, and this is
disadvantageous during compaction studies where pressure is applied on the solid.
Crystal engineering is used to make cocrystals and salts with modified mechanical
properties (e.g., hardness). Cocrystals with biologically safe coformers such as
fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with
hydrochloric acid and oxalic acid are prepared through solvent assisted grinding.
The presence (salt) or absence (cocrystal) of proton transfer in these
multicomponent crystals is unambiguously confirmed with single crystal X-ray
diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit
variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and
1:1). The nanoindentation technique was applied on single crystals of the salts
and cocrystals. The salts exhibit better hardness than the drug and cocrystals in
the order salts ? drug > cocrystals. The molecular origin of this mechanical
modulation is explained on the basis of slip planes in the crystal structure and
relative orientations of the molecules with respect to the nanoindentation
direction. The hydrochloride salt is the hardest solid in this family. This may
be useful for tableting of the drug during formulation and in drug development.
PMID- 25587627
TI - Heat shock, visible light or high calcium augment the cytotoxic effects of
Ailanthus altissima (Swingle) leaf extracts against Saccharomyces cerevisiae
cells.
AB - To gain new insight into the antimicrobial potential of Ailanthus altissima
Swingle, ethanol leaf extracts were evaluated for the antifungal effects against
the model yeast Saccharomyces cerevisae. The extracts inhibited the yeast growth
in a dose-dependent manner, and this effect could be augmented by heat shock,
exposure to visible light or exposure to high concentrations of Ca(2+). Using
transgenic yeast cells expressing the Ca(2+)-dependent photoprotein, aequorin, it
was found that the leaf extracts induced cytosolic Ca(2+) elevation. Experiments
on yeast mutants with defects in Ca(2+) transport demonstrated that the
cytotoxicity of the A. altissima leaf extracts (AaLEs) was mediated by transient
pulses of Ca(2+) ions which were released into the cytosol predominantly from the
vacuole. The investigation of the antifungal synergies involving AaLEs may
contribute to the development of optimal and safe combination therapies for the
treatment of drug-resistant fungal infections.
PMID- 25587628
TI - Improvement of urban lake water quality by removal of Escherichia coli through
the action of the bivalve Anodonta californiensis.
AB - High levels of fecal indicator bacteria, such as Escherichia coli, can be
indicative of poor water quality. The use of shellfish to reduce eutrophication
has been proposed, but application of bivalves to reduce bacterial levels has not
been extensively reported. Removal of E. coli by the native freshwater mussel
Anodonta californiensis was studied using laboratory batch systems and field
based flow-through systems. Batch systems were utilized to determine the fate and
inactivation of E. coli after uptake by the mussel. Batch experiments
demonstrated that uptake patterns followed first order kinetics and E. coli was
inactivated with less than 5% of the initial colonies recoverable in fecal matter
or tissue. Flow-through systems located at an urban impaired lake in San
Francisco, CA were utilized to determine uptake kinetics under environmentally
relevant conditions. The bivalves maintained a 1-log removal of E. coli for the
duration of exposure. The calculated uptake rates can be used in conjunction with
hydrologic models to determine the number of bivalves needed to maintain removal
of E. coli in different freshwater systems. The outcomes of this study support
the use of native freshwater bivalves to achieve the co-benefits of
rehabilitating a freshwater ecosystem and improving water quality via reduction
of E. coli in contaminated freshwater systems.
PMID- 25587630
TI - Combustion chemistry via metadynamics: benzyl decomposition revisited.
AB - Large polycyclic aromatic hydrocarbons (PAHs) are thought to be responsible for
the formation of soot particles in combustion processes. However, there are still
uncertainties on the course that leads small molecules to form PAHs. This is
largely due to the high number of reactions and intermediates involved.
Metadynamics combined with ab initio molecular dynamics can provide a very
precious contribution because offers the possibility to explore new possible
pathways and suggest new mechanisms. Here, we adopt this method to investigate
the chemical evolution of the benzyl radical, whose role is very important in
PAHs growth. This species has been intensely studied, and though most of its
chemistry is known, there are still open questions regarding its decomposition.
The simulation reproduces the most commonly accepted decomposition pathway and it
suggests also a new one which can explain recent experimental data that are in
contradiction with the old mechanism. In addition, quantitative free energy
evaluation of some key reaction steps sheds light on the role of entropy.
PMID- 25587629
TI - Corona-directed nucleic acid delivery into hepatic stellate cells for liver
fibrosis therapy.
AB - Strategies to modify nanoparticles with biological ligands for targeted drug
delivery in vivo have been widely studied but met with limited clinical success.
A possible reason is that, in the blood circulation, serum proteins could rapidly
form a layer of protein "corona" on the vehicle surface, which might block the
modified ligands and hamper their targeting functions. We speculate that
strategies for drug delivery can be designed based upon elegant control of the
corona formation on the vehicle surfaces. In this study, we demonstrate a retinol
conjugated polyetherimine (RcP) nanoparticle system that selectively recruited
the retinol binding protein 4 (RBP) in its corona components. RBP was found to
bind retinol, and direct the antisense oligonucleotide (ASO)-laden RcP carrier to
hepatic stellate cells (HSC), which play essential roles in the progression of
hepatic fibrosis. In both mouse fibrosis models, induced by carbon tetrachloride
(CCl4) and bile duct ligation (BDL), respectively, the ASO-laden RcP particles
effectively suppressed the expression of type I collagen (collagen I), and
consequently ameliorated hepatic fibrosis. Such findings suggest that this
delivery system, designed to exploit the power of corona proteins, can serve as a
promising tool for targeted delivery of therapeutic agents for the treatment of
hepatic fibrosis.
PMID- 25587631
TI - Pachymodulin, a new functional formyl peptide receptor 2 peptidic ligand isolated
from frog skin has Janus-like immunomodulatory capacities.
AB - Recruitment of leukocytes is essential to fight infections or to heal injuries;
however, excessive and/or prolonged responses favor the development of major
inflammatory pathologies, such as cardiovascular or neurodegenerative diseases.
Thus, it is of great interest to seek novel compounds that can regulate leukocyte
recruitment depending on the degree of inflammation. We have isolated and
characterized, by different chromatographic techniques, mass spectrometry, and
Edman sequencing, a new hexapeptide (SSLSKL) from the Mexican frog Pachymedusa
dacnicolor, which we named pachymodulin. In vitro, pachymodulin promotes the
migration of leukocytes through the binding and activation of the human and mouse
N-formyl peptide receptor 2 (huFPR2). In vivo, it exhibits opposite biological
activities: under homeostatic conditions, pachymodulin induces the recruitment of
leukocytes, whereas under inflammatory conditions, it inhibits this process.
Therefore, pachymodulin represents an interesting template in the quest to design
new immunomodulatory drugs in the therapy of immune-related diseases.
PMID- 25587632
TI - Combined biofouling and scaling in membrane feed channels: a new modeling
approach.
AB - A mathematical model was developed for combined fouling due to biofilms and
mineral precipitates in membrane feed channels with spacers. Finite element
simulation of flow and solute transport in two-dimensional geometries was coupled
with a particle-based approach for the development of a composite (cells and
crystals) foulant layer. Three fouling scenarios were compared: biofouling only,
scaling only and combined fouling. Combined fouling causes a quicker flux decline
than the summed flux deterioration when scaling and biofouling act independently.
The model results indicate that the presence of biofilms leads to more mineral
formation due to: (1) an enhanced degree of saturation for salts next to the
membrane and within the biofilm; and (2) more available surface for nucleation to
occur. The impact of biofilm in accelerating gypsum precipitation depends on the
composition of the feed water (eg the presence of NaCl) and the kinetics of
crystal nucleation and growth. Interactions between flow, solute transport and
biofilm-induced mineralization are discussed.
PMID- 25587633
TI - Preparation and properties of ion-imprinted hollow particles for the selective
adsorption of silver ions.
AB - Four kinds of silver ion-imprinted particles (Ag-IIPs) with different
morphologies were prepared by the surface ion-imprinting technology (SIIT) and
were used for the selective removal and concentration of silver ions from
wastewater. The favorable adsorptivity and selectivity of Ag-IIPs for Ag(+) were
confirmed by a series of adsorption experiments at a suitable pH value. The
adsorption mechanism was elucidated by analyzing the adsorption isotherms,
adsorption thermodynamics, and adsorption kinetics systematically. The Ag(+)
adsorption onto the Ag-IIPs was well-described by the Langmuir isotherm model,
and it was likely to be a monolayer chemical adsorption. This conclusion was also
confirmed by the thermodynamic parameters. Moreover, the adsorption kinetics
indicated that the adsorption rate would be controlled jointly by the
intraparticle diffusion and the inner surface adsorption process, and the latter
process was generally associated with the formation and breaking of chemical
bonds. Finally, the effects of different morphologies of the Ag-IIPs for Ag(+)
adsorption were also investigated. In aqueous solution, the adsorptivity of the
Ag(+) ion-imprinting single-hole hollow particles (Ag-IISHPs) for Ag(+) was
highest (80.5 mg g(-1)) because of a specific morphology that features a single
hole in the shell. In an oil-water mixture, Ag(+) in the water phase could be
adsorbed efficiently by the Ag(+) ion-imprinting Janus hollow particles (Ag
IIJHPs), with emulsifiability originating from the Janus structure.
PMID- 25587634
TI - Effects of biological and non-biological immunomodulatory therapies on the
immunogenicity of vaccines in patients with rheumatic diseases.
AB - Vaccinations are administered to patients to induce a protective immune response,
resulting in immunological memory. Preventing infection through the use of
vaccines is particularly important in immunocompromised and immunosuppressed
individuals given their increased frequency and severity of infections relative
to healthy individuals. Recent surveys show that the vaccination rate is still
alarmingly low in patients with rheumatic disease. In this review we briefly
discuss the different types of vaccines and then critically examine evidence
related to vaccination efficacy in patients with autoimmune disease and the
effects of immunomodulatory therapy, with an aim to provide guidance and optimize
the administration of vaccines in such individuals.
PMID- 25587636
TI - Low-temperature plasma ionization-mass spectrometry for the analysis of compounds
in organic aerosol particles.
AB - Low-temperature plasma ionization, a technique that causes minimal fragmentation
during ionization, is investigated as an ionization technique for mass
spectrometric detection of the compounds in ambient organic aerosols in real
time. The experiments presented in this paper demonstrate that ions are generated
from compounds in the aerosol particles. The utility of this technique for
detection of both positive and negative ions from the pyrolysate of multiple
natural polymers is presented. Ultimately, low-temperature plasma ionization is
shown to be a promising ionization technique for detection of compounds in
organic aerosols by mass spectrometry.
PMID- 25587637
TI - Phytochemical Characterization, Antimicrobial Activity, and Antioxidant Potential
of Equisetum hyemale L. (Equisetaceae) Extracts.
AB - Equisetum hyemale species is considered a medicinal plant used in the form of
infusions to combat infectious or inflammation diseases and also diuretic
effects, presenting several compounds related to these actions. In previous
studies different species of Equisetum showed several phenolic compounds. The
objective of this study was, for the first time, based on phytochemistry analysis
to evaluate the antioxidant and antimicrobial activity. The 70% ethanolic and
methanolic extracts of E. hyemale were characterized by spectrophotometric and
high-performance liquid chromatography with pulsed amperometric detector
analyses, as well as its antioxidant potential based on the scavenger activity of
2,2-diphenyl-1-picrylhydrazyl (DPPH). In addition was verified the antimicrobial
activity by broth microdilution technique against bacteria and fungi. The
extracts showed phytochemical similarity, which demonstrated the presence of
phenolic compounds, the scavenging activity for free radicals was about 30% and
was observed better antifungal activity against dermatophyte fungi, with minimum
inhibitory concentration and minimum fungicidal concentration of 0.62 mg/mL to
Trichophyton rubrum and Microsporum canis. The extracts exhibits great potential
to therapeutic applications or product development, since both possess antifungal
activity and antioxidant action associated with little difference in their
phytochemical composition.
PMID- 25587641
TI - Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications.
AB - Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference
between the pulmonary and systemic circulations. HPV is active in utero, reducing
pulmonary blood flow, and in adults helps to match regional ventilation and
perfusion although it has little effect in healthy lungs. Many factors affect HPV
including pH or PCO2, cardiac output, and several drugs, including
antihypertensives. In patients with lung pathology and any patient having one
lung ventilation, HPV contributes to maintaining oxygenation, so
anesthesiologists should be aware of the effects of anesthesia on this protective
reflex. Intravenous anesthetic drugs have little effect on HPV, but it is
attenuated by inhaled anesthetics, although less so with newer agents. The reflex
is biphasic, and once the second phase becomes active after about an hour of
hypoxia, this pulmonary vasoconstriction takes hours to reverse when normoxia
returns. This has significant clinical implications for repeated periods of one
lung ventilation.
PMID- 25587643
TI - Efficient hybrid mesoscopic solar cells with morphology-controlled CH3NH3PbI3
xClx derived from two-step spin coating method.
AB - A morphology-controlled CH3NH3PbI3-xClx film is synthesized via two-step solution
deposition by spin-coating a mixture solution of CH3NH3Cl and CH3NH3I onto the
TiO2/PbI2 film for the first time. It is revealed that the existence of CH3NH3Cl
is supposed to result in a preferential growth along the [110] direction of
perovskite, which can improve both the crystallinity and surface coverage of
perovskite and reduce the pinholes. Furthermore, the formation process of
CH3NH3PbI3-xClx perovskite is explored, in which intermediates containing
chlorine are suggested to exist. 13.12% of power conversion efficiency has been
achieved for the mesoscopic cell, higher than 12.08% of power conversion
efficiency of the devices fabricated without CH3NH3Cl via the same process. The
improvement mainly lies in the increasing open-circuit photovoltage which is
ascribed to the reduction of reverse saturation current density.
PMID- 25587642
TI - Optimal cutoffs of obesity measures in relation to cancer risk in postmenopausal
women in the Women's Health Initiative Study.
AB - BACKGROUND: Obesity is a risk factor for several cancers in postmenopausal women.
We attempted to determine cutoffs of adiposity measures in relation to risk of
obesity-related cancers among postmenopausal women and to examine the effects of
hormone therapy (HT) use on the cutoffs, neither of which has been broadly
studied. METHODS: We used data from the Women's Health Initiative cohort
(n=144,701) and applied Cox-proportional hazards regressions to each combination
of 17 cancer types and 6 anthropometric measures (weight, body mass index [BMI],
weight to height ratio, waist circumference, waist to hip ratio [WHR], and waist
to height ratio). Interactions between the anthropometric measures and HT use
were also examined. Cutoffs were determined by applying a grid search followed by
a two-fold cross validation method. Survival ROC analysis of 5- and 10-year
incidence followed. RESULTS: Breast, colorectal, colon, endometrium, kidney, and
all cancers combined were significantly positively associated with all six
anthropometric measures, whereas lung cancer among ever smokers was significantly
inversely associated with all measures except WHR. The derived cutoffs of each
obesity measure varied across cancers (e.g., BMI cutoffs for breast and
endometrium cancers were 30 kg/m(2) and 34 kg/m(2), respectively), and also
depended on HT use. The Youden indices of the cutoffs for predicting 5- and 10
year cancer incidence were higher among HT never users. CONCLUSION: Using a panel
of different anthropometric measures, we derived optimal cut-offs categorizing
populations into high- and low-risk groups, which differed by cancer type and HT
use. Although the discrimination abilities of these risk categories were
generally poor, the results of this study could serve as a starting point from
which to determine adiposity cutoffs for inclusion in risk prediction models for
specific cancer types.
PMID- 25587644
TI - Iodide, bromide, and ammonium in hydraulic fracturing and oil and gas
wastewaters: environmental implications.
AB - The expansion of unconventional shale gas and hydraulic fracturing has increased
the volume of the oil and gas wastewater (OGW) generated in the U.S. Here we
demonstrate that OGW from Marcellus and Fayetteville hydraulic fracturing
flowback fluids and Appalachian conventional produced waters is characterized by
high chloride, bromide, iodide (up to 56 mg/L), and ammonium (up to 420 mg/L).
Br/Cl ratios were consistent for all Appalachian brines, which reflect an origin
from a common parent brine, while the I/Cl and NH4/Cl ratios varied among brines
from different geological formations, reflecting geogenic processes. There were
no differences in halides and ammonium concentrations between OGW originating
from hydraulic fracturing and conventional oil and gas operations. Analysis of
discharged effluents from three brine treatment sites in Pennsylvania and a spill
site in West Virginia show elevated levels of halides (iodide up to 28 mg/L) and
ammonium (12 to 106 mg/L) that mimic the composition of OGW and mix
conservatively in downstream surface waters. Bromide, iodide, and ammonium in
surface waters can impact stream ecosystems and promote the formation of toxic
brominated-, iodinated-, and nitrogen disinfection byproducts during chlorination
at downstream drinking water treatment plants. Our findings indicate that
discharge and accidental spills of OGW to waterways pose risks to both human
health and the environment.
PMID- 25587645
TI - Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to
severe binge-eating disorder: a randomized clinical trial.
AB - IMPORTANCE: Binge-eating disorder (BED), a public health problem associated with
psychopathological symptoms and obesity and possibly with metabolic syndrome,
lacks approved pharmacotherapies. OBJECTIVE: To examine the efficacy and safety
of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to
severe BED. DESIGN, SETTING, AND PARTICIPANTS: We performed a randomized, double
blind, parallel-group, forced dose titration, placebo-controlled clinical trial
at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to
treat analyses included 259 and 255 adults with BED, respectively. INTERVENTIONS:
Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were
provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks
and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2)
days after the last dose. MAIN OUTCOMES AND MEASURES: We assessed the change in
binge-eating (BE) behaviors measured as days per week (baseline to week 11) with
a mixed-effects model using transformed log (BE days per week) + 1. Secondary
measures included BE cessation for 4 weeks. Safety assessments included treatment
emergent adverse events, vital signs, and change in weight. RESULTS: At week 11,
log-transformed BE days per week decreased with the 50-mg/d (least squares [LS]
mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change,
1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS
mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group.
Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-,
and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1
(1.57), respectively. The percentage of participants achieving 4-week BE
cessation was lower with the placebo group (21.3%) compared with the 50-mg/d
(42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence
of any treatment-emergent adverse events was 58.7% for the placebo group and
84.7% for the combined treatment group. In the treatment groups, 1.5% of
participants had serious treatment-emergent adverse effects. Events with a
frequency of at least 5% and changes in heart rate were generally consistent with
the known safety profile. The mean (SD) change in body weight was -0.1 (3.09),
3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group,
the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups,
respectively (P < .001 for each dose vs placebo group comparison in post hoc
analysis). CONCLUSIONS AND RELEVANCE: The 50- and 70-mg/d treatment groups
demonstrated efficacy compared with the placebo group in decreased BE days, BE
cessation, and global improvement. The safety profile was generally consistent
with previous findings in adults with attention-deficit/hyperactivity disorder.
Further investigation of lisdexamfetamine in BED is ongoing. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01291173.
PMID- 25587646
TI - The proportion of diploid 46,XX cells increases with time in women with Turner
syndrome--a 10-year follow-up study.
AB - In the normal population, loss of one of the sex chromosomes leading to monosomy
(45,X) is a part of the aging process. In Turner syndrome (TS), the classic
karyotype 45,X is found in up to 50% at birth, and others have a second cell
line; mosaicism. The aim was to study if the chromosomal pattern in TS women
changes over time. Fluorescence in situ hybridization was performed on buccal
smear cells obtained twice, 10 years apart, from 42 women with TS aged 26-66
years (mean+/-standard deviation: 42.0+/-11.6). DNA probes specific for
chromosomes X (DXZ1) and Y (DYZ3) were used and >100 cells were analyzed/patient.
Nineteen women had monosomy (45,X) (<10% 46,XX), nine had 45,X/46,XX mosaicism,
and 14 had iso, ring, or a marker chromosome at baseline. At 10 years, the
percentage of diploid cells had increased in 29 of 42 women (69%), with an
average increase of 5.7+/-13.0%. There was a positive correlation between age and
% change in diploid 46,XX or 46,XY cells (r=0.38, p=0.023). This new finding
might have relevance for the life expectancy in TS.
PMID- 25587647
TI - Targeting HER2 for the treatment of breast cancer.
AB - HER2 (ErbB2), a member of the HER family of tyrosine kinase receptors (HER1-4),
is a major driver of tumor growth in 20% of breast cancers. Treatment with the
anti-HER2 monoclonal antibody trastuzumab has revolutionized the outcome of
patients with this aggressive breast cancer subtype, but intrinsic and acquired
resistance is common. Growing understanding of the biology and complexity of the
HER2 signaling network and of potential resistance mechanisms has guided the
development of new HER2-targeted agents. Combinations of these drugs to more
completely inhibit the HER receptor layer, or combining HER2-targeted agents with
agents that target downstream signaling, alternative pathways, or components of
the host immune system, are being vigorously investigated in the preclinical and
clinical settings. As a result, the list of more effective and well tolerated FDA
approved new regimens for patients with HER2+ tumors is constantly growing.
PMID- 25587649
TI - Advances in nanoparticle imaging technology for vascular pathologies.
AB - Nanoparticle imaging agents for vascular pathologies are in development, and some
agents are already in clinical trials. Untargeted agents, with long circulation,
are excellent blood-pool agents, but molecularly targeted agents have significant
advantages due to the signal enhancement possible with nanoparticle presentation
of the contrast agent molecules. Molecular targets that are accessible directly
from the vasculature are optimal for such agents. Targets that are removed from
the vasculature, such as those on tumor cell surfaces, have limited accessibility
owing to the enhanced permeation and retention effect. Yet, efforts at molecular
targeting have tested small molecules, peptides, antibodies, and most recently
aptamers as possible targeting ligands. The future is bright for nanoparticle
based imaging of vascular pathologies.
PMID- 25587648
TI - Cardiovascular disease in adult survivors of childhood cancer.
AB - Treatment advances have increased survival in children with cancer, but
subclinical, progressive, irreversible, and sometimes fatal treatment-related
cardiovascular effects may appear years later. Cardio-oncologists have identified
promising preventive and treatment strategies. Dexrazoxane provides long-term
cardioprotection from doxorubicin-associated cardiotoxicity without compromising
the efficacy of anticancer treatment. Continuous infusion of doxorubicin is as
effective as bolus administration in leukemia treatment, but no evidence has
indicated that it provides long-term cardioprotection; continuous infusions
should be eliminated from pediatric cancer treatment. Angiotensin-converting
enzyme inhibitors can delay the progression of subclinical and clinical
cardiotoxicity. All survivors, regardless of whether they were treated with
anthracyclines or radiation, should be monitored for systemic inflammation and
the risk of premature cardiovascular disease. Echocardiographic screening must be
supplemented with screening for biomarkers of cardiotoxicity and perhaps by
identification of genetic susceptibilities to cardiovascular diseases; optimal
strategies need to be identified. The health burden related to cancer treatment
will increase as this population expands and ages.
PMID- 25587651
TI - Changing practice of anticoagulation: will target-specific anticoagulants replace
warfarin?
AB - The target-specific oral anticoagulants are a class of agents that inhibit factor
Xa or thrombin. They are effective and safe compared to warfarin for the
prevention of stroke and systemic embolism in patients with atrial fibrillation
and for the treatment of venous thromboembolism, and they are comparable to low
molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty.
For other indications, however, such as the prevention of stroke in patients with
mechanical heart valves, initial studies have been unfavorable for the newer
agents, leaving warfarin the anticoagulant of choice. Further studies are needed
before the target-specific anticoagulants can be recommended for patients with
cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also
persist about difficulties with the laboratory assessment of anticoagulant effect
and the lack of a specific reversal agent. For these reasons, we anticipate that
the vitamin K antagonists will continue to be important anticoagulants for years
to come.
PMID- 25587650
TI - ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.
AB - Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over
half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized
in the liver, and its main function is to cleave von Willebrand factor (VWF)
anchored on the endothelial surface, in circulation, and at the sites of vascular
injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of
the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or
acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly
reduced (>20%) in other forms of thrombotic microangiopathy secondary to
hematopoietic progenitor cell transplantation, infection, and disseminated
malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains
the initial treatment of choice to date, but novel therapeutics such as
recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13
deficiency has been shown to be a risk factor for the development of myocardial
infarction, stroke, cerebral malaria, and preeclampsia.
PMID- 25587652
TI - Extranuclear steroid receptors are essential for steroid hormone actions.
AB - Steroid hormones are produced throughout the phylogenetic tree, from plants to
mammals. In the past 40 years, steroid receptors localized to the nucleus have
been recognized as being important to mediating steroid action in many organs.
This action mainly arises from the regulation of key genes that are important for
organ development and function. These include but are not limited to genes
influencing the reproductive tract, mammary glands, bone, brain, fat
differentiation, pituitary hormone regulation, and metabolic effects in many
organs. Unfortunately, steroids also promote the development of hormone
responsive cancers, including breast, uterus, and prostate cancer. It has also
been shown that steroid receptors exist outside the nucleus in many organs and
cells, with unclear impact for normal development, health, and disease. This
review describes the evidence from many laboratories that these receptors exist
and function with nuclear receptors to provide the full impact of all steroid
hormones.
PMID- 25587653
TI - Obesity and cancer: local and systemic mechanisms.
AB - Obesity is a leading modifiable risk factor for the development of several
epithelial malignancies. In addition to increasing risk, obesity also confers
worse prognosis for many cancers. Obesity represents an overall state of energy
imbalance frequently associated with systemic effects including insulin
resistance, altered hormone signaling, and high circulating levels of
proinflammatory mediators. In addition to its systemic effects, obesity causes
subclinical white adipose inflammation including increased tissue levels of
proinflammatory mediators. Both local and systemic effects are likely to
contribute to the development and progression of cancer. An understanding of the
interplay between local and systemic alterations involved in the obesity-cancer
link provides the basis for developing interventions aimed at mitigating the
protumorigenic effects.
PMID- 25587654
TI - The JAK-STAT pathway: impact on human disease and therapeutic intervention.
AB - The Janus kinase (JAK)-signal transducer of activators of transcription (STAT)
pathway is now recognized as an evolutionarily conserved signaling pathway
employed by diverse cytokines, interferons, growth factors, and related
molecules. This pathway provides an elegant and remarkably straightforward
mechanism whereby extracellular factors control gene expression. It thus serves
as a fundamental paradigm for how cells sense environmental cues and interpret
these signals to regulate cell growth and differentiation. Genetic mutations and
polymorphisms are functionally relevant to a variety of human diseases,
especially cancer and immune-related conditions. The clinical relevance of the
pathway has been confirmed by the emergence of a new class of therapeutics that
targets JAKs.
PMID- 25587656
TI - Treatment of recurrent and severe Clostridium difficile infection.
AB - Clostridium difficile infection (CDI) is a serious complication of
hospitalization and antibiotic use with a high mortality and very high costs.
Despite appropriate treatment, a subset of patients develop chronic recurrent
CDI. Some other patients develop severe and life-threatening colitis. The risk
factors, pathogenesis, and treatment of recurrent CDI and severe CDI are
discussed in this review. In particular, fecal microbiota transplantation (FMT)
as a treatment strategy is outlined and a treatment algorithm incorporating FMT
is described.
PMID- 25587655
TI - The gut microbial endocrine organ: bacterially derived signals driving
cardiometabolic diseases.
AB - The human gastrointestinal tract is home to trillions of bacteria, which vastly
outnumber host cells in the body. Although generally overlooked in the field of
endocrinology, gut microbial symbionts organize to form a key endocrine organ
that converts nutritional cues from the environment into hormone-like signals
that impact both normal physiology and chronic disease in the human host. Recent
evidence suggests that several gut microbial-derived products are sensed by
dedicated host receptor systems to alter cardiovascular disease (CVD)
progression. In fact, gut microbial metabolism of dietary components results in
the production of proatherogenic circulating factors that act through a meta
organismal endocrine axis to impact CVD risk. Whether pharmacological
interventions at the level of the gut microbial endocrine organ will reduce CVD
risk is a key new question in the field of cardiovascular medicine. Here we
discuss the opportunities and challenges that lie ahead in targeting meta
organismal endocrinology for CVD prevention.
PMID- 25587658
TI - Lysosomal storage diseases: from pathophysiology to therapy.
AB - Lysosomal storage diseases are a group of rare, inborn, metabolic errors
characterized by deficiencies in normal lysosomal function and by intralysosomal
accumulation of undegraded substrates. The past 25 years have been characterized
by remarkable progress in the treatment of these diseases and by the development
of multiple therapeutic approaches. These approaches include strategies aimed at
increasing the residual activity of a missing enzyme (enzyme replacement therapy,
hematopoietic stem cell transplantation, pharmacological chaperone therapy and
gene therapy) and approaches based on reducing the flux of substrates to
lysosomes. As knowledge has improved about the pathophysiology of lysosomal
storage diseases, novel targets for therapy have been identified, and innovative
treatment approaches are being developed.
PMID- 25587659
TI - From de novo mutations to personalized therapeutic interventions in autism.
AB - The high heritability, early age at onset, and reproductive disadvantages of
autism spectrum disorders (ASDs) are consistent with an etiology composed of
dominant-acting de novo (spontaneous) mutations. Mutation detection by microarray
analysis and DNA sequencing has confirmed that de novo copy-number variants or
point mutations in protein-coding regions of genes contribute to risk, and some
of the underlying causal variants and genes have been identified. As our
understanding of autism genes develops, the spectrum of autism is breaking up
into quanta of many different genetic disorders. Given the diversity of
etiologies and underlying biochemical pathways, personalized therapy for ASDs is
logical, and clinical genetic testing is a prerequisite.
PMID- 25587660
TI - Social networks, social media, and innovating surgical education.
PMID- 25587657
TI - Understanding HIV latency: the road to an HIV cure.
AB - Treatment with antiretroviral therapy dramatically increases the survival of HIV
infected individuals. However, treatment has to be continued for life because it
does not lead to the full eradication of infection. HIV persists in resting
CD4(+) T cells, and possibly other cell types, and can reemerge from these cells
when therapy is interrupted. Here, we review molecular mechanisms that have been
proposed to contribute to HIV latency, as well as the relative roles of cis- and
trans-acting mechanisms. We also discuss existing and future therapeutic
opportunities regarding HIV latency that might lead to a future cure for HIV
infection.
PMID- 25587661
TI - Postmorbid learning of saxophone playing in a patient with frontotemporal
dementia.
AB - Some patients with frontotemporal dementia (FTD) show an artistic enhancement of
musical abilities. However, no patients with FTD, to date, have been reported to
be able to learn how to play a musical instrument after disease onset. Herein we
describe a patient (J. K.) who had never played any musical instruments
premorbidly, but who learned to play the saxophone after being diagnosed with a
behavioral variant of FTD. He mastered a repertoire that consisted of 10 pieces
of Korean folk songs over a period of three years. Furthermore, his saxophone
skills were high enough to outperform other students in his class.
PMID- 25587664
TI - Mild and selective Et2Zn-catalyzed reduction of tertiary amides under
hydrosilylation conditions.
AB - Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for
the reduction of tertiary amides under mild reaction conditions employing cost
effective polymeric silane (PMHS) as the hydride source. Crucial for the
catalytic activity was the addition of a substoichiometric amount of lithium
chloride to the reaction mixture. A series of amides containing different
additional functional groups were reduced to their corresponding amines, and the
products were isolated in good-to-excellent yields.
PMID- 25587663
TI - Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic
strategy in ovarian cancer.
AB - Plasminogen activator inhibitor (PAI)-1 is predictive of poor outcome in several
types of cancer. The present study investigated the biological role for PAI-1 in
ovarian cancer and potential of targeted pharmacotherapeutics. In patients with
ovarian cancer, PAI-1 mRNA expression in tumor tissues was positively correlated
with poor prognosis. To determine the role of PAI-1 in cell proliferation in
ovarian cancer, the effects of PAI-1 inhibition were examined in PAI-1-expressing
ovarian cancer cells. PAI-1 knockdown by small interfering RNA resulted in
significant suppression of cell growth accompanied with G2/M cell cycle arrest
and intrinsic apoptosis. Similarly, treatment with the small molecule PAI-1
inhibitor TM5275 effectively blocked cell proliferation of ovarian cancer cells
that highly express PAI-1. Together these results suggest that PAI-1 promotes
cell growth in ovarian cancer. Interestingly, expression of PAI-1 was increased
in ovarian clear cell carcinoma compared with that in serous tumors. Our results
suggest that PAI-1 inhibition promotes cell cycle arrest and apoptosis in ovarian
cancer and that PAI-1 inhibitors potentially represent a novel class of anti
tumor agents.
PMID- 25587665
TI - The squid ink polysaccharides protect tight junctions and adherens junctions from
chemotherapeutic injury in the small intestinal epithelium of mice.
AB - Gastrointestinal mucositis and infection by chemotherapy treatment are associated
with alterations in the functioning of the intestinal barrier, due to the
potential damage induced by anticancer drugs on the epithelial tight junctions
and adheren junction. We aimed to study the protective effect of dietary
polysaccharides on chemotherapy-induced injury in the epithelial cells. In the
current study, using mice that were intraperitoneally injected with 50 mg/kg
cyclophosphamide for 2 days, we reveal that polysaccharides from the ink of
Ommastrephes bartrami (OBP) enhanced the mRNA and protein expression levels of
Occludin, zonulae occluden (ZO)-1, and E-cadherin. Immunohistochemistry staining
of ZO-1 and E-cadherin confirmed the increase in the mRNA and protein levels. OBP
also remarkably enhanced the mRNA expression of other tight junction proteins, ZO
2, ZO-3, claudin-2, and cingulin. Our results may have important implications in
host defense, especially the immunopotentiation function of OBP on the
cyclophosphamide-induced epithelial cell injury, as well as intestinal disorders
involving inflammation and infection.
PMID- 25587666
TI - Peripheral Hearing and Cognition: Evidence From the Staying Keen in Later Life
(SKILL) Study.
AB - OBJECTIVES: Research has increasingly suggested a consistent relationship between
peripheral hearing and selected measures of cognition in older adults. However,
other studies yield conflicting findings. The primary purpose of the present
study was to further elucidate the relationship between peripheral hearing and
three domains of cognition and one measure of global cognitive status. It was
hypothesized that peripheral hearing loss would be significantly associated with
poorer performance across measures of cognition, even after adjusting for
documented risk factors. No study to date has examined the relationship between
peripheral hearing and such an extensive array of cognitive measures. DESIGN:
Eight hundred ninety-four older adult participants from the Staying Keen in Later
Life study cohort were eligible, agreed to participate, and completed the
baseline evaluation. Inclusion criteria were minimal to include a sample of older
adults with a wide range of sensory and cognitive abilities. Multiple linear
regression analyses were conducted to evaluate the extent to which peripheral
hearing predicted performance on a global measure of cognitive status, as well as
multiple cognitive measures in the domains of speed of processing (Digit Symbol
Substitution and Copy, Trail Making Test Part A, Letter and Pattern Comparison,
and Useful Field of View), executive function (Trail Making Test Part B and
Stroop Color-Word Interference Task), and memory (Digit Span, Spatial Span, and
Hopkins Verbal Learning Test). RESULTS: Peripheral hearing, measured as the three
frequency pure-tone average (PTA) in the better ear, accounted for a significant,
but minimal, amount of the variance in measures of speed of processing, executive
function, and memory, as well as global cognitive status. Alternative measures of
hearing (i.e., three-frequency PTAs in the right and left ears and a bilateral,
six-frequency PTA [three frequencies per ear]) yielded similar findings across
measures of cognition and did not alter the study outcomes in any meaningful way.
CONCLUSIONS: Consistent with literature suggesting a significant relationship
between peripheral hearing and cognition, and in agreement with our hypothesis,
peripheral hearing was significantly related to 10 of 11 measures of cognition
that assessed processing speed, executive function, or memory, as well as global
cognitive status. Although evidence, including the present results, suggests a
relationship between peripheral hearing and cognition, little is known about the
underlying mechanisms. Examination of these mechanisms is a critical need to
direct appropriate treatment.
PMID- 25587667
TI - Automated Vocal Analysis of Children With Hearing Loss and Their Typical and
Atypical Peers.
AB - OBJECTIVES: This study investigated automatic assessment of vocal development in
children with hearing loss compared with children who are typically developing,
have language delays, and have autism spectrum disorder. Statistical models are
examined for performance in a classification model and to predict age within the
four groups of children. DESIGN: The vocal analysis system analyzed 1913 whole
day, naturalistic acoustic recordings from 273 toddlers and preschoolers
comprising children who were typically developing, hard of hearing, language
delayed, or autistic. RESULTS: Samples from children who were hard of hearing
patterned more similarly to those of typically developing children than to the
language delayed or autistic samples. The statistical models were able to
classify children from the four groups examined and estimate developmental age
based on automated vocal analysis. CONCLUSIONS: This work shows a broad
similarity between children with hearing loss and typically developing children,
although children with hearing loss show some delay in their production of
speech. Automatic acoustic analysis can now be used to quantitatively compare
vocal development in children with and without speech-related disorders. The work
may serve to better distinguish among various developmental disorders and
ultimately contribute to improved intervention.
PMID- 25587669
TI - Delayed Stream Segregation in Older Adults: More Than Just Informational Masking.
AB - OBJECTIVE: To determine whether the time course for the buildup of auditory
stream segregation differs between younger and older adults. DESIGN: Word
recognition thresholds were determined for the first and last keywords in
semantically anomalous but syntactically correct sentences (e.g., "A rose could
paint a fish") when the target sentences were masked by speech-spectrum noise, 3
band vocoded speech, 16-band vocoded speech, intact and colocated speech, and
intact and spatially separated speech. A significant reduction in thresholds from
the first to the last keyword was interpreted as indicating that stream
segregation improved with time. RESULTS: The buildup of stream segregation is
slowed for both age groups when the masker is intact, colocated speech.
CONCLUSIONS: Older adults are more disadvantaged; for them, stream segregation is
also slowed even when a speech masker is spatially separated, conveys little
meaning (3-band vocoding), and vocal fine structure cues are impoverished but
envelope cues remain available (16-band vocoding).
PMID- 25587668
TI - Consensus on Hearing Aid Candidature and Fitting for Mild Hearing Loss, With and
Without Tinnitus: Delphi Review.
AB - OBJECTIVES: In many countries including the United Kingdom, hearing aids are a
first line of audiologic intervention for many people with tinnitus and aidable
hearing loss. Nevertheless, there is a lack of high quality evidence to support
that they are of benefit for tinnitus, and wide variability in their use in
clinical practice especially for people with mild hearing loss. The aim of this
study was to identify a consensus among a sample of UK clinicians on the criteria
for hearing aid candidature and clinical practice in fitting hearing aids
specifically for mild hearing loss with and without tinnitus. This will allow
professionals to establish clinical benchmarks and to gauge their practice with
that used elsewhere. DESIGN: The Delphi technique, a systematic methodology that
seeks consensus amongst experts through consultation using a series of iterative
questionnaires, was used. A three-round Delphi survey explored clinical consensus
among a panel of 29 UK hearing professionals. The authors measured panel
agreement on 115 statements covering: (i) general factors affecting the decision
to fit hearing aids, (ii) protocol-driven factors affecting the decision to fit
hearing aids, (iii) general practice, and (iv) clinical observations. Consensus
was defined as a priori >=70% agreement across the panel. RESULTS: Consensus was
reached for 58 of the 115 statements. The broad areas of consensus were around
factors important to consider when fitting hearing aids; hearing aid
technology/features offered; and important clinical assessment to verify hearing
aid fit (agreement of 70% or more). For patients with mild hearing loss, the
greatest priority was given by clinicians to patient-centered criteria for
fitting hearing aids: hearing difficulties, motivation to wear hearing aids, and
impact of hearing loss on quality of life (chosen as top five by at least 64% of
panelists). Objective measures were given a lower priority: degree of hearing
loss and shape of the audiogram (chosen as top five by less than half of
panelists). Areas where consensus was not reached were related to the use of
questionnaires to predict and verify hearing aid benefit for both hearing and
tinnitus; audiometric criteria for fitting hearing aids; and safety of using loud
sounds when verifying hearing aid fitting when the patient has tinnitus
(agreement of <70%). CONCLUSIONS: The authors identified practices that are
considered important when recommending or fitting hearing aid for a patient with
tinnitus. More importantly perhaps, they identified practical issues where there
are divided opinions. Their findings inform the design of clinical trials and
open up debate on the potential impact of practice differences on patient
outcomes.
PMID- 25587670
TI - The utility of Geographical Information Systems (GIS) in systems-oriented obesity
intervention projects: the selection of comparable study sites for a quasi
experimental intervention design--TX CORD.
AB - BACKGROUND: The Texas Childhood Obesity Research Demonstration project (TX CORD)
uses a systems-oriented approach to address obesity that includes individual and
family interventions, community-level action, as well as environmental and policy
initiatives. Given that randomization is seldom possible in community-level
intervention studies, TX CORD uses a quasi-experimental design. Comparable
intervention and comparison study sites are needed to address internal validity
bias. METHODS: TX CORD was designed to be implemented in low-income, ethnically
diverse communities in Austin and Houston, Texas. A three-stage Geographical
Information System (GIS) methodology was used to establish and ascertain the
comparability of the intervention and comparison study sites. Census tract (stage
1) and school (stage 2) data were used to identify spatially exclusive geographic
areas that were comparable. In stage 3, study sites were compared on demographic
characteristics, socioeconomic status (SES), food assets, and physical activity
(PA) assets. Student's t-test was used to examine significant differences between
the selected sites. RESULTS: The methodology that was used resulted in the
selection of catchment areas with demographic and socioeconomic characteristics
that fit the target population: ethnically diverse population; lower-median
household income; and lower home ownership rates. Additionally, the intervention
and comparison sites were statistically comparable on demographic and SES
variables, as well as food assets and PA assets. CONCLUSIONS: This GIS approach
can provide researchers, program evaluators, and policy makers with useful tools
for both research and practice. Area-level information that allows for robust
understanding of communities can enhance analytical procedures in community
health research and offer significant contributions in terms of community
assessment and engagement.
PMID- 25587673
TI - Formamidine hydrochloride as an amino surrogate: I2-catalyzed oxidative amidation
of aryl methyl ketones leading to free (N-H) alpha-ketoamides.
AB - A highly efficient molecular iodine catalyzed oxidative amidation of aryl methyl
ketones with formamidine hydrochloride has been developed. This reaction
represents a novel strategy for the synthesis of free (N-H) alpha-ketoamides.
Based on the experimental results, a self-sequenced iodination/Kornblum
oxidation/amidation/oxidation/decarbonylation mechanism was proposed.
PMID- 25587672
TI - Gender differences in treatment retention among individuals with co-occurring
substance abuse and mental health disorders.
AB - BACKGROUND: A significant number of individuals with co-occurring substance abuse
and mental health disorders do not engage, stay, and/or complete residential
treatment. Although prior research indicates that women and men differ in their
substance abuse treatment experiences, our knowledge of individuals with co
occurring substance abuse and mental health disorders as well as those attending
private residential treatment is limited. OBJECTIVES: The purpose of this study
is to examine gender differences on treatment retention for individuals with co
occurring substance abuse and mental health disorders who participate in private
residential treatment. METHODS: The participants were 1,317 individuals (539
women and 778 men) with co-occurring substance abuse and mental health disorders
receiving treatment at three private residential treatment centers. Bivariate
analyses, life tables, and Cox regression (survival analyses) were utilized to
examine gender effects on treatment retention, and identify factors that predict
treatment retention for men and women. RESULTS: This study found that women with
co-occurring disorders were more likely to stay longer in treatment when compared
to men. The findings indicate the factors influencing length of stay differ for
each gender, and include: type of substance used prior to admission; Addiction
Severity Index Composite scores; and Readiness to Change/URICA scores. Age at
admission was a factor for men only. CONCLUSIONS/IMPORTANCE: These findings can
be incorporated to develop and initiate program interventions to minimize early
attrition and increase overall retention in private residential treatment for
individuals with co-occurring substance use and mental health disorders.
PMID- 25587671
TI - Establishment of an oral infection model resembling the periodontal pocket in a
perfusion bioreactor system.
AB - Periodontal infection involves a complex interplay between oral biofilms,
gingival tissues and cells of the immune system in a dynamic microenvironment. A
humanized in vitro model that reduces the need for experimental animal models,
while recapitulating key biological events in a periodontal pocket, would
constitute a technical advancement in the study of periodontal disease. The aim
of this study was to use a dynamic perfusion bioreactor in order to develop a
gingival epithelial-fibroblast-monocyte organotypic co-culture on collagen
sponges. An 11 species subgingival biofilm was used to challenge the generated
tissue in the bioreactor for a period of 24 h. The histological and scanning
electron microscopy analysis displayed an epithelial-like layer on the surface of
the collagen sponge, supported by the underlying ingrowth of gingival
fibroblasts, while monocytic cells were also found within the sponge mass.
Bacterial quantification of the biofilm showed that in the presence of the
organotypic tissue, the growth of selected biofilm species, especially
Campylobacter rectus, Actinomyces oris, Streptococcus anginosus, Veillonella
dispar, and Porphyromonas gingivalis, was suppressed, indicating a potential
antimicrobial effect by the tissue. Multiplex immunoassay analysis of cytokine
secretion showed that interleukin (IL)-1 beta, IL-2, IL-4, and tumor necrosis
factor (TNF)-alpha levels in cell culture supernatants were significantly up
regulated in presence of the biofilm, indicating a positive inflammatory response
of the organotypic tissue to the biofilm challenge. In conclusion, this novel
host-biofilm interaction organotypic model might resemble the periodontal pocket
and have an important impact on the study of periodontal infections, by
minimizing the need for the use of experimental animal models.
PMID- 25587674
TI - Biosynthesis and function of extracellular glycans in cyanobacteria.
AB - The cell surface of cyanobacteria is covered with glycans that confer versatility
and adaptability to a multitude of environmental factors. The complex
carbohydrates act as barriers against different types of stress and play a role
in intra- as well as inter-species interactions. In this review, we summarize the
current knowledge of the chemical composition, biosynthesis and biological
function of exo- and lipo-polysaccharides from cyanobacteria and give an overview
of sugar-binding lectins characterized from cyanobacteria. We discuss
similarities with well-studied enterobacterial systems and highlight the unique
features of cyanobacteria. We pay special attention to colony formation and EPS
biosynthesis in the bloom-forming cyanobacterium, Microcystis aeruginosa.
PMID- 25587676
TI - Response to "Intralabyrinthine schwannomas: a case series with discussion of the
diagnosis and management" by Bouchetemple P, Heathcote K, Tollard E, Choussy O,
Dehesdin D, Marie JP. Otol Neurotol 2013;34(5):944-51.
PMID- 25587677
TI - The challenge of studying TiO2 nanoparticle bioaccumulation at environmental
concentrations: crucial use of a stable isotope tracer.
AB - The ecotoxicity of nanoparticles (NPs) is a growing area of research with many
challenges ahead. To be relevant, laboratory experiments must be performed with
well-controlled and environmentally realistic (i.e., low) exposure doses.
Moreover, when focusing on the intensively manufactured titanium dioxide (TiO2)
NPs, sample preparations and chemical analysis are critical steps to meaningfully
assay NP's bioaccumulation. To deal with these imperatives, we synthesized for
the first time TiO2 NPs labeled with the stable isotope (47)Ti. Thanks to the
(47)Ti labeling, we could detect the bioaccumulation of NPs in zebra mussels
(Dreissena polymorpha) exposed for 1 h at environmental concentrations via water
(7-120 MUg/L of (47)TiO2 NPs) and via their food (4-830 MUg/L of (47)TiO2 NPs
mixed with 1 * 10(6) cells/mL of cyanobacteria) despite the high natural Ti
background, which varied in individual mussels. The assimilation efficiency (AE)
of TiO2 NPs by mussels from their diet was very low (AE = 3.0 +/- 2.7%)
suggesting that NPs are mainly captured in mussel gut, with little penetration in
their internal organs. Thus, our methodology is particularly relevant in
predicting NP's bioaccumulation and investigating the factors influencing their
toxicokinetics in conditions mimicking real environments.
PMID- 25587675
TI - A novel chitosan-hydrogel-based nanoparticle delivery system for local inner ear
application.
AB - HYPOTHESIS: A chitosan-hydrogel-based nanoparticle (nanohydrogel) delivery system
can be used to deliver therapeutic biomaterials across the round window membrane
(RWM) into the inner ear in a mouse model. BACKGROUND: Delivering therapies to
the inner ear has always been a challenge for the otolaryngologist. Advances in
biomedical nanotechnology, increased understanding of the RWM diffusion
properties, and discovery of novel therapeutic targets and agents, have all
sparked interest in the controlled local delivery of drugs and biomaterials to
the inner ear using nanoparticles (NPs). METHODS: Fluorescently-labeled liposomal
NPs were constructed and loaded into a chitosan-based hydrogel to form a
nanohydrogel, and in vitro studies were performed to evaluate its properties and
release kinetics. Furthermore, the nanohydrogel was applied to the RWM of mice,
and perilymph and morphologic analysis were performed to assess the NP delivery
and distribution within the inner ear. RESULTS: NPs with an average diameter of
160 nm were obtained. In vitro experiments showed that liposomal NPs can persist
under physiologic conditions for at least two weeks without significant
degradation and that the nanohydrogel can carry and release these NPs in a
controlled and sustained manner. In vivo findings demonstrated that the
nanohydrogel can deliver intact nanoparticles into the perilymphatic system and
reach cellular structures in the scala media of the inner ear of our mouse model.
CONCLUSION: Our study suggests that the nanohydrogel system has great potential
to deliver therapeutics in a controlled and sustained manner from the middle ear
to the inner ear without altering inner ear structures.
PMID- 25587681
TI - A new wrinkle.
PMID- 25587682
TI - Krokodil: from Russia with love.
PMID- 25587683
TI - Josef Jadassohn: a dermatologic pioneer.
PMID- 25587678
TI - Evaluation of cetuximab as a candidate for targeted alpha-particle radiation
therapy of HER1-positive disseminated intraperitoneal disease.
AB - Although the epidermal growth factor receptor (EGFR), also known as HER1, has
been studied for over a decade, it continues to be a molecule of great interest
and focus of investigators for development of targeted therapies. The marketed
monoclonal antibody cetuximab binds to HER1, and thus might serve as the basis
for creation of imaging or therapies that target this receptor. The potential of
cetuximab as a vehicle for the delivery of alpha-particle radiation was
investigated in an intraperitoneal tumor mouse model. The effective working dose
of 10 MUCi of (212)Pb-cetuximab was determined from a dose (10-50 MUCi)
escalation study. Toxicity, as indicated by the lack of animal weight loss, was
not evident at the 10 MUCi dose of (212)Pb-cetuximab. A subsequent study
demonstrated (212)Pb-cetuximab had a therapeutic efficacy similar to that of
(212)Pb-trastuzumab (p = 0.588). Gemcitabine given 24 h prior to (212)Pb
cetuximab increased the median survival from 174 d to 283 d, but carboplatin
suppressed the effectiveness of (212)Pb-cetuximab. Notably, concurrent treatment
of tumor-bearing mice with (212)Pb-labeled cetuximab and trastuzumab provided
therapeutic benefit that was greater than either antibody alone. In conclusion,
cetuximab proved to be an effective vehicle for targeting HER1-expressing tumors
with alpha-radiation for the treatment of disseminated intraperitoneal disease.
These studies provide further evidence that the multimodality therapy regimens
may have greater efficacy and benefit in the treatment of cancer patients.
PMID- 25587684
TI - Trending.
PMID- 25587685
TI - Dermatologic etymology: primary morphology of skin lesions.
PMID- 25587686
TI - Medical problems in the trenches.
PMID- 25587687
TI - A championship quiz on sports-related dermatoses.
PMID- 25587689
TI - Structure evolution of nanoparticulate Fe2O3.
AB - The atomic structure and properties of nanoparticulate Fe2O3 are characterized
starting from its smallest Fe2O3 building unit through (Fe2O3)n clusters to
nanometer-sized Fe2O3 particles. This is achieved by combining global structure
optimizations at the density functional theory level, molecular dynamics
simulations by employing tailored, ab initio parameterized interatomic potential
functions and experiments. With the exception of nearly tetrahedral, adamantane
like (Fe2O3)2 small (Fe2O3)n clusters assume compact, virtually amorphous
structures with little or no symmetry. For n = 2-5 (Fe2O3)n clusters consist
mainly of two- and three-membered Fe-O rings. Starting from n = 5 they
increasingly assume tetrahedral shape with the adamantane-like (Fe2O3)2 unit as
the main building block. However, the small energy differences between different
isomers of the same cluster-size make precise structural assignment for larger
(Fe2O3)n clusters difficult. The tetrahedral morphology persists for Fe2O3
nanoparticles with up to 3 nm in diameter. Simulated crystallization of larger
nanoparticles with diameters of about 5 nm demonstrates pronounced melting point
depression and leads to formation of epsilon-Fe2O3 single crystals with hexagonal
morphology. This finding is in excellent agreement with the results obtained for
Fe2O3 nanopowders generated by laser vaporization and provides the first direct
indication that epsilon-Fe2O3 may be thermodynamically the most stable phase in
this size regime.
PMID- 25587688
TI - Sexual risk behaviors increasing among adolescents over time: comparison of two
cohorts in Spain.
AB - Despite advances in treatment and prevention, HIV/AIDS remains a serious health
and social problem. This study's objective is to examine sexual behavior, levels
of knowledge, and attitudes toward HIV/AIDS between two cohorts in Spanish
adolescents, and to analyze gender differences in these cohorts. Participants
were 2132 adolescents between 15 and 18 years of age: 1222 in 2006 (43.2% boys)
and 910 in 2012 (54.1% boys). The results indicate lower HIV knowledge and less
favorable attitudes about HIV/AIDS in the 2012 cohort. In addition, adolescents
from the 2012 cohort had their first sexual intercourse at an earlier age and
have more sexual partners than those from the 2006 cohort. Compared to boys,
girls engage in fewer risky behaviors, although they did not use condoms with
their stable partner; girls tended to use condom less when they were in a stable
relationship than boys. This study confirms the insufficiency of prevention
campaigns as well as the need to improve the impact from programs that promote
healthy sexual habits. Assuming comparability of cohorts, this study suggests
increased risk of HIV/AIDS over time.
PMID- 25587691
TI - Laser-assisted photothermal heating of a plasmonic nanoparticle-suspended droplet
in a microchannel.
AB - The present article reports the numerical and experimental investigations on the
laser-assisted photothermal heating of a nanoliter-sized droplet in a
microchannel when plasmonic particles are suspended in the droplet. Plasmonic
nanoparticles exhibit strong light absorption and scattering upon the excitation
of localized surface plasmons (LSPs), resulting in intense and rapid photothermal
heating in a microchannel. Computational models are implemented to theoretically
verify the photothermal behavior of gold nanoshell (GNS) and gold nanorod (GNR)
particles suspended in a liquid microdroplet. Experiments were conducted to
demonstrate rapid heating of a sub-100 nL droplet up to 100 degrees C with high
controllability and repeatability. The heating and cooling time to the steady
state is on the order of 1 second, while cooling requires less time than heating.
The effects of core parameters, such as nanoparticle structure, volumetric
concentration, microchannel depth, and laser power density on heating are
studied. The obtained results can be integrated into existing microfluidic
technologies that demand accurate and rapid heating of microdroplets in a
microchannel.
PMID- 25587690
TI - Macrophage-derived soluble CD163 level in young patients with Gaucher disease:
relation to phenotypes, disease severity and complications.
AB - OBJECTIVES: Bone and lung involvement are two major causes of morbidity in
Gaucher disease (GD). The soluble form of CD163 (sCD163) is a valuable diagnostic
biomarker for monitoring diseases with increased macrophage activation. We
determined sCD163 levels in 30 children and adolescence with GD compared with 30
healthy controls and assessed the relation to phenotypes, disease severity and
complications. METHODS: Thirty GD patients (10 had type 1 and 20 had type 3) were
studied stressing on skeletal, pulmonary or neurological manifestations, enzyme
replacement therapy (ERT), hematological profile, plasma chitotriosidase
activity, D-dimer and sCD163. Liver and spleen volumes and bone mineral density
(BMD) were assessed. RESULTS: sCD163 levels were markedly elevated in patients
compared with controls. D-dimer, chitotriosidase activity and sCD163 levels were
significantly increased in type 3 GD patients compared with type 1. sCD163 was
significantly elevated in GD patients with dysphagia, developmental delay,
pulmonary hypertension risk or abnormal BMD (osteopenia/osteoporosis) than those
without. GD patients receiving ERT every 2weeks had lower levels than those under
ERT for more than 2weeks. sCD163 was positively correlated with age, disease
duration, severity score index, D-dimer and chitotriosidase activity. The cutoff
value of sCD163 at 9400ng/mL could differentiate GD patients with and without
pulmonary hypertension risk with a sensitivity of 90% and specificity of 95%.
CONCLUSIONS: sCD163 is a biomarker for the clinical assessment of macrophage
proliferation and activity that would help in risk prediction of bone and lung
involvement and monitoring treatment response.
PMID- 25587692
TI - Skin Abnormalities in CHILD Syndrome Successfully Treated with Pathogenesis-based
Therapy.
PMID- 25587693
TI - A naturalistic retrospective review of weight gain in bipolar patients treated
with second generation antipsychotics.
PMID- 25587694
TI - Effects of clozapine on perceptual abnormalities and sensory gating: a
preliminary cross-sectional study in schizophrenia.
AB - The aim of the present study was to investigate the effect of second-generation
antipsychotics (clozapine or another second-generation antipsychotic) on
perceptual abnormalities related to sensory gating deficit. Although clozapine is
known to improve sensory gating assessed neurophysiologically, we hypothesized
that patients with schizophrenia treated with clozapine would report less
perceptual abnormalities related to sensory gating deficit than patients treated
with other second-generation antipsychotics do. Forty patients with a diagnosis
of schizophrenia were investigated (10 patients treated with clozapine and 30
patients treated with another second-generation antipsychotic drug). Perceptual
abnormalities were assessed with the Sensory Gating Inventory. Sensory gating was
assessed through electroencephalogram with the auditory event-related potential
method by measuring P50 amplitude changes in a dual click conditioning-testing
procedure. Patients treated with clozapine present normal sensory gating and
report less perceptual abnormalities related to sensory gating than patients
treated with other second-generation antipsychotics do. Although the cross
sectional design of this study is limited because causal inferences cannot be
clearly concluded, the present study suggests clinical and neurophysiological
advantages of clozapine compared with other second-generation antipsychotics and
provides a basis for future investigations on the effect of this treatment on
perceptual abnormalities related to sensory gating deficit in patients with
schizophrenia.
PMID- 25587695
TI - Spinal Reflexes During Postural Control Under Psychological Pressure.
AB - This study investigated the effect of psychological pressure on spinal reflex
excitability. Thirteen participants performed a balancing task by standing on a
balance disk with one foot. After six practice trials, they performed one
nonpressure and one pressure trial involving a performance-contingent cash reward
or punishment. Stress responses were successfully induced; state anxiety, mental
effort, and heart rates all increased under pressure. Soleus Hoffmann reflex
amplitude in the pressure trial was significantly smaller than in the nonpressure
trial. This modification of spinal reflexes may be caused by presynaptic
inhibition under the control of higher central nerve excitation under pressure.
This change did not prevent 12 of the 13 participants from successfully
completing the postural control task under pressure. These results suggest that
Hoffmann reflex inhibition would contribute to optimal postural control under
stressful situations.
PMID- 25587696
TI - The snow, the men, the shovel, the risk? ER admissions after snow shovelling: 13
winters in Bern.
PMID- 25587697
TI - Bismuth oxyiodide nanosheets: a novel high-energy anode material for lithium-ion
batteries.
AB - BiOI nanosheets are easily synthesized by direct thermal treatment of commercial
BiI3 powder, serving as a novel anode material for lithium-ion batteries. A high
volumetric capacity of ~5678 mA h cm(-3) was achieved. This work demonstrates
that the BiOI nanosheets hold great promise as high-energy anode material for
lithium-ion batteries.
PMID- 25587698
TI - Hierarchical molecular dynamics of bovine serum albumin in concentrated aqueous
solution below and above thermal denaturation.
AB - The dynamics of proteins in solution is a complex and hierarchical process,
affected by the aqueous environment as well as temperature. We present a
comprehensive study on nanosecond time and nanometer length scales below, at, and
above the denaturation temperature Td. Our experimental data evidence dynamical
processes in protein solutions on three distinct time scales. We suggest a
consistent physical picture of hierarchical protein dynamics: (i) self-diffusion
of the entire protein molecule is confirmed to agree with colloid theory for all
temperatures where the protein is in its native conformational state. At higher
temperatures T > Td, the self-diffusion is strongly obstructed by cross-linking
or entanglement. (ii) The amplitude of backbone fluctuations grows with
increasing T, and a transition in its dynamics is observed above Td. (iii) The
number of mobile side-chains increases sharply at Td while their average dynamics
exhibits only little variations. The combination of quasi-elastic neutron
scattering and the presented analytical framework provides a detailed microscopic
picture of the protein molecular dynamics in solution, thereby reflecting the
changes of macroscopic properties such as cluster formation and gelation.
PMID- 25587699
TI - The PAndemic INfluenza Triage in the Emergency Department (PAINTED) pilot cohort
study.
AB - BACKGROUND: Research needs to be undertaken rapidly in the event of an influenza
pandemic to develop and evaluate triage methods for people presenting to the
emergency department with suspected pandemic influenza. OBJECTIVES: We aimed to
pilot a research study to be undertaken in a pandemic to identify the most
accurate triage method for patients presenting to the emergency department with
suspected pandemic influenza. The objectives of the pilot study were to develop a
standardised clinical assessment form and secure online database; test both using
data from patients with seasonal influenza; seek clinician views on the usability
of the form; and obtain all regulatory approvals required for the main study.
DESIGN: Study methods were piloted using an observational cohort study and
clinician views were sought using qualitative, semistructured interviews.
SETTING: Six acute hospital emergency departments. PARTICIPANTS: Patients
attending the emergency department with suspected seasonal influenza during
winter 2012-13 and clinicians working in the emergency departments. MAIN OUTCOME
MEASURES: Adverse events up to 30 days were identified, but analysis of the pilot
data was limited to descriptive reporting of patient flow, data completeness and
patient characteristics. RESULTS: Some 165 patients were identified, of whom 10
withdrew their data, leaving 155 (94%) for analysis. Follow-up data were
available for 129 of 155 (83%), with 50 of 129 (39%) being admitted to hospital.
Three cases (2%) were recorded as having suffered an adverse outcome. There
appeared to be variation between the hospitals, allowing for small numbers. Three
of the hospitals identified 150 of 165 (91%) of the patients, and all 10
withdrawing patients were at the same hospital. The proportion with missing
follow-up data varied from 8% to 31%, and the proportion admitted varied from 4%
to 85% across the three hospitals with meaningful numbers of cases. All of the
deaths were at one hospital. There was less variation between hospitals in rates
of missing data, and for most key variables missing rates were between 5% and
30%. Higher missing rates were recorded for blood pressure (39%), inspired oxygen
(43%), capillary refill (36%) and Glasgow Coma Scale score (43%). Chest
radiography was performed in 51 of 118 cases, and electrocardiography in 40 of
111 cases with details recorded. Blood test results were available for 32 of 155
cases. The qualitative interviews revealed generally positive views towards the
standardised assessment form. Concerns about lack of space for free text were
raised but counterbalanced by appreciation that it fitted on to one A4 page. A
number of amendments were suggested but only three of these were suggested by
more than one participant, and no suggestions were made by more than two
participants. CONCLUSIONS: A standardised assessment form is acceptable to
clinicians and could be used to collect research data in an influenza pandemic,
but analysis may be limited by missing data. FUTURE WORK: An observational cohort
study to identify the most accurate triage method for predicting severe illness
in emergency department attendees with suspected pandemic influenza is set up and
ready to activate if, or when, a pandemic occurs. TRIAL REGISTRATION: Current
Controlled Trials ISRCTN56149622. FUNDING: This project was funded by the NIHR
Health Technology Assessment programme and will be published in full in Health
Technology Assessment; Vol. 19, No. 3. See the NIHR Journals Library website for
further project information.
PMID- 25587700
TI - The crystal structure of the versatile cytochrome P450 enzyme CYP109B1 from
Bacillus subtilis.
AB - The crystal structure of the versatile CYP109B1 enzyme from Bacillus subtilis has
been solved at 1.8 A resolution. This is the first structure of an enzyme from
this CYP family, whose members are prevalent across diverse species of bacteria.
In the crystal structure the enzyme has an open conformation with an access
channel leading from the heme to the surface. The substrate-free structure
reveals the location of the key residues in the active site that are responsible
for binding the substrate in the correct orientation for regioselective
oxidation. Importantly, there are significant differences among these residues in
members of the CYP109 and closely related CYP106 families and these likely
account for the variations in substrate binding and oxidation profiles observed
with these enzymes. A whole-cell oxidation biosystem was developed, which
contains CYP109B1 and a phthalate family oxygenase reductase (PFOR), from
Pseudomonas putida KT24440, as the electron transfer partner. This electron
transfer system is able to support CYP109B1 activity resulting in the
regioselective hydroxylation of both alpha- and beta-ionone in vivo and in vitro.
The PFOR is therefore a versatile electron transfer partner that is able to
support the activity of CYP enzymes from other bacterium. The crystal structure
of CYP109B1 has a positively charged proximal face and this explains why it can
interact with PFOR and adrenodoxin which are predominantly negatively charged
around their [2Fe-2S] clusters.
PMID- 25587702
TI - Dermatologists, imiquimod, and treatment of molluscum contagiosum in children:
righting wrongs.
PMID- 25587701
TI - Effect of anular closure on disk height maintenance and reoperated recurrent
herniation following lumbar diskectomy: two-year data.
AB - OBJECTIVE: To assess the potential benefits of disk reherniation reduction and
disk height maintenance in limited diskectomy combined with the implantation of
the anular closure device. SUMMARY AND BACKGROUND DATA: Postoperative disk height
loss is apparent in most patients undergoing lumbar diskectomy for herniated
nucleus pulposus. Less favorable patient outcomes are associated with significant
loss in disk height that can occur after aggressive disk tissue removal. More
conservative disk removals, however, are often burdened by the increased risk of
recurrent disk herniation. METHODS: Two prospective single-arm studies on
patients treated with limited diskectomy and an anular closure device were
conducted. Outcome measures included disk height maintenance relative to
preoperative values, Oswestry Disability Index, back pain, leg pain, and
complications such as reherniations. Patients were evaluated preoperatively and
postoperatively at 6 weeks and at 3-, 6-, 12-, and 24-month time points. RESULTS:
A total of 75 patients were included in this cohort consisting of 40 men and 35
women with an average age of 40 years. Disk height maintenance within the group
overall was 90% at 24 months. Overall, 97% of the treated disks demonstrated disk
height maintenance of at least 75% of preoperative levels at 12 months and 92% at
24 months. Disk height maintenance was correlated with less nucleus removal.
Patient disability, back pain, and leg pain were significantly improved from
preoperative levels at 6 weeks and maintained over the course of study. There was
a single symptomatic reherniation requiring surgical intervention within this
series. CONCLUSIONS: Limited lumbar diskectomy combined with the use of an anular
closure device provided very low rates of disk reherniation and exhibited
excellent disk height maintenance and sustained disability, leg pain, and back
pain improvement within a 24-month postoperative study period. As with prior
diskectomy studies, disk height maintenance was correlated with lower nucleus
removal, although recurrence was less than in prior reports of limited
diskectomy. Anular closure may allow for achievement of both objectives.
PMID- 25587703
TI - Respiratory Tissue Engineering: Current Status and Opportunities for the Future.
AB - Currently, lung disease and major airway trauma constitute a major global
healthcare burden with limited treatment options. Airway diseases such as chronic
obstructive pulmonary disease and cystic fibrosis have been identified as the
fifth highest cause of mortality worldwide and are estimated to rise to fourth
place by 2030. Alternate approaches and therapeutic modalities are urgently
needed to improve clinical outcomes for chronic lung disease. This can be
achieved through tissue engineering of the respiratory tract. Interest is growing
in the use of airway tissue-engineered constructs as both a research tool, to
further our understanding of airway pathology, validate new drugs, and pave the
way for novel drug therapies, and also as regenerative medical devices or as an
alternative to transplant tissue. This review provides a concise summary of the
field of respiratory tissue engineering to date. An initial overview of airway
anatomy and physiology is given, followed by a description of the stem cell
populations and signaling processes involved in parenchymal healing and tissue
repair. We then focus on the different biomaterials and tissue-engineered systems
employed in upper and lower respiratory tract engineering and give a final
perspective of the opportunities and challenges facing the field of respiratory
tissue engineering.
PMID- 25587704
TI - Intracortical recording interfaces: current challenges to chronic recording
function.
AB - Brain Computer Interfaces (BCIs) offer significant hope to tetraplegic and
paraplegic individuals. This technology relies on extracting and translating
motor intent to facilitate control of a computer cursor or to enable fine control
of an external assistive device such as a prosthetic limb. Intracortical
recording interfaces (IRIs) are critical components of BCIs and consist of arrays
of penetrating electrodes that are implanted into the motor cortex of the brain.
These multielectrode arrays (MEAs) are responsible for recording and conducting
neural signals from local ensembles of neurons in the motor cortex with the high
speed and spatiotemporal resolution that is required for exercising control of
external assistive prostheses. Recent design and technological innovations in the
field have led to significant improvements in BCI function. However, long-term
(chronic) BCI function is severely compromised by short-term (acute) IRI
recording failure. In this review, we will discuss the design and function of
current IRIs. We will also review a host of recent advances that contribute
significantly to our overall understanding of the cellular and molecular events
that lead to acute recording failure of these invasive implants. We will also
present recent improvements to IRI design and provide insights into the
futuristic design of more chronically functional IRIs.
PMID- 25587705
TI - Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.
AB - Diabetic nephropathy often progresses to end-stage kidney disease and,
ultimately, to renal replacement therapy. Hyperglycemia per se is expected to
have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This
study aims to establish the link between protein glycosylation and progression of
experimental diabetic kidney disease using orthogonal methods. Kidneys of
streptozotocin-diabetic and control rats were harvested at three different time
points post streptozotocin injection. A panel of 12 plant lectins was used in the
screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified
remarkable disease-associated differences in glycoprotein expression. Lectin
affinity chromatography followed by mass spectrometric analyses led to the
identification of several glycoproteins involved in salt-handling, angiogenesis,
and extracellular matrix degradation. Our data confirm a substantial link between
glycosylation signature and diabetes progression. Furthermore, as suggested by
our findings on dipeptidyl peptidase-IV, altered protein glycosylation may
reflect changes in biochemical properties such as enzymatic activity. Thus, our
study demonstrates the unexplored potential of protein glycosylation analysis in
the discovery of molecules linked to diabetic kidney disease.
PMID- 25587706
TI - Fractalkine-CX3CR1-dependent recruitment and retention of human CD1c+ myeloid
dendritic cells by in vitro-activated proximal tubular epithelial cells.
AB - Chemokines play pivotal roles in tissue recruitment and retention of leukocytes,
with CX3CR1 recently identified as a chemokine receptor that selectively targets
mouse kidney dendritic cells (DCs). We have previously demonstrated increased
tubulointerstitial recruitment of human transforming growth factor-beta (TGF
beta)-producing DCs in renal fibrosis and chronic kidney disease (CKD). However,
little is known about the mechanism of human DC recruitment and retention within
the renal interstitium. We identified CD1c+ DCs as the predominant source of
profibrotic TGF-beta and highest expressors of the fractalkine receptor CX3CR1
within the renal DC compartment. Immunohistochemical analysis of diseased human
kidney biopsies showed colocalization of CD1c+ DCs with fractalkine-positive
proximal tubular epithelial cells (PTECs). Human primary PTEC activation with
interferon-gamma and tumor necrosis factor-alpha induced both secreted and
surface fractalkine expression. In line with this, we found fractalkine-dependent
chemotaxis of CD1c+ DCs to supernatant from activated PTECs. Finally, in
comparison with unactivated PTECs, we showed significantly increased adhesion of
CD1c+ DCs to activated PTECs via a fractalkine-dependent mechanism. Thus, TGF
beta-producing CD1c+ DCs are recruited and retained in the renal
tubulointerstitium by PTEC-derived fractalkine. These cells are then positioned
to play a role in the development of fibrosis and progression of chronic kidney
disease.
PMID- 25587707
TI - Alcohol consumption is inversely associated with the risk of developing chronic
kidney disease.
AB - There are few reports of associations between alcohol consumption and risk of
chronic kidney disease (CKD). To investigate this further, we studied 5476
participants aged 28-75 years in the Prevention of Renal and Vascular End-Stage
Disease (PREVEND) study, a prospective population-based cohort, who were free of
CKD at baseline (1997/1998). Alcohol consumption was self-reported on a
questionnaire validated against serum high-density lipoprotein cholesterol. The
primary outcome was de novo CKD defined as a combination of a creatinine-cystatin
C-based estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m(2)
and/or the mean of two consecutive 24-h urinary albumin excretions over 30 mg.
During four serial follow-up examinations (median 10.2 years until February
2012), 903 participants developed CKD. Compared with those abstaining from
alcohol, the multivariable-adjusted hazard ratios (95% confidence interval) for
CKD risk were 0.85 (0.69-1.04) for occasional (under 10 g/week), 0.82 (0.69-0.98)
for light (10-69.9 g/week), 0.71 (0.58-0.88) for moderate (70-210 g/week), and
0.60 (0.42-0.86) for heavier (over 210 g/week) alcohol consumers (significant
trend). Similar inverse associations for alcohol consumption were found when CKD
was defined as eGFR <60 ml/min per 1.73 m(2) or as 24-h urinary albumin excretion
over 30 mg. Thus, in this population-based cohort, alcohol consumption was
inversely associated with the risk of developing CKD.
PMID- 25587708
TI - Incidence and risk factors for new-onset atrial fibrillation among patients with
end-stage renal disease undergoing renal replacement therapy.
AB - Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients
and negatively impacts patient outcomes. We explored the incidence and risk
factors for new-onset AF among patients with ESRD undergoing renal replacement
therapy, without a prior history of AF, retrieved from Taiwan's National Health
Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one
age- and gender-matched control and one similarly matched patient with chronic
kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD.
The study endpoint was the occurrence of new-onset AF and patients were followed
an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per
1000 person-years for ESRD, CKD, and control patients, respectively. Among
patients with ESRD, age, hypertension, heart failure, coronary artery disease,
peripheral arterial occlusive disease, and chronic obstructive pulmonary disease
were significant risk factors for new-onset AF. Thus, patients with ESRD had a
significantly higher risk of new-onset AF. The presence of multiple risk factors
was associated with a higher possibility of AF occurrence.
PMID- 25587710
TI - Organ donation after circulatory death in Switzerland: slow but constant
progress.
PMID- 25587709
TI - Renal developmental defects resulting from in utero hypoxia are associated with
suppression of ureteric beta-catenin signaling.
AB - Gestational stressors, including glucocorticoids and protein restriction, can
affect kidney development and hence final nephron number. Since hypoxia is a
common insult during pregnancy, we studied the influence of oxygen tension on
kidney development in models designed to represent a pathological hypoxic insult.
In vivo mouse models of moderate, transient, midgestational (12% O2, 48 h, 12.5
dpc) or severe, acute, early-gestational (5.5-7.5% O2, 8 h, 9.5-10.5 dpc) hypoxia
were developed. The embryo itself is known to mature under hypoxic conditions
with embryonic tissue levels of oxygen estimated to be 5%-8% (physiological
hypoxia) when the mother is exposed to ambient normoxia. Both in vivo models
generated phenotypes seen in patients with congenital anomalies of the kidney and
urinary tract (CAKUT). Severe, acute, early hypoxia resulted in duplex kidney,
while moderate, transient, midgestational hypoxia permanently reduced ureteric
branching and nephron formation. Both models displayed hypoxia-induced reductions
in beta-catenin signaling within the ureteric tree and suppression of the
downstream target gene, Ccnd1. Thus, we show a link between gestational hypoxia
and CAKUT, the phenotype of which varies with timing, duration, and severity of
the hypoxic insult.
PMID- 25587712
TI - Plasmon resonance hybridization in self-assembled copper nanoparticle clusters:
efficient and precise localization of surface plasmon resonance (LSPR) sensing
based on Fano resonances.
AB - In this work, we have investigated the hybridization of plasmon resonance modes
in completely copper (Cu)-based subwavelength nanoparticle clusters from simple
symmetric dimers to complex asymmetric self-assembled structures. The quality of
apparent bonding and antibonding plasmon resonance modes for all of the clusters
has been studied, and we examined the spectral response of each one of the
proposed configurations numerically using the finite-difference time domain
(FDTD) method. The effect of the geometric sizes of nanoparticles used and
substrate refractive index on the cross-sectional profiles of each of the studied
structures has been calculated and drawn. We proved that Fano-like resonance can
be formed in Cu-based heptamer clusters as in analogous noble metallic particles
(e.g., Au and Ag) by determining the coupling strength and interference between
sub-radiant and super-radiant resonance modes. Employing certain Cu nanodiscs in
designing an octamer structure, we measured the quality of the Fano dip formation
along the scattering diagram. Accurate tuning of the geometric sizes for the Cu
based octamer yields an opportunity to observe isotropic, deep, and narrow Fano
minima along the scattering profile that are in comparable condition with the
response of other plasmonic metallic substances. Immersing investigated final Cu
based octamer in various liquids with different refractive indices, we determined
the sensing accuracy of the cluster based on the performance of the Fano dip.
Plotting a linear diagram of plasmon energy differences over the refractive index
variations as a figure of merit (FoM), which we have quantified as 13.25. With
this method, the precision of the completely Cu-based octamer is verified
numerically using the FDTD tool. This study paves the way toward the use of Cu as
an efficient, low-cost, and complementary metal-oxide semiconductor (CMOS)
compatible plasmonic material with optical properties that are similar to
analogous plasmonic substances.
PMID- 25587713
TI - Synthesis of a red fluorescent dye-conjugated Ag@SiO2 nanocomposite for cell
immunofluorescence.
AB - In this work we describe a one-step approach for incorporating a red fluorophore
(2SBPO) into core-shell nanoparticles for metal-enhanced fluorescence
immunolabels. The 2SBPO-MEF nanoparticles are particularly attractive as cell
labels because their ~ 670 nm emission has minimal overlap with cell
autofluorescence and from overlap with many conventional probes. 2SBPO was
incorporated through physical entrapment during the Stober process. Antibody
based cell labels were then synthesized using covalent linkage. The nanoparticle
fluorescence was 7.5-fold higher than control nanoparticles lacking a metal core.
We demonstrated labeling of CD4 + HuT 78 T lymphocytes using anti-CD4-conjugated
nanoparticle labels. Cells labeled with anti-CD4 nanoparticles showed a 35-fold
fluorescence signal compared to anti-CD4 coreless controls. This simple synthesis
protocol can be applied to a variety of hydrophilic fluorophore types and has
broad potential in bioanalytical and biosensing applications.
PMID- 25587711
TI - Female streetwalkers' perspectives on migration and HIV/STI risks in a changing
economic and social environment: a qualitative study in Shanghai, China.
AB - China's 30-year economic boom has created a unique social and economic market for
commercial sex, as well as for a workforce of migrant women from rural China.
This qualitative study explores the impact of the rapidly changing social and
economic environment on migration patterns, knowledge of sexually transmitted
infections (STIs), STI risk behaviours and health beliefs among female
streetwalkers in Shanghai. Qualitative data were collected in 2010 through semi
structured in-depth interviews with 16 streetwalkers to characterise their
migration passages, sexual health and behaviours, and peer networks. Many
streetwalkers reported histories of childhood impoverishment, of family or
partner violence or trauma, of migration consistent with the timeline and routes
of economic development and of a scarcity in health, social or economic support.
Their knowledge of the prevention and treatment of HIV and STIs was limited. They
had little bargaining power on condom use and the majority resorted to vaginal
douching and self-management with antibiotics as preventative measures. The study
identifies streetwalkers' perspectives on the changing environment, their options
and actions and, finally, HIV/STI risks that were unique to this hidden
population.
PMID- 25587714
TI - The importance of research in undergraduate medical education.
AB - Currently medical information flows at great speed, bombarding medical students.
Students are unfamiliar with fundamental aspects of biomedical literature
appraisal. We assert that research performed during medical school will help to
reduce the gap between the information available and comprehension by the
student. The goal of the present review is to expound the importance of
performing research during the undergraduate medical years and the relevance of
research in other fields of medicine. We performed a literature review searching
MEDLINE with terms consistent with our objective. We discuss the conduct of
research projects during medical school training. The analysis of the articles
retrieved proves that research is feasible and that it is a critical process
during the undergraduate period for medical students.
PMID- 25587715
TI - Relationships between the Osteocalcin gene polymorphisms, serum osteocalcin
levels, and hepatitis B virus-related hepatocellular carcinoma in a Chinese
population.
AB - BACKGROUND: Available evidence has demonstrated that osteocalcin may play a role
in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved
in the cancer development. The aim of this study is to determine whether
osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV)
related hepatocellular carcinoma (HCC) among Chinese population. METHODS: A total
of 515 subjects were divided into four groups: 129 patients with chronic
hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154
patients with HBV-related HCC, and 170 healthy controls. The polymerase chain
reaction-restriction fragment length polymorphism strategy was used to detect
osteocalcin gene rs1800247 and rs1543297 polymorphisms. RESULTS: Compared with
healthy controls, the rs1800247 HH and Hh genotypes were associated with a
significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI
2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P <
0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247
had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95%
CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition,
we found significant decreased serum osteocalcin levels in HBV-related HCC
patients (11.73 +/- 8.18 ng/mL) compared with healthy controls (15.3 +/- 6.06
ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC
patients than healthy controls among the individuals with heterozygous Hh
genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no
significant differences in the genotype and allele of rs1543297 polymorphisms
between the groups of patients and healthy controls. CONCLUSIONS: These findings
for the first time suggest that genetic variant in osteocalcin gene rs1800247
polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse
association of serum osteocalcin levels with HCC.
PMID- 25587716
TI - Plasmid-mediated AmpC: prevalence in community-acquired isolates in Amsterdam,
the Netherlands, and risk factors for carriage.
AB - OBJECTIVES: The objective of this study was to determine the prevalence of pAmpC
beta-lactamases in community-acquired Gram negative bacteria in the Netherlands,
and to identify possible risk factors for carriage of these strains. METHODS:
Fecal samples were obtained from community-dwelling volunteers. Participants also
returned a questionnaire for analysis of risk factors. Screening for pAmpC was
performed with selective enrichment broth and a selective screening agar.
Confirmation of AmpC-production was performed with two double disc combination
tests: cefotaxime and ceftazidime with either boronic acid or cloxacillin as
inhibitor. Multiplex PCR was used as gold standard for detection of pAmpC. 16S
rRNA PCR and AFLP were performed as required, plasmids were identified by PCR
based replicon typing. Questionnaire results were analyzed with SPSS, version
20.0. RESULTS: Fecal samples were obtained from 550 volunteers; mean age 51 years
(range: 18-91), 61% were females. pAmpC was present in seven E. coli isolates
(7/550, 1.3%, 0.6-2.7 95% CI): six CMY-2-like pAmpC and one DHA. ESBL-encoding
genes were found in 52/550 (9.5%, 7.3-12.2 95% CI) isolates; these were
predominantly blaCTX-M genes. Two isolates had both ESBL and pAmpC. Admission to
a hospital in the previous year was the only risk factor we identified.
CONCLUSIONS: Our data indicate that the prevalence of pAmpC in the community
seems still low. However, since pAmpC-producing isolates were not identified as
ESBL producers by routine algorithms, there is consistent risk that further
increase of their prevalence might go undetected.
PMID- 25587717
TI - MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of
metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.
AB - Metastatic melanoma is the most aggressive form of this cancer. It is important
to understand factors that increase or decrease metastatic activity in order to
more effectively research and implement treatments for melanoma. Increased cell
invasion through the extracellular matrix is required for metastasis and is
enhanced by matrix metalloproteinases (MMPs). Tissue inhibitor of
metalloproteinases 3 (TIMP3) inhibits MMP activity. It was previously shown by
our group that miR-21, a potential regulator of TIMP3, is over-expressed in
cutaneous melanoma. It was therefore hypothesized that increased levels of miR-21
expression would lead to decreased expression of TIMP3 and thereby enhance the
invasiveness of melanoma cells. miR-21 over-expression in the melanoma cell lines
WM1552c, WM793b, A375 and MEL 39 was accomplished via transfection with pre-miR
21. Immunoblot analysis of miR-21-overexpressing cell lines revealed reduced
expression of TIMP3 as compared to controls. This in turn led to a significant
increase in the invasiveness of the radial growth phase cell line WM1552c and the
vertical growth phase cell line WM793b (p < 0.05), but not in the metastatic cell
lines A375 or MEL 39. The proliferation and migration of miR-21 over-expressing
cell lines was not affected. Reduced expression of TIMP3 was achieved by siRNA
knockdown and significantly enhanced invasion of melanoma cell lines, mimicking
the effects of miR-21 over-expression. Treatment of tumor cells with a linked
nucleic acid antagomir to miR-21 inhibited tumor growth and increased tumor
expression of TIMP3 in vivo in 01B74 Athymic NCr-nu/nu mice. Intra-tumoral
injections of anti-miR-21 produced similar effects. This data shows that
increased expression of miR-21 enhanced the invasive potential of melanoma cell
lines through TIMP3 inhibition. Therefore, inhibition of miR-21 in melanoma may
reduce melanoma invasiveness.
PMID- 25587718
TI - Modeling nociception in zebrafish: a way forward for unbiased analgesic
discovery.
AB - Acute and chronic pain conditions are often debilitating, inflicting severe
physiological, emotional and economic costs and affect a large percentage of the
global population. However, the development of therapeutic analgesic agents based
primarily on targeted drug development has been largely ineffective. An
alternative approach to analgesic development would be to develop low cost, high
throughput, untargeted animal based behavioral screens that model complex
nociceptive behaviors in which to screen for analgesic compounds. Here we
describe the development of a behavioral based assay in zebrafish larvae that is
effective in identifying small molecule compounds with analgesic properties. In a
place aversion assay, which likely utilizes supraspinal neuronal circuitry,
individually arrayed zebrafish larvae show temperature-dependent aversion to
increasing and decreasing temperatures deviating from rearing temperature.
Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound
and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool
aversion leading larvae to avoid rearing temperature in favor of otherwise
acutely aversive cooler temperatures. We show that small molecules with known
analgesic properties are able to inhibit acute and/or sensitized temperature
aversion.
PMID- 25587720
TI - Perchlorate in indoor dust and human urine in China: contribution of indoor dust
to total daily intake.
AB - Perchlorate is used in fireworks and China is the largest fireworks producer and
consumer in the world. Information regarding human exposure to perchlorate is
scarce in China, and exposure via indoor dust ingestion (EDI indoor dust) has
rarely been evaluated. In this study, perchlorate was found in indoor dust
(detection rate: 100%, median: 47.4 MUg/g), human urine (99%, 26.2 ng/mL),
drinking water (100%, 3.99 ng/mL), and dairy milk (100%, 12.3 ng/mL) collected
from cities that have fireworks manufacturing areas (Yueyang and Nanchang) and in
cities that do not have fireworks manufacturing industries (Tianjin,
Shijiazhuang, Yuxi and Guilin) in China. In comparison with perchlorate levels
reported for other countries, perchlorate levels in urine samples from fireworks
sites and nonfireworks sites in China were higher. Median indoor dust perchlorate
concentrations were positively correlated (r = 0.964, p < 0.001) with outdoor
dust perchlorate levels reported previously. The total daily intake (EDI total)
of perchlorate, estimated based on urinary levels, ranged from 0.090 to 27.72
MUg/kg body weight (bw)/day for all studied participants; the percentage of
donors who had EDI total exceeding the reference dose (RfD) recommended by the
United States Environmental Protection Agency (US EPA) was 79%, 48%, and 25% for
toddlers (median: 1.829 MUg/kg bw/day), adults (0.669 MUg/kg bw/day), and
children (median: 0.373 MUg/kg bw/day), respectively. Toddlers (0.258 MUg/kg
bw/day) had the highest median EDI indoor dust, which was 2 to 5 times greater
than the EDI indoor dust calculated for other age groups (the range of median
values: 0.044 to 0.127 MUg/kg bw/day). Contribution of indoor dust to EDItotal
was 26%, 28%, and 7% for toddlers, children, and adults, respectively. Indoor
dust contributed higher percentage to EDI total than that by dairy milk (0.5-5%).
PMID- 25587721
TI - Association between pornography use and sexual risk behaviors in adult consumers:
a systematic review.
AB - The purpose of this review was to determine whether an association exists between
sexual risk behaviors and pornography consumption. Consumption of pornography is
common, yet research examining its link with sexual risk behaviors is in its
infancy. Indicators of sexual risk behavior, including unsafe sex practices and a
higher number of sexual partners, have been linked to poor health outcomes. A
systematic literature search was performed using Medline, PsycINFO, Web of
Knowledge, Pubmed, and CINAHL. Studies were included if they assessed the
association between pornography use and indicators of sexual risk behaviors in an
adult population. A total of 17 were included in the review, and all were
assessed for research standards using the Quality Index Scale. For both Internet
pornography and general pornography, links with greater unsafe sex practices and
number of sexual partners were identified. Limitations of the literature,
including low external validity and poor study design, restrict the
generalizability of the findings. Accordingly, replication and more rigorous
methods are recommended for future research.
PMID- 25587723
TI - AVMA issues guidance on humane slaughter.
AB - First-of-its-kind document addresses each stage of slaughter process.
PMID- 25587724
TI - Potential confounding factors in cancer studies.
PMID- 25587726
TI - What is your diagnosis? Pulmonary osteoma.
PMID- 25587725
TI - Antimicrobial stewardship in companion animal practice.
PMID- 25587727
TI - What is your diagnosis? Biliary tract obstruction.
PMID- 25587728
TI - Diagnostic imaging in veterinary dental practice. Persistent deciduous teeth.
PMID- 25587729
TI - Pathology in practice. Mediastinal thyroid follicular carcinoma and adrenal
carcinoma.
PMID- 25587719
TI - The pathogenic role of persistent milk signaling in mTORC1- and milk-microRNA
driven type 2 diabetes mellitus.
AB - Milk, the secretory product of the lactation genome, promotes growth of the
newborn mammal. Milk delivers insulinotropic amino acids, thus maintains a
molecular crosstalk with the pancreatic beta-cell of the milk recipient.
Homeostasis of beta-cells and insulin production depend on the appropriate
magnitude of mTORC1 signaling. mTORC1 is activated by branched-chain amino acids
(BCAAs), glutamine, and palmitic acid, abundant nutrient signals of cow's milk.
Furthermore, milk delivers bioactive exosomal microRNAs. After milk consumption,
bovine microRNA-29b, a member of the diabetogenic microRNA-29- family, reaches
the systemic circulation and the cells of the milk consumer. MicroRNA-29b
downregulates branchedchain alpha-ketoacid dehydrogenase, a potential explanation
for increased BCAA serum levels, the metabolic signature of insulin resistance
and type 2 diabetes mellitus (T2DM). In non-obese diabetic mice, microRNA-29b
downregulates the antiapoptotic protein Mcl-1, which leads to early beta-cell
death. In all mammals except Neolithic humans, milk-driven mTORC1 signaling is
physiologically restricted to the postnatal period. In contrast, chronic
hyperactivated mTORC1 signaling has been associated with the development of age
related diseases of civilization including T2DM. Notably, chronic hyperactivation
of mTORC1 enhances endoplasmic reticulum stress that promotes apoptosis. In fact,
hyperactivated beta-cell mTORC1 signaling induced early beta-cell apoptosis in a
mouse model. The EPIC-InterAct Study demonstrated an association between milk
consumption and T2DM in France, Italy, United Kingdom, Germany, and Sweden. In
contrast, fermented milk products and cheese exhibit an inverse correlation.
Since the early 1950's, refrigeration technology allowed widespread consumption
of fresh pasteurized milk, which facilitates daily intake of bioactive bovine
microRNAs. Persistent uptake of cow's milk-derived microRNAs apparently transfers
an overlooked epigenetic diabetogenic program that should not reach the human
food chain.
PMID- 25587730
TI - Formulation and validation of a predictive model to correct blood glucose
concentrations obtained with a veterinary point-of-care glucometer in hemodiluted
and hemoconcentrated canine blood samples.
AB - OBJECTIVE: To determine the effect of PCV on veterinary point-of-care (POC)
glucometer measurements in canine blood samples and develop a formula to correct
the glucose concentration as measured by a point-of-care glucometer (POCgluc)
given a known PCV. DESIGN: Experimental and prospective study. SAMPLES: Blood
samples from 6 healthy dogs and from 30 hospitalized dogs. PROCEDURES: 60 mL of
heparinized blood was obtained from each of 6 healthy dogs. Samples were
processed into packed RBCs and plasma. Packed RBCs were resuspended with plasma
to achieve a range of PCVs from 0% to 94%. Duplicate POCgluc and PCV measurements
were obtained for each dilution; following POCgluc measurements, plasma samples
were analyzed for glucose concentration by a clinical laboratory biochemical
analyzer (LABgluc). A correction formula for POCgluc was developed. Measurements
of POCgluc, PCV, and LABgluc were also determined from blood samples of 30 dogs
admitted to the veterinary teaching hospital. RESULTS: Values of LABgluc for each
sample were similar at any PCV. As PCV decreased, POCgluc was falsely increased;
as PCV increased, POCgluc was falsely decreased, compared with LABgluc. The
absolute difference between POCgluc and LABgluc increased as the PCV changed from
50%. Compared with POCgluc, the corrected POCgluc had a significantly improved
correlation with LABgluc, which was also reflected in improvements in Clarke and
consensus error grid analyses. CONCLUSIONS AND CLINICAL RELEVANCE: Results
indicated that in dogs with hemodilution or hemoconcentration, POCgluc did not
reflect actual patient glucose concentrations. Use of a correction formula
reduced this error. Corrected POCgluc data had strong, significant correlations
with LABgluc data.
PMID- 25587731
TI - Diagnostic quality of percutaneous fine-needle aspirates and laparoscopic biopsy
specimens of the liver in rabbits (Oryctolagus cuniculus).
AB - OBJECTIVE: To evaluate diagnostic quality of liver percutaneous ultrasound-guided
fine-needle aspirates and laparoscopic biopsy specimens of rabbits (Oryctolagus
cuniculus). DESIGN: Prospective descriptive study. ANIMALS: 7 healthy adult
rabbits. PROCEDURES: 3 to 5 liver fine-needle aspirates were obtained with a 22
gauge needle under ultrasound guidance in anesthetized rabbits. Liver biopsy
specimens were also obtained with 1.7-mm (n = 2) or 3.0-mm (1) biopsy forceps by
direct laparoscopic observation. Fine-needle aspirates were cytologically
evaluated on a scale from 0 (suboptimal specimen) to 3 (optimal specimen) for
cellularity, cell distribution, cell preservation, cell morphology, and blood
contamination. Biopsy specimens were histologically evaluated on a scale from 0
(optimal specimen) to 5 (suboptimal specimen) for artifactual changes; numbers of
portal triads and central veins were quantified. RESULTS: Aspirates were
moderately to highly cellular (mean, 2.54) with good cell distribution (mean,
2.56), good cell preservation (mean, 2.20), and moderate blood contamination
(mean, 1.04). The 1.7-mm biopsy specimens had a mean score of 1.3 for artifactual
changes and contained a mean of 0.6 portal triads and 1.6 central veins/biopsy
specimen. The 3.0-mm liver biopsy specimens had a mean score of 2.7 for
artifactual changes, with a mean of 4.0 portal triads and 4.14 central
veins/biopsy specimen. All but one 3.0-mm liver biopsy specimen had >= 1 portal
triad suitable for histologic evaluation, and all had >= 1 central vein; in
contrast, only half of the 1.7-mm liver biopsy specimens had a discernible portal
triad or central vein. CONCLUSIONS AND CLINICAL RELEVANCE: For histologic
evaluation, advantages of obtaining 3.0-mm liver biopsy specimens, compared with
1.7-mm liver biopsy specimens or fine-needle aspirates, should be considered in
rabbits with suspected liver disease.
PMID- 25587732
TI - Internal obturator muscle transposition for treatment of perineal hernia in dogs:
34 cases (1998-2012).
AB - OBJECTIVE: To evaluate the outcome of dogs with perineal hernia treated with
transposition of the internal obturator muscle. DESIGN: Retrospective case
series. ANIMALS: 34 dogs. PROCEDURES: Medical records of dogs with perineal
hernia surgically treated from 1998 to 2012 were reviewed. Diagnostic methods and
surgical techniques were recorded. Dogs were assigned preoperative and
postoperative clinical sign scores. Complication and recurrence rates were
evaluated over time. Risk factors were determined. RESULTS: Median follow-up time
was 345 days (range, 22 to 1,423 days). Complications were observed in 10 dogs.
Tenesmus (n = 9), dyschezia (7), fecal impaction (3), stranguria (4),
hematochezia (2), urinary incontinence (2), diarrhea (1), urinary tract infection
(1), and megacolon (1) occurred following surgery. Bladder retroflexion at the
time of initial evaluation or surgery was not a risk factor for complication
(hazard ratio, 1.72). One year after surgery, 51.2% dogs were free of
complications. Three dogs developed a perineal hernia on the contralateral side
between 35 and 95 days after surgery. The 1-year recurrence rate was 27.4%.
Median time for recurrence was 28 days after surgery (range, 2 to 364 days).
Postoperative tenesmus was a risk factor for the development of recurrence
(hazard ratio, 2.29). CONCLUSIONS AND CLINICAL RELEVANCE: Internal obturator
muscle transposition was used for primary repair of perineal hernia in dogs.
Recurrence was recorded as long as 1 year after surgery. Tenesmus was a risk
factor for the development of recurrence after treatment of perineal hernia with
internal obturator muscle transposition.
PMID- 25587733
TI - Incidence of and risk factors for postoperative regurgitation and vomiting in
dogs: 244 cases (2000-2012).
AB - OBJECTIVE: To determine the incidence of and risk factors for postoperative
regurgitation and vomiting (PORV) in dogs. DESIGN: Retrospective cohort study.
ANIMALS: 244 client-owned dogs. PROCEDURES: Dogs referred for nonelective surgery
in the first 3 months of 2000 and 2012 were included. Breed; sex; age; weight;
body condition score; emergency status; food withholding status; history of
vomiting or regurgitation; American Society of Anesthesiologists score; presence
of diabetes or hypothyroidism; preoperative PCV and total solids concentration;
anesthesia protocol; corticosteroid, opioid, neuromuscular blocking agent, and
nitrous oxide usage; anesthesia time; surgery time; type of surgery; and
occurrence of vomiting or regurgitation within 24 hours after recovery from
anesthesia were recorded. Data were analyzed by means of the Fisher exact test,
Wilcoxon rank sum test, and logistic regression. RESULTS: 30 of 244 (12.3%) dogs
meeting study inclusion criteria developed PORV. There was no significant
difference in the incidence of PORV between the 2000 (12/111 [10.8%]) and 2012
(18/133 [13.5%]) cohorts, although the incidence of regurgitation was higher in
2012. Univariate logistic regression identified the most significant risk factors
as gastrointestinal surgery (OR, 11.15; 95% confidence interval [CI], 3.11 to
40.03), premedication without strong sedatives including either an alpha2
adrenoceptor agonist or acepromazine (OR, 5.36; 95% CI, 1.89 to 15.17), American
Society of Anesthesiologists score of 4 (OR, 5.25; 95% CI, 1.05 to 26.15),
history of vomiting or regurgitation (OR, 5.12; 95% CI, 1.83 to 14.31), emergency
surgery (OR, 4.08; 95% CI, 1.29 to 12.90), neurologic surgery (OR, 3.18; 95% CI,
1.02 to 9.92), sevoflurane inhalation anesthesia (OR, 2.78; 95% CI, 1.25 to
6.13), and being sexually intact (OR, 2.37; 95% CI, 1.07 to 5.27). Multivariate
analysis was not clinically useful owing to the low sensitivity and specificity
of the model. CONCLUSIONS AND CLINICAL RELEVANCE: Between 2000 and 2012, there
was no change in the incidence of PORV for dogs undergoing neurologic,
orthopedic, and soft tissue surgical procedures; however, the proportion of dogs
that regurgitated increased significantly in 2012. Preoperative antiemetic
prophylaxis should be considered in dogs undergoing gastrointestinal surgery and
in those in which other risk factors are present.
PMID- 25587734
TI - Computed tomographic features of clinical and subclinical middle ear disease in
domestic rabbits (Oryctolagus cuniculus): 88 cases (2007-2014).
AB - OBJECTIVE: To describe and compare CT abnormalities of the middle ear in rabbits
(Oryctolagus cuniculus) that had clinical or subclinical middle ear disease and
to determine the prevalence of otitis media and evaluate the role of predisposing
factors for otitis media in that species. DESIGN: Retrospective case series.
ANIMALS: 88 domestic rabbits. PROCEDURES: Medical records for rabbits that
underwent CT of the head in June 2007 through February 2014 were searched and
classified on the basis of reason for head CT (i.e., ear-related disease vs non
ear-related disease). The ears, upper respiratory tract, teeth, and other
important structures of each rabbit's head were evaluated. Follow-up information
was obtained for rabbits with CT abnormalities of the middle ear without clinical
signs (i.e., subclinical disease). RESULTS: 12 of 21 (57%) rabbits with clinical
signs of ear disease and 18 of 67 (27%) rabbits without clinical signs of ear
disease had CT abnormalities of the middle ear. In CT images, all affected ears
had soft tissue-attenuating material within the tympanic bulla. Tympanic bulla
lysis was associated with clinical middle ear disease. Most (12/18) rabbits with
subclinical middle ear disease remained subclinical after CT examination. Middle
ear CT-detected changes and lop-ear conformation or otitis externa were strongly
correlated; middle ear disease and upper respiratory tract disease were not
correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that subclinical
otitis media frequently affects rabbits, and those with bulla lysis should be
closely monitored. Lop-eared rabbits and rabbits with otitis externa had a higher
risk of developing otitis media.
PMID- 25587735
TI - Extensive placental choriovascular infiltration by maturing myeloid cells in down
syndrome-associated transient abnormal myelopoiesis.
AB - Transient abnormal myelopoiesis (TAM), a clonal proliferation of predominantly
megakaryocytic precursor cells, affects 4%-10% of newborns with Down syndrome.
Approximately 20%-30% of TAM survivors are at risk of development of acute
myeloid leukemia (myeloid leukemia associated with Down syndrome, ML-DS). We
report unusual placental findings in a female infant with trisomy 21 born at 38
weeks of gestation. In line with previous descriptions of placental pathology in
infants with TAM, abundant blast-like cells were present in the lumen of
chorionic and stem villous vessels. In addition, there was multifocal extensive
infiltration of the wall of chorionic vessels by maturing myeloid cells in a
pattern reminiscent of TAM- or leukemia-associated systemic infiltration. The
clinical significance of this unusual choriovascular involvement of the placenta
in TAM is undetermined.
PMID- 25587736
TI - Commentary on "A dietary restriction influences the progression but not the
initiation of MSG-induced nonalcoholic steatohepatitis".
PMID- 25587737
TI - Effects of several temporomandibular disorders on the stress distributions of
temporomandibular joint: a finite element analysis.
AB - The aim of this study was to evaluate stress distributions in the
temporomandibular joints (TMJs) with temporomandibular disorders (TMDs) for
comparison with healthy TMJs. A model of mandible and normal TMJs was developed
according to CT images. The interfaces between the discs and the articular
cartilages were treated as contact elements. Nonlinear cable elements were used
to simulate disc attachments. Based on this model, seven models of various TMDs
were established. The maximum stresses of the discs with anterior, posterior,
medial and lateral disc displacement (ADD, PDD, MDD and LDD) were 12.09, 9.33,
10.71 and 6.07 times magnitude of the identically normal disc, respectively. The
maximum stresses of the posterior articular eminences in ADD, PDD, MDD, LDD,
relaxation of posterior attachments and disc perforation models were 21, 59, 46,
21, 13 and 15 times greater than the normal model, respectively. TMDs could cause
increased stresses in the discs and posterior articular eminences.
PMID- 25587738
TI - Molecular design of boronic acid-functionalized squarylium cyanine dyes for
multiple discriminant analysis of sialic acid in biological samples: selectivity
toward monosaccharides controlled by different alkyl side chain lengths.
AB - We designed a new series of boronic acid-functionalized squarylium cyanine dyes
(SQ-BA) with different lengths of alkyl chain residues, suitable for multiple
discriminant analysis (MDA) of sialic acid (Neu5Ac) in biological samples. The SQ
BA dyes form aggregates based on hydrophobic interactions, which result in
quenched fluorescence in aqueous solutions. When the boronic acid binds with
saccharides, the fluorescence intensity increases as a result of dissociation to
the emissive monomeric complex. We inferred that different dye aggregate
structures (H-aggregates and J-aggregates) were induced depending on the alkyl
chain length, so that monosaccharides would be recognized in different ways
(especially, multipoint interaction with J-aggregates). A distinctive emission
enhancement of SQ-BA dyes with shorter-alkyl-chains in the presence of Neu5Ac was
observed (2.4-fold fluorescence enhancement; with formation constant 10(1.7) M(
1)), with no such enhancement for SQ-BA dyes with longer-alkyl-chain. In
addition, various enhancement factors for other monosaccharides were observed
depending on the alkyl chain length. Detailed thermodynamic and NMR studies of
the SQ-BA complexes revealed the unique recognition mechanism: the dye aggregate
with a shorter-alkyl-chain causes the slipped parallel structure and forms a
stable 2:1 complex with Neu5Ac, as distinct from longer-alkyl-chain dyes, which
form a 1:1 monomeric complex. MDA using the four SQ-BA dyes was performed for
human urine samples, resulting in the successful discrimination between normal
and abnormal Neu5Ac levels characteristic of disease. Thus, we successfully
controlled various responses to similar monosaccharides with a novel approach
that chemically modified not the boronic acid moiety itself but the length of the
alkyl chain residue attached to the dye in order to generate specificity.
PMID- 25587739
TI - Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.
AB - Natural honey contains an array of glycoproteins, proteoglycans and
glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins
into five peaks with molecular masses in the range from 10 to >200 kDa. The
fractionated proteins exhibited in vitro activities against Giardia lamblia with
IC50 values <= 25 MUg/mL. Results indicated that honey proteins were more active
as antiprotozoal agents than metronidazole. This study indicated the potential of
honey proteins and peptides as novel antigiardial agents.
PMID- 25587740
TI - Impact of therapeutic irradiation on healthy articular cartilage.
AB - Radiation-induced complications in bone and cartilage are of increasing concern
due to potential long-term effects in cancer survivors. Healthy articular
cartilage may be exposed to radiation during either chondrosarcoma treatment or
in-field radiotherapy of tumors located in close proximity to articulation.
Cartilage exposed to radiation undergoes bone differentiation and senescence,
which can lead to painful and disabling sequelae that can impair patient quality
of life. An understanding of the biological processes involved in healthy
cartilage response to radiotherapy may not only optimize the delivery of
therapeutic radiation but also reduce the risk of long-term sequelae in
irradiated cartilage. Over the last few decades, radiobiology studies have
focused primarily on signaling and repair of DNA damage pathways induced by
ionizing radiation in immortalized cells under conditions dramatically different
from human homeostasis. This research needs to be continued and broadened, since
the range of normal tissue responses to radiation exposure is still not fully
understood, despite being recognized as the major limiting factor in the rupture
of tissue homeostasis after radiotherapy. Human articular cartilage is an
avascular tissue with low intracellular oxygen levels and is comprised of a
single cell lineage of chondrocytes embedded in a highly dense and structured
extracellular matrix. These relatively unique features may impact inherent cell
radiation sensitivity and suggests that canonical cell responses to ionizing
radiation may not be applicable to articular cartilage. Despite the number of
studies in this field, radiation-induced modifications of chondrocyte proteome
remain unclear because of the dramatic variability in reported experimental
conditions. In this review, we propose to introduce cartilage tissue physiology
and microenvironment concepts, and then present a comprehensive synthesis of
cartilage radiation biology.
PMID- 25587741
TI - Radiobiological intercomparison of the 160 MeV and 230 MeV proton therapy beams
at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital.
AB - The purpose of this study was to determine the relative biological effectiveness
(RBE) along the axis of two range-modulated proton beams (160 and 230 MeV). Both
the depth and the dose dependence of RBE were investigated. Chinese hamster V79
WNRE cells, suspended in medium containing gelatin and cooled to 2 degrees C,
were used to obtain complete survival curves at multiple positions throughout the
entrance and 10 cm spread-out Bragg peak (SOBP). Simultaneous measurements of the
survival response to (60)Co gamma rays served as the reference data for the
proton RBE determinations. For both beams the RBE increased significantly with
depth in the 10 cm SOBP, particularly in the distal half of the SOBP, then rose
even more sharply at the distal edge, the most distal position measured. At a 4
Gy dose of gamma radiation (S = 0.34) the average RBE values for the entrance,
proximal half, distal half and distal edge were 1.07 +/- 0.01, 1.10 +/- 0.01,
1.17 +/- 0.01 and 1.21 +/- 0.01, respectively, and essentially the same for both
beams. At a 2 Gy dose of gamma radiation (S = 0.71) the average RBE values rose
to 1.13 +/- 0.03, 1.15 +/- 0.02, 1.26 +/- 0.02 and 1.30 +/- 0.02, respectively,
for the same four regions of the SOBP. The difference between the 4 Gy and 2 Gy
RBE values reflects the dose dependence of RBE as measured in these V79-WNRE
cells, which have a low alpha/beta value, as do other widely used cell lines that
also show dose-dependent RBE values. Late-responding tissues are also
characterized by low alpha/beta values, so it is possible that these cell lines
may be predictive for the response of such tissues (e.g., spinal cord, optic
nerve, kidney, liver, lung). However, in the very small number of studies of late
responding tissues performed to date there appears to be no evidence of an
increased RBE for protons at low doses. Similarly, RBE measurements using early
responding in vivo systems (mostly mouse jejunum, an early-responding tissue
which has a large alpha/beta ~ 10 Gy) have generally shown little or no
detectable dose dependence. It is useful to compare the RBE values reported here
to the commonly used generic clinical RBE of 1.1, which assumes no dependence on
depth or on dose. Our proximal RBEs obviously avoid the depth-related increase in
RBE and for doses of 4 Gy or more, the low-dose increase in RBE is also
minimized, as shown in this article. Thus the proximal RBE at a 4 Gy dose of 1.10
+/- 0.01, quoted above, represents an interesting point of congruence with the
clinical RBE for conditions where it could reasonably be expected in the
measurements reported here. The depth dependence of RBE reported here is
consistent with the majority of measurements, both in vitro and in vivo, by other
investigators. The dose dependence of RBE, on the other hand, is tissue specific
but has not yet been demonstrated for protons by RBE values in late-responding
normal tissue systems. This indicates a need for additional RBE determination as
function of dose, especially in late-responding tissues.
PMID- 25587742
TI - Brain injury special edition on sports concussion.
PMID- 25587743
TI - Neurochemical cascade of concussion.
AB - PRIMARY OBJECTIVE: The aim of this literature review was to systematically
describe the sequential metabolic changes that occur following concussive injury,
as well as identify and characterize the major concepts associated with the
neurochemical cascade. RESEARCH DESIGN: Narrative literature review. CONCLUSIONS:
Concussive injury initiates a complex cascade of pathophysiological changes that
include hyper-acute ionic flux, indiscriminant excitatory neurotransmitter
release, acute hyperglycolysis and sub-acute metabolic depression. Additionally,
these metabolic changes can subsequently lead to impaired neurotransmission,
alternate fuel usage and modifications in synaptic plasticity and protein
expression. The combination of these metabolic alterations has been proposed to
cause the transient and prolonged neurological deficits that typically
characterize concussion. Consequently, understanding the implications of the
neurochemical cascade may lead to treatment and return-to-play guidelines that
can minimize the chronic effects of concussive injury.
PMID- 25587744
TI - Chronic traumatic encephalopathy: contributions from the Boston University Center
for the Study of Traumatic Encephalopathy.
AB - OBJECTIVE: Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease
associated with repetitive brain trauma (RBT). Initially described in boxers, CTE
has now been found in other contact sport athletes with a history of RBT. In
recent years, there has been tremendous media attention regarding CTE, primarily
because of the deaths of high profile American football players who were found to
have CTE upon neuropathological examination. However, the study of CTE remains in
its infancy. This review focuses on research from the Centre for the Study of
Traumatic Encephalopathy (CSTE) at Boston University. METHODS: This study reviews
the formation of the CSTE, major CSTE publications and current ongoing research
projects at the CSTE. RESULTS: The neuropathology of CTE has been well-described.
Current research focuses on: methods of diagnosing the disease during life
(including the development of biomarkers), examination of CTE risk factors
(including genetic susceptibility and head impact exposure variables);
description of the clinical presentation of CTE; development of research
diagnostic criteria for Traumatic Encephalopathy Syndrome; and assessment of
mechanism and pathogenesis. CONCLUSIONS: Current research at the BU CSTE is aimed
at increasing understanding of the long-term consequences of repetitive head
impacts and attempting to begin to answer several of the unanswered questions
regarding CTE.
PMID- 25587745
TI - Developing guidelines for return to play: consensus and evidence-based
approaches.
AB - BACKGROUND: Sports-related concussions are commonplace at all levels of play and
across all age groups. The dynamic, evolving nature of this injury coupled with a
lack of objective biomarkers creates a challenging management issue for the
sports medicine team. Athletes who return to play following a concussion are
known to be at higher risk for an additional brain injury, which necessitates a
careful, informed return to play (RTP) process. AIM: The goal of this paper is to
outline historical attempts at developing RTP guidelines and trace their
evolution over time, culminating in a discussion of the process and outcomes of
the most recent consensus statements/guidelines published by the international
Concussion In Sport Group (CISG), the American Academy of Neurology (AAN), the
National Athletic Trainers' Association, and the 2013 Team Physician Consensus
Statement Update. METHOD: An evaluation of the pros and cons of these guidelines
is presented along with suggestions for future directions. In addition, the
Institute of Medicine recently conducted a comprehensive report outlining the
current state of evidence regarding youth concussions, which provides specific
recommendations for future research. CONCLUSIONS: The different methodologies
utilized in the development of consensus statements have distinct advantages and
disadvantages, and both approaches add value to the everyday management of sports
concussions. Importantly, the overall approach for management of sports
concussion is remarkably similar using either consensus-based or formal evidence
based methods, which adds confidence to the current guidelines and allows
practitioners to focus on accepted standards of clinical care. Moving forward,
careful study designs need to be utilized to avoid bias in selection of research
subjects, collection of data, and interpretation of results. Although useful,
clinicians must venture beyond consensus statements to examine reviews of the
literature that are published in much greater frequency than consensus
statements.
PMID- 25587746
TI - Sleep disturbances in athletic concussion.
AB - BACKGROUND: Sleep disturbances are a common symptom following concussions to
include athletic concussion. REVIEW: This review applies literature on sleep
following traumatic brain injury and concussion to sport concussions and places
these considerations in the context of sleep and athletic performance. It also
includes a description of sleep abnormalities in sleep duration, quality and
timing as well as recommended treatment approaches. Finally, it includes a brief
discussion of emerging paradigms of sleep and concussion recovery.
PMID- 25587747
TI - Acceptability, feasibility, and efficacy of a supportive group intervention for
caregivers of newly diagnosed leukemia patients.
AB - This study describes the development of a supportive group-based intervention for
family caregivers of newly diagnosed leukemia patients. We assessed the
feasibility, acceptability, and efficacy of the group on caregiver distress and
quality of life, as well as patient distress utilizing a sequential cohort design
comparing a pre-intervention control group with the intervention group. Patients
and caregiver dyads completed measures at 4 time points: within 1 week of
diagnosis (T1), 2-week follow-up (T2), 6-week follow-up (T3), and 12-week follow
up (T4). Significant interaction effects were observed for both caregiver
distress and quality of life, whereby those receiving the intervention
demonstrated improved quality of life and reduced distress over time. Overall,
results support the acceptability, feasibility, and preliminary efficacy of the
group intervention.
PMID- 25587748
TI - Simultaneous utilization of cellobiose, xylose, and acetic acid from
lignocellulosic biomass for biofuel production by an engineered yeast platform.
AB - The inability of fermenting microorganisms to use mixed carbon components derived
from lignocellulosic biomass is a major technical barrier that hinders the
development of economically viable cellulosic biofuel production. In this study,
we integrated the fermentation pathways of both hexose and pentose sugars and an
acetic acid reduction pathway into one Saccharomyces cerevisiae strain for the
first time using synthetic biology and metabolic engineering approaches. The
engineered strain coutilized cellobiose, xylose, and acetic acid to produce
ethanol with a substantially higher yield and productivity than the control
strains, and the results showed the unique synergistic effects of pathway
coexpression. The mixed substrate coutilization strategy is important for making
complete and efficient use of cellulosic carbon and will contribute to the
development of consolidated bioprocessing for cellulosic biofuel. The study also
presents an innovative metabolic engineering approach whereby multiple substrate
consumption pathways can be integrated in a synergistic way for enhanced
bioconversion.
PMID- 25587749
TI - Designing micellar nanocarriers with improved drug loading and stability based on
solubility parameter.
AB - The objective of this study is to demonstrate the feasibility of using solubility
parameter as guidance for the design and identification of a stable micellar
system with a high drug loading capacity for oral drug delivery. Using
hydroxycamptothecin (HCPT) as a model drug, the effect of three hydrophobic
blocks (fatty glycerides) grafted onto chitosan on the drug loading and stability
of HCPT-loaded micellar nanoparticles formed by pH precipitation method were
studied systematically. The Flory-Huggins interaction parameter (chiFH)
calculated by the group contribution method (GCM) and molecular dynamics
simulation (MDS) was used to assess the compatibility between HCPT and the
copolymers. The predicted order of compatibility between three chitosan
derivatives and HCPT was verified experimentally. A high drug loading and
remarkably stable micellar system for oral administration based on succinylated
glycerol monooleate-chitosan was discovered in this study. Our study suggests
that the miscibility between drug and copolymer is crucial to drug loading and
stability of the micellar system. Thus, the calculation of chiFH using GCM and
MDS methods is useful for guiding the design or screening of a suitable copolymer
for preparing drug-loaded micellar nanocarrier systems.
PMID- 25587750
TI - Chemical bath deposition of ZnO on functionalized self-assembled monolayers:
selective deposition and control of deposit morphology.
AB - We have developed a method by which to selectively and reproducibly deposit ZnO
films on functionalized self-assembled monolayers (SAMs) using chemical bath
deposition (CBD). The deposition bath is composed of zinc acetate and
ethylenediamine. The deposition reaction pathways are shown to be similar to
those observed for sulfides and selenides, even though ethylenediamine acts as
both an oxygen source and a complexing agent. On -COOH terminated SAMs, Zn
carboxylate surface complexes act as nucleation sites for ion-by-ion growth,
leading to the formation of adherent ZnO nanocrystallites. Cluster-by-cluster
growth is also observed, which produces weakly adherent micrometer-sized ZnO
crystallites. On -CH3 and -OH terminated SAMs, only micrometer-sized ZnO
crystallites are observed because Zn(2+) does not complex with the SAM terminal
group, preventing nucleation of the nanocrystalline phase. The application of
either ultrasound ("sonication-assisted CBD") or stirring promotes ion-by-ion ZnO
growth on -COOH terminated SAMs. Stirring produces smoother but less reproducible
ZnO films than sonication-assisted CBD.
PMID- 25587751
TI - TRIM proteins regulate autophagy: TRIM5 is a selective autophagy receptor
mediating HIV-1 restriction.
AB - The tripartite motif protein family (TRIM) constitutes a class of immune
regulated proteins with antiviral, immune, cancer, and other properties
reminiscent of those ascribed to autophagy. We show that TRIMs have dual roles in
autophagy: as regulators and as cargo receptors. As regulators, TRIMs nucleate
the core autophagy machinery by acting as platforms that assemble ULK1 and BECN1
into a functional complex in preparation for autophagy. TRIMs also act as novel
selective autophagy receptors as exemplified by TRIM5/TRIM5alpha, a known HIV-1
restriction factor with a hitherto poorly defined mode of action. TRIM5
recognizes and targets HIV-1 for autophagic destruction. TRIM5 interactions with
mammalian Atg8 proteins are required for this effector function. This establishes
TRIM family members as regulators of autophagy, explains the antiretroviral
mechanism of TRIM5, and defines a new basis for selective autophagy.
PMID- 25587752
TI - Ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand for dye
sensitized solar cells: synthesis, photo- and electrochemical properties, and
adsorption behavior to the TiO2 surface.
AB - Two novel ruthenium sensitizers with a hexylthiophene-modified terpyridine ligand
(TUS-35 and TUS-36) were synthesized to improve the molar absorptivity of the
previously reported ruthenium sensitizer (TBA)[Ru{4'-(3,4-dicarboxyphenyl)-4,4"
dicarboxyterpyridine}(NCS)3], TBA = tetrabutylammonium (TUS-21). A relatively
strong absorption appeared at ~380 nm, and the molar absorption coefficient at
the metal-to-ligand charge transfer (MLCT) band decreased in TUS-35 by
introducing a 2-hexylthiophene unit to the 5-position of the terpyridine-derived
ligand. For comparison, a relatively strong absorption was observed at ~350 nm
without decreasing the molar absorption coefficient at the MLCT band in TUS-36 by
introducing a 2-hexylthiophene unit to the 4-position of the terpyridine-derived
ligand. On the other hand, the energy levels of the highest occupied molecular
orbitals and the lowest unoccupied molecular orbitals of these two sensitizers
were found to be almost equal to those of TUS-21. The adsorption behavior of TUS
35 and TUS-36 was similar to that of (TBA)[Ru{4'-(3,4
dicarboxyphenyl)terpyridine}(NCS)3] (TUS-20), which binds to the TiO2 surface by
using the 3,4-dicarboxyphenly unit, rather than that of TUS-21, which adsorbs to
the TiO2 photoelectrode using one of the carboxyl groups at the terminal
pyridines of the terpyridine-derived ligand. Therefore, TUS-35 and TUS-36 are
considered to bind to the TiO2 surface by using the 3,4-dicarboxyphenly unit just
like TUS-20. The dye-sensitized solar cells (DSCs) with TUS-35 and TUS-36 showed
a relatively lower conversion efficiency (6.4% and 5.7%, respectively) compared
to the DSC with TUS-21 (10.2%). Open-circuit photovoltage decay and
electrochemical impedance spectroscopy measurements revealed that the promoted
charge recombination and/or charge transfer of the injected electrons in the TiO2
photoelectrode is a main reason for the inferior performances of TUS-35 and TUS
36.
PMID- 25587753
TI - Low-temperature NMR characterization of reaction of sodium pyruvate with hydrogen
peroxide.
AB - It was proposed that the reaction of sodium pyruvate and H2O2 generates the
intermediate 2-hydroperoxy-2-hydroxypropanoate, which converts into acetate, CO2,
and H2O ( Aleksankin et al. Kernenergie 1962 , 5 , 362 - 365 ). These conclusions
were based on the products generated in (18)O-enriched water and H2O2 reacting
with pyruvic acid at room temperature; however, the lifetime of 2-hydroperoxy-2
hydroxypropanoate at room temperature is too short for direct spectroscopic
observation. Therefore, we applied the combination of low-temperature and (13)C
NMR techniques to verify, for the first time, the formation of 2-deuteroperoxy-2
deuteroxypropanoate in mixtures of D2O and methanol-d4 and to monitor directly
each species involved in the reaction between D2O2 and (13)C-enriched pyruvate.
Our NMR results confirm the formation of 2-deuteroperoxy-2-deuteroxypropanoate,
where the respective chemical shifts are supported by density functional theory
(DFT) calculations. At near-neutral apparent pD (pD*) and -35 degrees C, the
formation of 2-deuteroperoxy-2-deuteroxypropanoate occurred with k = 2.43 * 10(
3) dm(3).mol(-1).s(-1). The subsequent decomposition of 2-deuteroperoxy-2
deuteroxypropanoate into acetate, CO2, and D2O occurred with k = 2.58 * 10(-4) s(
1) at -35 degrees C. In order to provide a full kinetic analysis, we also
monitored the equilibrium of pyruvate and methanol with the hemiacetal (2
deuteroxy-2-methoxypropanoate). The kinetics for the reaction of sodium pyruvate
and D2O2 were fitted by taking into account all these equilibria and species.
PMID- 25587754
TI - Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein
kinase R-like endoplasmic reticulum kinase (PERK).
AB - The structure-based design and optimization of a novel series of selective PERK
inhibitors are described resulting in the identification of 44 as a potent,
highly selective, and orally active tool compound suitable for PERK pathway
biology exploration both in vitro and in vivo.
PMID- 25587756
TI - Help your institution's reputation and publish in Analytical Chemistry.
PMID- 25587755
TI - Bronchodilating drugs for chronic obstructive pulmonary disease: current status
and future trends.
AB - Inhaled bronchodilators, including long-acting muscarinic receptor antagonists
(LAMA) and long-acting beta2-adrenoreceptor agonists (LABA), are the mainstay of
pharmacological treatment of stable chronic obstructive pulmonary disease (COPD).
Among approved LAMA, tiotropium bromide, glycopyrronium bromide, and umeclidinium
bromide are administered once daily, whereas aclidinium bromide is administered
every 12 h. New LAMA are under development for COPD. Among the approved LABA,
indacaterol has a 24 h duration of action, whereas salmeterol and formoterol
require twice-daily administration. New once-daily LABA, including vilanterol,
olodaterol, milveterol, carmoterol, and abediterol, are in development. LAMA/LABA
fixed dose combinations (FDCs) provide the convenience of two bronchodilators
with different mechanism of action in a single inhaler.
Indacaterol/glycopyrronium, umeclidinium/vilanterol, and olodaterol/tiotropium
FDCs have been approved or are under approval and are likely to become a standard
pharmacological strategy for COPD. Inhaled dual-pharmacology compounds, combining
muscarinic antagonism and beta2-agonism (MABA) in a single molecule, potentially
provide additive or synergistic bronchodilation over either inhaled
antimuscarinic or beta2-agonist monotherapy.
PMID- 25587757
TI - Clinical application of a custom AmpliSeq library and ion torrent PGM sequencing
to comprehensive mutation screening for deafness genes.
AB - BACKGROUND: Congenital hearing loss is one of the most common sensory disorders,
with 50-70% of cases attributable to genetic causes. Although recent advances in
the identification of deafness genes have resulted in more accurate molecular
diagnosis, leading to the better determination of suitable clinical
interventions, difficulties remain with regard to clinical applications due to
the extreme genetic heterogeneity of deafness. AIM: Toward more effective genetic
testing, we adopted Massively Parallel DNA Sequencing (MPS) of target genes using
an Ion PGMTM system and an Ion AmpliSeqTM panel to diagnose common mutations
responsible for deafness and discover rare causative gene mutations. Before its
clinical application, we investigated the accuracy of MPS-based genetic testing.
RESULTS: We compared the results of Invader assay-based genetic screening, the
accuracy of which has already been verified in previous studies, with those of
MPS-based genetic testing for a large population of Japanese deafness patients
and revealed that over 99.98% of the results were the same for each genetic
testing system. CONCLUSION: The Ion Personal Genome Machine system had sufficient
uniformity and accuracy for application to the clinical diagnosis of common
causative mutations and efficiently identified rare causative mutations and/or
mutation candidates.
PMID- 25587758
TI - Cardiovascular risk and metabolic syndrome in obese youth enrolled in a
multidisciplinary medical weight management program: implications of
musculoskeletal pain, cardiorespiratory fitness, and health-related quality of
life.
AB - BACKGROUND: Obese youth demonstrate the same obesity-associated morbidities
observed in obese adults, including poor cardiorespiratory fitness, poor quality
of life, and reports of musculoskeletal pain. The purposes of this study were to
compare the prevalence of cardiovascular risk factors and evaluate the odds of
metabolic syndrome in obese youth based on measures of cardiorespiratory fitness,
quality of life, and pain. METHODS: A medical chart review of 183 obese youth in
a medical weight management program was conducted. Measures of cardiovascular
risk and metabolic syndrome were recorded. Groups were categorized based on
Progressive Aerobic Cardiovascular Endurance Run (PACER) score, Pediatric Quality
of Life (PedsQL)-Physical Function score, PedsQL-Psychosocial Health score, and
reports of musculoskeletal pain. Statistical analysis included independent t
tests, Mann-Whitney U-test, chi-squared test, and logistic regression. RESULTS:
Thirty-three percent of the entire sample had C-reactive protein (CRP) levels
>3.0 mg/dL and 30% were categorized as having metabolic syndrome. Patients with
lower PACER scores demonstrated a greater prevalence of CRP levels >3.0 mg/dL
versus those with higher PACER scores (45% vs. 12%; P=0.01). There were no other
differences in the prevalence of cardiovascular risk factors or metabolic
syndrome when categorized by PACER, PedsQL, or pain. Those with CRP levels >3.0
mg/dL demonstrated increased odds of metabolic syndrome-[odds (95% confidence
interval, CI): 4.93 (1.24-19.61); P=0.02]. CONCLUSIONS: Overall, results do not
show differences in cardiovascular risk in obese youth when categorized by PACER,
PedsQL, or reports of MSK pain. Elevated CRP may be a useful predictor of
metabolic syndrome in obese youth and warrants further investigation.
PMID- 25587771
TI - Dopamine-melanin nanofilms for biomimetic structural coloration.
AB - This article describes the formation of dopamine-melanin thin films (50-200 nm
thick) at an air/dopamine solution interface under static conditions. Beneath
these films, spherical melanin granules formed in bulk liquid phase. The
thickness of dopamine-melanin films at the interface relied mainly on the
concentration of dopamine solution and the reaction time. A plausible mechanism
underlining dopamine-melanin thin film formation was proposed based on the
hydrophobicity of dopamine-melanin aggregates and the mass transport of the
aggregates to the air/solution interface as a result of convective flow. The
thickness of the interfacial films increased linearly with the dopamine
concentration and the reaction time. The dopamine-melanin thin film and granules
(formed in bulk liquid phase) with a double-layered structure were transferred
onto a solid substrate to mimic the (keratin layer)/(melanin granules) structure
present in bird plumage, thereby preparing full dopamine-melanin thin-film
reflectors. The reflected color of the thin-film reflectors depended on the film
thickness, which could be adjusted according to the dopamine concentration. The
reflectance of the resulted reflectors exhibited a maximal reflectance value of 8
11%, comparable to that of bird plumage (~11%). This study provides a useful,
simple, and low-cost approach to the fabrication of biomimetic thin-film
reflectors using full dopamine-melanin materials.
PMID- 25587772
TI - Intramolecular cycloadditions of photogenerated azaxylylenes with oxadiazoles
provide direct access to versatile polyheterocyclic ketopiperazines containing a
spiro-oxirane moiety.
AB - Photogenerated azaxylylenes undergo intramolecular cycloadditions to 1,3,4
oxadiazole pendants, which are accompanied by concomitant release of dinitrogen,
yielding functionalized ketopiperazinoquinolinols containing an oxirane moiety
fused to the quinolinole moiety while spiro-connected to diketopiperazine. These
primary photoproducts are reactive versatile intermediates which can be further
derivatized under nucleophilic SN1- or SN2-like ring opening of the oxirane
moiety. The oxidized quinolinones undergo new rearrangements under the conditions
of the Schmidt reaction, leading to unprecedented triazacanoindolinones.
PMID- 25587774
TI - Sequencing analysis and characterization of the plasmid pBIF10 isolated from
Bifidobacterium longum.
AB - A resident plasmid, pBIF10, was isolated from Bifidobacterium longum B200304, and
the full-length sequence of pBIF10 was analyzed. In this sequence, we identified
at least 17 major open reading frames longer than 200 bp. A tetracycline
resistance gene, tetQ, was identified and verified to confer antibiotic
resistance to tetracycline. The plasmid replicon with replication protein B gene
(repB) and a typical iteron was identified in pBIF10. An artificial clone vector
was constructed with the replicon of pBIF10; the results showed that repB
controlled plasmid replication in other bifidobacteria host cells at low
transformation frequency. Taken together, the analysis and characterization of
pBIF10 provided necessary information for the understanding of antibiotic
resistance mediated by a plasmid in a Bifidobacterium strain. GC% and repB
sequence analyses indicated that pBIF10 was a molecular hybrid of at least 2
other bacterial genera plasmids.
PMID- 25587775
TI - A review of gene therapy in canine and feline models of lysosomal storage
disorders.
AB - Lysosomal storage disorders (LSDs) are inherited diseases that result from the
intracellular accumulation of incompletely degraded macromolecules. The majority
of LSDs affect both the peripheral and central nervous systems and are not
effectively treated by enzyme replacement therapy, substrate reduction therapy,
or bone marrow transplantation. Advances in adeno-associated virus and retroviral
vector development over the past decade have resurged gene therapy as a promising
therapeutic intervention for these monogenic diseases. Animal models of LSDs
provide a necessary intermediate to optimize gene therapy protocols and assess
the safety and efficacy of treatment prior to initiating human clinical trials.
Numerous LSDs are naturally occurring in large animal models and closely
reiterate the lesions, biochemical defect, and clinical phenotype observed in
human patients, and whose lifetime is sufficiently long to assess the effect on
symptoms that develop later in life. Herein, we review that gene therapy in large
animal models (dogs and cats) of LSDs improved many manifestations of disease,
and may be used in patients in the near future.
PMID- 25587773
TI - Blood diagnostic biomarkers for major depressive disorder using multiplex DNA
methylation profiles: discovery and validation.
AB - Aberrant DNA methylation in the blood of patients with major depressive disorder
(MDD) has been reported in several previous studies. However, no comprehensive
studies using medication-free subjects with MDD have been conducted. Furthermore,
the majority of these previous studies has been limited to the analysis of the
CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the
present study is to identify DNA methylation markers that distinguish patients
with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of
peripheral leukocytes was conducted in two set of samples, a discovery set (20
medication-free patients with MDD and 19 controls) and a replication set (12
medication-free patients with MDD and 12 controls), using Infinium
HumanMethylation450 BeadChips. Significant diagnostic differences in DNA
methylation were observed at 363 CpG sites in the discovery set. All of these
loci demonstrated lower DNA methylation in patients with MDD than in the
controls, and most of them (85.7%) were located in the CGIs in the gene promoter
regions. We were able to distinguish patients with MDD from the control subjects
with high accuracy in the discriminant analysis using the top DNA methylation
markers. We also validated these selected DNA methylation markers in the
replication set. Our results indicate that multiplex DNA methylation markers may
be useful for distinguishing patients with MDD from non-psychiatric controls.
PMID- 25587776
TI - Metabolism of (14)C-labeled polychlorinated biphenyl congeners by wheat cell
suspension cultures.
AB - The metabolism of [UL-(14)C]-2,2',5,5'-tetrachlorobiphenyl ((14)C-PCB-52), [UL
(14)C]-2,2',4,4',5,5'-hexachlorobiphenyl ((14)C-PCB-153, and a congeneric mixture
of [UL-(14)C]-labeled polychlorinated biphenyls ((14)C-PCB-Mix) was studied in
cell suspension cultures of wheat (Triticum aestivum L. cv. 'Heines Koga II').
About 50% of applied (14)C-PCB-52 (20 MUg/assay) was transformed during 96 h of
incubation. While 7.6% on non-extractable residues emerged, turnover of (14)C-PCB
52 was mainly due to soluble polar metabolites. These were subjected to chemical
glycoside cleavage. In the resulting hydrolysate, four aglycons were identified
by GC-EIMS, namely four tetrachloro-hydroxy-biphenyl isomers (C6H6Cl4O, M(+.) at
m/z = 306, 308, 310 and 312), and one trichloro-hydroxy-biphenyl (C6H7Cl3O, M(+.)
at m/z = 272, 274 and 276). Number and character of hydroxylated products pointed
to cytochromes P450 as enzymatic catalysts of hydroxylation. (14)C-PCB-153 was
metabolized by wheat to minor degree if at all. Due to GC-EIMS analysis, of (14)C
PCB-Mix consisted of biphenyl, one mono-, four di-, seven tri-, eleven tetra-,
and four pentachlorobiphenyls besides traces of further mono- and
hexachlorobiphenyls. Among these were PCB-28, PCB-52, PCB 101, and PCB-118
(identified by seven key congeners standard). The mixture resembled industrial
products Clophen A30 or Aroclor 1016. Metabolic turnover of applied (14)C-PCB-Mix
(15 MUg/assay) was 30% after 96 h; 8.4% of non-extractable residues emerged.
Using DDE (p,p'-dichlorodiphenyl-dichloroethylene) as internal standard it was
demonstrated that biphenyl, one monochloro-, two dichloro-, and one
trichlorobiphenyl were completely metabolized to polar products. Partial
metabolization occurred with one di-, five tri-, and four tetrachlorobiphenyls.
Two tri-, four tetra-, and all pentachlorbiphenyls proved to be stable. Due to
strong interference by matrix, evaluation of three congeners was not possible. In
addition to wheat, results of similar experiments with cell cultures of other
species are briefly mentioned.
PMID- 25587777
TI - Biodegradation of endosulfan isomers and its metabolite endosulfate by two
biosurfactant producing bacterial strains of Bordetella petrii.
AB - The main objective of the investigation was to study the biodegradation of
endosulfan isomers and its major metabolite endosulfate by two biosurfactant
producing bacterial strains of Bordetella petrii. The significance of the study
is to evaluate the capability of biosurfactant producing bacterial strains in
enhancing the bioavailability of endosulfan. Sixty bacterial strains were
isolated from the endosulfan degrading bacterial consortium and were screened for
endosulfan degradation and biosurfactant production. Among those, two strains
Bordetella petrii I GV 34 (Gene bank Accession No KJ02262) and Bordetella petrii
II GV 36 (Gene bank Accession No KJ022625) were capable of degrading endosulfan
with simultaneous biosurfactant production. Bordetella petrii I degraded 89% of
alpha and 84% of beta isomers of endosulfan whereas Bordetella petrii II degraded
82% of both the isomers. Both the strains were able to reduce the surface tension
up to 19.6% and 21.4% with a minimum observed surface tension of 45 Dynes/cm and
44 Dynes/cm, respectively. The study revealed that the strains have the potential
to enhance the degradation endosulfan residues in contaminated sites and water by
biosurfactant production.
PMID- 25587778
TI - Kresoxim methyl dissipation kinetics and its residue effect on soil extra
cellular and intra-cellular enzymatic activity in four different soils of India.
AB - The rate of degradation of kresoxim methyl and its effect on soil extra-cellular
(acid phosphatase, alkaline phosphatase and beta-glucosidase) and intra-cellular
(dehydrogenase) enzymes were explored in four different soils of India. In all
the tested soils, the degradation rate was faster at the beginning, which slowed
down with time indicating a non-linear pattern of degradation. Rate of
degradation in black soil was fastest followed by saline, brown and red soils,
respectively and followed 1st or 1st + 1st order kinetics with half-life ranging
between 1-6 days for natural soil and 1-19 days for sterile soils. The rate of
degradation in natural against sterilized soils suggests that microbial
degradation might be the major pathway of residue dissipation. Although small
changes in enzyme activities were observed, kresoxim methyl did not have any
significant deleterious effect on the enzymatic activity of the various test
soils in long run. Simple correlation studies between degradation percentage and
individual enzyme activities did not establish any significant relationships. The
pattern and change of enzyme activity was primarily due to the effect of the
incubation period rather than the effect of kresoxim methyl itself.
PMID- 25587779
TI - Evaluation of hydrocarbons and organochlorine pesticides and their tolerant
microorganisms from an agricultural soil to define its bioremediation
feasibility.
AB - The concentrations of hydrocarbons and organochlorine pesticides (OCPs),
nutrients and tolerant microorganisms in an agricultural soil from a locality in
Tepeaca, Puebla, Mexico, were determined to define its feasibility for
bioremediation. The OCPs detected were heptachlor, aldrin, trans-chlordane,
endosulfan I, endosulfan II, 1,1,1-bis-(4-chlorophenyl)-2,2-trichloroethane (4,4'
DDT), 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (4,4'-DDE) and endrin aldehyde,
with values of 0.69-30.81 ng g(-1). The concentration of hydrocarbons in the soil
of Middle Hydrocarbons Fraction (MHF), C10 to C28, was 4608-27,748 mg kg(-1) and
1117-19,610 mg kg(-1) for Heavy Hydrocarbons Fraction (HHF), C28 to C35, due to
an oil spill from the rupture of a pipeline. The soil was deficient in nitrogen
(0.03-0.07%) and phosphorus (0 ppm), and therefore it was advisable to fertilize
to bio-stimulate the native microorganisms of soil. In the soil samples,
hydrocarbonoclast fungi 3.72 * 10(2) to 44.6 * 10(2) CFU g(-1) d.s. and
hydrocarbonoclast bacteria (0.17 * 10(5) to 8.60 * 10(5) CFU g(-1) d.s.) were
detected, with a tolerance of 30,000 mg kg(-1) of diesel. Moreover,
pesticideclast fungi (5.13 * 10(2) to 42.2 * 10(2) CFU g(-1) d.s.) and
pesticideclast bacteria (0.15 * 10(5) to 9.68 * 10(5) CFU g(-1) d.s.) were
determined with tolerance to 20 mg kg(-1) of OCPs. Fungi and bacteria tolerant to
both pollutants were also quantified. Therefore, native microorganisms had
potential to be stimulated to degrade hydrocarbons and pesticides or both
pollutants. The concentration of pollutants and the microbial activity analyzed
indicated that bioremediation of the soil contaminated with hydrocarbons and
pesticides using bio-stimulation of native microorganisms was feasible.
PMID- 25587780
TI - Determination of pesticide residues in animal origin baby foods by gas
chromatography coupled with triple quadrupole mass spectrometry.
AB - A simple, fast and multiresidue method for the determination of pesticide
residues in baby foods of animal origin has been developed in order to check the
compliance with the Maximum Residue Levels (MRLs) set at a general value of 0.01
mg/kg by Commission Directive 2006/125/EC for infant foods. The main classes of
organochlorine, organophosphorus and pyrethroid compounds have been considered,
which are mainly fat soluble pesticides. The analytical procedure consists in the
extraction of baby food samples by acetonitrile (ACN) followed by a clean up
using C18 solid-phase extraction column eluted with ACN. The compounds were
determined by gas chromatography-triple quadrupole mass spectrometry equipped
with a Programmed Temperature Vaporizer (PTV) injection and a backflush system.
In order to compensate for matrix effects PTV and matrix matched standard
calibrations have been used. The method has been fully validated for 57
pesticides according to the Document SANCO/12571/2013. Accuracy and precision
(repeatability) have been studied by recoveries at two spiking levels, the Limit
of Quantitation (LOQ) (0.003-0.008 mg/kg) and 10 time greater (0.03-0.08 mg/kg),
and the results were in the acceptable range of 70-120% with Relative Standards
Deviations (RSD) <=20%. Selectivity, linearity, LOQ and uncertainty of
measurement were also determined for all the compounds. The method has been also
applied for the analysis of 18 baby food animal origin samples, bought form the
local market in Rome (Italy), and no pesticide in the scope of the method has
been found above the MRL or the LOQ.
PMID- 25587781
TI - Urinary phytoestrogens in relation to metabolic disturbances among children and
adolescents.
AB - Previous studies have examined whether phytoestrogens affect glucose and lipid
metabolism. However, data on children and adolescents are still limited, with
most of the evidence pertaining to one phytoestrogen, namely genistein. To
investigate the effect of six phytoestrogens [daidezin, enterodiol,
enterolactone, equol, genistein and O-Desmethylangolensin (O-DMA)] on metabolic
disturbances among youths, a cross-sectional study was conducted using a sample
of 2,429 children and adolescents, 6-18 years, from the 2009-2010 National Health
and Nutrition Examination Surveys (NHANES). The main outcome measures were body
mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP),
high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and total
cholesterol (TC), fasting glucose, triglycerides and glycohemoglobin. SBP was
inversely related to enterolactone and equol. Triglycerides were inversely
related to daidezin, equol, genistein and O-DMA. Whereas TC and LDL-C were
inversely related to equol, an HDL-C was inversely related to genistein and O
DMA. Whereas fasting glucose was associated with enterodiol (beta = 0.33, 95% CI:
0.028, 0.63), a positive relationship was observed between enterodiol and risk of
HDL-C >= 35 mg dl(-1) (beta = 0.04, 95% CI: 0.01, 0.07). In conclusion, certain
phytoestrogens may contribute either positively or negatively to disturbances in
lipid and glucose metabolism. Large prospective cohort studies are needed to
confirm our study findings.
PMID- 25587782
TI - Assessment of T-2 toxin effect and its metabolite HT-2 toxin combined with
insulin-like growth factor I, leptin and ghrelin on progesterone secretion by
rabbit ovarian fragments.
AB - Assessment of A-trichothecene mycotoxins (T-2 and HT-2 toxins) effect combined
with growth factor IGF-I, and the metabolic hormones leptin and ghrelin on
progesterone secretion by rabbit ovarian fragments was studied. Rabbit ovarian
fragments were incubated without (control group) or with T-2/HT-2 toxin, or their
combinations with insulin-like growth factor I (IGF-I), leptin or ghrelin at
various concentrations for 24 h. Secretion of progesterone was determined by
ELISA. First, T-2 toxin and HT-2 toxins at all doses used (0.01, 0.1, 1, 10, and
100 ng mL(-1)) were not shown to be potential regulators of progesterone
secretion in rabbit ovarian fragments. Second, T-2 toxin but not HT-2 toxin
combined with IGF-I was shown to be potential regulator of progesterone secretion
in rabbit ovarian fragments. T-2 toxin at all doses used (0.01; 0.1; 1; 10; and
100 ng mL(-1)) combined with IGF-I (at dose 100 ng mL(-1)) significantly (P <
0.05) decreased progesterone secretion by rabbit ovarian fragments. Third, T-2
toxin and HT-2 toxin at all doses used in the study (0.01, 0.1, 1, 10, and 100 ng
mL(-1)) combined with leptin (at dose 1000 ng mL(-1)) were not shown to be
potential regulators of progesterone secretion in rabbit ovarian fragments.
Furthermore, T-2 toxin and HT-2 toxin at all doses used in the study (0.01, 0.1,
1, 10, and 100 ng mL(-1)) combined with ghrelin (500 ng mL(-1)) were not shown to
be potential regulators of progesterone secretion in rabbit ovarian fragments.
Results in this study showed that trichothecene as T-2 toxin combined with IGF-I
but not HT-2 toxin was able to decrease progesterone secretion in rabbit ovarian
fragments in vitro. Experimental results of T-2 and HT-2 toxins combined with
leptin and ghrelin did not confirm ability to modulate progesterone secretion by
ovarian fragments in rabbits.
PMID- 25587783
TI - An assessment of Salmonella survival in pig manure and its separated solid and
liquid fractions during storage.
AB - The objective of this study was to examine Salmonella survival in pig manure and
its separated fractions during storage. Salmonella declined, but significant
reductions were not observed in the manure and liquid until day 56, whereas
counts in the solids were lower by day 7. The Salmonella inoculum initially
impacted counts but not after days 28-56. By day 112 Salmonella was undetectable
in the manure and liquid but was recovered from the solids. There was no clear
dominance of particular serotypes and antibiotic resistance transfer was not
found. Storage duration and pH impacted Salmonella counts in all samples, with
duration having the greatest effect. Of the nutrients, nitrate had the greatest
impact in the manure and, together with phosphate, it also affected counts in the
liquid fraction. This study demonstrates that if pig manure or its separated
fractions are stored under controlled conditions at 10.5 degrees C for 84-112
days Salmonella is reduced or eliminated, irrespective of the initial load.
PMID- 25587784
TI - Listeria monocytogenes batch culture growth response to metabolic inhibitors.
AB - In certain environments nutrient and energy sources available to microorganisms
can be limited. Foodborne pathogens must efficiently adapt in order to be
successfully transmitted through the food chain to their hosts. For the
intracellular foodborne pathogen Listeria monocytogenes, little is known
regarding its response to nutrient/energy-limiting conditions. The alternative
stress responsive sigma factor sigma(B) has been reported to contribute to
survival under specific stresses. Therefore, the effects of several metabolic
inhibitors on growth of L. monocytogenes wild-type and a DeltasigB mutant were
examined. In the absence of inhibitors, both strains reached stationary phase
after 18 h at 23 degrees C and 10 h at 37 degrees C. All of the metabolic
inhibitors slowed growth of either strain, with few differences observed among
the different inhibitors.
PMID- 25587785
TI - Synthesis and herbicidal activity of novel 1-(Diethoxy-phosphoryl)-3-(4-one-1H
1,2,3-triazol-1-yl)-propan-2-yl carboxylic esters.
AB - A series of novel compounds, namely 1-(diethoxyphosphoryl)-3-(4-ones-1H-1,2,3
triazol-1-yl)propan-2-yl carboxylic esters, were designed on the basis of the
diazafulvene intermediate of imidazole glycerol phosphate dehydratase (IGPD) and
high-activity inhibitors of IGPD, and synthesized as inhibitors targeting IGPD in
plants. Their structures were confirmed by 1H-NMR, 13C-NMR, 31P-NMR and HR-MS.
The herbicidal evaluation performed by a Petri dish culture method showed that
most compounds possessed moderate to good herbicidal activities. Six compounds
were chosen for further herbicidal evaluation on barnyard grass by pot
experiments. 1-(Diethoxyphosphoryl)-3-(4-phenyl-1H-1,2,3-triazol-1-yl)propan-2-yl
2-(naphthalen-1-yl)acetate (5-A3) and ethyl 1-(2-acetoxy-3
(diethoxyphosphoryl)propyl)-1H-1,2,3-triazole-4-carboxylate (5-B4) showed good
herbicidal activities. Compared with the compounds with the best herbicidal
activity ever reported, both compounds 5-A3 and 5-B4, which can inhibit the
growth of barnyard grass at the concentration of 250g/hm2, efficiently gave rise
to a nearly 4-fold increase of the herbicidal potency. However, their herbicidal
activities were lower than that of acetochlor (62.5 g/hm2) in the pot
experiments.
PMID- 25587786
TI - Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal
and antimycobacterial activity.
AB - Infectious diseases, such as tuberculosis and invasive mycoses, represent serious
health problems. As a part of our long-term efforts to find new agents for the
treatment of these diseases, a new series of pyrazine analogs of chalcones
bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The
structures of the compounds were corroborated by IR and NMR spectroscopy and
their purity confirmed by elemental analysis. The susceptibility of eight fungal
strains to the studied compounds was tested. The results have been compared with
the activity of some previously reported propyl derivatives. The only strain that
was susceptible to the studied compounds was Trichophyton mentagrophytes. It was
found that replacing a non-branched propyl with a branched isopropyl did not have
a decisive and unequivocal influence on the in vitro antifungal activity against
T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes
comparable with that of fluconazole was exhibited by nitro-substituted
derivatives. Unfortunately, no compound exhibited efficacy comparable with that
of terbinafine, which is the most widely used agent for treating mycoses caused
by dermatophytes. Some of the prepared compounds were assayed for
antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was
also displayed by nitro-substituted compounds. The results of the present study
are in a good agreement with our previous findings and confirm the positive
influence of electron-withdrawing groups on the B-ring of chalcones on the
antifungal and antimycobacterial activity of these compounds.
PMID- 25587787
TI - Phenolic content and antioxidant capacity in algal food products.
AB - The study objective was to investigate total phenolic content using Folin
Ciocalteu's method, to assess nine phenols by HPLC, to determine antioxidant
capacity of the water soluble compounds (ACW) by a photochemiluminescence method,
and to calculate the correlation coefficients in commercial algal food products
from brown (Laminaria japonica, Eisenia bicyclis, Hizikia fusiformis, Undaria
pinnatifida) and red (Porphyra tenera, Palmaria palmata) seaweed, green
freshwater algae (Chlorella pyrenoidosa), and cyanobacteria (Spirulina
platensis). HPLC analysis showed that the most abundant phenolic compound was
epicatechin. From spectrophotometry and ACW determination it was evident that
brown seaweed Eisenia bicyclis was the sample with the highest phenolic and ACW
values (193 mg.g-1 GAE; 7.53 umol AA.g-1, respectively). A linear relationship
existed between ACW and phenolic contents (r = 0.99). Some algal products seem to
be promising functional foods rich in polyphenols.
PMID- 25587788
TI - The giant adhesin SiiE of Salmonella enterica.
AB - Salmonella enterica is a Gram-negative, food-borne pathogen, which colonizes the
intestinal tract and invades enterocytes. Invasion of polarized cells depends on
the SPI1-encoded type III secretion system (T3SS) and the SPI4-encoded type I
secretion system (T1SS). The substrate of this T1SS is the non-fimbrial giant
adhesin SiiE. With a size of 595 kDa, SiiE is the largest protein of the
Salmonella proteome and consists of 53 repetitive bacterial immunoglobulin (BIg)
domains, each containing several conserved residues. As known for other T1SS
substrates, such as E. coli HlyA, Ca2+ ions bound by conserved D residues within
the BIg domains stabilize the protein and facilitate secretion. The adhesin SiiE
mediates the first contact to the host cell and thereby positions the SPI1-T3SS
to initiate the translocation of a cocktail of effector proteins. This leads to
actin remodeling, membrane ruffle formation and bacterial internalization. SiiE
binds to host cell apical membranes in a lectin-like manner. GlcNAc and alpha2-3
linked sialic acid-containing structures are ligands of SiiE. Since SiiE shows
repetitive domain architecture, we propose a zipper-like binding mediated by each
individual BIg domain. In this review, we discuss the characteristics of the SPI4
T1SS and the giant adhesin SiiE.
PMID- 25587789
TI - Synthesis of chromonylthiazolidines and their cytotoxicity to human cancer cell
lines.
AB - Nine new chromonylthiazolidine derivatives were successfully semi-synthesized
from paeonol. All of the compounds, including starting materials, the
intermediate compound and products, were evaluated for their cytotoxic effects
toward eight human cancer cell lines. The synthesized chromonylthiazolidines
displayed weak cytotoxic effects against the tested cancer cell lines, but
selective cytotoxic effects were observed. Compounds 3a and 3b showed the most
selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 +/- 3.6
MUg/mL) and breast cancer (IC50 32.8 +/- 1.4 MUg/mL) cell lines, respectively.
The results suggest that chromoylthiazolidines are potential low-cost, and
selective anticancer agents.
PMID- 25587790
TI - Degradation dynamics of glyphosate in different types of citrus orchard soils in
China.
AB - Glyphosate formulations that are used as a broad-spectrum systemic herbicide have
been widely applied in agriculture, causing increasing concerns about residues in
soils. In this study, the degradation dynamics of glyphosate in different types
of citrus orchard soils in China were evaluated under field conditions.
Glyphosate soluble powder and aqueous solution were applied at 3000 and 5040 g
active ingredient/hm2, respectively, in citrus orchard soils, and periodically
drawn soil samples were analyzed by high performance liquid chromatography. The
results showed that the amount of glyphosate and its degradation product
aminomethylphosphonic acid (AMPA) in soils was reduced with the increase of time
after application of glyphosate formulations. Indeed, the amount of glyphosate in
red soil from Hunan and Zhejiang Province, and clay soil from Guangxi Province
varied from 0.13 to 0.91 ug/g at 42 days after application of aqueous solution.
Furthermore, the amount of glyphosate in medium loam from Zhejiang and Guangdong
Province, and brown loam from Guizhou Province varied from less than 0.10 to 0.14
ug/g, while the amount of AMPA varied from less than 0.10 to 0.99 ug/g at 42 days
after application of soluble powder. Overall, these findings demonstrated that
the degradation dynamics of glyphosate aqueous solution and soluble powder as
well as AMPA depend on the physicochemical properties of the applied soils, in
particular soil pH, which should be carefully considered in the application of
glyphosate herbicide.
PMID- 25587792
TI - Interplay of condensation and chelation in binary and ternary Th(IV) systems.
AB - Th(IV) readily undergoes hydrolysis and condensation in aqueous solutions to form
polynuclear molecular species and the system becomes increasingly complicated
when organic chelators or other metals are present in solution, leading to the
formation of complexes with vastly different structural topologies. Five
compounds containing binary and ternary Th(IV) complexes have been synthesized
and structurally characterized using single-crystal X-ray diffraction, including
Na4[Th6O2(C10O7N2H14)6].20.5H2O (Th6hedta), [Th(C9O6NH12)(H2O)(NO3)].1.5H2O
(Th(ntp)), [Th2Al8(OH)14(H2O)12(C6O5NH8)4](NO3)6.17.5H2O (Th2Al8heidi), (C4N2H12)
[Th2Fe2(OH)2(H2O)2(C6O7H4)2(C6O7H5)2].6H2O (Th2Fe2cit), (C4N2H12)
[ThFe2O(H2O)3(C11O9N2H13)2].6H2O (ThFe2dhpta). Additional chemical
characterization by infrared spectroscopy and thermogravimetric analysis provides
information on the chelation by the organic ligands and thermal stability. These
molecular complexes can be utilized to understand aqueous speciation in mixed
metal solutions and also provide information regarding contaminant adsorption on
iron(III) and aluminum(III) oxide surfaces.
PMID- 25587791
TI - R-loops highlight the nucleus in ALS.
AB - Amyotrophic lateral sclerosis (ALS) is a severely debilitating neurodegenerative
disease linked to mutations in various genes implicated in cytoplasmic RNA
metabolism. Recent studies from genetic models have also helped reveal
connections between various ALS-linked factors and RNA-DNA hybrid (R-loop)
regulation. Here, we examine how such hybrid-regulatory processes are pointing to
a key role for the nucleus in ALS. We also present a potential molecular
mechanism in which hybrids may represent at least one of the long sought after
missing links between different ALS genes. Our opinion is that RNA-DNA hybrids
will play a key role in deciphering ALS and other human diseases.
PMID- 25587793
TI - Barriers to health-care and psychological distress among mothers living with HIV
in Quebec (Canada).
AB - Health-care providers play a major role in providing good quality care and in
preventing psychological distress among mothers living with HIV (MLHIV). The
objectives of this study are to explore the impact of health-care services and
satisfaction with care providers on psychological distress in MLHIV. One hundred
MLHIV were recruited from community and clinical settings in the province of
Quebec (Canada). Prevalence estimation of clinical psychological distress and
univariate and multivariable logistic regression models were performed to predict
clinical psychological distress. Forty-five percent of the participants reported
clinical psychological distress. In the multivariable regression, the following
variables were significantly associated with psychological distress while
controlling for sociodemographic variables: resilience, quality of communication
with the care providers, resources, and HIV disclosure concerns. The multivariate
results support the key role of personal, structural, and medical resources in
understanding psychological distress among MLHIV. Interventions that can support
the psychological health of MLHIV are discussed.
PMID- 25587794
TI - Psychological Stress and Immunological Modulations in Early-stage Melanoma
Patients.
AB - Mental stress may have a negative impact on the immune state of cancer patients,
in whom immunologic surveillance is essential for survival. This study
investigated the immunological response of 19 patients with early-stage melanoma
and a matched control group undergoing the Determination Stress Test before
surgery. Cytokine and chemokine levels and lymphocyte subpopulations were
measured at baseline and post-stress test time-points. Following the stress test
lower levels of interleukin (IL)-6 were observed in the melanoma group compared
with healthy volunteers (p = 0.044). IL-10 increased significantly in the control
group 30 min after the stress test (p = 0.002) in comparison with the melanoma
group (p = 0.407). CCL5/Rantes decreased significantly in the melanoma group,
whereas CD16/CD56+ natural killer cells increased in both groups, with a sharp
decrease below baseline after stress in the melanoma group (p = 0.001). This
pilot study shows an altered immunological response to stressors in melanoma
patients.
PMID- 25587795
TI - How likely is another nonmelanoma skin cancer?: better informing patients and
clinicians.
PMID- 25587797
TI - Overcoming the distance barrier in relation to treatment for haematology
patients: Queensland findings.
AB - OBJECTIVE: The aim of the present study was to document the financial and
psychosocial impact of relocation for specialist haematology treatment in
Queensland. METHODS: This study was a qualitative exploratory study comprising 45
in-depth interviews with haematology patients supported by the Leukaemia
Foundation of Queensland. RESULTS: The findings indicate that decentralisation of
treatment is assisting haematology patients to overcome the profound difficulties
associated with travelling to the metropolitan area for treatment. CONCLUSION:
Fostering specialist outreach and building capacity in regional cancer centres
are service delivery strategies that are greatly appreciated by regional, rural
and remote haematology patients who are stressed by the many challenges
associated with leaving home to travel distances for specialist treatment. It is
the hope and expectation that these findings will make a contribution to
informing future health policy and service delivery planning.
PMID- 25587796
TI - Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria
Syndrome fibroblasts are comparable to normal middle-age and old-age cells.
AB - For the past several decades, research in understanding the molecular basis of
human aging has progressed significantly with the analysis of premature aging
syndromes. Progerin, an altered form of lamin A, has been identified as the cause
of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a
contributing causative factor in normal aging. However, the question of whether
HGPS actually recapitulates the normal aging process at the cellular and
organismal level, or simply mimics the aging phenotype is widely debated. In the
present study we analyzed publicly available microarray datasets for fibroblasts
undergoing cellular aging in culture, as well as fibroblasts derived from young,
middle-age, and old-age individuals, and patients with HGPS. Using GeroScope
pathway analysis and drug discovery platform we analyzed the activation states of
65 major cellular signaling pathways. Our analysis reveals that signaling pathway
activation states in cells derived from chronologically young patients with HGPS
strongly resemble cells taken from normal middle-aged and old individuals. This
clearly indicates that HGPS may truly represent accelerated aging, rather than
being just a simulacrum. Our data also points to potential pathways that could be
targeted to develop drugs and drug combinations for both HGPS and normal aging.
PMID- 25587801
TI - CEUS.
PMID- 25587800
TI - A novel in vivo approach to assess radial and axial distensibility of large and
intermediate pulmonary artery branches.
AB - Pulmonary arteries (PAs) distend to accommodate increases in cardiac output. PA
distensibility protects the right ventricle (RV) from excessive increases in
pressure. Loss of PA distensibility plays a critical role in the fatal
progression of pulmonary arterial hypertension (PAH) toward RV failure. However,
it is unclear how PA distensibility is distributed across the generations of PA
branches, mainly because of the lack of appropriate in vivo methods to measure
distensibility of vessels other than the large, conduit PAs. In this study, we
propose a novel approach to assess the distensibility of individual PA branches.
The metric of PA distensibility we used is the slope of the stretch ratio
pressure relationship. To measure distensibility, we combined invasive
measurements of mean PA pressure with angiographic imaging of the PA network of
six healthy female dogs. Stacks of 2D images of the PAs, obtained from either
contrast enhanced magnetic resonance angiography (CE-MRA) or computed tomography
digital subtraction angiography (CT-DSA), were used to reconstruct 3D surface
models of the PA network, from the first bifurcation down to the sixth generation
of branches. For each branch of the PA, we calculated radial and longitudinal
stretch between baseline and a pressurized state obtained via acute embolization
of the pulmonary vasculature. Our results indicated that large and intermediate
PA branches have a radial distensibility consistently close to 2%/mmHg. Our axial
distensibility data, albeit affected by larger variability, suggested that the
PAs distal to the first generation may not significantly elongate in vivo,
presumably due to spatial constraints. Results from both angiographic techniques
were comparable to data from established phase-contrast (PC) magnetic resonance
imaging (MRI) and ex vivo mechanical tests, which can only be used in the first
branch generation. Our novel method can be used to characterize PA distensibility
in PAH patients undergoing clinical right heart catheterization (RHC) in
combination with MRI.
PMID- 25587799
TI - Spontaneous Gamma Activity in Schizophrenia.
AB - IMPORTANCE: A major goal of translational neuroscience is to identify neural
circuit abnormalities in neuropsychiatric disorders that can be studied in animal
models to facilitate the development of new treatments. Oscillations in the gamma
band (30-100 Hz) of the electroencephalogram have received considerable interest
as the basic mechanisms underlying these oscillations are understood, and gamma
abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on
hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased
spontaneous broadband gamma power, but this phenomenon has not been identified
clearly in patients with SZ. OBJECTIVE: To examine spontaneous gamma power and
its relationship to evoked gamma oscillations in the auditory cortex of patients
with SZ. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study
including 24 patients with chronic SZ and 24 matched healthy control participants
at the Veterans Affairs Boston Healthcare System from January 1, 2009, through
December 31, 2012. Electroencephalograms were obtained during auditory steady
state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a
resting state in 18 participants in each group. MAIN OUTCOMES AND MEASURES:
Electroencephalographic activity in the auditory cortex was estimated using
dipole source localization. Auditory steady-state response (ASSR) measures
included the phase-locking factor and evoked power. Spontaneous gamma power was
measured as induced (non-phase-locked) gamma power in the ASSR data and as total
gamma power in the resting-state data. RESULTS: The ASSR phase-locking factor was
reduced significantly in patients with SZ compared with controls for the 40-Hz
stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012])
but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 =
0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212],
respectively), repeating previous findings. The mean [SD] broadband-induced (30
100 Hz) gamma power was increased in patients with SZ compared with controls
during steady-state stimulation (6.579 [3.783] vs 3.984 [1.843]; F1,46 = 9.128 [P
= .004]; d = 0.87) but not during rest (0.006 [0.003] vs 0.005 [0.002]; F1,34 =
1.067 [P = .309]; d = 0.35). Induced gamma power in the left hemisphere of the
patients with SZ during the 40-Hz stimulation was positively correlated with
auditory hallucination symptoms (tangential, rho = 0.587 [P = .031]; radial, rho
= 0.593 [P = .024]) and negatively correlated with the ASSR phase-locking factor
(baseline: rho = -0.572 [P = .024]; ASSR: rho = -0.568 [P = .032]). CONCLUSIONS
AND RELEVANCE: Spontaneous gamma activity is increased during auditory steady
state stimulation in SZ, reflecting a disruption in the normal balance of
excitation and inhibition. This phenomenon interacts with evoked oscillations,
possibly contributing to the gamma ASSR deficit found in SZ. The similarity of
increased spontaneous gamma power in SZ to the findings of increased spontaneous
gamma power in animal models of NMDAR hypofunction suggests that spontaneous
gamma power could serve as a biomarker for the integrity of NMDARs on parvalbumin
expressing inhibitory interneurons in humans and in animal models of
neuropsychiatric disorders.
PMID- 25587802
TI - Perceived norms of premarital heterosexual relationships and sexuality among
female college students in Tehran.
AB - This paper describes perceptions of the societal acceptability and acceptability
among peers of different types of premarital heterosexual relationships in Iran.
Sources of variation in subjective norms are assessed. Results derive from a
survey conducted in 2005 of a representative sample of 1743 female college
students from four multidisciplinary universities in Tehran using two-stage
random cluster sampling. An anonymous pilot-tested questionnaire was used.
Respondents displayed remarkable heterogeneity and ambiguity concerning the
social acceptability of premarital heterosexual friendship, dating and physical
contact, but expressed greater certainty about the unacceptability of premarital
sex. The majority (77.5%) reported that premarital sex was socially prohibited,
while about one third (33.1%) were unsure about the social acceptability of
having a boyfriend and dating before marriage. Peer norms were perceived to be
more liberal but, nevertheless, very few peers were thought to be in favour of
premarital intercourse. Older students, those with educated fathers and those
studying in a mixed-sex university perceived norms to be more liberal than their
counterparts. Access to satellite television, a major source of exposure to new
information and values about sexuality, was a major predictor of liberal peer
norms. It appears that a significant proportion of young people in Tehran have
broken with tradition with regard to premarital social interaction and romantic
friendships, but the majority still conforms to traditional cultural and
religious values regarding abstinence before marriage.
PMID- 25587803
TI - Memantine plus vitamin D prevents axonal degeneration caused by lysed blood.
AB - Intracranial hemorrhage, whether due to traumatic brain injury or ruptured
cerebral aneurysm, is characterized by major neurological damage and a high
mortality rate. Apart from cerebral vasospasm and mass effect, brain injury
results from the release of unclotted blood that contacts neurons causing calcic
stress. The combination of memantine with vitamin D, a neurosteroid hormone, may
prevent blood neurotoxicity. Our purpose was to examine the potential protective
effects of memantine + vitamin D against lysed or clotted blood in cortical
neuronal cultures. We provide the first evidence that cortical axons in contact
with lysed blood degenerate less after exposure to lysed blood in microfluidic
neuronal cultures enriched with both memantine and vitamin D compared to control
medium and cultures enriched with only memantine or only vitamin D. The reported
synergistic neuroprotective effect of memantine + vitamin D, the combination
originating an effect stronger than the sum, strongly encourages using both drugs
following intracranial hemorrhage.
PMID- 25587804
TI - Effects of an eccentric training personalized by a low rate of perceived exertion
on the maximal capacities in chronic heart failure: a randomized controlled
trial.
AB - BACKGROUND: The eccentric (ECC) training, in spite of its potential interest
(slightest request of the cardiorespiratory system) compared with the concentric
(CON) training, is not applied during the rehabilitation of the chronic heart
failure (CHF). The main reasons are the difficulty personalizing the ECC
exercises by avoiding the muscle complications and the lack of information
concerning the specific effects on the maximal capacities in CHF patients. AIM:
To compare - following a prior study on the feasibility and on the functional
impacts - the effects on maximal capacities and tolerance in CHF of ECC training
tailored by a low rate of perceived exertion (RPE) and those of conventionally
tailored CON training. DESIGN: Prospective randomized comparative study. SETTING:
A Rehabilitation Department in a University Hospital. POPULATION: CHF outpatients
with reduced ejection fraction randomized to either ECC (N.=21) or CON training
(N.=21). METHODS: ECC and CON training were respectively tailored by a low RPE
(RPE between 9 and 11 on the Borg scale) and a heart rate (HR) corresponding to
the first ventilatory threshold. Cardiopulmonary exercise test, maximal muscle
strength tests (quadriceps, triceps surae) and 6-minute walk test were performed
before and after training. Tolerance to training was assessed by RPE, muscle
soreness, increase of HR, blood pressure and plasma NT-proBNP. RESULTS:
Improvement in peak work rate was similar for both groups (+20%, P<0.01), but VO2
peak and VO2 at the first ventilatory threshold were only increased in the CON
group (+13.5%, P<0.01). Maximal strength of the triceps surae was increased in
the ECC group only (+23%, P<0.01). Improvement in the walk test distance was
similar in both groups, but the corresponding VO2 was only increased after CON
training. Tolerance to training was good in both groups, except higher increment
of training HR in the CON group (P<0.05). CONCLUSIONS AND CLINICAL REHABILITATION
IMPACT: ECC training tailored by a low RPE is well tolerated in CHF patients and
induces an improvement in maximal capacities similar to that with conventional
CON training despite lower demands on the cardiorespiratory system, showing a
better energetic efficiency, potentially interesting for these patients with
reduced energetic reserve.
PMID- 25587805
TI - Fluctuating water temperatures affect development, physiological responses and
cause sex reversal in fathead minnows.
AB - Natural and human activities can result in both high temporal and spatial
variability in water temperature. Rapid temperature changes have the potential to
dramatically affect physiological processes in aquatic organisms and, due to
their limited mobility, fish early life stages are particularly vulnerable to
ambient temperature fluctuations. In this study, we examined how the magnitude
and frequency of temperature fluctuations affect survival, growth, development,
expression of thermoresponsive genes, and gonadal differentiation in fathead
minnows, Pimephales promelas. We exposed individuals (0 to 4 days post
fertilization) of known genotypic sex to fluctuations of Delta4 degrees C over
12-h, Delta8 degrees C over 12- and 24-h, and three stable temperatures (21, 25,
and 29 degrees C) for up to 45 d. Expression of hsp70 in fish exposed to the
highest-magnitude, highest-frequency fluctuating treatment cycled in concert with
temperature and was upregulated initially during exposure, and may have
contributed to temperature fluctuations having little effect on time to and size
at hatching (whole-organism responses). This treatment also caused fish to
undergo nondirectional sex reversal. These results indicate that hsp70 may be
involved in mediating thermal stress from subdaily temperature fluctuations and
that sex determination in fathead minnows can be influenced by cycling
temperatures.
PMID- 25587806
TI - Carcinosarcomas: tumors in transition?
AB - Carcinosarcomas are rare, biphasic tumors that are comprised of carcinomatous and
sarcomatous elements. While the exact mechanism by which these two phenotypes
arise within a single tumor remains unclear, molecular evidence indicates that
the epitheliod and spindle-cell components share a clonal origin. We propose that
the biphasic nature of these neoplasms may represent an extreme case of
epithelial plasticity, in which an epithelial-like cell undergoes a transition to
a more mesenchymal phenotype. The present review will discuss both the
histological and molecular biological evidence of the involvement of epithelial
plasticity in driving the mixed phenotypes observed in carcinosarcomas.
PMID- 25587807
TI - Global health diplomacy: concepts, issues, actors, instruments, fora and cases.
PMID- 25587808
TI - Medical and ethical concerns regarding women with hyperandrogenism and elite
sport.
PMID- 25587809
TI - Women with hyperandrogenism in elite sports: scientific and ethical rationales
for regulating.
AB - The recent implementation by some major sports-governing bodies of policies
governing eligibility of females with hyperandrogenism to compete in women's
sports has raised a lot of attention and is still a controversial issue. This
short article addresses two main subjects of controversy: the existing scientific
basis supporting performance enhancing of high blood T levels in elite female
athletes, and the ethical rationale and considerations about these policies.
Given the recently published data about both innate and acquired hyperandrogenic
conditions and their prevalence in elite female sports, we claim that the high
level of androgens are per se performance enhancing. Regulating women with
clinical and biological hyperandrogenism is an invitation to criticism because
biological parameters of sex are not neatly divided into only two categories in
the real world. It is, however, the responsibility of the sports-governing bodies
to do their best to guarantee a level playing field to all athletes. In order not
cloud the discussions about the policies on hyperandrogenism in sports, issues of
sports eligibility and therapeutic options should always be considered and
explained separately, even if they may overlap. Finally, some proposals for
refining the existing policies are made in the present article.
PMID- 25587810
TI - Iridium(III)-catalyzed C-7 selective C-H alkynylation of indolines at room
temperature.
AB - An iridium-catalyzed direct C-7 selective C-H alkynylation of indolines at room
temperature, for the first time, has been developed via C-H bond activation.
Furthermore, the first example of direct C-H alkynylation of carbazoles at the C1
position is also achieved. More importantly, the resulting product can be readily
transformed into C7-alkynylated indoles, further widening the C-7 derivatization
of indoles and highlighting the synthetic utility of this methodology.
PMID- 25587811
TI - Next generation laser-based standoff spectroscopy techniques for Mars
exploration.
AB - In the recent Mars 2020 Rover Science Definition Team Report, the National
Aeronautics and Space Administration (NASA) has sought the capability to detect
and identify elements, minerals, and most importantly, biosignatures, at fine
scales for the preparation of a retrievable cache of samples. The current Mars
rover, the Mars Science Laboratory Curiosity, has a remote laser-induced
breakdown spectroscopy (LIBS) instrument, a type of quantitative elemental
analysis, called the Chemistry Camera (ChemCam) that has shown that laser-induced
spectroscopy instruments are not only feasible for space exploration, but are
reliable and complementary to traditional elemental analysis instruments such as
the Alpha Particle X-Ray Spectrometer. The superb track record of ChemCam has
paved the way for other laser-induced spectroscopy instruments, such as Raman and
fluorescence spectroscopy. We have developed a prototype remote LIBS-Raman
fluorescence instrument, Q-switched laser-induced time-resolved spectroscopy
(QuaLITy), which is approximately 70 000 times more efficient at recording
signals than a commercially available LIBS instrument. The increase in detection
limits and sensitivity is due to our development of a directly coupled system,
the use of an intensified charge-coupled device image detector, and a pulsed
laser that allows for time-resolved measurements. We compare the LIBS
capabilities of our system with an Ocean Optics spectrometer instrument at 7 m
and 5 m distance. An increase in signal-to-noise ratio of at least an order of
magnitude allows for greater quantitative analysis of the elements in a LIBS
spectrum with 200-300 MUm spatial resolution at 7 m, a Raman instrument capable
of 1 mm spatial resolution at 3 m, and bioorganic fluorescence detection at
longer distances. Thus, the new QuaLITy instrument fulfills all of the NASA
expectations for proposed instruments.
PMID- 25587812
TI - Rivaroxaban for thromboprophylaxis in a patient receiving electroconvulsive
therapy.
PMID- 25587813
TI - Transient expressive aphasia after bitemporal electroconvulsive therapy: a rarely
documented reversible phenomenon.
PMID- 25587814
TI - Pancreatoduodenectomy With Systematic Mesopancreas Dissection Using a Supracolic
Anterior Artery-first Approach.
AB - OBJECTIVE: To describe the details of the surgical technique of
pancreatoduodenectomy (PD) with systematic mesopancreas dissection (SMD-PD),
using a supracolic anterior artery-first approach. BACKGROUND: An artery-first
approach in PD has been advocated in pancreatic cancer to judge resectability,
clear the superior mesenteric artery margin from invasion, or reduce blood loss.
However, the efficacy of an artery-first approach in mesopancreas dissection
remains unclear. METHODS: This study involved 162 consecutive patients who
underwent PD with curative intent. The patients were divided into 82 SMD-PDs and
80 conventional PDs (CoPD) and then stratified further according to the
dissection level, that is, level 1 was applied to 24 simple mesopancreas
divisions for early inflow occlusion including 11 SMD-PDs, level 2 for 63 en bloc
mesopancreas resections (26 SMD-PDs), and level 3 for 75 patients who underwent a
hemicircumferential superior mesenteric artery plexus resection to keep the
margin free from cancer invasion (45 SMD-PDs). The clinical and imaging results
were collected to assess the feasibility and validity of SMD-PD with an artery
first approach. RESULTS: Blood loss and operation duration were significantly
less in the SMD-PD group than in the CoPD group among the total 162 patients. The
imaging analysis showed that four fifths of pancreatic arterial branches came
from the right dorsal aspect of the superior mesenteric artery and cancer
abutment occurred exclusively from the same direction indicating the validity of
an artery-first approach. CONCLUSIONS: SMD-PD using an SAA is feasible across PD
cases, with acceptable short-term outcomes, and we propose this procedure as a
promising option for PD.
PMID- 25587815
TI - Enhancing mechanical properties of highly efficient polymer solar cells using
size-tuned polymer nanoparticles.
AB - The low mechanical durability of polymer solar cells (PSCs) has been considered
as one of the critical hurdles for their commercialization. We described a facile
and powerful strategy for enhancing the mechanical properties of PSCs while
maintaining their high power conversion efficiency (PCE) by using monodispersed
polystyrene nanoparticles (PS NPs). We prepared highly monodispersed, size
controlled PS NPs (60, 80, and 100 nm), and used them to modify the poly(3,4
ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) anode buffer layer
(ABL). The PS NPs played two important roles; i.e., they served as (1) binders in
the PEDOT:PSS films, and (2) interfacial modifiers between ABL and the active
layer, resulting in remarkable improvement of the mechanical integrity of the
PSCs. The addition of PS NPs enhanced the inherent mechanical toughness of the
PEDOT:PSS ABL due to their elastic properties, allowing the modified ABL to
tolerate higher mechanical deformations. In addition, the adhesion energy (Gc)
between the active layer and the modified PEDOT:PSS layer was enhanced
significantly, i.e., by a factor of more than 1.5. The Gc value has a strong
relationship with the sizes of the PS NP, showing the greatest enhancement when
the largest size PS NPs (100 nm) were used. In addition, PS NPs significantly
improve the air-stability of the PSCs by suppressing moisture adsorption and
corrosion of the electrodes. Thus, the modification of ABL with PS NPs
effectively enhances both the mechanical and the long-term stabilities of the
PSCs without sacrificing their PCE values, demonstrating their great potential as
applications in flexible organic electronics.
PMID- 25587816
TI - Potential mental health consequences for workers in the Ebola regions of West
Africa--a lesson for all challenging environments.
PMID- 25587817
TI - Exhausted but not cynical: burnout in therapists working within Improving Access
to Psychological Therapy Services.
AB - BACKGROUND: Burnout is common in mental health professionals and has serious
personal and professional consequences. Levels and predictors of burnout for
therapists within "Improving Access to Psychological Therapies" (IAPT) services
are thus far unknown. AIMS: This study investigated levels and predictors of
three burnout dimensions--Emotional Exhaustion (EE), Depersonalisation (DP) and
Personal Accomplishment (PA)--in IAPT therapists. METHODS: Therapists from eight
services completed a web-based survey measuring burnout levels and hypothesised
burnout predictors. Reponses were matched to demographic information on clients
with whom they had completed treatment in the last 2 months. RESULTS: 116 (n)
therapists showed comparatively high levels of EE, and relatively low levels of
DP and PA. These were predicted by some factors from the General Burnout Model
and by Work Involvement styles. Stressful Involvement, in particular in-sessions
feelings of anxiety predicted EE and DP, and Healing Involvement predicted
Personal Accomplishment. The most important predictors of therapist burnout were
service-related, particularly work demands and autonomy, and in-session feelings.
CONCLUSIONS: Addressing these factors in IAPT services may prevent therapist
burnout.
PMID- 25587818
TI - Staff views on wellbeing for themselves and for service users.
AB - BACKGROUND: Wellbeing is an important outcome in the context of recovery from
mental illness. The views of mental health professionals on wellbeing may
influence their approach to supporting recovery. AIMS: This study aims to explore
views held by mental health staff about factors influencing their own wellbeing
and that of service users with psychosis. METHODS: Semi-structured interviews
were conducted with 14 mental health staff in South London who had worked with
people with psychosis. Thematic analysis was used to analyse the data and
comparisons were made between staff views of wellbeing for themselves and service
users. RESULTS: Staff participants held similar conceptualisations of wellbeing
for themselves and for service users. However, they suggested a differential
impact on wellbeing for a number of factors, such as balance, goals and
achievement, and work. Staff employed a more deficit-based perspective on
wellbeing for service users and a more strengths-based view for themselves.
CONCLUSIONS: Staff stated a recovery orientation in principle, but struggled to
focus on service user strengths in practice. A stronger emphasis in clinical
practice on amplifying strengths to foster self-management is indicated, and
staff may need support to achieve this emphasis, e.g. through specific
interventions and involvement of peer support workers.
PMID- 25587819
TI - Stigma, American military personnel and mental health care: challenges from Iraq
and Afghanistan.
AB - BACKGROUND: Since 2001, more than 2.5 million United States military personnel
have been deployed for combat. Over one million have served multiple deployments.
Combat generally involved repeated exposure to highly traumatic events. Personnel
were also victims of military sexual trauma (MST), a major risk factor for
psychiatric illness. Most survivors do not seek or receive mental health care.
Stigma is one of the main barriers to that care. AIMS: To explore the impact of
stigma on personnel with psychiatric illness, and suggest some innovative ways to
potentially reduce stigma and improve care. METHODS: Cinahl and PubMed databases
were searched from 2001 to 2014. RESULTS: Anonymity, the use of non-stigmatizing
language, peer-to-peer, and stigma-reduction programs help military personnel
receive mental health care. Technology offers the opportunity for effective and
appropriate education and treatment. CONCLUSIONS: Although stigma is formidable,
several innovative services are available or being developed for military victims
of trauma. Commitment of resources for program development and further research
to explore which interventions offer the best clinical outcomes are needed to
increase efforts to combat stigma and ensure quality care.
PMID- 25587822
TI - Screening of bioconstituents and in vitro cytotoxicity of Clematis gouriana
leaves.
AB - Clematis gouriana (Ranunculaceae), a perennial herb, is used by the local
inhabitants of the western Himalayan region for its medicinal properties. Major
bioconstituents of C. gouriana leaves using different solvent extracts were
obtained and analysed. The results revealed promising contents of phenolics (from
18.19 +/- 0.10 to 22.17 +/- 0.10 mg g(-1)) as gallic acid and flavonoids (from
2.83 +/- 0.01 to 6.52 +/- 0.08 mg g(-1)) as quercetin equivalent in different
extracts. Aqueous acetone extract showed higher antioxidant activity with IC50
value of 129.11 and 25.35 MUg mL(-1) against DPPH and ABTS free radicals,
respectively. Antioxidant yield ranged from 16.87 +/- 0.27 to 24.48 +/- 0.13 mg
g(-1) of Trolox equivalent in different extracts as measured by the FRAP assay.
Furthermore, ethylacetate extract exhibited strong in vitro cytotoxicity against
Chinese hamster ovary and glioma cell lines. Proximate composition (proteins,
fats, ash and minerals) of C. gouriana leaves was also assessed. Results
demonstrated the potential of C. gouriana bioconstituents as nutraceuticals.
PMID- 25587824
TI - In situ nondestructive identification of natural dyes in ancient textiles by
reflection fourier transform mid-infrared (FT-MIR) spectroscopy.
AB - Silk embroideries and cotton grounds of ancient Caucasian (Kaitag) textiles were
analyzed in situ by a portable Fourier transform infrared (FT-IR) spectrometer
equipped with a reflection module. Differently colored areas were analyzed for
the purpose of identifying the dyes fixed on the fibers. The spectra so obtained
were elaborated by calculating the corresponding second derivative, and a library
search was then performed using a database including the second derivative
spectra of a large range of historical dyes and the corresponding undyed fibers.
The results presented here suggest that this technique, combined with the library
search method, has a good capability of recognizing natural dyes on both types of
ancient textile fibers, in an entirely non-destructive way.
PMID- 25587823
TI - Oxygen isotope fractionation in phosphates: the role of dissolved complex anions
in isotope exchange.
AB - Oxygen isotope fractionation factors for phosphates were calculated by means of
the increment method. The results suggest that Ag3PO4 and BiPO4 are enriched in
(18)O relative to AgPO4, and the three phosphates are consistently depleted in
(18)O relative to Ba3[PO4]2; fluorapatite and chlorapatite exhibit a similar
behaviour of oxygen isotope fractionation with consistent enrichment of (18)O
relative to hydroxyapatite. The valence, radii and coordination of metal cations
play a quantitative role in dictating the (18)O/(16)O partitioning in these
phosphates of different compositions. The calculated fractionation factors for
the Ag3PO4-H2O system are in agreement with experimental determinations derived
from enzyme-catalysed isotope exchange between dissolved inorganic phosphate and
water at the longest reaction durations at low temperatures. This demonstrates
that the precipitated Ag3PO4 has completely captured the oxygen isotope
fractionation in the dissolved inorganic phosphate. The calculated fractionation
factors for the F/Cl-apatite-water systems are in agreement with the enzyme
catalysed experimental fractionations for the dissolved phosphate-water system at
the longest reaction durations but larger than fractionations derived from
bacteria-facilitated exchange and inorganic precipitation experiments as well as
natural observations. For the experimental calibrations of oxygen isotope
fractionation involving the precipitation of dissolved phosphate species from
aqueous solutions, the fractionation between precipitate and water is primarily
dictated by the isotope equilibration between the dissolved complex anions and
water prior to the precipitation. Therefore, the present results provide a
quantitative means to interpret the temperature dependence of oxygen isotope
fractionation in inorganic and biogenic phosphates.
PMID- 25587825
TI - The number of in-out catheterisations is reduced by mobilising the postoperative
patient with bladder needs to the toilet in the recovery room: A randomised
clinical trial.
AB - BACKGROUND: Many patients are diagnosed with postoperative urine retention in the
recovery room and treated with in-out catheterisation (IOC). OBJECTIVES: We
hypothesised that the use of IOC could be reduced by mobilising patients to the
toilet to pass urine instead of offering a bedpan or urinal. DESIGN: A
randomised, controlled, nonblinded study with two groups. SETTING: University
Hospital, October 2009 to June 2012. PATIENTS: One hundred and fifty-two patients
scheduled for surgery for cervical or lumbar disc herniation. Inclusion criteria
were a bladder volume more than 350 ml and/or the need to pass urine in the
recovery room. INTERVENTIONS: Participants were randomised in the recovery room
for mobilisation to the toilet (Group I) or use of a bedpan or urinal in the bed
(Group C). MAIN OUTCOME MEASURES: The number of IOC cases in the recovery room
(primary outcome) and the duration of stay in the recovery room. RESULTS:
Thirteen of 67 patients (19%) in Group I and 38 of 71 patients in Group C (54%)
required IOC (P < 0.001). The median (IQR) durations of stay in the RR were 125
(97 to 125) min in Group I and 157 (115 to 214) min in Group C (P = 0.006). The
median times from arrival to first general ward mobilisation were 85 (37 to 139)
min in Group I and 180 (118 to 245) min in Group C (P < 0.001). CONCLUSION:
Patients were mobilised early after disc herniation intervention to permit toilet
visits in the recovery room. This strategy decreased the number of IOCs, duration
of stay in the recovery room and time from arrival to first mobilisation in the
general ward.
PMID- 25587826
TI - Evolution of ventilator settings during general anaesthesia for neurosurgery: An
observational study in a German centre over 15 years.
PMID- 25587827
TI - Synthesis of a highly dispersive sinapinic acid@graphene oxide (SA@GO) and its
applications as a novel surface assisted laser desorption/ionization mass
spectrometry for proteomics and pathogenic bacteria biosensing.
AB - Graphene oxide (GO)-modified sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic
acid, SA) (SA@GO) was synthesized and characterized; it was then investigated as
a new surface assisted laser desorption/ionization mass spectrometry (SALDI-MS)
for proteomics and pathogenic bacteria biosensing. SA@GO could effectively
decrease the time necessary for sweet spotting searching, reducing the amount of
organic matrix and solvent and enhance the sensitivity. SA@GO shows high
performance as a matrix alone without the need to add trifluoroacetic acid (TFA).
However, the analysis of the intact bacteria cells shows improvement in the
signal intensity (2-5 fold) and offers a low limit of detection. All these
analyses could be performed with low concentrations (1-10 fmol) and tiny volumes
(0.5-1 MUL). This study demonstrated that the exploration of new hybrid materials
is pivotal to achieve high performance and high ionization. Because of the plane
of GO, it assists protein-protein interactions that make it undergo softer
ionization.
PMID- 25587828
TI - Synthesis of isoindolinones via a ruthenium-catalyzed cyclization of N
substituted benzamides with allylic alcohols.
AB - N-Substituted aromatic and heteroaromatic amides reacted with substituted allylic
alcohols in the presence of a ruthenium catalyst, AgSbF6 and a Cu(OAc)2.H2O
oxidant, affording 3-substituted isoindolinone derivatives with diverse
substituents in good to excellent yields. A possible reaction mechanism involving
a five-membered ruthenacycle intermediate was proposed and strongly supported by
experimental evidence.
PMID- 25587829
TI - Physical properties of high Li-ion content N-propyl-N-methylpyrrolidinium
bis(fluorosulfonyl)imide based ionic liquid electrolytes.
AB - Electrolytes based on bis(fluorosulfonyl)imide (FSI) with a range of LiFSI salt
concentrations were characterized using physical property measurements, as well
as NMR, FT-IR and Raman spectroscopy. Different from the behavior at lower
concentrations, the FSI electrolyte containing 1 : 1 salt to IL mole ratio showed
less deviation from the KCl line in the Walden plot, suggesting greater ionic
dissociation. Diffusion measurements show higher mobility of lithium ions
compared to the other ions, which suggests that the partial conductivity of Li(+)
is higher at this higher composition. Changes in the FT-IR and Raman peaks
indicate that the cis-FSI conformation is preferred with increasing Li salt
concentration.
PMID- 25587830
TI - Iron-doping-enhanced photoelectrochemical water splitting performance of
nanostructured WO3: a combined experimental and theoretical study.
AB - In this paper, we have studied Fe-doping of nanostructured tungsten trioxide
(WO3) and its pronounced effect in promoting the photoelectrochemical (PEC) water
splitting performance. Vertically aligned Fe-doped WO3 nanoflakes on fluorine
doped tin oxide (FTO) were synthesized via the hydrothermal method. An X-ray
photoelectron spectroscopy (XPS) analysis confirmed the Fe(3+) substitution at
the W(6+) site in the prepared films. Broadened visible light absorption was
observed in doped films, likely due to the formation of extra band states through
doping. The Fe-doping was shown to greatly improve the PEC water splitting
performance of WO3. More specifically, the 2 mol% Fe-doped WO3 achieved a
photocurrent density of 0.88 mA cm(-2) at 1.23 V versus RHE, approximately 30%
higher than that of the undoped WO3 (0.69 mA cm(-2) at 1.23 V versus RHE). This
enhancement was attributed to the reduced band gap and the doping-enhanced charge
carrier density as confirmed by the absorption spectra and the Mott-Schottky
plots, respectively. Finally, first-principles density functional theory (DFT)
calculations confirmed that the formation of oxygen vacancies was favored after
Fe-doping, contributing to the increased charge carrier density in slightly doped
films.
PMID- 25587831
TI - MS-based methods for biomarkers of Parkinson's disease: what is the future?
PMID- 25587832
TI - Bioanalytical laboratory automation development: why should we and how could we
collaborate?
PMID- 25587833
TI - Metabolic profiling of epithelial ovarian cancer cell lines: evaluation of
harvesting protocols for profiling using NMR spectroscopy.
AB - BACKGROUND: Metabolic profiling represents a novel technology for analyzing tumor
cells. Epithelial ovarian carcinoma has a low survival rate due to the
development of aggressive and chemotherapy-resistant cells. A tailored and
reliable protocol is presented for profiling of chemoresistant cells using the
cell line SKOV3 and a multiresistant subline SKOV3R. RESULTS: Harvesting
protocols with cold methanol or MilliQ freeze/thaw cycles were compared.
Increased reproducibility using MilliQ was evidenced. Importantly, both
approaches resulted in similar profiles. Compared with parental SKOV3, the SKOV3R
cells showed a significantly different profile. CONCLUSION: The MilliQ protocol
is preferred owing to higher reproducibility and increased sample preparation
options. The resulting metabolic profiles summarize metabolic alterations in
chemoresistant cells consistent with a progressed and aggressive phenotype.
PMID- 25587834
TI - Quantitation of 25-hydroxyvitamin D2 and D3 in serum and plasma by LCMS/MS.
AB - OBJECTIVE: We developed and validated an analytical method for quantifying 25
hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) in serum and plasma.
METHODS: Samples, pretreated with zinc sulfate and methanol, were extracted with
hexane. Separation was achieved via UHPLC and 25OHD quantification was
accomplished by a triple quadrupole mass spectrometer. RESULTS: Imprecision was
3.6-15.1%CV and bias 88.0-126.0%. Extraction efficiency was 76.5-110.5%, whereas
the matrix effect ranged from -46.7 to -32.0%. The method was applied to
authentic specimens. The results showed no significant difference between serum
and plasma; strong correlation with paired values from an external laboratory;
and analyte stability for 15 days. CONCLUSION: This method provides reliable and
accurate measurement of 25OHD for use in clinical practice.
PMID- 25587835
TI - Applying dried blood spot sampling with LCMS quantification in the clinical
development phase of tasquinimod.
AB - BACKGROUND: Tasquinimod is an orally active anticancer drug in late clinical
development. Here we describe the development and validation of a bioanalytical
method based upon dried blood spot analysis in combination with LCMS/MS and
stable isotope dilution. RESULTS & DISCUSSION: The present method was validated
for accuracy, precision, linearity, selectivity, carry-over and ruggedness. Data
elucidating stability of tasquinimod in dried blood spots and in blood at ambient
temperature was investigated and found adequate. Furthermore, in a clinical
study, incurred samples reanalysis was performed, and the correlation of blood
concentration versus plasma concentrations of tasquinimod was investigated.
CONCLUSION: The method described here is suitable for bioanalysis of tasquinimod
in whole blood from humans in clinical studies.
PMID- 25587836
TI - Determination of riociguat and its major human metabolite M-1 in human plasma by
stable-isotope dilution LCMS/MS.
AB - BACKGROUND: Riociguat (BAY 63-2521) is an oral NO-independent as well as NO
synergistic stimulator of soluble guanylate cyclase (sGC) for the treatment of
pulmonary hypertension. BAY 60-4552 (M-1) is its pharmacologically active major
metabolite. An isotope dilution LC-ESI-MS/MS method has been developed and
validated for the simultaneous determination of riociguat and M-1 in lithium
heparinized human plasma. RESULTS: The validated concentration range covers 0.500
MUg/l (LLOQ) to 100 MUg/l (ULOQ) for both analytes. Interassay accuracy and
precision (%CV) for both analytes ranged from 92.7 to 111% and from 2.61 to
9.89%, respectively. CONCLUSION: The method proved to be selective, specific,
sufficiently sensitive, highly reproducible and robust for the analysis of large
numbers of samples.
PMID- 25587838
TI - Justifying the lack of incurred sample reproducibility in a study: considerations
and strategies.
AB - In 2012 with the issuance of its Guideline on Bioanalytical Method Validation,
the European Medicine Agency (EMA) made the incurred sample reproducibility (ISR)
assessment a requirement for studies to be submitted to European authorities.
Since then 2012, European agencies have started to issue deficiencies to
pharmaceutical companies for lack of ISRs in studies submitted recently but
performed prior to the issuance of the 2012 Guideline. It now becomes the
applicant's responsibility to justify scientifically the departure from the new
guideline even for less recent studies. This article details the different
strategies to provide an adequate justification for the absence of ISR data in
studies performed prior to February 2012 but submitted to European agencies after
that date.
PMID- 25587837
TI - Simultaneous determination of levodopa, carbidopa, entacapone, tolcapone, 3-O
methyldopa and dopamine in human plasma by an HPLC-MS/MS method.
AB - BACKGROUND: In this study, we developed and validated a HPLC-MS/MS method capable
of simultaneously determining levodopa, carbidopa, entacapone, tolcapone, 3-O
methyldopa and dopamine in human plasma. RESULTS & METHODOLOGY: Chromatographic
separation was achieved using a C8 column with a mobile phase consisting of a
gradient of water and acetonitrile:methanol (90:10 v/v), both containing 0.1%
formic acid. The developed method was selective, sensitive (LD<7.0 ng ml(-1)),
linear (r>0.99), precise (RSD<11.3%), accurate (RE<11.8%) and free of residual
and matrix effects. The developed method was successfully applied in plasma
patients with Parkinson's disease using Stalevo(r). CONCLUSION: The new method
can be used for the clinical monitoring of these substances and applied to
adjustments in drug dosages.
PMID- 25587840
TI - Enrichment of phosphorylated peptides and proteins by selective precipitation
methods.
AB - Protein phosphorylation is one of the most prominent post-translational
modifications involved in the regulation of cellular processes. Fundamental
understanding of biological processes requires appropriate bioanalytical methods
for selectively enriching phosphorylated peptides and proteins. Most of the
commonly applied enrichment approaches include chromatographic materials
including Fe(3+)-immobilized metal-ion affinity chromatography or metal oxides.
In the last years, the introduction of several non-chromatographic isolation
technologies has increasingly attracted the interest of many scientists. Such
approaches are based on the selective precipitation of phosphorylated peptides
and proteins by applying various metal cations. The excellent performance of
precipitation-based enrichment methods can be explained by the absence of any
stationary phase, resin or sorbent, which usually leads to unspecific binding.
This review provides an overview of recently published methods for the selective
precipitation of phosphorylated peptides and proteins.
PMID- 25587839
TI - Recommendations for adaptation and validation of commercial kits for biomarker
quantification in drug development.
AB - Increasingly, commercial immunoassay kits are used to support drug discovery and
development. Longitudinally consistent kit performance is crucial, but the degree
to which kits and reagents are characterized by manufacturers is not
standardized, nor are the approaches by users to adapt them and evaluate their
performance through validation prior to use. These factors can negatively impact
data quality. This paper offers a systematic approach to assessment, method
adaptation and validation of commercial immunoassay kits for quantification of
biomarkers in drug development, expanding upon previous publications and
guidance. These recommendations aim to standardize and harmonize user practices,
contributing to reliable biomarker data from commercial immunoassays, thus,
enabling properly informed decisions during drug development.
PMID- 25587841
TI - Detection of the disease-associated form of the prion protein in biological
samples.
AB - Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases
that occur in a variety of mammals. In TSEs, a chromosomally encoded protein
(PrPC) undergoes a conformational change to the disease-associated form (PrPd).
PrPd is capable of inducing a change in additional molecules of PrPC to the PrPd
conformation. TSEs are inevitably fatal and cross-species transmission is known
to occur, and there is potential for transmission via blood transfusion and organ
transplantation in humans. Thus, there is interest in high-quality diagnostics
for both humans and animals. This review summarizes methods of TSE detection
currently in use in diagnostic settings and discusses recent advances in PrPd
detection that afford substantial enhancements in sensitivity over currently
approved methods for use in clinical settings.
PMID- 25587842
TI - SERS-based approaches toward genetic profiling.
AB - In the last decade surface-enhanced Raman scattering (SERS) has experienced an
important resurgence, and as a consequence it has seen wide application in the
biological field, especially for DNA identification. SERS-based DNA detection can
be carried out directly and indirectly and, in the latter approach, it relies on
the use of SERS tags, whose role is to indirectly prove the recognition and
binding of a specific oligonucleotide sequence. Herein, the role of SERS tags is
analyzed focusing specifically on the use of DNA identification for genetic
profiling.
PMID- 25587843
TI - Additive-free thick graphene film as an anode material for flexible lithium-ion
batteries.
AB - This work demonstrates a simple route to develop mechanically flexible electrodes
for Li-ion batteries (LIBs) that are usable as lightweight effective conducting
networks for both cathodes and anodes. Removing electrochemically dead elements,
such as binders, conducting agents and metallic current collectors, from the
battery components will allow remarkable progress in this area. To investigate
the feasibility of using thick, additive-free graphene films as anodes for
flexible LIBs, we have synthesized and tested thick, additive-free, freestanding
graphene films as anodes, first in a coin cell and further in a flexible full
cell. As an anode material in a half cell, it showed a discharge capacity of
about 350 mA h g(-1) and maintained nearly this capacity over 50 cycles at
various current rates. This film was also tested as an anode material in a full
cell with a LiCoO2 cathode and showed good electrochemical performance. Because
the graphene-based flexible film showed good performance in half- and full coin
cells, we used this film as a flexible anode for flexible LIBs. No conducting
agent or binder was used in the anode side, which helped in realizing the
flexible LIBs. Using this, we demonstrate a thin, lightweight and flexible
lithium ion battery with good electrochemical performance in both its flat and
bent states.
PMID- 25587844
TI - The role of personality traits and profiles in posttrauma comorbidity.
AB - Many service members experience symptoms of posttraumatic stress disorder (PTSD)
after deployment. PTSD can vary widely in its presentation and associated
features, such as comorbid conditions. Research has shown that veterans with PTSD
and an internalizing personality profile are more likely to experience
internalizing comorbidity (e.g., anxiety, depression), whereas veterans with PTSD
and an externalizing personality profile are more likely to experience
externalizing comorbidity (e.g., substance abuse, aggression). To date, however,
this research has been limited by a focus on diagnosable disorders and
personality categories. In a nonclinical sample of 224 National Guard/Reserve
service members who had served since 2001, we explored whether personality traits
(measured continuously) moderated associations of PTSD symptom severity with the
severity of internalizing (depression, anxiety) and externalizing (alcohol abuse,
aggression) symptoms. Results showed that the association of PTSD with anxiety
was stronger when extraversion was lower (corresponding to an internalizing
personality profile). Moreover, the association of PTSD with alcohol abuse was
stronger when extraversion was high and conscientiousness was low (corresponding
to an externalizing personality profile). Surprisingly, this association was also
stronger when extraversion was low and conscientiousness was high. Results offer
additional insights into prior research on personality and comorbidity.
PMID- 25587845
TI - N-Halamine-modified antimicrobial polypropylene nonwoven fabrics for use against
airborne bacteria.
AB - Disinfecting, nonbleaching compound 1-chloro-2,2,5,5-tetramethyl-4
imidazolidinone (MC) was uniformly coated onto polypropylene melt-blown nonwoven
fabrics having basis-weights of 22 and 50 g/m(2) in order to impart antimicrobial
properties via a pad-dry technique. The antimicrobial efficacies of the tested
fabrics loaded with MC compound were evaluated against bioaerosols of
Staphylococcus aureus and Escherichia coli O157:H7 utilizing a colony counting
method. It was determined that both types of coated fabrics exhibited superior
antimicrobial efficacy upon exposure to aerosol generation for 3 h. The effect of
the coating on air permeability was found to be minimal. Samples were stable for
a 6 month time period when they were stored in darkness. However, when the
fabrics were exposed to fluorescent light, partial chlorine loss was observed.
The MC-coated fabrics exhibited great potential for use in protective face masks
and air filters to combat airborne pathogens.
PMID- 25587846
TI - Chronic pain: cytokines, lymphocytes and chemokines.
AB - Chronic pain is a debilitating condition and, in most cases, difficult to treat.
A prominent example of this is neuropathic pain. Understanding pathophysiological
mechanisms of pain and, therefore, making this knowledge into an effective
treatment is still a challenge to experts. Pain can now be considered as a neuro
immune disorder, since recent data indicate critical involvement of innate and
adaptive immune responses following injury, and this interaction plays an
important role in the onset and perpetuation of chronic pain. The aim of this
article is to review the relationship between immune system and chronic pain,
especially about neuropathic pain, and focusing on cytokines, chemokines and
lymphocytes.
PMID- 25587847
TI - Evolution of synthetic signaling scaffolds by recombination of modular protein
domains.
AB - Signaling scaffolds are proteins that interact via modular domains with multiple
partners, regulating signaling networks in space and time and providing an ideal
platform from which to alter signaling functions. However, to better exploit
scaffolds for signaling engineering, it is necessary to understand the full
extent of their modularity. We used a directed evolution approach to identify,
from a large library of randomly shuffled protein interaction domains, variants
capable of rescuing the signaling defect of a yeast strain in which Ste5, the
scaffold in the mating pathway, had been deleted. After a single round of
selection, we identified multiple synthetic scaffold variants with diverse domain
architectures, able to mediate mating pathway activation in a pheromone-dependent
manner. The facility with which this signaling network accommodates changes in
scaffold architecture suggests that the mating signaling complex does not possess
a single, precisely defined geometry into which the scaffold has to fit. These
relaxed geometric constraints may facilitate the evolution of signaling networks,
as well as their engineering for applications in synthetic biology.
PMID- 25587848
TI - Is there a gender bias in recommendations for further rehabilitation in primary
care of patients with chronic pain after an interdisciplinary team assessment?
AB - OBJECTIVE: To examine potential gender bias in recommendations of further
examination and rehabilitation in primary care for patients with chronic
musculoskeletal pain after an interdisciplinary team assessment. METHODS: The
population consisted of consecutive patients (n = 589 women, 262 men) referred
during a 3-year period from primary healthcare for assessment by
interdisciplinary teams at a pain specialist rehabilitation clinic. Patient data
were collected from the Swedish Quality Registry for Pain Rehabilitation. The
outcome was defined as the examination or rehabilitation that was specified in
the patient's record. RESULTS: Men had a significantly higher likelihood than
women of being recommended physiotherapy and radiological examination, and the
gender difference was not explained by confounding variables and covariates (age,
marital status, ethnicity, education, working status, pain severity, pain
interference, pain sites, anxiety and depression). There was no significant
gender difference in recommendations to treatment by specialist physician,
occupational therapist, psychologist or social worker. CONCLUSION: Our findings
indicate that the interdisciplinary teams in specialist healthcare may
discriminate against women with chronic pain when physiotherapy and radiological
investigation are recommended. The team's choice of recommendations might be
influenced by gendered attitudes, but this field of research needs to be studied
further.
PMID- 25587849
TI - Layer-by-layer polymer coated gold nanoparticles for topical delivery of imatinib
mesylate to treat melanoma.
AB - The aim of this study was to investigate the feasibility of using layer-by-layer
polymer coated gold nanoparticles (AuNP) as a carrier for topical iontophoretic
delivery of imatinib mesylate (IM). AuNP were prepared by the Turkevich method
and were stabilized and functionalized using polyvinylpyrrolidone and
polyethylene imine. The functionalized AuNP were then sequentially coated with
anionic poly(styrenesulfonate) and cationic polyethylene imine and loaded with
IM. The layer-by-layer polymer coated AuNP (LbL-AuNP) showed average particle
size and zeta-potential of 98.5 +/- 4.3 nm and 32.3 +/- 1.3 mV respectively.
After LbL coating of AuNP, the surface plasmon resonance wavelength shifted from
518 to 530 nm. The loading efficiency of IM in LbL-AuNP was found to be 28.3 +/-
2.3%, which was greatest for any small molecule loaded in AuNP. In vitro skin
penetration studies in excised porcine ear skin showed that iontophoresis (0.47
mA/cm(2)) application enhanced the skin penetration of IM loaded AuNP by 6.2-fold
compared to passive application. Tape stripping studies showed that iontophoresis
of IM loaded LbL-AuNP retained 7.8- and 4.9-fold greater IM in stratum corneum
and viable skin respectively compared with iontophoresis of free IM. LbL-AuNP
were taken up rapidly (15 min) by B16F10 murine melanoma cells. Furthermore, IM
loaded LbL-AuNP significantly (p < 0.001) decreased B16F10 cell viability
compared to free IM. We have shown for the first time that IM can be delivered by
topical application using LbL coated gold nanoparticles to treat melanoma.
PMID- 25587850
TI - High-throughput profiling of nanoparticle-protein interactions by fluorescamine
labeling.
AB - A rapid, high throughput fluorescence assay was designed to screen interactions
between proteins and nanoparticles. The assay employs fluorescamine, a primary
amine specific fluorogenic dye, to label proteins. Because fluorescamine could
specifically target the surface amines on proteins, a conformational change of
the protein upon interaction with nanoparticles will result in a change in
fluorescence. In the present study, the assay was applied to test the
interactions between a selection of proteins and nanoparticles made of
polystyrene, silica, or iron oxide. The particles were also different in their
hydrodynamic diameter, synthesis procedure, or surface modification. Significant
labeling differences were detected when the same protein incubated with different
particles. Principal component analysis (PCA) on the collected fluorescence
profiles revealed clear grouping effects of the particles based on their
properties. The results prove that fluorescamine labeling is capable of detecting
protein-nanoparticle interactions, and the resulting fluorescence profile is
sensitive to differences in nanoparticle's physical properties. The assay can be
carried out in a high-throughput manner, and is rapid with low operation cost.
Thus, it is well suited for evaluating interactions between a larger number of
proteins and nanoparticles. Such assessment can help to improve our understanding
on the molecular basis that governs the biological behaviors of nanomaterials. It
will also be useful for initial examination of the bioactivity and
reproducibility of nanomaterials employed in biomedical fields.
PMID- 25587851
TI - A paradigm shift in biomass technology from complete to partial cellulose
hydrolysis: lessons learned from nature.
AB - A key characteristic of current biomass technology is the requirement for
complete hydrolysis of cellulose and hemicellulose, which stems from the
inability of microbial strains to use partially hydrolyzed cellulose, or
cellodextrin. The complete hydrolysis paradigm has been practiced over the past 4
decades with major enzyme companies perfecting their cellulase mix for maximal
yield of monosaccharides, with corresponding efforts in strain development focus
almost solely on the conversion of monosaccharides, not cellodextrin, to
products. While still in its nascent infancy, a new paradigm requiring only
partial hydrolysis has begun to take hold, promising a shift in the biomass
technology at its fundamental core. The new paradigm has the potential to reduce
the requirement for cellulase enzymes in the hydrolysis step and provides new
strategies for metabolic engineers, synthetic biologists and alike in engineering
fermenting organisms. Several recent publications reveal that microorganisms
engineered to metabolize cellodextrins, rather than monomer glucose, can reap
significant energy gains in both uptake and subsequent phosphorylation. These
energetic benefits can in turn be directed for enhanced robustness and increased
productivity of a bioprocess. Furthermore, the new cellodextrin metabolism endows
the biocatalyst the ability to evade catabolite repression, a cellular regulatory
mechanism that is hampering rapid conversion of biomass sugars to products.
Together, the new paradigm offers significant advantages over the old and
promises to overcome several critical barriers in biomass technology. More
research, however, is needed to realize these promises, especially in discovery
and engineering of cellodextrin transporters, in developing a cost-effective
method for cellodextrin generation, and in better integration of cellodextrin
metabolism to endogenous glycolysis.
PMID- 25587852
TI - Electrocatalytic activity of molybdenum disulfide nanosheets enhanced by self
doped polyaniline for highly sensitive and synergistic determination of adenine
and guanine.
AB - Recently, easy, green, and low-cost liquild exfoliation of bulk materials to
obtain thin-layered nanostructure significantly emerged. In this work, thin
layered molybdenum disulfide (MoS2) nanosheets were fabricated through
intercalation of self-doped polyaniline (SPAN) to layer space of bulk MoS2 by
ultrasonic exfoliating method to effectively prevent reaggregation of MoS2
nanosheets. The obtained hybrid showed specific surface area, a large number of
electroactive species, and open accessible space, accompanied by rich negative
charged and special conjugated structure, which was applied to adopt positively
charged guanine and adenine, based on their strong pi-pi* interactions and
electrostatic adsorption. Also, the SPAN-MoS2 interface exhibited the synergistic
effect and good electrocatalytic activity compared with the sole SPAN or MoS2
modified electrode.
PMID- 25587853
TI - Three conformers of 2-furoic acid: structure changes induced with near-IR laser
light.
AB - Conformers of 2-furoic acid were studied using the matrix-isolation technique
combined with narrow-band near-IR excitations with tunable laser light. Two
conformers of the compound were trapped from the gas phase into low-temperature
Ar or Ne matrixes with the population ratio of nearly 1:1. The two forms differ
from each other by 180 degrees rotation of the carboxylic group with respect to
the furan ring. In both structures, the OH group adopts the cis orientation, with
its H atom directed toward the C?O bond of the O?C-O-H group. Narrow-band near-IR
excitations of the OH stretching overtone vibrations resulted in transformation
of one of the initially observed conformers into a third conformational
structure. This near-IR-induced isomerization concerned rotation of the OH group
from the initial cis orientation to the trans conformation with the hydrogen atom
directed toward the oxygen atom of the furan ring. In the photoproduced
conformer, the hydrogen-bond-like O-H...O interaction (between O-H and the oxygen
atom of the furan ring) is rather weak. Nevertheless, this interaction stabilized
the structure so that it was present in the matrix for several hours after the
near-IR-induced generation. The spontaneous conversion of the photogenerated,
higher-energy form back into the more stable conformer with the carboxylic group
in cis orientation was monitored for 2-furoic acid isolated in Ar and Ne
matrixes. The speed of this process was found to be dependent on temperature and
on the matrix material. The experimentally determined half-life times of this
conformational conversion occurring in the dark are t1/2 = 1390 min (Ar, 5.5 K);
t1/2 = 630 min (Ar, 15 K); t1/2 = 240 min (Ne, 5.5 K). The three conformers of 2
furoic acid observed in the present work were identified by comparison of their
infrared spectra with the spectra theoretically calculated for the candidate
structures.
PMID- 25587854
TI - Simple method provides resolution of albumin, lipoprotein, free fraction, and
chylomicron to enhance the utility of protein binding assays.
AB - Medicinal chemists have been encouraged in recent years to embrace high speed
protein binding assays. These methods employ dialysis membranes in 96-well format
or spin filters. Membrane-based methods do not separate lipoprotein binding from
albumin binding and introduce interference despite membrane binding controls.
Ultracentrifugation methods, in contrast, do not introduce interference if
density gradients can be avoided and they resolve lipoprotein from albumin. A new
generation of compact, fast ultracentrifuges facilitates the rapid and fully
informative separation of plasma into albumin, albumin/fatty acid complex,
lipoprotein, protein-free, and chylomicron fractions with no need of salt or
sugar density gradients. We present a simple and fast ultracentrifuge method here
for two platinum compounds and a taxane that otherwise bound irreversibly to
dialysis membranes and which exhibited distinctive lipoprotein binding behaviors.
This new generation of ultracentrifugation methods underscores a need to further
discuss protein binding assessments as they relate to medicinal chemistry
efforts.
PMID- 25587855
TI - Assessing Callous-Unemotional Traits in Preschool Children With Disruptive
Behavior Problems Using Peer Reports.
AB - The goal of this study was to examine the extent to which preschoolers with
externalizing behavior problems (EBP) can identify behaviors indicative of
callous-unemotional (CU) traits among their peers. Participants for this study
included 86 preschool children (69% boys; Mage = 5.07 years) with at-risk or
clinically elevated levels of EBP who were attending a summer treatment camp.
Data collected from the children, their peers, and the counselors who worked at
the summer camp examined preschoolers' social preference, likability, and
behaviors indicative of CU. Parents and preschool teachers also reported on
children's CU traits and severity of behavioral impairment, as well as school
readiness. Peer nominations of CU traits showed (a) excellent factor structure as
evidenced by clear CU items (e.g., "don't feel bad when they do something wrong")
versus more prosocial items ("share," "cooperate"); (b) moderate construct
validity when compared to counselor reports of the CU factor as well as preschool
teacher reported ratings of CU traits and severity of behavioral impairment; and
(c) good utility as evidenced by associations with peer and counselor rated
social preference, likability, and school readiness measures as rated by both
parents and preschool teachers. These findings indicate that as early as
preschool, children with EBP can identify peers who engage in behaviors
indicative of CU traits, which have significant implications for children's
social status and overall school readiness.
PMID- 25587858
TI - Xanthohumol, a polyphenol chalcone present in hops, activating Nrf2 enzymes to
confer protection against oxidative damage in PC12 cells.
AB - Xanthohumol (2',4',4-trihydroxy-6'-methoxy-3'-prenylchalcone, Xn), a polyphenol
chalcone from hops (Humulus lupulus), has received increasing attention due to
its multiple pharmacological activities. As an active component in beers, its
presence has been suggested to be linked to the epidemiological observation of
the beneficial effect of regular beer drinking. In this work, we synthesized Xn
with a total yield of 5.0% in seven steps and studied its neuroprotective
function against oxidative-stress-induced neuronal cell damage in the neuronlike
rat pheochromocytoma cell line PC12. Xn displays moderate free-radical-scavenging
capacity in vitro. More importantly, pretreatment of PC12 cells with Xn at
submicromolar concentrations significantly upregulates a panel of phase II
cytoprotective genes as well as the corresponding gene products, such as
glutathione, heme oxygenase, NAD(P)H: quinone oxidoreductase, thioredoxin, and
thioredoxin reductase. A mechanistic study indicates that the alpha,beta
unsaturated ketone structure in Xn and activation of the transcription factor
Nrf2 are key determinants for the cytoprotection of Xn. Targeting the Nrf2 by Xn
discloses a previously unrecognized mechanism underlying the biological action of
Xn. Our results demonstrate that Xn is a novel small-molecule activator of Nrf2
in neuronal cells and suggest that Xn might be a potential candidate for the
prevention of neurodegenerative disorders.
PMID- 25587859
TI - Medicare at 50--origins and evolution.
PMID- 25587860
TI - Happy to be the new editor.
PMID- 25587856
TI - H5N1 Virus Hemagglutinin Inhibition of cAMP-Dependent CFTR via TLR4-Mediated
Janus Tyrosine Kinase 3 Activation Exacerbates Lung Inflammation.
AB - The host tolerance mechanisms to avian influenza virus (H5N1) infection that
limit tissue injury remain unknown. Emerging evidence indicates that cystic
fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent Cl(-)
channel, modulates airway inflammation. Janus tyrosine kinase (JAK) 3, a JAK
family member that plays a central role in inflammatory responses, prominently
contributes to the dysregulated innate immune response upon H5N1 attachment;
therefore, this study aims to elucidate whether JAK3 activation induced by H5N1
hemagglutinin (HA) inhibits cAMP-dependent CFTR channels. We performed short
circuit current, immunohistochemistry and molecular analyses of the airway
epithelium in Jak3(+/+) and Jak3(+/-) mice. We demonstrate that H5N1 HA
attachment inhibits cAMP-dependent CFTR Cl(-) channels via JAK3-mediated adenylyl
cyclase (AC) suppression, which reduces cAMP production. This inhibition leads to
increased nuclear factor-kappa B (NF-kappaB) signaling and inflammatory
responses. H5N1 HA is detected by TLR4 expressed on respiratory epithelial cells,
facilitating JAK3 activation. This activation induces the interaction between
TLR4 and Galphai protein, which blocks ACs. Our findings provide novel insight
into the pathogenesis of acute lung injury via the inhibition of cAMP-dependent
CFTR channels, indicating that the administration of cAMP-elevating agents and
targeting JAK3 may activate host tolerance to infection for the management of
influenza virus-induced fatal pneumonia.
PMID- 25587861
TI - Portraiture: a methodology through which success and positivity can be explored
and reflected.
AB - AIM: To present an overview of portraiture. BACKGROUND: Nursing is increasingly
embracing more arts-based approaches as research methodologies. Portraiture has
an underlying philosophy and process that enables the illumination of real people
in real settings through the 'painting' of their stories. It is a complex
methodology in which the researcher attempts to illuminate meaning of personal
stories and events presented as narrative. DATA SOURCES: Interview data were
collected from nine participants from three nursing settings. Nurses were invited
to participate in an interview or conversation designed to elicit data to address
the research questions; the aim was to gain insight into the nurses' common
shared meanings and shared contemplations of their feelings about resilience.
Criteria for inclusion in this study required that all nurse participants were
English speaking, registered with the Nurses and Midwives Board of Western
Australia and that each had over five years' experience in the Western Australian
healthcare environment. This was to enable reflection on significant and ongoing
changes within the workplace as a possible source of resilient behaviours. REVIEW
METHODS: This is a methodological paper. DISCUSSION: Portraiture blends
aesthetics and empiricism while drawing on features of narrative, case study,
phenomenology and ethnography. The portraits stand as individual vignettes
revealing recognisable themes and enabling patterns of experience to emerge from
each topic being studied. Each portrait requires the researcher to constantly
reflect on the participant's experiences by incorporating ethnographic
observations, interview responses, impressionistic records, the interpretation of
context, and the researcher's experiences and insights. It is a methodology that
concentrates on success and positivity to immerse the reader in carefully painted
and perceptive stories of success and positivity in times of adversity.
CONCLUSION: This paper describes some of the hallmarks of the portraiture method,
one of which is to portray success and positivity, and points to the relationship
this approach may have with contemporary social science and positive psychology
research. IMPLICATIONS FOR RESEARCH/PRACTICE: The illumination of resilience as a
strategy to be learned and fostered in nurses in times of adversity has
implications for managers and nursing practice. Resilience education engenders a
more resilient workforce and has implications for nurses choosing to or being
able to stay in nursing during times of stress and adversity.
PMID- 25587862
TI - Reflecting on the use of photo elicitation with children.
AB - AIM: To reflect on the use of photo elicitation as a data collection method when
conducting research with primary school age children (nine to 11 years).
BACKGROUND: There is recognition that children feel an affinity with the visual
medium; as a result, visual methods can be useful when conducting research with
children. Photo elicitation is one such method, but there has been little
discussion of its use with primary school children within a health context. This
paper considers the main issues that researchers should consider. DATA SOURCES:
This paper draws on a research study conducted by the author that used an
ethnographic approach and photo elicitation to identify the assets underpinning
children's wellbeing. REVIEW METHODS: A reflective discussion is used to
highlight issues relating to the use of photo elicitation to collect data from
primary school children. DISCUSSION: Photo elicitation is not without its
challenges: it creates additional ethical considerations, and can be more time
consuming and expensive. However, children value the opportunity to be involved
in research and have their opinions sought, and photo elicitation provides a
method of collecting data that is appropriate for children's developmental and
cognitive maturational stages. CONCLUSION: Photo elicitation can be a positive
experience for children, and one that is not only fun and engaging, but that is
also empowering and valuing of their contributions. IMPLICATIONS FOR
RESEARCH/PRACTICE: Research that uses photo elicitation needs to be carefully
planned to ensure that the study is supported appropriately. The visual process
can offer a unique insight into children's lives that allows health professionals
to deepen their understanding of children's experiences.
PMID- 25587857
TI - Sirtuin 1: A Target for Kidney Diseases.
AB - Sirtuin 1 (SIRT1) is an evolutionarily conserved NAD(+)-dependent histone
deacetylase that is necessary for caloric restriction-related lifespan extension.
SIRT1, as an intracellular energy sensor, detects the concentration of
intracellular NAD(+) and uses this information to adapt cellular energy output to
cellular energy requirements. Previous studies on SIRT1 have confirmed its
beneficial effects on cellular immunity to oxidative stress, reduction of
fibrosis, suppression of inflammation, inhibition of apoptosis, regulation of
metabolism, induction of autophagy and regulation of blood pressure. All of the
above biological processes are involved in the pathogenesis of kidney diseases.
Therefore, the activation of SIRT1 may become a therapeutic target to improve the
clinical outcome of kidney diseases. In this review, we give an overview of SIRT1
and its molecular targets as well as SIRT1-modulated biological processes, with a
particular focus on the role of SIRT1 in kidney diseases.
PMID- 25587863
TI - Exploring interprofessional practices in rapid response systems: a case study
protocol.
AB - AIM: To describe the development of a proposed case study protocol investigating
interprofessional relationships in a rapid response system (RRS) in a
socioculturally complex clinical environment. BACKGROUND: Suboptimal care of
deteriorating ward patients remains a concern for many acute healthcare
organisations. Despite the advent of RRSs, emergency response teams are not
always used to their full potential. How and why interprofessional relationships
influence practices associated with the care and management of ward patients at
risk of clinical deterioration requires investigation. DATA SOURCES: Theoretical
and empirical literature describing case study research and RRSs. Review methods
An integrative review approach of the literature, focusing on key terms relating
to 'case study research' and 'rapid response system', provided context and
informed development of the study protocol. DISCUSSION: A single-site mixed
method instrumental case study protocol was developed using methodological
triangulation and a multi-level model to examine interprofessional relationships
between a broad range of stakeholders. Concurrent data collection and analysis
will occur using document review of clinical scenarios, non-participant
observations and semi-structured interviews. CONCLUSION: Case study research is
an effective method for investigating socioculturally complex clinical
environments. A strength of this approach is the flexibility in the choice of
methods, which allows the researcher to build the design most suitable for the
subjects or phenomena being investigated. Although this flexibility may be
considered a potential weakness, rigour can be achieved by application of the
strategies described. IMPLICATIONS FOR RESEARCH/PRACTICE: Findings from this
research will provide rich descriptive insights into RRS relationships and
healthcare professional practices during day-to-day management of acute ward
patients at risk of or experiencing clinical deterioration. Description of this
structured case study research approach will also inform other researchers.
PMID- 25587864
TI - The construction of context-mechanisms-outcomes in realistic evaluation.
AB - AIM: To discuss the construction of context-mechanisms-outcomes (CMOs) developed
as part of a realistic evaluation study of two aggression management training
programmes. BACKGROUND: Realistic evaluation draws on theories and methods
derived from the social sciences. It provides a distinctive account of the nature
of programmes and how they work. Realistic evaluation is a form of evaluation
that is driven by theory, and was based by Pawson and Tilley ( 1997 ) on the
philosophy of critical realism. Critical realism is an important perspective in
modern philosophy and social science, but it is largely absent in the field of
healthcare research. REVIEW METHODS: This paper provides a critical discussion on
the construction of CMOs as part of a realistic evaluation study. DATA SOURCES:
This paper draws on the personal experiences of the author in using realistic
evaluation to evaluate training in aggression management. DISCUSSION: Realistic
evaluation stresses four key linked concepts for explaining and understanding
programmes: 'mechanism', 'context', 'outcome pattern' and 'context-mechanisms
outcomes (CMO) pattern configuration'. A CMO configuration is a proposition
stating what it is about an initiative that works, for whom and in what
circumstances. In this way, the effectiveness of the programme is understood,
with an explanation of why the outcomes developed as they did and how the
programme was able to react to underlying mechanisms and in what contexts.
Therefore, a realistic evaluation researcher is not just inspecting outcomes to
see if an initiative (implementation) works, but is analysing the outcomes to
discover if the conjectured mechanism or context theories are confirmed. This
analysis provides not only evidence of effectiveness, but also an explanation
that helps to develop and improve the content and the targeting of future
programmes. CONCLUSION: The development of CMOs requires a great deal of skill on
the part of the researcher and requires a flexibility of approach when collecting
and analysing the data and in understanding the topic being investigated.
IMPLICATIONS FOR RESEARCH/PRACTICE: Applications of realistic evaluation have
focused largely on evaluating initiatives in the field of social policy and, more
recently, social work practice. To date, however, there have been few published
realistic evaluation studies within nursing; therefore this study is novel in its
use of the methodology.
PMID- 25587865
TI - Research methods for formal consensus development.
AB - AIM: This paper reviews three research methods for developing consensus.
BACKGROUND: Consensus statements and guidelines are increasingly used to clarify
and standardise practice, and inform health policy, when relevant and rigorous
evidence is lacking. Clinicians need to evaluate the quality of practice
guidelines to determine whether to incorporate them into clinical practice or
reject them. Formal methods of developing consensus provide a scientific method
that uses expert panel members to evaluate current evidence and expert opinions
to produce consensus statements for clinical problems. DATA SOURCES: Online
search for relevant literature was conducted in Medline and CINAHL. REVIEW
METHODS: A literature review of consensus, consensus development and research
methods papers published in English in peer-reviewed journals. DISCUSSION: The
three methods of developing consensus discussed are the Delphi technique, nominal
group technique and the consensus development conference. The techniques and
their respective advantages are described, and examples from the literature are
provided. The three methods are compared and a flowchart to assist researchers
selecting an appropriate method is included. Online resources with information on
the development and evaluation of clinical guidelines are reviewed. CONCLUSION:
This paper will help researchers to select an appropriate research method for
developing consensus statements and guidelines. IMPLICATIONS FOR
RESEARCH/PRACTICE: When developing consensus guidelines for clinical practice,
researchers should use a formal research method to ensure rigour and credibility.
PMID- 25587866
TI - Blogs as a way to elicit feedback on research and engage stakeholders.
AB - AIM: To reflect on the potential of blogs to enhance engagement with research,
create a dialogue between researchers and nurses, and provide feedback to
researchers. BACKGROUND: Blogs can create opportunities to share ideas, provide
an arena for interaction, and rapidly and effectively initiate dialogue and
feedback on research. DATA SOURCES: This paper draws on analysis of comments on a
blog post about the findings of a peer-reviewed journal article. REVIEW METHODS:
Content analysis of web blog discussion. DISCUSSION: It is unclear if the readers
of the blog would have accessed this article any other way. Therefore, posting
research findings on a blog can engage a new audience of nurses and provide a way
to feed back comments and responses to researchers. This highlights the potential
value of online forums for 'knowledge translation' and draws attention to virtual
collegiality, which can provide a way for nurses in diverse locations to share
their experiences and ideas, and gain support and information. CONCLUSION:
Research findings were brought to life through the participation of blog
commenters, who validated findings reported in the research. IMPLICATIONS FOR
PRACTICE/RESEARCH: Given the rapid uptake of social media, it is inevitable that
it will become an increasingly important feature of research. This paper
demonstrates how the nexus can occur between more formal social enquiry and less
formal engagement in critique and knowledge translation. The authors argue that
the rapid uptake and exchange of information through social media can provide an
indication of the social relevance of the research.
PMID- 25587867
TI - A gift for engaging all types of patients.
PMID- 25587871
TI - 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted decomposition of
difluorocarbene and the subsequent trifluoromethylation.
AB - Difluorocarbene derived from various carbene precursors could be effectively
decomposed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). This decomposition
process was successfully applied in the subsequent trifluoromethylation of a
variety of (hetero)aryl iodides without the addition of an external fluoride ion.
Mechanistic investigation revealed the detailed difluorocarbene conversion
process in which the decomposed difluorocarbene is finally transformed into a
fluoride ion and carbon monoxide.
PMID- 25587868
TI - DNA Sequence Modulates Geometrical Isomerism of the trans-8,9- Dihydro-8-(2,6
diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)- 9-hydroxy Aflatoxin B1 Adduct.
AB - Aflatoxin B(1) (AFB(1)), a mycotoxin produced by Aspergillus flavus, is oxidized
by cytochrome P450 enzymes to aflatoxin B(1)-8,9-epoxide, which alkylates DNA at
N7-dG. Under basic conditions, this N7-dG adduct rearranges to yield the trans
8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxy
aflatoxin B(1) (AFB(1)-FAPY) adduct. The AFB(1)-FAPY adduct exhibits geometrical
isomerism involving the formamide moiety. NMR analyses of duplex
oligodeoxynucleotides containing the 5'-XA-3', 5'-XC-3', 5'-XT-3', and 5'-XY-3'
sequences (X = AFB(1)-FAPY; Y = 7-deaza-dG)demonstrate that the equilibrium
between E and Z isomers is controlled by major groove hydrogen bonding
interactions.Structural analysis of the adduct in the 5'-XA-3' sequence indicates
the preference of the E isomer of the formamide group,attributed to formation of
a hydrogen bond between the formyl oxygen and the N(6) exocyclic amino group of
the 3'-neighboradenine. While the 5'-XA-3' sequence exhibits the E isomer, the 5'
XC-3' sequence exhibits a 7:3 E:Z ratio at equilibrium at 283K. The E isomer is
favored by a hydrogen bond between the formyl oxygen and the N(4)-dC exocyclic
amino group of the 3'-neighbor cytosine. The 5'-XT-3' and 5'-XY-3' sequences
cannot form such a hydrogen bond between the formyl oxygen and the 3'-neighbor T
or Y, respectively, and in these sequence contexts the Z isomer is favored.
Additional equilibria between alpha and beta anomers and the potential to exhibit
atropisomers about the C5-N(5) bond do not depend upon sequence. In each of the
four DNA sequences, the AFB(1)-FAPY adduct maintains the beta deoxyribose
configuration. Each of these four sequences feature the atropisomer of the AFB(1)
moiety that is intercalated above the 5'-face of the damaged guanine. This
enforces the Ra axialc onformation for the C5-N(5) bond.
PMID- 25587870
TI - DNA methylation abnormalities in congenital heart disease.
AB - Congenital heart defects represent the most common malformation at birth,
occurring also in ~50% of individuals with Down syndrome. Congenital heart
defects are thought to have multifactorial etiology, but the main causes are
largely unknown. We have explored the global methylation profile of fetal heart
DNA in comparison to blood DNA from control subjects: an absolute correlation
with the type of tissue was detected. Pathway analysis revealed a significant
enrichment of differential methylation at genes related to muscle contraction and
cardiomyopathies in the developing heart DNA. We have also searched for abnormal
methylation profiles on developing heart-tissue DNA of syndromic and non
syndromic congenital heart defects. On average, 3 regions with aberrant
methylation were detected per sample and 18 regions were found differentially
methylated between groups. Several epimutations were detected in candidate genes
involved in growth regulation, apoptosis and folate pathway. A likely pathogenic
hypermethylation of several intragenic sites at the MSX1 gene, involved in
outflow tract morphogenesis, was found in a fetus with isolated heart
malformation. In addition, hypermethylation of the GATA4 gene was present in
fetuses with Down syndrome with or without congenital heart defects, as well as
in fetuses with isolated heart malformations. Expression deregulation of the
abnormally methylated genes was detected. Our data indicate that epigenetic
alterations of relevant genes are present in developing heart DNA in fetuses with
both isolated and syndromic heart malformations. These epimutations likely
contribute to the pathogenesis of the malformation by cis-acting effects on gene
expression.
PMID- 25587872
TI - Deciphering the GPER/GPR30-agonist and antagonists interactions using molecular
modeling studies, molecular dynamics, and docking simulations.
AB - The G-protein coupled estrogen receptor 1 GPER/GPR30 is a transmembrane seven
helix (7TM) receptor involved in the growth and proliferation of breast cancer.
Due to the absence of a crystal structure of GPER/GPR30, in this work, molecular
modeling studies have been carried out to build a three-dimensional structure,
which was subsequently refined by molecular dynamics (MD) simulations (up to 120
ns). Furthermore, we explored GPER/GPR30's molecular recognition properties by
using reported agonist ligands (G1, estradiol (E2), tamoxifen, and fulvestrant)
and the antagonist ligands (G15 and G36) in subsequent docking studies. Our
results identified the E2 binding site on GPER/GPR30, as well as other receptor
cavities for accepting large volume ligands, through GPER/GPR30 pi-pi,
hydrophobic, and hydrogen bond interactions. Snapshots of the MD trajectory at 14
and 70 ns showed almost identical binding motifs for G1 and G15. It was also
observed that C107 interacts with the acetyl oxygen of G1 (at 14 ns) and that at
70 ns the residue E275 interacts with the acetyl group and with the oxygen from
the other agonist whereas the isopropyl group of G36 is oriented toward Met141,
suggesting that both C107 and E275 could be involved in the protein activation.
This contribution suggest that GPER1 has great structural changes which explain
its great capacity to accept diverse ligands, and also, the same ligand could be
recognized in different binding pose according to GPER structural conformations.
PMID- 25587874
TI - Duchenne muscular dystrophy gene therapy in the canine model.
AB - Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by
dystrophin deficiency. Gene therapy has significantly improved the outcome of
dystrophin-deficient mice. Yet, clinical translation has not resulted in the
expected benefits in human patients. This translational gap is largely due to the
insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show
minimum dystrophic symptoms and they do not respond to the gene therapy vector in
the same way as human patients do. Further, the size of a mouse is hundredfolds
smaller than a boy, making it impossible to scale-up gene therapy in a mouse
model. None of these limitations exist in the canine DMD (cDMD) model. For this
reason, cDMD dogs have been considered a highly valuable platform to test
experimental DMD gene therapy. Over the last three decades, a variety of gene
therapy approaches have been evaluated in cDMD dogs using a number of non-viral
and viral vectors. These studies have provided critical insight for the
development of an effective gene therapy protocol in human patients. This review
discusses the history, current status and future directions of the DMD gene
therapy in the canine model.
PMID- 25587873
TI - Gene expression in asthmatic airway smooth muscle: a mixed bag.
AB - It has long been known that airway smooth muscle (ASM) contraction contributes
significantly to the reversible airflow obstruction that defines asthma. It has
also been postulated that phenotypic changes in ASM contribute to the airway
hyper-responsiveness (AHR) that is a characteristic feature of asthma. Although
there is agreement that the mass of ASM surrounding the airways is significantly
increased in asthmatic compared with non-asthmatic airways, it is still uncertain
whether there are quantitative or qualitative changes in the level of expression
of the genes and proteins involved in the canonical contractile pathway in ASM
that could account for AHR. This review will summarize past attempts at
quantifying gene expression changes in the ASM of asthmatic lungs as well as non
asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of
consistent findings in asthmatic samples coupled with the relative concordance of
results from stimulated ASM cells suggests that changes to the contractility of
ASM tissues in asthma may be dependent on the presence of an inflammatory
environment surrounding the ASM layer. Removal of the ASM from this environment
could explain why hypercontractility is rarely seen ex vivo.
PMID- 25587875
TI - Emergence of Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter
baumannii Clinical Isolates Collected from Some Libyan Hospitals.
AB - The aim of the present study was to investigate the molecular mechanism of
carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii
clinical isolates recovered from Libyan hospitals between April 2013 and April
2014. In total, 49 strains (24 P. aeruginosa and 25 A. baumannii) were isolated,
including 21 P. aeruginosa and 22 A. baumannii isolates (87.75%) resistant to
imipenem (minimum inhibitory concentrations >=16 MUg/ml). The blaVIM-2 gene was
detected in 19 P. aeruginosa isolates. All imipenem-resistant P. aeruginosa
isolates showed the presence of OprD mutations. Acquired OXA-carbapenemase
encoding genes were present in all A. baumannii isolates: blaOXA-23 (n=19) and
blaOXA-24 (n=3). Finally, a total of 13 and 17 different sequence types were
assigned to the 21 P. aeruginosa and the 22 A. baumannii carbapenem-resistant
isolates, respectively. This study is the first report describing imipenem
resistant P. aeruginosa and A. baumannii isolated from patients in Libya. We
report the first case of co-occurrence of blaVIM-2 with oprD porin loss in
identical isolates of P. aeruginosa in Libya and demonstrate that these oprD
mutations can be used as a tool to study the clonality in P. aeruginosa isolates.
We also report the first identification of multidrug-resistant A. baumannii
isolates harboring blaOXA-23-like, blaOXA-24-like, and blaOXA-48-like genes in
Libya.
PMID- 25587876
TI - Modeling flight attendants' exposure to secondhand smoke in commercial aircraft:
historical trends from 1955 to 1989.
AB - Flight attendants were exposed to elevated levels of secondhand smoke (SHS) in
commercial aircraft when smoking was allowed on planes. During flight attendants'
working years, their occupational SHS exposure was influenced by various factors,
including the prevalence of active smokers on planes, fliers' smoking behaviors,
airplane flight load factors, and ventilation systems. These factors have likely
changed over the past six decades and would affect SHS concentrations in
commercial aircraft. However, changes in flight attendants' exposure to SHS have
not been examined in the literature. This study estimates the magnitude of the
changes and the historic trends of flight attendants' SHS exposure in U.S.
domestic commercial aircraft by integrating historical changes of contributing
factors. Mass balance models were developed and evaluated to estimate flight
attendants' exposure to SHS in passenger cabins, as indicated by two commonly
used tracers (airborne nicotine and particulate matter (PM)). Monte Carlo
simulations integrating historical trends and distributions of influence factors
were used to simulate 10,000 flight attendants' exposure to SHS on commercial
flights from 1955 to 1989. These models indicate that annual mean SHS PM
concentrations to which flight attendants were exposed in passenger cabins
steadily decreased from approximately 265 MUg/m(3) in 1955 and 1960 to 93
MUg/m(3) by 1989, and airborne nicotine exposure among flight attendants also
decreased from 11.1 MUg/m(3) in 1955 to 6.5 MUg/m(3) in 1989. Using duration of
employment as an indicator of flight attendants' cumulative occupational exposure
to SHS in epidemiological studies would inaccurately assess their lifetime
exposures and thus bias the relationship between the exposure and health effects.
This historical trend should be considered in future epidemiological studies.
PMID- 25587877
TI - Positional quality assessment of orthophotos obtained from sensors onboard multi
rotor UAV platforms.
AB - In this study we explored the positional quality of orthophotos obtained by an
unmanned aerial vehicle (UAV). A multi-rotor UAV was used to obtain images using
a vertically mounted digital camera. The flight was processed taking into account
the photogrammetry workflow: perform the aerial triangulation, generate a digital
surface model, orthorectify individual images and finally obtain a mosaic image
or final orthophoto. The UAV orthophotos were assessed with various spatial
quality tests used by national mapping agencies (NMAs). Results showed that the
orthophotos satisfactorily passed the spatial quality tests and are therefore a
useful tool for NMAs in their production flowchart.
PMID- 25587878
TI - Dual-tree complex wavelet transform and image block residual-based multi-focus
image fusion in visual sensor networks.
AB - This paper presents a novel framework for the fusion of multi-focus images
explicitly designed for visual sensor network (VSN) environments. Multi-scale
based fusion methods can often obtain fused images with good visual effect.
However, because of the defects of the fusion rules, it is almost impossible to
completely avoid the loss of useful information in the thus obtained fused
images. The proposed fusion scheme can be divided into two processes: initial
fusion and final fusion. The initial fusion is based on a dual-tree complex
wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast
and SML are employed to fuse the low- and high-frequency coefficients,
respectively, and an initial composited image is obtained. In the final fusion
process, the image block residuals technique and consistency verification are
used to detect the focusing areas and then a decision map is obtained. The map is
used to guide how to achieve the final fused image. The performance of the
proposed method was extensively tested on a number of multi-focus images,
including no-referenced images, referenced images, and images with different
noise levels. The experimental results clearly indicate that the proposed method
outperformed various state-of-the-art fusion methods, in terms of both subjective
and objective evaluations, and is more suitable for VSNs.
PMID- 25587879
TI - Measurement of gas-liquid two-phase flow in micro-pipes by a capacitance sensor.
AB - A capacitance measurement system is developed for the measurement of gas-liquid
two-phase flow in glass micro-pipes with inner diameters of 3.96, 2.65 and 1.56
mm, respectively. As a typical flow regime in a micro-pipe two-phase flow system,
slug flow is chosen for this investigation. A capacitance sensor is designed and
a high-resolution and high-speed capacitance measurement circuit is used to
measure the small capacitance signals based on the differential sampling method.
The performance and feasibility of the capacitance method are investigated and
discussed. The capacitance signal is analyzed, which can reflect the voidage
variation of two-phase flow. The gas slug velocity is determined through a cross
correlation technique using two identical capacitance sensors. The simulation and
experimental results show that the presented capacitance measurement system is
successful. Research work also verifies that the capacitance sensor is an
effective method for the measurement of gas liquid two-phase flow parameters in
micro-pipes.
PMID- 25587880
TI - "As needed" case management across aging services in response to depression.
AB - A lack of clarity on how and where case management for older adults is delivered
persists, even as evidence supports its use to respond to depression. We used in
depth interviews with managers (n = 20) and staff surveys (n = 142) from 17
service agencies to explore the provision of case management services in adult
day services, homecare, senior centers, and supportive housing. Limited case
management services were found. Barriers included limited time and resources,
especially for senior centers and supportive housing. Results revealed a concern
about the role, feasibility, and availability of case management for older adults
within these settings.
PMID- 25587881
TI - Low-dose Anti-thymocyte Globulin Inhibits Human B-cell Differentiation into
Antibody-Secreting Cells.
AB - Anti-thymocyte globulin (ATG) is used in the treatment of acute organ rejection.
We studied in vitro the effect of low-dose ATG on B-cell activation and
differentiation to antibody-secreting cells, as this may have an effect on B cell
driven autoimmune diseases, such as pemphigus vulgaris. Immunoglobulin production
was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) and
CD19+ B cells from healthy donors and from patients with different autoimmune
diseases. B-cell proliferation, viability and differentiation were analysed using
flow cytometry. Differentiation of B cells to immunoglobulin G (IgG) secreting
cells was significantly reduced by ATG, but not by control unspecific IgG from
non-immunized rabbits (rIgG). B-cell viability was not altered by sub-depleting
concentrations of ATG. In contrast, B-cell proliferation was enhanced by ATG.
When PBMC from patients with autoimmune diseases were studied, specific
autoantibodies could be detected in 1 out of 10 patients. In this patient, who
had pemphigus vulgaris, ATG not only decreased total IgG, but decreased also
specific anti-desmoglein-3. In conclusion, these data suggest that ATG at low
concentrations inhibits B-cell differentiation and function.
PMID- 25587882
TI - Edema and telangiectasia of the chest caused by neuroendocrine carcinoma.
PMID- 25587883
TI - Reliability of arterial spin labelling measurements of perfusion within the
quadriceps during steady-state exercise.
AB - Arterial spin labelling (ASL) provides a potential method to non-invasively
determine muscle blood flow and examine the impact of interventions such as
supplementation and training. However, it's a method with intrinsically low
signal, leading to limitations in accuracy and temporal resolution. To examine
these limitations, the current study measured perfusion via ASL on three
occasions in the rectus femoris of 10 healthy adults, during light and moderate
exercise, over three different exercise durations. For data sampled over 9 min,
light intensity exercise gave an average perfusion of 35.0 +/- 5.1 ml/min.100g(
1) with a coefficient of variation (COV) of 16% and single intraclass correlation
coefficient (ICC) of 0.67. For the moderate bout, perfusion was 51.3 +/- 5.6
ml/min.100g(-1) (COV 10%, ICC 0.82). When the same data were analyzed over 5 min
24 s, perfusion was 37.8 +/- 11.13 (COV 30%, ICC 0.13) during light and 49.5 +/-
8.8 ml/min.100g(-1) (COV 18%, ICC 0.52) during moderate exercise. When sampling
was reduced to 1 min 48 s, perfusion was 41.2 +/- 13.7 (COV 33%, ICC 0.26) during
light and 49.5 +/- 13.6 ml/min.100g(-1) (COV 28%, ICC 0.04) during moderate
exercise. For 9 min a significant perfusion difference was found between the
exercise intensities; however, this was not the case for sampling over 5 min 24 s
or 1 min 48 s. Such findings illustrate the potential of ASL to non-invasively
monitor muscle perfusion under steady-state conditions, but highlight that
extended exercise protocols are necessary in order to generate date of sufficient
reliability to be able to discriminate intervention dependent perfusion
differences.
PMID- 25587884
TI - Spectroscopic and crystallographic investigations of novel BODIPY-derived metal
organic frameworks.
AB - To explore new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-derived metal
organic frameworks (MOFs), we employed 2,6-dicarboxyl-1,3,5,7-tetramethyl-8
phenyl-4,4-difluoroboradiazaindacene (H2L) as a ligand to successfully synthesize
five coordination polymers, namely, {[Zn2(L)2(bpp)].2H2O.2EtOH}n (1),
{[Cd2(L)2(bpp)].2H2O.EtOH}n (2), {[Cd2(L)(bpe)3(NO3)2].2H2O.DMF.EtOH}n (3),
{[Cd(L)(bpe)0.5(DMF)(H2O)]}n (4), and {[Cd(L)(bpe)0.5].1.5H2O.DMF}n (5) (bpp =
1,3-bi(4-pyridyl)propane, bpe = 1,2-bi(4-pyridyl)ethane). Except for two 2D-layer
coordination polymers 3 and 4, the rest samples exhibit 3D metal-organic
frameworks with certain pore sizes, especially MOFs 1 and 5. Spectroscopic and
crystallographic investigations demonstrate that the absorption and emission
energies of the BODIPY chromophores are sensitive to the coordination modes.
Moreover, in case 2, the transition metal centers coordinated with the
dicarboxylate ligands L(2-) are capable of forming the two BODIPY units in
coplanar arrangements (theta = 37.9 degrees ), simultaneously suppressing the
uncommon J-dimer absorption band centered at 705 nm with a long tail into the
near-infrared region at room temperature. On the other hand, in comparison with
the ligand H2L, the emission of monomer-like BODIPY in case 3 is enhanced in the
solid state by a considerably long distance between the parallel BODIPY planes
(about 14.0 A).
PMID- 25587886
TI - The challenge of quality improvement in surgical care.
PMID- 25587887
TI - [Functional differences in the microcirculatory units of the eye].
AB - This review describes the most important regions of microcirculation within the
eye - their architecture as well as their function. A special emphasis is put on
the functional heterogeneity of the microvessels and their role regarding the
specific functions localised within the different regions of the eye (e.g. oxygen
release by the iris capillaries, production of aqueous humor within the ciliary
processes). The microvasculature of choroidea and retina will be described in
more detail. The precise adjustment of the blood flow to the functional needs of
the inner retina is a very important aspect in the retinal vessels. Here, also
pericytes can influence the vessel calibre like in the brain capillaries. Very
important is the vascular reaction in general to states of hypoxia, especially to
the hypoxic and radical producing states within the photoreceptors. The following
reaction of neovascularisation will also be examined. Finally, we describe the
metabolic situation of the ganglion cells and nerve fibers leading to and within
the optic cup also with regard to glaucoma.
PMID- 25587885
TI - Linker of nucleoskeleton and cytoskeleton (LINC) complex-mediated actin-dependent
nuclear positioning orients centrosomes in migrating myoblasts.
AB - Myoblast migration is essential for muscle development and repair; however, the
factors that contribute to the polarity of migrating myoblasts are relatively
unknown. We find that randomly migrating C2C12 myoblasts orient their centrosomes
in the direction of migration. Using wounded monolayers, we further show that
centrosome orientation is stimulated by the serum factor lysophosphatidic acid
(LPA) and involves the rearward movement of the nucleus while the centrosome is
maintained at the cell centroid. The rate of nuclear movement correlated with
that of actin retrograde flow and both cytochalasin D and blebbistatin prevented
nuclear movement and centrosome orientation. Actin-dependent rearward nuclear
movement in fibroblasts is mediated by assembly of nuclear membrane nesprin-2G
and SUN2 LINC complexes into transmembrane actin-associated nuclear (TAN) lines
anchored by A-type lamins and emerin. In C2C12 myoblasts, depletion of nesprin
2G, SUN2 or lamin A/C prevented nuclear movement and endogenous nesprin-2G and a
chimeric GFP-mini-nesprin-2G formed TAN lines during nuclear movement. Depleting
nesprin-2G strongly interfered with directed cell migration and reduced the
efficiency of myoblast fusion into multinucleated myotubes. Our results show that
nuclear movement contributes to centrosome orientation and polarity for efficient
migration and fusion of myoblasts. Given that mutations in the genes encoding A
type lamins, nesprin-2 and SUN2 cause Emery-Dreifuss muscular dystrophy and
related myopathies, our results have implications for understanding the mechanism
of disease pathogenesis.
PMID- 25587889
TI - Control or non-control state: that is the question! An asynchronous visual P300
based BCI approach.
AB - OBJECTIVE: Brain-computer interfaces (BCI) based on event-related potentials
(ERP) were proven to be a reliable synchronous communication method. For everyday
life situations, however, this synchronous mode is impractical because the system
will deliver a selection even if the user is not paying attention to the
stimulation. So far, research into attention-aware visual ERP-BCIs (i.e.,
asynchronous ERP-BCIs) has led to variable success. In this study, we investigate
new approaches for detection of user engagement. APPROACH: Classifier output and
frequency-domain features of electroencephalogram signals as well as the
hybridization of them were used to detect the user's state. We tested their
capabilities for state detection in different control scenarios on offline data
from 21 healthy volunteers. MAIN RESULTS: The hybridization of classifier output
and frequency-domain features outperformed the results of the single methods, and
allowed building an asynchronous P300-based BCI with an average correct state
detection accuracy of more than 95%. SIGNIFICANCE: Our results show that all
introduced approaches for state detection in an asynchronous P300-based BCI can
effectively avoid involuntary selections, and that the hybrid method is the most
effective approach.
PMID- 25587890
TI - Over reporting of congenital syphilis in Guangzhou, China.
AB - The purpose of this study was to evaluate the rationality of congenital syphilis
(CS) cases reported by physicians in hospitals of various levels in Guangzhou,
China. The over-reporting rate was calculated. The results suggested that 49.1%
(54 out of 110) of the CS cases reviewed were identified as cases that should be
reported; 18 of the 54 CS case were confirmed CS cases and 50.9% (56 out of 110)
were identified as over reported. Factors associated with CS case
misclassification were analysed. To decrease the incidence of CS, antenatal care
management and rapid plasma reagin titres should be provided and the follow up
for children should be raised.
PMID- 25587888
TI - The first structure-activity relationship studies for designer receptors
exclusively activated by designer drugs.
AB - Over the past decade, two independent technologies have emerged and been widely
adopted by the neuroscience community for remotely controlling neuronal activity:
optogenetics which utilize engineered channelrhodopsin and other opsins, and
chemogenetics which utilize engineered G protein-coupled receptors (Designer
Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other
orthologous ligand-receptor pairs. Using directed molecular evolution, two types
of DREADDs derived from human muscarinic acetylcholine receptors have been
developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits
neuronal firing. Importantly, these DREADDs were not activated by the native
ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO),
a pharmacologically inert ligand. CNO has been used extensively in rodent models
to activate DREADDs, and although CNO is not subject to significant metabolic
transformation in mice, a small fraction of CNO is apparently metabolized to
clozapine in humans and guinea pigs, lessening the translational potential of
DREADDs. To effectively translate the DREADD technology, the next generation of
DREADD agonists are needed and a thorough understanding of structure-activity
relationships (SARs) of DREADDs is required for developing such ligands. We
therefore conducted the first SAR studies of hM3Dq. We explored multiple regions
of the scaffold represented by CNO, identified interesting SAR trends, and
discovered several compounds that are very potent hM3Dq agonists but do not
activate the native human M3 receptor (hM3). We also discovered that the approved
drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq
over hM3.
PMID- 25587893
TI - A survey of the European Venous Forum on education and training in venous surgery
and phlebology in Europe.
AB - AIM: Venous training in Europe is lacking a formal curriculum among various
specialties related to management of venous diseases. We conducted a survey in
order to have a snapshot on the actual education and training level among
physicians practicing currently venous surgery and phlebology in Europe. METHODS:
From April 7, 2014 to June 11, 2014 a survey was carried out using the Survey
Monkey system, including 11 main questions covering all the domains of training
and education in venous surgery and phlebology. The questionnaire was sent to all
physicians included in the current mailing list of the European Venous Forum
(EVF) and the Mediterranean League of Angiology and Vascular Surgery. Two
questions were particularly addressed to those physicians who had attended the
EVF hands-on workshop (HOW) at least once. RESULTS: The response rate was 24%
(97/400) and 51.5% of them were practicing in a hospital service. Most responders
were vascular surgeons (67.7%), followed by angiologists (19.4%). Only half of
the responders felt as being competent to manage the whole spectrum of venous
diseases successfully after completion of their training, while a few were able
to perform endovenous ablations and even less more advanced venous interventions.
Formal training in Duplex ultrasound was undertaken only in 55.2%. The majority
suggested that a venous training program should be a separate part of their
specialty rotation and should be organized at a national or European level, or
even by a specific scientific society. Over 95% of those physicians who already
participated in the EVF HOW considered the knowledge they acquired there as
useful for their practice. CONCLUSION: There is currently an important need for
more specialized venous training for all physicians involved in the diagnosis and
management of venous diseases. Therefore all local, national and international
initiatives should be encouraged to improve education in this field.
PMID- 25587892
TI - Telemedicine: interventional decentralised blood pressure telemonitoring
(idTBPM).
AB - Telemedicine comprises different methods of bridging a spatial distance between
doctor, medical and care services and patients. These include mere data
transmissions as well as alarm functionalities, consultations and therapy
recommendations. A special form of telemedicine application is the interventional
decentralised telemonitoring (idTM). Here the patient-practitioner relationship
forms the basis for therapy control and optimisation using telemetrical medical
data. To identify areas of indication of idTM, a detailed definition of
transferred parameters, alarm conditions and intervention algorithms is required
as a well as cost efficiency and feasibility studies. The quality of the
telemedical application is determined by the medical quality of the derived
actions.
PMID- 25587891
TI - Design of a pulsatile flow facility to evaluate thrombogenic potential of
implantable cardiac devices.
AB - Due to expensive nature of clinical trials, implantable cardiac devices should
first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an
important class of these devices, have been shown to be associated with
thromboembolic complications. Although various in vitro systems have been
designed to quantify blood-cell damage and platelet activation caused by
nonphysiological hemodynamic shear stresses in these PHVs, very few systems
attempt to characterize both blood damage and fluid dynamics aspects of PHVs in
the same test system. Various numerical modeling methodologies are also evolving
to simulate the structural mechanics, fluid mechanics, and blood damage aspects
of these devices. This article presents a completely hemocompatible small-volume
test-platform that can be used for thrombogenicity studies and experimental fluid
mechanics characterization. Using a programmable piston pump to drive freshly
drawn human blood inside a cylindrical column, the presented system can simulate
various physiological and pathophysiological conditions in testing PHVs. The
system includes a modular device-mounting chamber, and in this presented case, a
23 mm St. Jude Medical (SJM) Regents(r) mechanical heart valve (MHV) in aortic
position was used as the test device. The system was validated for its capability
to quantify blood damage by measuring blood damage induced by the tester itself
(using freshly drawn whole human blood). Blood damage levels were ascertained
through clinically relevant assays on human blood while fluid dynamics were
characterized using time-resolved particle image velocimetry (PIV) using a blood
mimicking fluid. Blood damage induced by the tester itself, assessed through
Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis
(Drabkins assay), was within clinically accepted levels. The hydrodynamic
performance of the tester showed consistent, repeatable physiological pressure
and flow conditions. In addition, the system contains proximity sensors to
accurately capture leaflet motion during the entire cardiac cycle. The PIV
results showed skewing of the leakage jet, caused by the asymmetric closing of
the two leaflets. All these results are critical to characterizing the blood
damage and fluid dynamics characteristics of the SJM Regents(r) MHV, proving the
utility of this tester as a precise system for assessing the hemodynamics and
thrombogenicity for various PHVs.
PMID- 25587894
TI - 'Even though it's a small checkbox, it's a big deal': stresses and strains of
managing sexual identity(s) on Facebook.
AB - Facebook offers a socialisation context in which young people from ethnic, gender
and sexual minorities must continually manage the potential for prejudice and
discrimination in the form of homophobia and racism. In-depth interviews were
conducted with eight young women, aged 16-19 years, who self-identified as queer
and as women of colour. A detailed analysis of these interviews--focusing in
particular on how young people described navigating expectations of rejection
from family and friends--offered insight into the psychological and health
consequences associated with managing sexual identity(s) while online. The
'closet' ultimately takes on new meaning in this virtual space: participants
described trying to develop social relationships within Facebook, which demands
sharing one's thoughts, behaviours and ideas, while also hiding and silencing
their emerging sexuality. In this 'virtual closet', tempering self-presentation
to offset social exclusion has become a continuous, yet personally treacherous,
activity during the daily practice of using Facebook.
PMID- 25587895
TI - Keratin-chitosan membranes as scaffold for tissue engineering of human cornea.
AB - PURPOSE: To study the attachment and growth of human corneal cells on keratin
chitosan membranes. The end goal is to develop a bioengineered cornea based on
this material. METHODS: Keratin-chitosan membranes were prepared as previously
described by Tanabe et al., 2002. Briefly, 7.15 mg/cm2 of keratin dialysate was
mixed with 10 wt% chitosan solution and 20 wt% glycerol. The solution was cast
into a silicone mold and dried at 50oC for 36 hours. Eyes were attained from a
local eye bank after penetrant-keratoplastic surgery. Human epithelial, stromal
and endothelial cells were obtained of the limbal, stromal and endothelial
regions. Cells were cultured on keratin-chitosan membranes, as well as on plastic
dishes as controls. When cultured cells reached confluence, they were fixed,
incubated with primary antibodies (E-cadherin, cytokeratin high molecular weight
(CK), vimentin and Na+/K+ ATPase) and visualized by indirect immunocytochemistry.
RESULTS: Epithelial, stromal and endothelial cells were able to attach and grow
on keratin-chitosan membranes. All the cells maintained their morphology and
cellular markers, both in the membrane and on the culture plate. Epithelial cells
stained positively for CK and E-cadherin. A positive vimentin stain was observed
in all stromal cells, while endothelial cells were positive for vimentin and
Na+/K+ ATPase, but negative for E-cadherin. CONCLUSIONS: Keratin-chitosan
membranes have been shown to be a good scaffold for culturing epithelial, stromal
and endothelial corneal cells; therefore, future applications of keratin-chitosan
membranes may be developed for reconstruction of the cornea.
PMID- 25587896
TI - Combining agent-based modeling and life cycle assessment for the evaluation of
mobility policies.
AB - This article presents agent-based modeling (ABM) as a novel approach for
consequential life cycle assessment (C-LCA) of large scale policies, more
specifically mobility-related policies. The approach is validated at the
Luxembourgish level (as a first case study). The agent-based model simulates the
car market (sales, use, and dismantling) of the population of users in the period
2013-2020, following the implementation of different mobility policies and
available electric vehicles. The resulting changes in the car fleet composition
as well as the hourly uses of the vehicles are then used to derive consistent LCA
results, representing the consequences of the policies. Policies will have
significant environmental consequences: when using ReCiPe2008, we observe a
decrease of global warming, fossil depletion, acidification, ozone depletion, and
photochemical ozone formation and an increase of metal depletion, ionizing
radiations, marine eutrophication, and particulate matter formation. The study
clearly shows that the extrapolation of LCA results for the circulating fleet at
national scale following the introduction of the policies from the LCAs of single
vehicles by simple up-scaling (using hypothetical deployment scenarios) would be
flawed. The inventory has to be directly conducted at full scale and to this aim,
ABM is indeed a promising approach, as it allows identifying and quantifying
emerging effects while modeling the Life Cycle Inventory of vehicles at
microscale through the concept of agents.
PMID- 25587897
TI - Detailed phenotypic and molecular analyses of genetically modified mice generated
by CRISPR-Cas9-mediated editing.
AB - The bacterial CRISPR-Cas9 system has been adapted for use as a genome editing
tool. While several recent reports have indicated that successful genome editing
of mice can be achieved, detailed phenotypic and molecular analyses of the mutant
animals are limited. Following pronuclear micro-injection of fertilized eggs with
either wild-type Cas9 or the nickase mutant (D10A) and single or paired guide RNA
(sgRNA) for targeting of the tyrosinase (Tyr) gene, we assessed genome editing in
mice using rapid phenotypic readouts (eye and coat color). Mutant mice with
insertions or deletions (indels) in Tyr were efficiently generated without
detectable off-target cleavage events. Gene correction of a single nucleotide by
homologous recombination (HR) could only occur when the sgRNA recognition sites
in the donor DNA were modified. Gene repair did not occur if the donor DNA was
not modified because Cas9 catalytic activity was completely inhibited. Our
results indicate that allelic mosaicism can occur following -Cas9-mediated
editing in mice and appears to correlate with sgRNA cleavage efficiency at the
single-cell stage. We also show that larger than expected deletions may be
overlooked based on the screening strategy employed. An unbiased analysis of all
the deleted nucleotides in our experiments revealed that the highest frequencies
of nucleotide deletions were clustered around the predicted Cas9 cleavage sites,
with slightly broader distributions than expected. Finally, additional analysis
of founder mice and their offspring indicate that their general health,
fertility, and the transmission of genetic changes were not compromised. These
results provide the foundation to interpret and predict the diverse outcomes
following CRISPR-Cas9-mediated genome editing experiments in mice.
PMID- 25587899
TI - Transcription activator-like effector nuclease (TALEN)-mediated CLYBL targeting
enables enhanced transgene expression and one-step generation of dual reporter
human induced pluripotent stem cell (iPSC) and neural stem cell (NSC) lines.
AB - Targeted genome engineering to robustly express transgenes is an essential
methodology for stem cell-based research and therapy. Although designer nucleases
have been used to drastically enhance gene editing efficiency, targeted addition
and stable expression of transgenes to date is limited at single gene/locus and
mostly PPP1R12C/AAVS1 in human stem cells. Here we constructed transcription
activator-like effector nucleases (TALENs) targeting the safe-harbor like gene
CLYBL to mediate reporter gene integration at 38%-58% efficiency, and used both
AAVS1-TALENs and CLYBL-TALENs to simultaneously knock-in multiple reporter genes
at dual safe-harbor loci in human induced pluripotent stem cells (iPSCs) and
neural stem cells (NSCs). The CLYBL-TALEN engineered cell lines maintained robust
reporter expression during self-renewal and differentiation, and revealed that
CLYBL targeting resulted in stronger transgene expression and less perturbation
on local gene expression than PPP1R12C/AAVS1. TALEN-mediated CLYBL engineering
provides improved transgene expression and options for multiple genetic
modification in human stem cells.
PMID- 25587898
TI - Prevention of herpes simplex virus induced stromal keratitis by a glycoprotein B
specific monoclonal antibody.
AB - The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in
patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis
(HSK) is a major health problem in industrialized countries and often results in
blindness. To overcome this obstacle, we have previously developed an HSV-gB
specific monoclonal antibody (mAb 2c) that proved to be highly protective in
immunodeficient NOD/SCID-mice towards genital infections. In the present study,
we examined the effectivity of mAb 2c in preventing the immunopathological
disease HSK in the HSK BALB/c mouse model. Therefore, mice were inoculated with
HSV-1 strain KOS on the scarified cornea to induce HSK and subsequently either
systemically or topically treated with mAb 2c. Systemic treatment was performed
by intravenous administration of mAb 2c 24 h prior to infection (pre-exposure
prophylaxis) or 24, 40, and 56 hours after infection (post-exposure
immunotherapy). Topical treatment was performed by periodical inoculations (5
times per day) of antibody-containing eye drops as control, starting at 24 h post
infection. Systemic antibody treatment markedly reduced viral loads at the site
of infection and completely protected mice from developing HSK. The
administration of the antiviral antibody prior or post infection was equally
effective. Topical treatment had no improving effect on the severity of HSK. In
conclusion, our data demonstrate that mAb 2c proved to be an excellent drug for
the treatment of corneal HSV-infections and for prevention of HSK and blindness.
Moreover, the humanized counterpart (mAb hu2c) was equally effective in
protecting mice from HSV-induced HSK when compared to the parental mouse
antibody. These results warrant the future development of this antibody as a
novel approach for the treatment of corneal HSV-infections in humans.
PMID- 25587901
TI - Action control bridges the planning-behaviour gap: a longitudinal study on
physical exercise in young adults.
AB - OBJECTIVES: Maintaining physical exercise levels may not only require motivation
and planning but also action control which is supposed to mediate between
planning and exercise. DESIGN: Behavioural intention, action planning, coping
planning and past behaviour were assessed at baseline, and action control and
concurrent exercise were measured one month later in 497 young adults. METHOD:
Three nested structural models were specified to examine different mediation
mechanisms. One model reflected the intention-planning-behaviour chain, the other
one focused on the intention-action control-behaviour chain and the third model
comprised the full sequence. RESULTS: Indirect effects from intentions on
exercise involved either planning or action control as mediating variables. In
Model 3, all three constructs (action planning, coping planning and action
control) were sequential mediators between intentions and later physical exercise
levels. Action and coping planning were not directly but indirectly related to
exercise via action control. CONCLUSIONS: Findings support the sequential
mediation for planning and action control as antecedents of physical exercise.
Action control is needed for exercise, because planning in itself is not always
sufficient. Maintaining exercise levels may be attributed to effective self
regulatory strategies such as action control in combination with planning.
PMID- 25587900
TI - A behaviorally-explicit approach for delivering vaccine baits to mesopredators to
control epizootics in fragmented landscapes.
AB - Despite the widespread use of aerial baiting to manage epizootics among free
ranging populations, particularly in rabies management, bait acceptance and
seroconversion rates often are lower than required to eliminate spread of
disease. Our objectives in this study, therefore, were to evaluate the
performance of stratified bait distribution models derived from resource
selection functions (RSF) on uptake of placebo rabies baits by raccoons (Procyon
lotor) and Virginia opossums (Didelphis virginiana), as well as the probability
of bait uptake as a function of proximity to bait distribution areas in
fragmented agricultural ecosystems. Among 478 raccoons and 108 opossums evaluated
for presence of Rhodamine B (RB) across 8 sites, only 26% of raccoons and 20% of
opossums exhibited marking consistent with bait consumption 14-24 days post
baiting. The effective area treated, based on 90% kernel density estimators of
marked individuals, ranged from 99-240 ha larger than bait distribution zones,
with RB marked individuals captured up to 753 m beyond the bait zone. Despite
incorporation of RSF data into bait distribution models, no differences in uptake
rates were observed between treatment and control sites. These data likely
reflect the underlying constraints imposed by the loss and fragmentation of
habitat on animal movement in heterogeneous landscapes, forcing individuals to
optimize movements at coarse (i.e., patch-level) rather than fine spatial scales
in highly fragmented environments. Our data also confirm that the probability of
bait acceptance decreases with increasing distance from bait zone interiors, even
within the zone itself. Thus, although bait acceptance was confirmed beyond bait
zone boundaries, the proportion of vaccinated individuals may comprise a small
minority of the population at increasing distances from baiting interiors. These
data suggest focal baiting creates a buffered area of treated individuals around
bait zones or bait stations, but repeated treatments may be needed to achieve
sufficient uptake to eradicate disease.
PMID- 25587902
TI - Transforming growth factor beta1 and aldosterone.
AB - PURPOSE OF REVIEW: It is well established that blocking the renin-angiotensin
aldosterone system (RAAS) is effective for the treatment of cardiovascular and
renal complications in hypertension and diabetes mellitus. Although the induction
of transforming growth factor beta1 (TGFbeta1) by components of the RAAS mediates
the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it
is still controversial as to whether TGFbeta1 can be a target to prevent such
complications. Here, we review recent findings on the role of TGFbeta1 in fluid
homeostasis, focusing on the relationship with aldosterone. RECENT FINDINGS:
TGFbeta1 suppresses the adrenal production of aldosterone and renal tubular
sodium reabsorption. We have generated mice with TGFbeta1 mRNA expression graded
in five steps, from 10 to 300% of normal, and found that blood pressure and
plasma volume are negatively regulated by TGFbeta1. Notably, the 10% hypomorph
exhibits primary aldosteronism and sodium and water retention due to markedly
impaired urinary excretion of water and electrolytes. SUMMARY: These results
identify TGFbeta signalling as an important counterregulatory system against
aldosterone. Understanding the molecular mechanisms for the suppressive effects
of TGFbeta1 on adrenocortical and renal function may further our understanding of
primary aldosteronism, as well as assist in the development of novel therapeutic
strategies for hypertension.
PMID- 25587904
TI - Hydrogen sulfide: role in vascular physiology and pathology.
AB - PURPOSE OF REVIEW: Hydrogen sulfide (H2S), a colorless gas that is endogenously
generated in mammals from cysteine, has important biological functions. Within
the vasculature it regulates vessel tone and outgrowth of new vessels. This
review summarizes recent literature on H2S signaling in the vasculature and its
therapeutic potential in vascular disorders RECENT FINDINGS: H2S is able to
induce vasorelaxation via ATP-sensitive potassium channels in vascular smooth
muscle cells. Large-conductance calcium-dependent K+-channels and Kv7 voltage
gated K+-channels are also involved in H2S signaling. Vascular endothelial growth
factor is the key downstream mediator that is involved in H2S induced
angiogenesis. By having both direct effects on its receptor and increasing the
bioavailability of vascular endothelial growth factor, H2S is proangiogenic. H2S
based therapies in vascular diseases are an expanding area of research. The
applications of several compounds, such as natural donors and synthetic slow
release compounds, have been extensively studied in vascular diseases such as
hypertension, ischemia-reperfusion disorders and preeclampsia. SUMMARY: H2S has a
key role in vascular homeostasis during physiology and in pathological states.
H2S-based therapies may have a role in several vascular diseases.
PMID- 25587903
TI - Molecular mechanisms regulating vascular tone by peroxisome proliferator
activated receptor gamma.
AB - PURPOSE OF REVIEW: This review summarizes recent findings on the regulation of
vascular tone by the nuclear receptor transcription factor, peroxisome
proliferator activated receptor (PPAR) gamma. Much of the recent work utilizes
genetic tools to interrogate the significance of PPARgamma in endothelial and
smooth muscle cells and novel PPARgamma target genes have been identified. RECENT
FINDINGS: Endothelial PPARgamma prevents inflammation and oxidative stress, while
promoting vasodilation by controlling the regulation of NADPH oxidase, catalase
and superoxide dismutase gene expression. Moreover, the protective functions of
endothelial PPARgamma appear more prominent during disease conditions. Novel
findings also suggest a role for endothelial PPARgamma as a mediator of whole
body metabolism. In smooth muscle cells, PPARgamma regulates vascular tone by
targeting genes involved with contraction and relaxation signaling cascades, some
of which is via transcriptional activation, and some through novel mechanisms
regulating protein turnover. Furthermore, aberrant changes in renin-angiotensin
system components and exacerbated responses to angiotensin II induced vascular
dysfunction are observed when PPARgamma function is lost in smooth muscle cells.
SUMMARY: With these recent advances based partially on lessons from patients with
PPARgamma mutants, we conclude that vascular PPARgamma is protective and plays an
important role in the regulation of vascular tone.
PMID- 25587908
TI - Multivariate normative comparison, a novel method for more reliably detecting
cognitive impairment in HIV infection.
AB - OBJECTIVE: The objective of this study is to assess whether multivariate
normative comparison (MNC) improves detection of HIV-1-associated neurocognitive
disorder (HAND) as compared with Frascati and Gisslen criteria. METHODS: One
hundred and three HIV-1-infected men with suppressed viremia on combination
antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male
controls (comparable regarding age, ethnicity, sexual orientation, premorbid
intelligence and educational level), aged at least 45 years, underwent
neuropsychological assessment covering six cognitive domains (fluency, attention,
information processing speed, executive function, memory, and motor function).
Frascati and Gisslen criteria were applied to detect HAND. Next, MNC was
performed to compare the cognitive scores of each HIV-positive individual against
the cognitive scores of the control group. RESULTS: HIV-infected men showed
significantly worse performance on the cognitive domains of attention,
information processing speed and executive function compared with HIV-uninfected
controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%;
95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected
men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying
Gisslen criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected
men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better
specificity but reduced sensitivity. MNC identified cognitive impairment in 17%
(95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group
(P = 0.02, one-tailed), showing an optimal balance between sensitivity and
specificity. CONCLUSION: Prevalence of cognitive impairment in HIV-1-infected men
with suppressed viremia on cART estimated by MNC was much higher than that
estimated by Gisslen criteria, while the false positive rate was greatly reduced
compared with the Frascati criteria. VIDEO ABSTRACT: :
PMID- 25587910
TI - Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles as a
potential candidate to eliminate intracellular reactive oxygen species.
AB - Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles
(MMSNs-HRP) have been synthesized by a NHS/EDC coupling between the amino groups
of horseradish peroxidase (HRP) and the carboxyl groups on the MMSNs surface. It
is found that the immobilized HRP on MMSNs still retain high activity and the
MMSNs-HRP can eliminate the reactive oxygen species (ROS) in Chinese hamster
ovary (CHO) cells induced by the addition of H2O2 aqueous solution. Further, the
fluorescent MMSN-HRP-CD nanoparticles have been prepared by attaching
biocompatible, fluorescent carbon dots (CDs) to MMSNs-HRP. We have also
investigated the effect of an applied magnetic field on cellular uptake of MMSNs
HRP-CDs and found that the internalization of MMSNs-HRP-CDs by CHO cells could be
enhanced within 2 hours under the magnetic field. This work provides us with a
novel and efficient method to eliminate ROS in living cells by using HRP
immobilized nanoparticles.
PMID- 25587909
TI - HIV-associated mucosal gene expression: region-specific alterations.
AB - OBJECTIVE: Despite the use of HAART to control HIV, systemic immune activation
and inflammation persists with the consequence of developing serious non-AIDS
events. The mechanisms that contribute to persistent systemic immune activation
have not been well defined. The intestine is the major source of "sterile"
inflammation and plays a critical role in immune function; thus, we sought to
determine whether intestinal gene expression was altered in virally controlled
HIV-infected individuals. DESIGN AND METHODS: Gene expression was compared in
biopsy samples collected from HIV-uninfected and HIV-infected individuals from
the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix
gene arrays were performed on tissues and pathway analyses were conducted. Gene
expression was correlated with systemic markers of intestinal barrier dysfunction
and inflammation and intestinal microbiota composition. RESULTS: Genes involved
in cellular immune response, cytokine signaling, pathogen-influenced signaling,
humoral immune response, apoptosis, intracellular and second messenger signaling,
cancer, organismal growth and development, and proliferation and development were
upregulated in the intestine of HIV-infected individuals with differences
observed in the ileum, right, and left colon. Gene expression in the ileum
primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and
TLR2 with serum TNF) whereas expression in the colon correlated with the
microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). CONCLUSION:
These data demonstrate persistent, proinflammatory changes in the intestinal
mucosa of virally suppressed HIV-infected individuals. These changes in
intestinal gene expression may be the consequence of or contribute to barrier
dysfunction and intestinal dysbiosis observed in HIV.
PMID- 25587911
TI - Influence of the -CH2X substituent on the regioselectivity of intramolecular meta
photocycloaddition reactions.
AB - In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin
by an intramolecular meta-photocycloaddition, it was found that the
regioselectivity of the reaction depends strongly on the substituent -CH2X in the
ortho-position to the tether. Electropositive groups X (X = H, Me, TMS, TES) gave
preferentially the linear isomer (regioisomeric ratio = 87/13 to >95/5), whereas
electronegative substituents (X = OH, OAc, F) showed a clear preference for the
angular isomer (regioisomeric ratio = 75/25 to >95/5). The silylated and
fluorinated products were obtained as single isomers in moderate yield.
PMID- 25587912
TI - Editorial.
PMID- 25587905
TI - Pharmacotherapy of glaucoma.
AB - Glaucoma is a group of diseases involving the optic nerve and associated
structures, which is characterized by progressive visual field loss and typical
changes of the optic nerve head (ONH). The only known treatment of the disease is
reduction of intraocular pressure (IOP), which has been shown to reduce glaucoma
progression in a variety of large-scale clinical trials. Nowadays, a relatively
wide array of topical antiglaucoma drugs is available, including prostaglandin
analogues, carbonic anhydrase inhibitors, beta-receptor antagonists, adrenergic
agonists, and parasympathomimetics. In clinical routine, this allows for
individualized treatment taking risk factors, efficacy, and safety into account.
A major challenge is related to adherence to therapy. Sustained release devices
may help minimize this problem but are not yet available for clinical routine
use. Another hope arises from non-IOP-related treatment concepts. In recent
years, much knowledge has been gained regarding the molecular mechanisms that
underlie the disease process in glaucoma. This also strengthens the hope that
glaucoma therapy beyond IOP lowering will become available. Implementing this
concept with clinical trials remains, however, a challenge.
PMID- 25587913
TI - Asymmetric sternotomy and sternal wound complications: assessment using 3
dimensional computed tomography reconstruction.
AB - OBJECTIVE: Wound complications after midline sternotomy result in significant
morbidity and mortality. Despite many known risk factors, the influence of
sternal asymmetry has largely been ignored. The purpose of this study was to
assess the utility of 3-dimensional computed tomographic scan reconstructions to
assess sternal asymmetry and determine its relationship with sternal wound
infection. METHODS: A retrospective chart review was conducted for patients who
underwent midline sternotomy and received a postoperative computed tomographic
scan between 2009 and 2010. Cases were composed of all patients who had a sternal
wound infection after undergoing sternotomy. Controls were randomly selected from
patients without poststernotomy wound complications. Sternal asymmetry was
defined as the difference between the left and the right sternal halves and was
expressed as a percentage of the total sternal volume. RESULTS: Twenty-six cases
were identified and 32 controls were selected as described earlier. The patients
were similar in baseline characteristics and risk factors including age, sex,
smoking status, diabetes, chronic obstructive pulmonary disease, preoperative
creatinine, and operative time. Univariate factors associated with sternal wound
infection include an asymmetry of 10% or greater, body mass index, and internal
mammary artery harvest. In a multivariate logistic regression, independent
predictors of sternal wound infection included an asymmetry of 10% or greater
(odds ratio, 3.6; P = 0.03) and diabetes (odds ratio, 3.3; P = 0.0442).
CONCLUSIONS: Our data suggest an association between asymmetric sternotomy and
sternal wound infections. We recommend an assessment of sternal asymmetry to be
performed in patients with sternal wound infection and if it is found to be 10%
or greater, the surgeon should implement measures that stabilize the sternum.
PMID- 25587914
TI - Preoperative vascular imaging for predicting intraoperative modification of
peripheral arterial cannulation during minimally invasive mitral valve surgery.
AB - OBJECTIVE: Minimally invasive mitral valve surgery using peripheral cannulation
for cardiopulmonary bypass (CBP) is increasingly prevalent. Although conceptually
straightforward, peripheral CBP involves challenges and risks specific to this
method of perfusion. The utility of preoperative vascular imaging in predicting
these technical challenges and preventing vascular complications was studied.
METHODS: We performed a retrospective analysis of 73 consecutive patients
undergoing minimally invasive mitral valve surgery using femorofemoral CBP with
intraluminal aortic occlusion balloon catheter. All patients underwent
preoperative computed tomography angiogram or magnetic resonance angiography to
study the iliofemoral axes. RESULTS: None of the patients operated with this
technique was found to have arterial stenoses. Patients with a femoral artery
diameter of less than 7.3 mm needed bilateral or side-graft arterial cannulation
significantly more frequently than patients with larger femoral arteries (46.2%
vs 9.1%, P = 0.001). There was a trend toward more frequent modification of
arterial cannulation strategy in patients with body surface area less than 1.7 m
compared with larger patients (body surface area, 1.7-2.0) (26.3% vs 8.3%, P =
0.07). Patients needing high CBP flow rate (>5 L/min) were no more likely to need
dual arterial cannulation (18.2% vs 19.1%, P = 0.68). No patient experienced a
vascular complication. CONCLUSIONS: This preliminary study suggests that
preoperative vascular imaging and patient evaluation may predict difficulties
with femoral cannulation and perfusion, which can lead to better preoperative
planning and potentially prevent vascular complications. Further data will be
accumulated and analyzed to confirm these findings.
PMID- 25587915
TI - Concomitant grafting of both postbifurcation internal thoracic artery branches.
AB - OBJECTIVE: We aimed to assess the clinical outcome and graft patency after
concomitant grafting of both postbifurcation internal thoracic artery (ITA)
branches. METHODS: Between 2007 and 2013, 17 patients (14 men; mean [SD] age, 60
[9.3] years) underwent skeletonized bifurcated ITA grafting. Respective targets
were restricted to non-left anterior descending (LAD) area. In all patients, a
complementary standard ITA was used to graft the LAD artery. Graft patency was
assessed by standard coronary angiography or serial multidetector computed
tomography. RESULTS: Of the bifurcated conduits, 94% were right ITA. Respective
right ITA target sets were first and second obtuse marginal arteries (M1-M2) (n =
12), ramus-M1 (n = 2), and distal right coronary artery-posterior descending
artery (n = 2). Right ITAs were mobilized retroaortic (via the transverse sinus)
in 14 patients (82%) (to circumflex artery targets). Circumflex artery targets
comprised 88.2% of all anastomoses (30/34). There were no early mortalities,
myocardial infarctions, or hypoperfusion syndromes. During median follow-up of 44
months (range, 3-63), there was no late mortality. Overall reintervention rate
was 11.7%, and bifurcated ITA-related reintervention rate was 5.8%. At 5 years,
freedom from major adverse cardiac or cerebrovascular event related to bifurcated
ITA respective territory was 87% (Kaplan-Meier). Coronary imaging was achieved in
76% of the patients (elective multidetector computed tomography, n = 9; symptoms
directed coronary catheterization, n = 4). Bifurcation branch patency rate was
88.4% (23/26) at a median of 3.5 years. CONCLUSIONS: Grafting both
postbifurcation ITA branches is technically feasible and may be selectively
considered. Current observations are valid for skeletonized conduits and limited
to non-LAD targets. These preliminary findings should be corroborated by larger
data sets.
PMID- 25587916
TI - Processing of Materials for Regenerative Medicine Using Supercritical Fluid
Technology.
AB - The increase in the world demand of bone and cartilage replacement therapies
urges the development of advanced synthetic scaffolds for regenerative purposes,
not only providing mechanical support for tissue formation, but also promoting
and guiding the tissue growth. Conventional manufacturing techniques have severe
restrictions for designing these upgraded scaffolds, namely, regarding the use of
organic solvents, shearing forces, and high operating temperatures. In this
context, the use of supercritical fluid technology has emerged as an attractive
solution to design solvent-free scaffolds and ingredients for scaffolds under
mild processing conditions. The state-of-the-art on the technological endeavors
for scaffold production using supercritical fluids is presented in this work with
a critical review on the key processing parameters as well as the main advantages
and limitations of each technique. A special stress is focused on the strategies
suitable for the incorporation of bioactive agents (drugs, bioactive glasses, and
growth factors) and the in vitro and in vivo performance of supercritical CO2
processed scaffolds.
PMID- 25587917
TI - Current practice of periprocedural haematological management for patients
undergoing image-guided procedures.
AB - OBJECTIVE: To evaluate current UK practice of periprocedural haematological
management for image-guided procedures in relation to Cardiovascular and
Interventional Radiological Society guidelines, which provide recommendations
according to bleeding risk of procedures from Category 1 (lowest) to 3 (highest).
METHODS: Survey of practice in UK radiology departments conducted over a 1-year
period RESULTS: 48 radiology departments responded. The percentage of departments
that stop antithrombotics pre-procedurally are as follows (for Category 1, 2 and
3, respectively): aspirin (31.3%, 43.8%, 54.2%); clopidogrel (54.2%, 68.8%,
72.9%); therapeutic low-molecular-weight heparin (56.3%, 77.1%, 75.0%). The
percentage of departments that perform pre-procedural laboratory testing are as
follows (for Category 1, 2 and 3, respectively): international normalized ratio
(INR; 81.3%, 95.8%, 93.8%); activated partial thrombin time ratio (APTTR; 60.4%,
75.0%, 93.8%); platelet (77.1%, 91.7%, 95.7%); haemoglobin (70.8%, 85.4%, 87.5%).
Mean threshold (standard deviation) of laboratory results for conducting
procedures (Level 1, 2 and 3, respectively) are as follows: INR [1.53 (0.197),
1.47 (0.186), 1.47 (0.188)]; APTTR [1.50 (0.392), 1.50 (0.339), 1.48 (0.344)];
platelet count (x10(3) cells per microlitre) [74.4 (28.7), 79.9 (29.1), 80.5
(29.3)]; haemoglobin (grams per decilitre) [9.05 (1.40), 9.00 (1.33), 8.92
(1.21)]. No department practices conformed to current recommendations for (1) pre
procedural cessation of antithrombotics and (2) pre-procedural laboratory
testing. Two (4.2%) department practices conformed to recommendations for
thresholds of haematological parameters. CONCLUSION: Current peri-procedural
haematological management is variable and often does not conform to existing
recommendations. Further research into the impact of this variation in practice
on patient outcome is required. ADVANCES IN KNOWLEDGE: This study demonstrates
wide variation in practice in haematological management for image-guided
procedures.
PMID- 25587919
TI - Gate-tunable photoresponse of defective graphene: from ultraviolet to visible.
AB - We report the gate-tunable photoresponse of a defective graphene over the
ultraviolet (UV) and the visible light illumination, where the defect was
generated by plasma irradiation. Plasma induced Dirac point shift indicates the p
doping effect. Interestingly the defective-graphene field effect transistor
(defective-GFET) showed a negative shift upon UV illumination, whereas the device
showed a positive shift under visible light illumination, along with the change
in the photocurrent. The defective-GFET device showed a high photoresponsivity of
37 mA W(-1) under visible light, that is ~3 times higher than that of the
pristine graphene device. Photoinduced molecular desorption causes the UV light
responsivity to 18 mA W(-1). This study shows that the tunable photodetector with
high responsivity is feasible by introducing an artificial defect on graphene
surface.
PMID- 25587918
TI - Head lice.
AB - INTRODUCTION: Head louse infection is diagnosed by finding live lice, as eggs
take 7 days to hatch (but a few may take longer, up to 13 days) and may appear
viable for weeks after death of the egg. Infestation may be more likely in school
children, with risks increased in children with more siblings or of lower
socioeconomic group. Factors such as longer hair make diagnosis and treatment
more difficult. METHODS AND OUTCOMES: We conducted a systematic review and aimed
to answer the following clinical question: What are the effects of physically
acting treatments for head lice? We searched: Medline, Embase, The Cochrane
Library, and other important databases up to March 2014 (Clinical Evidence
reviews are updated periodically; please check our website for the most up-to
date version of this review). We included harms alerts from relevant
organisations such as the US Food and Drug Administration (FDA) and the UK
Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found six
studies that met our inclusion criteria. We performed a GRADE evaluation of the
quality of evidence for interventions. CONCLUSIONS: In this systematic review, we
present information relating to the effectiveness and safety of the following
interventions: 1,2-octanediol, dimeticone, herbal and essential oils, and
isopropyl myristate.
PMID- 25587924
TI - Structural insight into MtmC, a bifunctional ketoreductase-methyltransferase
involved in the assembly of the mithramycin trisaccharide chain.
AB - More and more post-PKS tailoring enzymes are recognized as being multifunctional
and codependent on other tailoring enzymes. One of the recently discovered
intriguing examples is MtmC, a bifunctional TDP-4-keto-d-olivose ketoreductase
methyltransferase, which-in codependence with glycosyltransferase MtmGIV-is a key
contributor to the biosynthesis of the critical trisaccharide chain of the
antitumor antibiotic mithramycin (MTM), produced by Streptomyces argillaceus. We
report crystal structures of three binary complexes of MtmC with its methylation
cosubstrate SAM, its coproduct SAH, and a nucleotide TDP as well as crystal
structures of two ternary complexes, MtmC-SAH-TDP-4-keto-d-olivose and MtmC-SAM
TDP, in the range of 2.2-2.7 A resolution. The structures reveal general and
sugar-specific recognition and catalytic structural features of MtmC. Depending
on the catalytic function that is conducted by MtmC, it must bind either NADPH or
SAM in the same cofactor binding pocket. A tyrosine residue (Tyr79) appears as a
lid covering the sugar moiety of the substrate during the methyl transfer
reaction. This residue swings out of the active site by ~180 degrees in the
absence of the substrate. This unique conformational change likely serves to
release the methylated product and, possibly, to open the active site for binding
the bulkier cosubstrate NADPH prior to the reduction reaction.
PMID- 25587925
TI - Luteolin attenuate the D-galactose-induced renal damage by attenuation of
oxidative stress and inflammation.
AB - Luteolin is reported to have antioxidant and anti-inflammatory properties. In
this study, we investigated the protective effect of luteolin against the renal
damage induced by D-galactose (D-gal). The levels of creatinine (Cr) and urea
nitrogen (BUN) were evaluated in plasma, kidney sections were stained with
haematoxylin-eosin, followed by assessment of the antioxidant and anti
inflammatory activity. Furthermore, we also investigated the expression of the
p38 mitogen-activated protein kinase (p38 MAPK) and its phosphorylated
activation. The results of luteolin treatment showed that the renal damages were
attenuated. Luteolin could significantly ameliorate D-gal-induced oxidative
damage and suppress the inflammatory response. Moreover, the result also shows
that luteolin could significantly inhibit the p38 MAPK phosphorylation in the
kidneys from the model of D-gal-treated mice. Therefore, our research suggests
that luteolin might be involved in the attenuated oxidative stress and
inflammatory responses, hence the protective effects against D-gal-induced renal
damage.
PMID- 25587926
TI - Reported foodborne outbreaks due to fresh produce in the United States and
European Union: trends and causes.
AB - The consumption of fruit and vegetables continues to rise in the United States
and European Union due to healthy lifestyle recommendations. Meanwhile, the rate
of foodborne illness caused by the consumption of these products remains high in
both regions, representing a significant public health and financial issue. This
study addresses the occurrence of reported foodborne outbreaks associated with
fresh fruits and vegetables consumption in the United States and European Union
during the period 2004-2012, where data are available. Special attention is paid
to those pathogens responsible for these outbreaks, the mechanisms of
contamination, and the fresh produce vehicles involved. Norovirus is shown to be
responsible for most of the produce-related outbreaks, followed by Salmonella.
Norovirus is mainly linked with the consumption of salad in the United States and
of berries in the European Union, as demonstrated by the Multiple Correspondence
Analysis (MCA). Salmonella was the leading cause of multistate produce outbreaks
in the United States and was the pathogen involved in the majority of sprouts
associated outbreaks. As is reflected in the MCA, the pattern of fresh produce
outbreaks differed in the United States and European Union by the type of
microorganism and the food vehicle involved.
PMID- 25587927
TI - Antimicrobial potential of cauliflower, broccoli, and okara byproducts against
foodborne bacteria.
AB - The antimicrobial potential of cauliflower, broccoli, and okara byproducts was
assessed against Gram-positive and Gram-negative bacteria. Salmonella enterica
serovar Typhimurium, Escherichia coli O157:H7, Bacillus cereus, and Listeria
monocytogenes serovar 4b growth behavior was assessed under exposure to 5%
vegetable byproducts added to the reference medium, buffered peptone water (0.1%
[wt/vol]), at 37 degrees C. Although the byproducts were not effective against L.
monocytogenes, they were bactericidal against Salmonella Typhimurium, E. coli
O157:H7, and B. cereus. The most promising results were achieved with the
cauliflower-Salmonella Typhimurium combination, because the bacterial population
was reduced by 3.11 log10 cycles after 10 h of incubation at 37 degrees C as a
result of 5% cauliflower addition. Further studies were carried out for this
combination, at different cauliflower concentrations (0, 0.5, 1, 5, 10, and 15%)
and at temperatures in the range of 5-37 degrees C. The greatest inactivation
level (6.11 log10 cycles) was achieved at refrigeration temperature (5 degrees C)
using 15% cauliflower addition. Both temperature and cauliflower concentration
significantly (p<=0.05) influenced the Salmonella Typhimurium inactivation level.
The kinetic parameters were adjusted to mathematical models. The modified
Gompertz mathematical model provided an accurate fit (root-mean-square error
(RMSE) [0.00009-0.21] and adjusted-R(2) [0.81-0.99]) to experimental Salmonella
Typhimurium survival curves describing inactivation kinetics of the pathogen to
the antimicrobial effect of cauliflower byproduct.
PMID- 25587928
TI - Chemometric Analysis of Some Biologically Active Groups of Drugs on the Basis
Chromatographic and Molecular Modeling Data.
AB - In this work, three different groups of drugs such as 12 analgesic drugs, 11
cardiovascular system drugs and 36 "other" compounds, respectively, were analyzed
with cluster analysis (CA), principal component analysis (PCA) and factor
analysis (FA) methods. All chemometric analysis were based on the chromatographic
parameters (logk and logk(w)) determined by means of high-performance liquid
chromatography (HPLC) and also by molecular modeling descriptors calculated using
various computer programs (HyperChem, Dragon, and the VCCLAB). The clustering of
compounds were obtained by CA (using various algorithm as e.g. Ward method or
unweighted pair-group method using arithmetic averages as well as Euclidean or
Manhattan distance), and allowed to build dendrograms linked drugs with similar
physicochemical and pharmacological properties were discussed. Moreover, the
analysis performed for analyzed groups of compounds with the use of FA or PCA
methods indicated that almost all information reached in input chromatographic
parameters as well as in molecular modeling descriptors can be explained by first
two factors. Additionally, all analyzed drugs were clustered according to their
chemical structure and pharmacological activity. Summarized, the performed
classification analysis of studied drugs was focused on similarities and
differences in methods being used for chemometric analysis as well as focused
abilities to drugs classification (clustering) according to their molecular
structures and pharmacological activity performed on the basis of chromatographic
experimental and molecular modeling data. Thus, the most important application of
statistically important molecular descriptors taken from QSRR models to
classification analysis allow detailed biological (pharmacological)
classification of analyzed drugs.
PMID- 25587929
TI - Detection of Staphylococcus aureus by functional gold nanoparticle-based affinity
surface-assisted laser desorption/ionization mass spectrometry.
AB - Staphylococcus aureus is one of the common pathogenic bacteria responsible for
bacterial infectious diseases and food poisoning. This study presents an
analytical method based on the affinity nanoprobe-based mass spectrometry that
enables detection of S. aureus in aqueous samples. A peptide aptamer
DVFLGDVFLGDEC (DD) that can recognize S. aureus and methicillin-resistant S.
aureus (MRSA) was used as the reducing agent and protective group to generate DD
immobilized gold nanoparticles (AuNPs@DD) from one-pot reactions. The thiol group
from cysteine in the peptide aptamer, i.e., DD, can interact with gold ions to
generate DD-immobilized AuNPs in an alkaline solution. The generated AuNPs@DD has
an absorption maximum at ~518 nm. The average particle size is 7.6 +/- 1.2 nm.
Furthermore, the generated AuNPs@DD can selectively bind with S. aureus and MRSA.
The conjugates of the target bacteria with AuNPs were directly analyzed by
surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The
gold ions generated from the AuNPs@DD anchored on the target bacteria were
monitored. Gold ions (m/z 197 and 394) were only generated from the conjugates of
the target bacterium-AuNP@DD in the SALDI process. Thus, the gold ions could be
used as the indicators for the presence of the target bacteria. The detection
limit of S. aureus using this method is in the order of a few tens of cells. The
low detection limit is due to the ease of generation of gold cluster ion derived
from AuNPs under irradiation with a 355 nm laser beam. Apple juice mixed with S.
aureus was used as the sample to demonstrate the suitability of the method for
real-world application. Because of its low detection limit, this approach can
potentially be used to screen the presence of S. aureus in complex samples.
PMID- 25587930
TI - Controlled formation of core-shell structures with uniform AlPO4 nanoshells.
AB - Uniform AlPO4 nanoshells are successfully achieved on different core materials by
controlling their formation kinetics in solution. The application of this coating
protocol to LiCoO2 shows an obvious improvement in its battery performance.
PMID- 25587931
TI - Understanding viral neuraminidase inhibition by substituted difluorosialic acids.
AB - Mechanism-based inhibition of influenza neuraminidases by difluorosialic acids
(DFSA) is not only rendered highly specific by incorporation of 4-amino or 4
guanidine substituents but also the half-life for reactivation is greatly
increased. Measurement of rate constants for spontaneous hydrolysis of a series
of such substituted DFSAs reveals, surprisingly, that inherent inductive effects
play very little role in this rate reduction and that interactions with the
enzyme are more important.
PMID- 25587933
TI - Correction to: Comparing the Personality Disorder Interview for DSM-IV (PDI-IV)
and SCID-II Borderline Personality Disorder Scales: An Item-Response Theory
Analysis.
PMID- 25587932
TI - Pulse-coupled BZ oscillators with unequal coupling strengths.
AB - Coupled chemical oscillators are usually studied with symmetric coupling, either
between identical oscillators or between oscillators whose frequencies differ.
Asymmetric connectivity is important in neuroscience, where synaptic strength
inequality in neural networks commonly occurs. While the properties of the
individual oscillators in some coupled chemical systems may be readily changed,
enforcing inequality between the connection strengths in a reciprocal coupling is
more challenging. We recently demonstrated a novel way of coupling chemical
oscillators, which allows for manipulation of individual connection strengths.
Here we study two identical, pulse-coupled Belousov-Zhabotinsky (BZ) oscillators
with unequal connection strengths. When the pulse perturbations contain KBr
(inhibitor), this system exhibits simple out-of-phase and complex oscillations,
oscillatory-suppressed states as well as temporally periodic patterns (N : M) in
which the two oscillators exhibit different numbers of peaks per cycle. The N : M
patterns emerge due to the long-term effect of the inhibitory pulse
perturbations, a feature that has not been considered in earlier works. Time
delay was previously shown to have a profound effect on the system's behaviour
when pulse coupling was inhibitory and the coupling strengths were equal. When
the coupling is asymmetric, however, delay produces no qualitative change in
behaviour, though the 1 : 2 temporal pattern becomes more robust. Asymmetry in
instantaneous excitatory coupling via AgNO3 injection produces a previously
unseen temporal pattern (1 : N patterns starting with a double peak) with time
delay and high [AgNO3]. Numerical simulations of the behaviour agree well with
theoretical predictions in asymmetrical pulse-coupled systems.
PMID- 25587934
TI - Sesquiterpenoid tropolone glycosides from Liriosma ovata.
AB - Two new sesquiterpenoid tropolone glycosides, liriosmasides A (1) and B (2),
along with two known compounds, secoxyloganin and oplopanpheside C, were isolated
from a methanol extract of the roots of Liriosma ovata. The structures of 1 and 2
were elucidated by spectroscopic methods including 1D and 2D NMR and by high
resolution mass spectrometry involving an ultra-high-performance liquid
chromatography-quadrupole-orbital ion trap mass spectrometric (UHPLC-Q-Orbitrap
MS) method. Compound 1 showed weak inhibitory activity against HIV RNase H.
PMID- 25587936
TI - Nanocarrier-mediated inhibition of macrophage migration inhibitory factor
attenuates secondary injury after spinal cord injury.
AB - Spinal cord injury (SCI) can lead to permanent motor and sensory deficits.
Following the initial traumatic insult, secondary injury mechanisms characterized
by persistent heightened inflammation are initiated and lead to continued and
pervasive cell death and tissue damage. Anti-inflammatory drugs such as
methylprednisolone (MP) used clinically have ambiguous benefits with debilitating
side effects. Typically, these drugs are administered systemically at high doses,
resulting in toxicity and paradoxically increased inflammation. Furthermore,
these drugs have a small time window postinjury (few hours) during which they
need to be infused to be effective. As an alternative to MP, we investigated the
effect of a small molecule inhibitor (Chicago sky blue, CSB) of macrophage
migration inhibitory factor (MIF) for treating SCI. The pleiotropic cytokine MIF
is known to contribute to upregulation of several pro-inflammatory cytokines in
various disease and injury states. In vitro, CSB administration alleviated
endotoxin-mediated inflammation in primary microglia and macrophages.
Nanocarriers such as liposomes can potentially alleviate systemic side effects of
high-dose therapy by enabling site-specific drug delivery to the spinal cord.
However, the therapeutic window of 100 nm scale nanoparticle localization to the
spinal cord after contusion injury is not fully known. Thus, we first
investigated the ability of nanocarriers of different sizes to localize to the
injured spinal cord up to 2 weeks postinjury. Results from the study showed that
nanocarriers as large as 200 nm in diameter could extravasate into the injured
spinal cord up to 96 h postinjury. We then formulated nanocarriers (liposomes)
encapsulating CSB and administered them intravenously 48 h postinjury, within the
previously determined 96 h therapeutic window. In vivo, in this clinically
relevant contusion injury model in rats, CSB administration led to preservation
of vascular and white matter integrity, improved wound healing, and an increase
in levels of arginase and other transcripts indicative of a resolution phase of
wound healing. This study demonstrates the potential of MIF inhibition in SCI and
the utility of nanocarrier-mediated drug delivery selectively to the injured
cord.
PMID- 25587938
TI - Differential effects of cerium oxide nanoparticles on rice, wheat, and barley
roots: a fourier transform infrared (FT-IR) microspectroscopy study.
AB - Cerium oxide nanoparticles (nCeO2) have extensive industrial applications, and
concerns regarding their threat to the environment have been raised. This study
includes structural analysis of intact root xylem of rice (Oryza sativaL.), wheat
(Triticum aestivumL.), and barley (Hordeum vulgareL.) seedlings exposed to nCeO2
suspensions (0, 62.5, 125, 250, and 500 mg L(-1)). Fourier transform infrared
microspectroscopy was applied to determine compositional alterations in the root
xylem, and principal component analysis (PCA) was carried out to examine spectral
differences between nCeO2 treatments. Results demonstrated that nCeO2 at >= 125
mg L(-1) changed the region of spectra around 1696-1760 cm(-1) in rice root, 125
and 250 mg L(-1) modified 1744-1792 cm(-1) in wheat, and 62.5 and 125 mg L(-1)
altered 1727-1760 cm(-1) in barley. PCA afforded the clustering of nCeO2
treatments at 0 and 62.5 mg L(-1) in rice and wheat and 0 and 500 mg L(-1) in
barley. Furthermore, major peaks at 1744 or 1760 cm(-1) appeared in primary PC
and 1728 cm(-1) in secondary PC score loadings. These findings illustrated that
nCeO2 induced compositional modifications in the root xylem of cereals.
PMID- 25587935
TI - Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified
nanoliposomes.
AB - Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration
lowering drug to reduce blood plasma cholesterol levels in the clinic. However,
the therapeutic effects of this drug are negatively impacted by its poor water
solubility and low oral absorption efficiency. In this study, a PEGylated G5
PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water
solubility, transepithelial transport, and oral absorption of PB. The uptake
mechanism was explored in vitro in Caco-2 cells with the results suggesting that
the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG)
was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae
endocytosis pathways. Additionally, plasma lipid concentration lowering effects
of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse
model. Compared with saline treated group, treatment with PB-liposome/G5-PEG
significantly inhibited the increase of plasma total cholesterol (TC) and
triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid
concentration lowering effects and plasma drug concentration were greater than PB
alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG
significantly increased the oral absorption of PB and therefore significantly
improved its pharmacodynamic effects.
PMID- 25587939
TI - Cumulative trauma, hyperarousal, and suicidality in the general population: a
path analysis.
AB - Although trauma exposure and posttraumatic stress disorder (PTSD) both have been
linked to suicidal thoughts and behavior, the underlying basis for this
relationship is not clear. In a sample of 357 trauma-exposed individuals from the
general population, younger participant age, cumulative trauma exposure, and all
three Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PTSD
clusters (reexperiencing, avoidance, and hyperarousal) were correlated with
clinical levels of suicidality. However, logistic regression analysis indicated
that when all PTSD clusters were considered simultaneously, only hyperarousal
continued to be predictive. A path analysis confirmed that posttraumatic
hyperarousal (but not other components of PTSD) fully mediated the relationship
between extent of trauma exposure and degree of suicidal thoughts and behaviors.
PMID- 25587941
TI - Relay iron/chiral Bronsted acid catalysis: enantioselective hydrogenation of
benzoxazinones.
AB - An asymmetric hydrogenation reaction of benzoxazinones has been accomplished via
a relay iron/chiral Bronsted acid catalysis. This approach provides a variety of
chiral dihydrobenzoxazinones in good to high yields (75-96%) and
enantioselectivities (up to 98:2 er). It is noteworthy that challenging 3-alkyl
substituted substrates underwent highly enantioselective reduction. A key to
success is the utilization of a nonchiral phosphine ligand to reduce
disadvantageous background reactions through tuning the catalytic activity of
Fe3(CO)12.
PMID- 25587940
TI - Kinetic and thermodynamic characterization of a novel low-temperature-active
xylanase from Arthrobacter sp. GN16 isolated from the feces of Grus nigricollis.
AB - We previously presented the cloning, heterologous expression, and
characterization of a novel multidomain endoxylanase from Arthrobacter sp. GN16
isolated from the feces of Grus nigricollis. Molecular and biochemical
characterization studies indicate that the glycoside hydrolase (GH) family 10
domain at the N-terminus of the multidomain xylanase (rXynAGN16L) is a low
temperature-active endoxylanase. Many low-temperature-active enzymes contain
regions of high local flexibility related to their kinetic and thermodynamic
properties compared with mesophilic and thermophilic enzymes. However, the
thermodynamic property of low-temperature-active xylanases, including rXynAGN16L,
has rarely been reported. In this study, the kinetic and thermodynamic properties
of rXynAGN16L were determined using different substrates and temperature
conditions to completely characterize its activity properties. The kinetic
property of rXynAGN16L is similar to some low-temperature-active GH 10
endoxylanases. Moreover, the thermodynamic property indicates that rXynAGN16L is
typically characterized as a low-temperature-active enzyme.
PMID- 25587942
TI - NMR signal enhancement for hyperpolarized fluids continuously generated in
hydrogenation reactions with parahydrogen.
AB - In the present study we analyze the factors which can lower hyperpolarization of
fluids produced in a continuous flow regime by the parahydrogen-induced
polarization technique. We use the findings of this analysis to examine the flow
rate dependence of propane hyperpolarization produced in the heterogeneous
propylene hydrogenation by parahydrogen over Rh/TiO2 catalyst. We have estimated
the maximum attainable propane (1)H hyperpolarization yield and the corrected
percentage of pairwise hydrogen addition in heterogeneous hydrogenation, which
was found to be ~7%. The approach developed for polarization analysis is useful
for the optimization of experimental setup and reaction conditions to obtain
maximum hyperpolarization for parahydrogen-based catalyst-free continuously
generated fluids applicable in biomedical magnetic resonance imaging.
PMID- 25587944
TI - Sharing individual patient data from clinical trials.
PMID- 25587945
TI - Addressing the challenge of gray-zone medicine.
PMID- 25587946
TI - Guiding choice--ethically influencing referrals in ACOs.
PMID- 25587947
TI - On the death of a colleague.
PMID- 25587943
TI - Epigenetic regulation in human melanoma: past and future.
AB - The development and progression of melanoma have been attributed to independent
or combined genetic and epigenetic events. There has been remarkable progress in
understanding melanoma pathogenesis in terms of genetic alterations. However,
recent studies have revealed a complex involvement of epigenetic mechanisms in
the regulation of gene expression, including methylation, chromatin modification
and remodeling, and the diverse activities of non-coding RNAs. The roles of gene
methylation and miRNAs have been relatively well studied in melanoma, but other
studies have shown that changes in chromatin status and in the differential
expression of long non-coding RNAs can lead to altered regulation of key genes.
Taken together, they affect the functioning of signaling pathways that influence
each other, intersect, and form networks in which local perturbations disturb the
activity of the whole system. Here, we focus on how epigenetic events intertwine
with these pathways and contribute to the molecular pathogenesis of melanoma.
PMID- 25587948
TI - Trends in opioid analgesic abuse and mortality in the United States.
AB - BACKGROUND: The use of prescription opioid medications has increased greatly in
the United States during the past two decades; in 2010, there were 16,651 opioid
related deaths. In response, hundreds of federal, state, and local interventions
have been implemented. We describe trends in the diversion and abuse of
prescription opioid analgesics using data through 2013. METHODS: We used five
programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance
(RADARS) System to describe trends between 2002 and 2013 in the diversion and
abuse of all products and formulations of six prescription opioid analgesics:
oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The
programs gather data from drug-diversion investigators, poison centers, substance
abuse treatment centers, and college students. RESULTS: Prescriptions for opioid
analgesics increased substantially from 2002 through 2010 in the United States
but then decreased slightly from 2011 through 2013. In general, RADARS System
programs reported large increases in the rates of opioid diversion and abuse from
2002 to 2010, but then the rates flattened or decreased from 2011 through 2013.
The rate of opioid-related deaths rose and fell in a similar pattern. Reported
nonmedical use did not change significantly among college students. CONCLUSIONS:
Postmarketing surveillance indicates that the diversion and abuse of prescription
opioid medications increased between 2002 and 2010 and plateaued or decreased
between 2011 and 2013. These findings suggest that the United States may be
making progress in controlling the abuse of opioid analgesics. (Funded by the
Denver Health and Hospital Authority.).
PMID- 25587949
TI - Multiple-system atrophy.
PMID- 25587950
TI - Images in clinical medicine. Actinomycetoma.
PMID- 25587951
TI - Case records of the Massachusetts General Hospital. Case 2-2015. A 25-year-old
man with abdominal pain, syncope, and hypotension.
PMID- 25587952
TI - Practical, legal, and ethical issues in expanded access to investigational drugs.
PMID- 25587953
TI - One-unit versus two-unit cord-blood transplantation.
PMID- 25587954
TI - One-unit versus two-unit cord-blood transplantation.
PMID- 25587955
TI - One-unit versus two-unit cord-blood transplantation.
PMID- 25587956
TI - Cardiovascular risk and events and country income stratum.
PMID- 25587957
TI - Cardiovascular risk and events and country income stratum.
PMID- 25587958
TI - Cardiovascular risk and events and country income stratum.
PMID- 25587959
TI - Cardiovascular risk and events and country income stratum.
PMID- 25587960
TI - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
PMID- 25587961
TI - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
PMID- 25587962
TI - FOLFOXIRI and bevacizumab for metastatic colorectal cancer.
PMID- 25587964
TI - Community-acquired pneumonia.
PMID- 25587963
TI - Community-acquired pneumonia.
PMID- 25587965
TI - Community-acquired pneumonia.
PMID- 25587966
TI - Community-acquired pneumonia.
PMID- 25587967
TI - Community-acquired pneumonia.
PMID- 25587968
TI - Coronary heart disease and genetic variants with low phospholipase A2 activity.
PMID- 25587971
TI - Images in clinical medicine. Intracranial arteriovenous malformation.
PMID- 25587972
TI - In Vitro Effects of Resin Infiltration on Enamel Erosion Inhibition.
AB - Resin-based materials that show promising effects for preventing the progression
of erosion have been studied. This in vitro study evaluated the effects of
applying resin-based materials, including resin infiltration, on previously
eroded enamel subjected to erosive challenges. The influence of enamel surface
etching prior to application of the material was also studied. Bovine enamel
blocks were immersed in hydrochloric acid (HCl), 0.01 M (pH 2.3), for 30 seconds
in order to form a softened erosion lesion. The blocks were then randomly divided
into nine groups (n=12) and treated as follows: C = control without treatment;
Hel = pit & fissure resin sealant (Helioseal Clear); Adh = two-step self-etching
adhesive system (AdheSe); Tet = two-step conventional adhesive system (Tetric N
bond); and Inf = infiltrant (Icon). The Helno, Adhno, Tetno, and Infno groups
received the same materials without (or with no) surface conditioning. The depth
of the material's penetration into softened erosion lesions was qualitatively
analyzed using reflection and fluorescence confocal microscopy. After application
of the materials, the blocks were immersed in HCl for two minutes; this step was
followed by immersion in artificial saliva for 120 minutes four times a day for
five days (erosive cycling). Both the enamel alteration and material thickness
were analyzed using profilometry, and the results were submitted to Kruskal
Wallis and Dunn tests (p>0.05). Images from the confocal microscopy showed
minimal penetration of Adh/Adhno and deep penetration of Inf/Infno into the
erosive lesions. The groups Hel, Adh, Inf, Tetno, and Infno resulted in the
formation of a layer of material over the enamel, which was effective in
inhibiting the progression of erosion. In conclusion, the infiltrant, with or
without etching, was able to penetrate and protect the enamel against dental
erosion. The other resin-based materials, except for the two-step conventional
adhesive, were able to penetrate and inhibit the progression of erosive lesions
only when they were applied after enamel etching.
PMID- 25587973
TI - Shear bond strength of porcelain veneers rebonded to enamel.
AB - In this laboratory research, shear bond strength (SBS) and mode of failure of
veneers rebonded to enamel in shear compression were determined. Three groups (A,
B, and C; n=10 each) of mounted molar teeth were finished flat using wet 600-grit
silicon carbide paper, and 30 leucite-reinforced porcelain veneers (5.0 * 0.75
mm) were air abraded on the internal surface with 50 MUm aluminum oxide, etched
with 9.5% hydrofluoric acid, and silanated. The control group (A) veneer
specimens were bonded to enamel after etching with 37% phosphoric acid using
bonding resin and a dual cure resin composite cement. Groups B and C were
prepared similarly to group A with the exception that a release agent was placed
before the veneer was positioned on the prepared enamel surface and the resin
cement was subsequently light activated. The debonded veneers from groups B and C
were placed in a casting burnout oven and heated to 454 degrees C/850 degrees F
for 10 minutes to completely carbonize the resin cement and stay below the glass
transition temperature (Tg) of the leucite-reinforced porcelain. The recovered
veneers were then prepared for bonding. The previously bonded enamel surfaces in
group B were air abraded using 50 MUm aluminum oxide followed by 37% phosphoric
acid etching, while group C enamel specimens were acid etched only. All specimens
were thermocycled between 5 degrees C and 55 degrees C for 2000 cycles using a 30
second dwell time and stored in 37 degrees C deionized water for 2 weeks. SBS was
determined at a crosshead speed of 1.0 mm/min. SBS results in MPa for the groups
were (A) = 20.6+/-5.1, (B) = 18.1+/-5.5, and (C) = 17.2+/-6.1. One-way analysis
of variance indicated that there were no significant interactions (alpha=0.05),
and Tukey-Kramer post hoc comparisons (alpha=0.05) detected no significant
pairwise differences. An adhesive mode of failure at the enamel interface was
observed to occur more often in the experimental groups (B = 40%, C = 50%).
Rebonding the veneers produced SBS values that were not significantly different
from the control group. Also, no significant difference in SBS values were
observed whether the debonded enamel surface was air abraded and acid etched or
acid etched only.
PMID- 25587974
TI - A high fuel consumption efficiency management scheme for PHEVs using an adaptive
genetic algorithm.
AB - A high fuel efficiency management scheme for plug-in hybrid electric vehicles
(PHEVs) has been developed. In order to achieve fuel consumption reduction, an
adaptive genetic algorithm scheme has been designed to adaptively manage the
energy resource usage. The objective function of the genetic algorithm is
implemented by designing a fuzzy logic controller which closely monitors and
resembles the driving conditions and environment of PHEVs, thus trading off
between petrol versus electricity for optimal driving efficiency. Comparison
between calculated results and publicized data shows that the achieved efficiency
of the fuzzified genetic algorithm is better by 10% than existing schemes. The
developed scheme, if fully adopted, would help reduce over 600 tons of CO2
emissions worldwide every day.
PMID- 25587976
TI - Thermocouple and infrared sensor-based measurement of temperature distribution in
metal cutting.
AB - In metal cutting, the magnitude of the temperature at the tool-chip interface is
a function of the cutting parameters. This temperature directly affects
production; therefore, increased research on the role of cutting temperatures can
lead to improved machining operations. In this study, tool temperature was
estimated by simultaneous temperature measurement employing both a K-type
thermocouple and an infrared radiation (IR) pyrometer to measure the tool-chip
interface temperature. Due to the complexity of the machining processes, the
integration of different measuring techniques was necessary in order to obtain
consistent temperature data. The thermal analysis results were compared via the
ANSYS finite element method. Experiments were carried out in dry machining using
workpiece material of AISI 4140 alloy steel that was heat treated by an induction
process to a hardness of 50 HRC. A PVD TiAlN-TiN-coated WNVG 080404-IC907 carbide
insert was used during the turning process. The results showed that with
increasing cutting speed, feed rate and depth of cut, the tool temperature
increased; the cutting speed was found to be the most effective parameter in
assessing the temperature rise. The heat distribution of the cutting tool, tool
chip interface and workpiece provided effective and useful data for the
optimization of selected cutting parameters during orthogonal machining.
PMID- 25587977
TI - Received signal strength recovery in green WLAN indoor positioning system using
singular value thresholding.
AB - Green WLAN is a promising technique for accessing future indoor Internet
services. It is designed not only for high-speed data communication purposes but
also for energy efficiency. The basic strategy of green WLAN is that all the
access points are not always powered on, but rather work on-demand. Though
powering off idle access points does not affect data communication, a serious
asymmetric matching problem will arise in a WLAN indoor positioning system due to
the fact the received signal strength (RSS) readings from the available access
points are different in their offline and online phases. This asymmetry problem
will no doubt invalidate the fingerprint algorithm used to estimate the mobile
device location. Therefore, in this paper we propose a green WLAN indoor
positioning system, which can recover RSS readings and achieve good localization
performance based on singular value thresholding (SVT) theory. By solving the
nuclear norm minimization problem, SVT recovers not only the radio map, but also
online RSS readings from a sparse matrix by sensing only a fraction of the RSS
readings. We have implemented the method in our lab and evaluated its
performances. The experimental results indicate the proposed system could recover
the RSS readings and achieve good localization performance.
PMID- 25587975
TI - A customized metal oxide semiconductor-based gas sensor array for onion quality
evaluation: system development and characterization.
AB - A gas sensor array, consisting of seven Metal Oxide Semiconductor (MOS) sensors
that are sensitive to a wide range of organic volatile compounds was developed to
detect rotten onions during storage. These MOS sensors were enclosed in a
specially designed Teflon chamber equipped with a gas delivery system to pump
volatiles from the onion samples into the chamber. The electronic circuit mainly
comprised a microcontroller, non-volatile memory chip, and trickle-charge real
time clock chip, serial communication chip, and parallel LCD panel. User
preferences are communicated with the on-board microcontroller through a
graphical user interface developed using LabVIEW. The developed gas sensor array
was characterized and the discrimination potential was tested by exposing it to
three different concentrations of acetone (ketone), acetonitrile (nitrile), ethyl
acetate (ester), and ethanol (alcohol). The gas sensor array could differentiate
the four chemicals of same concentrations and different concentrations within the
chemical with significant difference. Experiment results also showed that the
system was able to discriminate two concentrations (196 and 1964 ppm) of
methlypropyl sulfide and two concentrations (145 and 1452 ppm) of 2-nonanone, two
key volatile compounds emitted by rotten onions. As a proof of concept, the gas
sensor array was able to achieve 89% correct classification of sour skin infected
onions. The customized low-cost gas sensor array could be a useful tool to detect
onion postharvest diseases in storage.
PMID- 25587978
TI - A speedy cardiovascular diseases classifier using multiple criteria decision
analysis.
AB - Each year, some 30 percent of global deaths are caused by cardiovascular
diseases. This figure is worsening due to both the increasing elderly population
and severe shortages of medical personnel. The development of a cardiovascular
diseases classifier (CDC) for auto-diagnosis will help address solve the problem.
Former CDCs did not achieve quick evaluation of cardiovascular diseases. In this
letter, a new CDC to achieve speedy detection is investigated. This investigation
incorporates the analytic hierarchy process (AHP)-based multiple criteria
decision analysis (MCDA) to develop feature vectors using a Support Vector
Machine. The MCDA facilitates the efficient assignment of appropriate weightings
to potential patients, thus scaling down the number of features. Since the new
CDC will only adopt the most meaningful features for discrimination between
healthy persons versus cardiovascular disease patients, a speedy detection of
cardiovascular diseases has been successfully implemented.
PMID- 25587979
TI - Development and experimental validation of a numerical tool for structural health
and usage monitoring systems based on chirped grating sensors.
AB - The interest of the aerospace industries in structural health and usage
monitoring systems is continuously increasing. Among the techniques available in
literature those based on Fibre Bragg Grating sensors are much promising thanks
to their peculiarities. Different Chirped Bragg Grating sensor configurations
have been investigated in this paper. Starting from a numerical model capable of
simulating the spectral response of a grating subjected to a generic strain
profile (direct problem), a new code has been developed, allowing strain
reconstruction from the experimental validation of the program, carried out
through different loading cases applied on a chirped grating. The wavelength of
the reflection spectrum for a chirped FBG has a one-to-one correspondence to the
position along the gauge section, thus allowing strain reconstruction over the
entire sensor length. Tests conducted on chirped FBGs also evidenced their
potential for SHM applications, if coupled with appropriate numerical strain
reconstructions tools. Finally, a new class of sensors-Draw Tower Grating arrays
has been studied. These sensors are applicable to distributed sensing and load
reconstruction over large structures, thanks to their greater length. Three
configurations have been evaluated, having different spatial and spectral
characteristics, in order to explore possible applications of such sensors to SHM
systems.
PMID- 25587980
TI - Frequency noise suppression of a single mode laser with an unbalanced fiber
interferometer for subnanometer interferometry.
AB - We present a method of noise suppression of laser diodes by an unbalanced
Michelson fiber interferometer. The unstabilized laser source is represented by
compact planar waveguide external cavity laser module, ORIONTM (Redfern
Integrated Optics, Inc.), working at 1540.57 nm with a 1.5-kHz linewidth. We
built up the unbalanced Michelson interferometer with a 2.09 km-long arm based on
the standard telecommunication single-mode fiber (SMF-28) spool to suppress the
frequency noise by the servo-loop control by 20 dB to 40 dB within the Fourier
frequency range, remaining the tuning range of the laser frequency.
PMID- 25587981
TI - Improving the performance of an electronic nose by wine aroma training to
distinguish between drip coffee and canned coffee.
AB - Coffee aroma, with more than 600 components, is considered as one of the most
complex food aromas. Although electronic noses have been successfully used for
objective analysis and differentiation of total coffee aromas, it is difficult to
use them to describe the specific features of coffee aroma (i.e., the type of
smell). This is because data obtained by electronic noses are generally based on
electrical resistance/current and samples are distinguished by principal
component analysis. In this paper, we present an electronic nose that is capable
of learning the wine related aromas using the aroma kit "Le Nez du Vin," and the
potential to describe coffee aroma in a similar manner comparable to how wine
experts describe wine aroma. The results of our investigation showed that the
aromas of three drip coffees were more similar to those of pine and honey in the
aroma kit than to the aromas of three canned coffees. Conversely, the aromas of
canned coffees were more similar to the kit coffee aroma. In addition, the
aromatic patterns of coffees were different from those of green tea and red wine.
Although further study is required to fit the data to human olfaction, the
presented method and the use of vocabularies in aroma kits promise to enhance
objective discrimination and description of aromas by electronic noses.
PMID- 25587982
TI - Cumulative effect and predictive value of genetic variants associated with type 2
diabetes in Han Chinese: a case-control study.
AB - BACKGROUND: Genome-wide association studies (GWAS) have identified dozens of
single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We
have previously confirmed the associations of genetic variants in HHEX, CDKAL1,
VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect
and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes
in Han Chinese are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We conducted
a two-stage case-control study consisting of 2,925 cases and 3,281 controls to
examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han
Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio
(OR) = 1.41, P = 9.91 * 10-16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34
* 10-10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 * 10-4 for rs1552224) and
SLC30A8 (OR = 1.19, P = 1.43 * 10-5 for rs13266634). We further evaluated the
cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs
at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or
more risk alleles had a nearly 4-fold increased risk for developing type 2
diabetes compared with those carrying less than 6 risk alleles [adjusted OR =
3.68, 95% confidence interval (CI): 2.76-4.91]. Adding the genetic factors to
clinical factors slightly improved the prediction of type 2 diabetes, with the
area under the receiver operating characteristic curve increasing from 0.76 to
0.78. However, the difference was statistically significant (P < 0.0001).
CONCLUSIONS/SIGNIFICANCE: We confirmed associations of SNPs in KCNQ1,
CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The
utilization of genetic information may improve the accuracy of risk prediction in
combination with clinical characteristics for type 2 diabetes.
PMID- 25587985
TI - Right tail of the distribution of depressive symptoms is stable and follows an
exponential curve during middle adulthood.
AB - BACKGROUND: Previous research has reported that the mean of depressive symptoms
is stable in the general population through middle adulthood. To understand the
stability of depressive symptoms during middle adulthood, we investigated the
nature of the distribution of depressive symptoms. METHODS: We analyzed 24,890
subjects aged 15 to 84 years who participated in the Active Survey of Health and
Welfare, Japan. Depressive symptoms were assessed using the Japanese version of
the Center for Epidemiologic Studies Depression Scale (CES-D). The descriptive
statistics and frequency curves of the distributions were then compared according
to age group. RESULTS: The distribution of depressive symptoms was stable through
middle adulthood. The right tail which covers clinical depression was more stable
than the left tail or peak of the distributions. The right tail of the
distribution during middle adulthood exhibited a linear pattern with a log-normal
scale. CONCLUSIONS: The right tail of the distribution of depressive symptoms is
stable and exhibits an exponential pattern during middle adulthood.
PMID- 25587983
TI - Detection and quantification of microparticles from different cellular lineages
using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on
microparticle assessment.
AB - Microparticles, also called microvesicles, are submicron extracellular vesicles
produced by plasma membrane budding and shedding recognized as key actors in
numerous physio(patho)logical processes. Since they can be released by virtually
any cell lineages and are retrieved in biological fluids, microparticles appear
as potent biomarkers. However, the small dimensions of microparticles and soluble
factors present in body fluids can considerably impede their quantification.
Here, flow cytometry with improved methodology for microparticle resolution was
used to detect microparticles of human and mouse species generated from
platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells
from the male reproductive tract. A family of soluble proteins, the secreted
phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with
microparticles in biological fluids and that catalyze the hydrolysis of membrane
phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid
frequently used to assess microparticles, and might even clear microparticles, we
further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and
X, on microparticle quantification. We observed that if enriched in fluids,
certain sPLA2 enzymes impair the quantification of microparticles depending on
the species studied, the source of microparticles and the means of detection
employed (surface phosphatidylserine or protein antigen detection). This study
provides analytical considerations for appropriate interpretation of
microparticle cytofluorometric measurements in biological samples containing
sPLA2 enzymes.
PMID- 25587984
TI - Identification of microRNAs and target genes in the fruit and shoot tip of Lycium
chinense: a traditional Chinese medicinal plant.
AB - Although Lycium chinense (goji berry) is an important traditional Chinese
medicinal plant, little genome information is available for this plant,
particularly at the small-RNA level. Recent findings indicate that the
evolutionary role of miRNAs is very important for a better understanding of gene
regulation in different plant species. To elucidate small RNAs and their
potential target genes in fruit and shoot tissues, high-throughput RNA sequencing
technology was used followed by qRT-PCR and RLM 5'-RACE experiments. A total of
60 conserved miRNAs belonging to 31 families and 30 putative novel miRNAs were
identified. A total of 62 significantly differentially expressed miRNAs were
identified, of which 15 (14 known and 1 novel) were shoot-specific, and 12 (7
known and 5 novel) were fruit-specific. Additionally, 28 differentially expressed
miRNAs were recorded as up-regulated in fruit tissues. The predicted potential
targets were involved in a wide range of metabolic and regulatory pathways. GO
(Gene Ontology) enrichment analysis and the KEGG (Kyoto Encyclopedia of Genes and
Genomes) database revealed that "metabolic pathways" is the most significant
pathway with respect to the rich factor and gene numbers. Moreover, five miRNAs
were related to fruit maturation, lycopene biosynthesis and signaling pathways,
which might be important for the further study of fruit molecular biology. This
study is the first, to detect known and novel miRNAs, and their potential
targets, of L. chinense. The data and findings that are presented here might be a
good source for the functional genomic study of medicinal plants and for
understanding the links among diversified biological pathways.
PMID- 25587986
TI - Biomimetic remineralization of demineralized dentine using scaffold of CMC/ACP
nanocomplexes in an in vitro tooth model of deep caries.
AB - Currently, it is still a tough task for dentists to remineralize dentine in deep
caries. The aim of this study was to remineralize demineralized dentine in a
tooth model of deep caries using nanocomplexes of carboxymethyl
chitosan/amorphous calcium phosphate (CMC/ACP) based on mimicking the stabilizing
effect of dentine matrix protein 1 (DMP1) on ACP in the biomineralization of
dentine. The experimental results indicate that CMC can stabilize ACP to form
nanocomplexes of CMC/ACP, which is able to be processed into scaffolds by
lyophilization. In the single-layer collagen model, ACP nanoparticles are
released from scaffolds of CMC/ACP nanocomplexes dissolved and then infiltrate
into collagen fibrils via the gap zones (40 nm) to accomplish intrafibrillar
mineralization of collagen. With this method, the completely demineralized
dentine was partially remineralized in the tooth mode. This is a bottom-up
remineralizing strategy based on non-classical crystallization theory. Since
nanocomplexes of CMC/ACP show a promising effect of remineralization on
demineralized dentine via biomimetic strategy, thereby preserving dentinal tissue
to the maximum extent possible, it would be a potential indirect pulp capping
(IPC) material for the management of deep caries during vital pulp therapy based
on the concept of minimally invasive dentistry (MID).
PMID- 25587989
TI - Sitting on a sloping seat does not reduce the strain sustained by the postural
chain.
AB - The objective of this study was to explore the effect of a forward sloping seat
on posture and muscular activity of the trunk and lower limbs. To this aim,
twelve asymptomatic participants were tested in six conditions varying seat slope
(0 degrees , 15 degrees forward) and height (high, medium, low). Angular
position of head, trunk and pelvis was assessed with an inertial orientation
system, and muscular activity of 11 superficial postural muscles located in the
trunk and lower limbs was estimated using normalized EMG. Results showed that a
forward sloping seat, compared to a flat seat, induced a greater activity of the
soleus (p<0.01), vastus lateralis (p<0.05) and vastus medialis (p<0.05), as well
a lower hip flexion (p<0.01). In contrast, no significant variation of head,
trunk and pelvis angular position was observed according to seat slope. It was
concluded that forward sloping seats increase the load sustained by the lower
limbs, without a systematic improvement of body posture.
PMID- 25587987
TI - Event-related potentials reveal preserved attention allocation but impaired
emotion regulation in patients with epilepsy and comorbid negative affect.
AB - Patients with epilepsy have a high prevalence of comorbid mood disorders. This
study aims to evaluate whether negative affect in epilepsy is associated with
dysfunction of emotion regulation. Event-related potentials (ERPs) are used in
order to unravel the exact electrophysiological time course and investigate
whether a possible dysfunction arises during early (attention) and/or late
(regulation) stages of emotion control. Fifty epileptic patients with (n = 25)
versus without (n = 25) comorbid negative affect plus twenty-five matched
controls were recruited. ERPs were recorded while subjects performed a face- or
house-matching task in which fearful, sad or neutral faces were presented either
at attended or unattended spatial locations. Two ERP components were analyzed:
the early vertex positive potential (VPP) which is normally enhanced for faces,
and the late positive potential (LPP) that is typically larger for emotional
stimuli. All participants had larger amplitude of the early face-sensitive VPP
for attended faces compared to houses, regardless of their emotional content. By
contrast, in patients with negative affect only, the amplitude of the LPP was
significantly increased for unattended negative emotional expressions. These VPP
results indicate that epilepsy with or without negative affect does not interfere
with the early structural encoding and attention selection of faces. However, the
LPP results suggest abnormal regulation processes during the processing of
unattended emotional faces in patients with epilepsy and comorbid negative
affect. In conclusion, this ERP study reveals that early object-based attention
processes are not compromised by epilepsy, but instead, when combined with
negative affect, this neurological disease is associated with dysfunction during
the later stages of emotion regulation. As such, these new neurophysiological
findings shed light on the complex interplay of epilepsy with negative affect
during the processing of emotional visual stimuli and in turn might help to
better understand the etiology and maintenance of mood disorders in epilepsy.
PMID- 25587990
TI - Amyopathic dermatomyositis-related thrombophilia.
PMID- 25587993
TI - Revisiting susceptibility testing in MDR-TB by a standardized quantitative
phenotypic assessment in a European multicentre study.
AB - OBJECTIVES: Treatment outcome of MDR-TB is critically dependent on the proper use
of second-line drugs as per the result of in vitro drug susceptibility testing
(DST). We aimed to establish a standardized DST procedure based on quantitative
determination of drug resistance and compared the results with those of genotypes
associated with drug resistance. METHODS: The protocol, based on MGIT 960 and the
TB eXiST software, was evaluated in nine European reference laboratories.
Resistance detection at a screening drug concentration was followed by
determination of resistance levels and estimation of the resistance proportion.
Mutations in 14 gene regions were investigated using established techniques.
RESULTS: A total of 139 Mycobacterium tuberculosis isolates from patients with
MDR-TB and resistance beyond MDR-TB were tested for 13 antituberculous drugs:
isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, para
aminosalicylic acid, ethionamide, amikacin, capreomycin, ofloxacin, moxifloxacin
and linezolid. Concordance between phenotypic and genotypic resistance was >80%,
except for ethambutol. Time to results was short (median 10 days). High-level
resistance, which precludes the therapeutic use of an antituberculous drug, was
observed in 49% of the isolates. The finding of a low or intermediate resistance
level in 16% and 35% of the isolates, respectively, may help in designing an
efficient personalized regimen for the treatment of MDR-TB patients. CONCLUSIONS:
The automated DST procedure permits accurate and rapid quantitative resistance
profiling of first- and second-line antituberculous drugs. Prospective validation
is warranted to determine the impact on patient care.
PMID- 25587991
TI - Life-style and genome structure of marine Pseudoalteromonas siphovirus B8b
isolated from the northwestern Mediterranean Sea.
AB - Marine viruses (phages) alter bacterial diversity and evolution with impacts on
marine biogeochemical cycles, and yet few well-developed model systems limit
opportunities for hypothesis testing. Here we isolate phage B8b from the
Mediterranean Sea using Pseudoalteromonas sp. QC-44 as a host and characterize it
using myriad techniques. Morphologically, phage B8b was classified as a member of
the Siphoviridae family. One-step growth analyses showed that this siphovirus had
a latent period of 70 min and released 172 new viral particles per cell. Host
range analysis against 89 bacterial host strains revealed that phage B8b infected
3 Pseudoalteromonas strains (52 tested, >99.9% 16S rRNA gene nucleotide identity)
and 1 non-Pseudoaltermonas strain belonging to Alteromonas sp. (37 strains from 6
genera tested), which helps bound the phylogenetic distance possible in a phage
mediated horizontal gene transfer event. The Pseudoalteromonas phage B8b genome
size was 42.7 kb, with clear structural and replication modules where the former
were delineated leveraging identification of 16 structural genes by virion
structural proteomics, only 4 of which had any similarity to known structural
proteins. In nature, this phage was common in coastal marine environments in both
photic and aphotic layers (found in 26.5% of available viral metagenomes), but
not abundant in any sample (average per sample abundance was 0.65% of the reads).
Together these data improve our understanding of siphoviruses in nature, and
provide foundational information for a new 'rare virosphere' phage-host model
system.
PMID- 25587992
TI - Plasma IL-5 concentration and subclinical carotid atherosclerosis.
AB - OBJECTIVE: Genetic variants robustly associated with coronary artery disease were
reported in the vicinity of the interleukin (IL)-5 locus, and animal studies
suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this
work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis,
as determined by measures of baseline severity and change over time of carotid
intima-media thickness (cIMT). METHODS: We used biobank and databases of IMPROVE,
a large European prospective cohort study of high-risk individuals (n = 3534)
free of clinically overt cardiovascular disease at enrollment, in whom composite
and segment-specific measures of cIMT were recorded at baseline and after 15 and
30 months. IL-5 was measured with an immunoassay in plasma samples taken at
baseline. RESULTS: IL-5 levels were lower in women than in men, lower in the
South than in North of Europe, and showed positive correlations with most
established risk factors. IL-5 showed significant inverse relationships with cIMT
change over time in the common carotid segment in women, but no significant
relationships to baseline cIMT in either men or women. CONCLUSIONS: Our results
suggest that IL-5 may be part of protective mechanisms operating in early
atherosclerosis, at least in women. However, the relationships are weak and
whereas IL-5 has been proposed as a potential molecular target to treat
allergies, it is difficult to envisage such a scenario in coronary artery
disease.
PMID- 25587994
TI - Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB
agents.
AB - OBJECTIVES: The discovery and development of TB drugs has met limited success,
with two new drugs approved over the last 40 years. Part of the difficulty
resides in the lack of well-established in vitro or in vivo targets of potency
and physicochemical and pharmacokinetic parameters. In an attempt to benchmark
and compare such properties for anti-TB agents, we have experimentally determined
and compiled these parameters for 36 anti-TB compounds, using standardized and
centralized assays, thus ensuring direct comparability across drugs and drug
classes. METHODS: Potency parameters included growth inhibition, cidal activity
against growing and non-growing bacteria and activity against intracellular
mycobacteria. Pharmacokinetic parameters included basic physicochemical
properties, solubility, permeability and metabolic stability. We then attempted
to establish correlations between physicochemical, in vitro and in vivo
pharmacokinetic and pharmacodynamic indices to tentatively inform future drug
discovery efforts. RESULTS: Two-thirds of the compounds tested showed
bactericidal and intramacrophage activity. Most compounds exhibited favourable
solubility, permeability and metabolic stability in standard in vitro
pharmacokinetic assays. An analysis of human pharmacokinetic parameters revealed
associations between lipophilicity and volume of distribution, clearance, plasma
protein binding and oral bioavailability. Not surprisingly, most compounds with
favourable pharmacokinetic properties complied with Lipinski's rule of five.
CONCLUSIONS: However, most attempts to detect in vitro-in vivo correlations were
unsuccessful, emphasizing the challenges of anti-TB drug discovery. The objective
of this work is to provide a reference dataset for the TB drug discovery
community with a focus on comparative in vitro potency and pharmacokinetics.
PMID- 25587995
TI - The transcriptomic response of Acinetobacter baumannii to colistin and doripenem
alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model.
AB - OBJECTIVES: Colistin remains a last-line treatment for MDR Acinetobacter
baumannii and combined use of colistin and carbapenems has shown synergistic
effects against MDR strains. In order to understand the bacterial responses to
these antibiotics, we analysed the transcriptome of A. baumannii following
exposure to each. METHODS: RNA sequencing was employed to determine changes in
the transcriptome following treatment with colistin and doripenem, both alone and
in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to
mimic the PK of both antibiotics in patients. RESULTS: After treatment with
colistin (continuous infusion at 2 mg/L), >400 differentially regulated genes
were identified, including many associated with outer membrane biogenesis, fatty
acid metabolism and phospholipid trafficking. No genes were differentially
expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15
min, but 45 genes were identified as differentially expressed after 1 h of growth
under this condition. Treatment of A. baumannii with both colistin and doripenem
together for 1 h resulted in >450 genes being identified as differentially
expressed. More than 70% of these gene expression changes were also observed
following colistin treatment alone. CONCLUSIONS: These data suggest that colistin
causes gross damage to the outer membrane, facilitates lipid exchange between the
inner and outer membrane and alters the normal asymmetric outer membrane
composition. The transcriptional response to colistin was highly similar to that
observed for an LPS-deficient strain, indicating that many of the observed
changes are responses to outer membrane instability resulting from LPS loss.
PMID- 25587997
TI - Analysis of thin-film polymers using attenuated total internal reflection-Raman
microspectroscopy.
AB - Two methods commonly employed for molecular surface analysis and thin-film
analysis of microscopic areas are attenuated total reflection infrared (ATR-IR)
microspectroscopy and confocal Raman microspectroscopy. In the former method, the
depth of the evanescent probe beam can be controlled by the wavelength of light,
the angle of incidence, or the refractive index of the internal reflection
element. Because the penetration depth is proportional to the wavelength of
light, one could interrogate a smaller film thickness by moving from the mid
infrared region to the visible region employing Raman spectroscopy. The
investigation of ATR Raman microspectroscopy, a largely unexplored technique
available to Raman microspectroscopy, was carried out. A Renishaw inVia Raman
microscope was externally modified and used in conjunction with a solid immersion
lens (SIL) to perform ATR Raman experiments. Thin-film polymer samples were
analyzed to explore the theoretical sampling depth for experiments conducted
without the SIL, with the SIL, and with the SIL using evanescent excitation. The
feasibility of micro-ATR Raman was examined by collecting ATR spectra from films
whose thickness measured from 200 to 60 nm. Films of these thicknesses were
present on a much thicker substrate, and features from the underlying substrate
did not become visible until the thin film reached a thickness of 68 nm.
PMID- 25587996
TI - Avibactam confers susceptibility to a large proportion of ceftazidime-resistant
Pseudomonas aeruginosa isolates recovered from cystic fibrosis patients.
PMID- 25587998
TI - No evidence of complementary water use along a plant species richness gradient in
temperate experimental grasslands.
AB - Niche complementarity in resource use has been proposed as a key mechanism to
explain the positive effects of increasing plant species richness on ecosystem
processes, in particular on primary productivity. Since hardly any information is
available for niche complementarity in water use, we tested the effects of plant
diversity on spatial and temporal complementarity in water uptake in experimental
grasslands by using stable water isotopes. We hypothesized that water uptake from
deeper soil depths increases in more diverse compared to low diverse plant
species mixtures. We labeled soil water in 8 cm (with 18O) and 28 cm depth (with
2H) three times during the 2011 growing season in 40 temperate grassland
communities of varying species richness (2, 4, 8 and 16 species) and functional
group number and composition (legumes, grasses, tall herbs, small herbs). Stable
isotope analyses of xylem and soil water allowed identifying the preferential
depth of water uptake. Higher enrichment in 18O of xylem water than in 2H
suggested that the main water uptake was in the upper soil layer. Furthermore,
our results revealed no differences in root water uptake among communities with
different species richness, different number of functional groups or with time.
Thus, our results do not support the hypothesis of increased complementarity in
water use in more diverse than in less diverse communities of temperate grassland
species.
PMID- 25587999
TI - Electrostatic interaction between nonuniformly charged colloids: experimental and
numerical study.
AB - The influence of the surface charge distribution on the interaction between
nanosized particles in water is reported. The distribution of charges at the
surface of initially neutral microemulsion droplets has been modulated by
additions of various oligomeric cationic surfactants. The osmotic compressibility
of the doped microemulsions was measured by light and small-angle neutrons
scattering and reveals that the overall effective interaction induced by the
ionic groups is repulsive. However, particular charge distributions decrease the
osmotic compressibility much less than others. Independent measurements of the
activity of the bromide counterions with specific electrodes evidence a
significant decrease in the effective charge, which, however, cannot account for
the osmotic compressibility in the framework of the primitive model. The q
dependence of the structure factor reveals an attractive contribution over a
short distance. Numerical studies assign this attractive contribution to the
overlap of hydration shells that are extended as a result of the charge
localization.
PMID- 25588001
TI - Development of a Veterans Affairs hybrid operating room for transcatheter aortic
valve replacement in the cardiac catheterization laboratory.
AB - IMPORTANCE: Transcatheter aortic valve replacement (TAVR) revolutionized the
treatment of aortic stenosis. Developing a TAVR program with a custom-built
hybrid operating room (HOR) outside the surgical operating room area poses unique
challenges in Veterans Affairs (VA) institutions. OBJECTIVE: To present the
process by which the San Francisco VA Medical Center developed a VA-approved TAVR
program, in which an HOR exists in a cardiac catheterization laboratory, as a
guideline for future programs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
review of each required approval process for developing an HOR in a cardiac
catheterization laboratory in a VA designated for complex surgery. Participants
included San Francisco VA Medical Center health care professionals and
individuals responsible for new program initiation in VA institutions. EXPOSURES:
External reviews by industry vendors, the VA Central Office, and the Office for
Construction, Facilities, and Management and an internal Healthcare Failure Mode
and Effect Analysis. MAIN OUTCOMES AND MEASURES: The timeline for each process.
RESULTS: Developing a TAVR program required vetting and approval from industry
vendors, who provided training and expertise. Architectural plans for
construction of the HOR began in 2010-2011, followed by approval from Edwards
Lifesciences, Inc, in 2012 and fundamentals training on February 8 and 9, 2013.
Following a pilot launch of the first VA TAVR program at the Houston VA Medical
Center, subsequent programs were required to submit a plan to the VA Central
Office for proposed restructuring of their clinical programs. After the San
Francisco VA Medical Center proposal submission on February 3, 2013, a site visit
consisting of a National Chief of Catheterization Laboratory Managers, a cardiac
surgeon, and an interventional cardiologist with TAVR experience was conducted on
April 12, 2013. During construction, HOR plans were inspected by the Office for
Construction, Facilities, and Management followed by on-site inspection on August
8, 2013, to assess the adequacy of the HOR, newly built restricted corridors,
equipment storage areas, and altered staff and patient flow patterns. Last, a
Healthcare Failure Mode and Effect Analysis was performed to mitigate any
negative effects of the HOR not being colocated in the surgical operating room
area. Approval was then granted on November 13, 2013. Our first 10 TAVR cases
were successfully completed as of April 2, 2014. CONCLUSIONS AND RELEVANCE: The
primary factor for development of a successful TAVR program is integration of the
heart valve team. Particular adaptations to the cardiac catheterization
laboratory environment are required to accommodate an uncompromised HOR in which
cardiac and vascular surgeons can be as comfortable as their interventional
cardiology colleagues.
PMID- 25588000
TI - Laterality across languages: Results from a global dichotic listening study using
a smartphone application.
AB - Left-hemispheric language dominance has been suggested by observations in
patients with brain damages as early as the 19th century, and has since been
confirmed by modern behavioural and brain imaging techniques. Nevertheless, most
of these studies have been conducted in small samples with predominantly Anglo
American background, thus limiting generalization and possible differences
between cultural and linguistic backgrounds may be obscured. To overcome this
limitation, we conducted a global dichotic listening experiment using a
smartphone application for remote data collection. The results from over 4,000
participants with more than 60 different language backgrounds showed that left
hemispheric language dominance is indeed a general phenomenon. However, the
degree of lateralization appears to be modulated by linguistic background. These
results suggest that more emphasis should be placed on cultural/linguistic
specificities of psychological phenomena and on the need to collect more diverse
samples.
PMID- 25588002
TI - Decreased plasma iron in Alzheimer's disease is due to transferrin desaturation.
AB - Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with
an idiopathic anemia. We examined iron-binding plasma proteins from AD patients
and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL)
Flagship Study of Ageing using size exclusion chromatography-inductively coupled
plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation
was directly compared to routine pathological testing. We found a significant
decrease in transferrin-associated iron in AD that was missed by routine
pathological tests of transferrin saturation, and that was able to discriminate
between AD and controls. The AD cases showed no significant difference in
transferrin concentration, only a decrease in total transferrin-bound iron. These
findings support that a previously identified decrease in plasma iron levels in
AD patients within the AIBL study is attributable to decreased loading of iron
into transferrin, and that this subtle but discriminatory change is not observed
through routine pathological testing.
PMID- 25588003
TI - Apparent increase of reported hemorrhagic disease in the midwestern and
northeastern USA.
AB - We investigated temporal and spatial trends in reporting of hemorrhagic disease
(HD) in the midwestern and northeastern US using a 33-yr (1980-2012)
questionnaire-based data set. This data set was supported by an additional 19 yr
(1994-2012) of bluetongue virus (BTV) and epizootic hemorrhagic disease virus
(EHDV) isolation results from clinically affected white-tailed deer (Odocoileus
virginianus) in these regions. Both the number of counties that were reported
positive for HD and the northern latitudinal range of reported HD increased with
time. A similar increase was observed with both the number of states annually
reporting HD and the number of counties where HD was reported. Large-scale
outbreaks occurred in 1988, 1996, 2007, and 2012, and the scale of these
individual outbreaks also increased with time. The predominant virus isolated
from these regions was EHDV-2, but the prevalence of EHDV-6, which was first
detected in 2006, appears to be increasing. Temporally, the extent of regional HD
reporting was correlated with regional drought conditions. The significance of
increases in reported HD and the incursions and establishment of new BTV and EHDV
in the US currently are unknown.
PMID- 25588005
TI - The prevalence and clinical significance of Chlamydia infection in island and
mainland populations of Victorian koalas (Phascolarctos cinereus).
AB - Chlamydia infection is known to impact the health of koalas (Phascolarctos
cinereus) in New South Wales (NSW) and Queensland, but the clinical significance
of Chlamydia infections in Victorian koalas is not well described. We examined
the prevalence of Chlamydia infection and assessed associated health parameters
in two Victorian koala populations known to be Chlamydia positive. The same
testing regimen was applied to a third Victorian population in which Chlamydia
had not been detected. We examined 288 koalas and collected samples from the
urogenital sinus and conjunctival sacs. Detection and differentiation of
Chlamydia species utilized real-time PCR and high-resolution melting curve
analysis. Chlamydia pecorum was detected in two populations (prevalences: 25% and
41%, respectively) but only from urogenital sinus swabs. Chlamydia was not
detected in the third population. Chlamydia pneumoniae was not detected.
Chlamydia pecorum infection was positively associated with wet bottom (indicating
chronic urinary tract disease) in one Chlamydia-positive population and with
abnormal urogenital ultrasound findings in the other Chlamydia-positive
population. The prevalence of wet bottom was similar in all populations
(including the Chlamydia-free population), suggesting there is another
significant cause (or causes) of wet bottom in Victorian koalas. Ocular disease
was not observed. This is the largest study of Chlamydia infection in Victorian
koalas, and the results suggest the potential for epidemiologic differences
related to Chlamydia infections between Victorian koalas and koalas in Queensland
and NSW and also between geographically distinct Victorian populations. Further
studies to investigate the genotypes of C. pecorum present in Victorian koalas
and to identify additional causes of wet bottom in koalas are indicated.
PMID- 25588006
TI - Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free
ranging prairie dogs (Cynomys spp.), Colorado, USA.
AB - Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral
sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN
F1/V307) has been developed for prairie dogs. This vaccine is incorporated into
palatable bait along with rhodamine B as a biomarker. We conducted trials in
August and September 2012 to demonstrate uptake and apparent safety of the RCN
F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging
prairie dogs and other associated small rodents readily consumed vaccine-laden
baits during field trials with no apparent adverse effects; most sampled prairie
dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts
of prairie dogs and their burrows revealed no evidence of prairie dog decline
after vaccine exposure. No vaccine-related morbidity, mortality, or gross or
microscopic lesions were observed. Poxviruses were not isolated from any animal
sampled prior to bait distribution or on sites that received placebo baits. We
isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus
maniculatus) captured on sites where vaccine-laden baits were distributed. Based
on these findings, studies examining the utility and effectiveness of oral
vaccination to prevent plague-induced mortality in prairie dogs and associated
species are underway.
PMID- 25588007
TI - Epidemiology and pathology of Toxoplasma gondii in free-ranging California sea
lions (Zalophus californianus).
AB - The coccidian parasite Toxoplasma gondii infects humans and warm-blooded animals
worldwide. The ecology of this parasite in marine systems is poorly understood,
although many marine mammals are infected and susceptible to clinical
toxoplasmosis. We summarized the lesions associated with T. gondii infection in
the California sea lion (Zalophus californianus) population and investigated the
prevalence of and risk factors associated with T. gondii exposure, as indicated
by antibody. Five confirmed and four suspected cases of T. gondii infection were
identified by analysis of 1,152 medical records of necropsied sea lions from 1975
2009. One suspected and two confirmed cases were identified in aborted fetuses
from a sea lion rookery. Toxoplasmosis was the primary cause of death in five
cases, including the two fetuses. Gross and histopathologic findings in T. gondii
infected sea lions were similar to those reported in other marine mammals. The
most common lesions were encephalitis, meningitis, and myocarditis. The antibody
prevalence in stranded, free-ranging sea lions for 1998-2009 was 2.5% (+/-0.03%;
IgG titer 640). There was an increase in odds of exposure in sea lions with
increasing age, suggesting cumulative risk of exposure and persistent antibody
over time. The occurrence of disseminated T. gondii infection in aborted fetuses
confirms vertical transmission in sea lions, and the increasing odds of exposure
with age is consistent with additional opportunities for horizontal transmission
in free-ranging sea lions over time. These data suggest that T. gondii may have
two modes of transmission in the sea lion population. Overall, clinical disease
was uncommon in our study which, along with low prevalence of T. gondii antibody,
suggests substantially less-frequent exposure and lower susceptibility to
clinical disease in California sea lions as compared to sympatric southern sea
otters (Enhydra lutris nereis).
PMID- 25588008
TI - Modeling the environmental growth of Pseudogymnoascus destructans and its impact
on the white-nose syndrome epidemic.
AB - White-nose syndrome (WNS) has had a devastating effect on North American bat
populations. The causal agent of WNS is the fungal pathogen, Pseudogymnoascus
destructans (Pd), which has been shown to persist in caves after the eradication
of host populations. As nonpathogenic Pseudogymnoascus spp. display saprophytic
growth and are among the most commonly isolated fungi from caves, we examined
whether Pd could grow in cave sediments and the contribution such growth could
have to WNS disease progression. We inoculated a range of diverse cave sediments
and demonstrated the growth of Pd in all sediments tested. These data indicate
that environmental growth of Pd could lead to the accumulation of spores above
the estimated infection threshold for WNS, allowing environment-to-bat infection.
The obtained growth parameters were then used in a susceptible-infected
susceptible mathematic model to determine the possible contribution of
environmental Pd growth to WNS disease progression in a colony of little brown
bats (Myotis lucifugus). This model suggests that the environmental growth of Pd
would increase WNS infection rates, particularly in colonies experiencing longer
hibernation periods or in hibernacula with high levels of organic detritus. The
model also suggests that once introduced, environmental Pd growth would allow the
persistence of this pathogen within infected hibernacula for decades, greatly
compromising the success of bat reintroduction strategies. Together these data
suggest that Pd is not reliant on its host for survival and is capable of
environmental growth and amplification that could contribute to the rapid
progression and long-term persistence of WNS in the hibernacula of threatened
North American bats.
PMID- 25588009
TI - Prevalence of the generalist flea Pulex simulans on black-tailed prairie dogs
(Cynomys ludovicianus) in New Mexico, USA: the importance of considering
imperfect detection.
AB - If a parasite is not detected during a survey, one of two explanations is
possible: the parasite was truly absent or it was present but not detected. We
fit occupancy models to account for imperfect detection when combing fleas
(Siphonaptera) from black-tailed prairie dogs (Cynomys ludovicianus) during June
August 2012 in the Vermejo Park Ranch, New Mexico, USA. With the use of detection
histories from combing events during monthly trapping sessions, we fit occupancy
models for two flea species: Oropsylla hirusta (a prairie dog specialist) and
Pulex simulans (a generalist). Detection probability was <100% for both species
and about 21% lower for P. simulans. Pulex simulans may be especially difficult
to detect because it is about half the size of O. hirusta. Monthly occupancy
(prevalence) for P. simulans was estimated at 24% (June, 95% confidence interval
= 19-30), 39% (July, 32-47), and 56% (August, 49-64) in new prairie dog colonies,
and 43% (32-54), 61% (49-71), and 79% (70-87) in old colonies. These results
suggest P. simulans can attain high prevalence on prairie dogs, especially in old
colonies. If P. simulans is highly prevalent on prairie dogs, it may serve as a
"bridge vector" between Cynomys and other mammalian hosts of the plague bacterium
Yersinia pestis, and even function as a reservoir of Y. pestis between outbreaks.
PMID- 25588010
TI - Experimental susceptibility of wood ducks (Aix sponsa) for West Nile virus.
AB - Detection of West Nile virus (WNV) has been reported in a variety of wild ducks
in the US, but little is known about the pathogenesis and outcome of exposure of
the disease in these species. Previous experimental studies of WNV in ducks
either have challenged a small number of ducks with WNV or have tested
domesticated ducks. To determine susceptibility and immune response, we
challenged 7-wk-old Wood Ducks (Aix sponsa) with a 1999 American Crow (Corvus
brachyrhynchos) isolate of WNV. Wood Ducks were susceptible to infection with the
virus, and, although clinical signs or mortality were not observed, microscopic
lesions were noted, particularly in the heart and brain. West Nile virus viremia
peaked on day 2 postinfection (pi) at 10(4.54) plaque-forming units (PFU) of
virus/mL serum and WNV was shed orally (between 10(2) and 10(2.9) PFU per swab)
and cloacally. Specific anti-WNV antibody response was rapid, with anti-WNV IgM
detected on day 3 pi followed on day 5 pi by anti-WNV IgG. Neutralizing
antibodies were detected by plaque-reduction neutralization assay in one duck on
day 4 pi, and in all sampled ducks on day 5. These results indicate that Wood
Ducks are susceptible to WNV, but it is unlikely that significant WNV mortality
events occur in Wood Ducks or that they play a significant role in transmission.
However, WNV viremia was sufficient, in theory, to infect mosquitoes, and oral
and cloacal shedding of the virus may increase the risk of infection to other
waterbirds.
PMID- 25588011
TI - Ichthyophonus sp. (Ichthyophonae, Ichthyophonida) infection in a South American
amphibian, the hylid frog Hypsiboas pulchellus.
AB - We report infection by Ichthyophonus sp. in a South American amphibian, the hylid
frog Hypsiboas pulchellus in Uruguay. This frog had a large subcutaneous mass
over the urostyle and dorsal musculature comprised of parasitic cysts with mild
granulomatous inflammation but otherwise appeared healthy.
PMID- 25588012
TI - Surveillance and characterization of Riemerella anatipestifer from wild birds in
South Korea.
AB - We conducted surveillance for Riemerella anatipestifer (RA) in wild birds along
the East Asian-Australasian flyway in South Korea. Detected RA were characterized
by serotype, antibiotic susceptibility, and sequence analysis of the 16S rRNA
gene. We collected 944 wild birds of 34 species from 19 of South Korea's major
migratory wild bird habitats between 2011 and 2012. We identified RA by PCR and
rRNA gene sequence in 71/102 (69.6%) pharyngeal swabs and 19/944 (2.0%) cloacal
swabs of wild birds. Most RA positives (71/75 [95%] pharyngeal and 19/704 [(2.6%]
cloacal) were from three duck species (family Anatidae): Mallard Duck (Anas
platyrhynchos), Northern Pintail (Anas acuta), and Spot-billed Duck (Anas
poecilorhyncha). Thirty-three RA isolates obtained and examined were highly
resistant to aminoglycosides: kanamycin (100%), gentamicin (94%), amikacin (91%),
neomycin (88%), and streptomycin (82%). Six isolates were identified as serotype
4 by agar gel precipitation. Serotypes 1 and 7, which are known virulent
serotypes, were also identified in three isolates from wild duck species.
PMID- 25588013
TI - Influence of ecologic factors on prevalence of meningeal worm
(Parelaphostrongylus tenuis) infection in South Dakota, USA.
AB - The meningeal worm (Parelaphostrongylus tenuis) is a nematode parasite that
commonly infects white-tailed deer (Odocoileus virginianus; WTD) throughout the
deciduous forest biome and deciduous-coniferous ecotone of eastern and central
North America; the species is not known to occur west of the grassland biome of
central North America. We used county-specific prevalence data to evaluate
potential effects of landscape and climatologic factors on the spatial
distribution of meningeal worm infection in South Dakota, US. Probability of
infection increased 4-fold between eastern and western South Dakota and 1.3-fold
for each 1-cm increase in summer precipitation. Sixty-three percent of WTD had
only a single worm in the cranium. Expansion of meningeal worm infection across
western South Dakota may be inherently low due to the combined effects of arid
climate and potential attributes of the Missouri River that limit regional
movements by infected WTD. Use of landscape genetic analyses to identify
potential relationships between landscape features and population genetic
structure of infected deer and parasites may contribute to a greater
understanding of regional heterogeneity in meningeal worm infection rates across
South Dakota, particularly in counties adjacent to the Missouri River. Future
research evaluating heterogeneity in prevalence and intensity of infection
between fawn and yearling deer, and the potential role of yearling male deer as
dispersal agents of meningeal worms across the Missouri River, also is warranted.
PMID- 25588014
TI - Chemical immobilization of free-ranging fallow deer (Dama dama): effect of needle
length on induction time.
AB - We evaluated impact of the needle length, sex, and body condition on chemical
immobilization induction time in 50 (29 males and 21 females) free-ranging fallow
deer (Dama dama) in Sweden, 2006-11. Induction time is probably the single most
important factor when immobilizing free-ranging wildlife with the use of a remote
drug-delivery system. Induction times should be short to minimize stress and risk
of injury, and to ensure that immobilized animals can be found and clinically
monitored as soon as possible. We measured the distance between the darting
location and where we recovered the immobilized animal and also the time
occurring between the two events. We used two types of needles: 2.0 * 30- or 2.0
* 40-mm barbed needles with side ports. The most important result is that a 10-mm
longer dart needle can reduce the retrieval time substantially (>20 min) until an
animal is under monitoring. On average after the darting, the retrieval time
decreased from 51 to 29 min and the distance decreased from 519 m from the
darting location to 294 m. We suggest that a needle length of 40 mm is preferable
for immobilization of wild fallow deer, especially for animals in over-average-to
fat body condition.
PMID- 25588015
TI - Norwegian words: A lexical database for clinicians and researchers.
AB - All words have properties linked to form, meaning and usage patterns which
influence how easily they are accessed from the mental lexicon in language
production, perception and comprehension. Examples of such properties are
imageability, phonological and morphological complexity, word class, argument
structure, frequency of use and age of acquisition. Due to linguistic and
cultural variation the properties and the values associated with them differ
across languages. Hence, for research as well as clinical purposes, language
specific information on lexical properties is needed. To meet this need, an
electronically searchable lexical database with more than 1600 Norwegian words
coded for more than 12 different properties has been established. This article
presents the content and structure of the database as well as the search options
available in the interface. Finally, it briefly describes some of the ways in
which the database can be used in research, clinical practice and teaching.
PMID- 25588016
TI - Genomic characterisation of three Mapputta group viruses, a serogroup of
Australian and Papua New Guinean bunyaviruses associated with human disease.
AB - The Mapputta serogroup tentatively contains the mosquito-associated viruses
Mapputta, Maprik, Trubanaman and Gan Gan. Interestingly, this serogroup has
previously been associated with an acute epidemic polyarthritis-like illness in
humans; however, there has been no ensuing genetic characterisation. Here we
report the complete genome sequences of Mapputta and Maprik viruses, and a new
Mapputta group candidate, Buffalo Creek virus, previously isolated from
mosquitoes and detected by serology in a hospitalised patient. Phylogenetic
analyses indicate that the group is one of the earliest diverged groups within
the genus Orthobunyavirus of the family Bunyaviridae. Analyses show that these
three viruses are related to the recently sequenced Australian bunyaviruses from
mosquitoes, Salt Ash and Murrumbidgee. A notable feature of the Mapputta group
viruses is the absence of the NSs (non-structural) ORF commonly found on the S
segment of other orthobunyaviruses. Viruses of the Mapputta group have been
isolated from geographically diverse regions ranging from tropical Papua New
Guinea to the semi-arid climate of south-eastern Australia. The relevance of this
group to human health in the region merits further investigation.
PMID- 25588018
TI - Novel psychoactive substances (designer drugs): overview and pharmacology of
modulators of monoamine signaling.
AB - Novel psychoactive substances are newly used designer drugs ("internet drugs",
"research chemicals", "legal highs") potentially posing similar health risks to
classic illicit substances. Chemically, many novel psychoactive substances can be
classified as phenethylamines, amphetamines, synthetic cathinones, piperazines,
pipradrols/piperidines, aminoindanes benzofurans, and tryptamines.
Pharmacologically, these substances interact with various monoaminergic targets.
Typically, stimulants inhibit the transport of dopamine and noradrenaline
(pipradrols, pyrovalerone cathinones) or induce the release of these monoamines
(amphetamines and methamphetamine-like cathinones), entactogens predominantly
enhance serotonin release (phenylpiperazines, aminoindanes, para-substituted
amphetamines, and MDMA-like cathinones) similar to MDMA (ecstasy), and
hallucinogens (tryptamines, hallucinogenic phenethylamines) are direct agonists
at serotonergic 5-HT2A receptors. Synthetic cannabinoids are another group of
novel substances which all act as agonists at the cannabinoid CB1 receptor
similar to THC but are chemically diverse. In particular, the relative
serotonergic vs dopaminergic activity (determined by the dopamine/serotonin
transporter inhibition ratio in vitro) can be helpful to predict the desired
psychotropic but also the toxic effects of novel substances as well as their
potential for addiction. Although the use of novel psychoactive substances mostly
produces minor or moderate poisonings, serious complications occur. Serotonergic
drugs (entactogens and hallucinogens) are associated with acute serotonin
syndrome, hyperthermia, seizures, and hyponatremia. Dopaminergic drugs are highly
addictive and acute toxicity includes prolonged stimulation, insomnia, agitation,
and psychosis. Agitation, anxiety, paranoia, hypertension, and rarely myocardial
infarction and renal failure are seen with synthetic cannabinoids. Treatment is
supportive.
PMID- 25588017
TI - FTIR metabolomic fingerprint reveals different modes of action exerted by
structural variants of N-alkyltropinium bromide surfactants on Escherichia coli
and Listeria innocua cells.
AB - Surfactants are extremely important agents to clean and sanitize various
environments. Their biocidal activity is a key factor determined by the
interactions between amphiphile structure and the target microbial cells. The
object of this study was to analyze the interactions between four structural
variants of N-alkyltropinium bromide surfactants with the Gram negative
Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological
and conductometric methods with a previously described FTIR bioassay were used to
assess the metabolomic damage exerted by these compounds. All surfactants tested
showed more biocidal activity in L. innocua than in E. coli. N
tetradecyltropinium bromide was the most effective compound against both species,
while all the other variants had a reduced efficacy as biocides, mainly against
E. coli cells. In general, the most prominent metabolomic response was observed
for the constituents of the cell envelope in the fatty acids (W1) and amides (W2)
regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions).
This response was particularly strong and negative in L. innocua, when cells were
challenged by N-tetradecyltropinium bromide, and by the variant with a smaller
head and a 12C tail (N-dodecylquinuclidinium bromide). Tail length was critical
for microbial inhibition especially when acting against E. coli, maybe due the
complex nature of Gram negative cell envelope. Statistical analysis allowed us to
correlate the induced mortality with the metabolomic cell response, highlighting
two different modes of action. In general, gaining insights in the interactions
between fine structural properties of surfactants and the microbial diversity can
allow tailoring these compounds for the various operative conditions.
PMID- 25588019
TI - Experimental evidence of replica symmetry breaking in random lasers.
AB - Spin-glass theory is one of the leading paradigms of complex physics and
describes condensed matter, neural networks and biological systems, ultracold
atoms, random photonics and many other research fields. According to this theory,
identical systems under identical conditions may reach different states. This
effect is known as replica symmetry breaking and is revealed by the shape of the
probability distribution function of an order parameter named the Parisi overlap.
However, a direct experimental evidence in any field of research is still
missing. Here we investigate pulse-to-pulse fluctuations in random lasers, we
introduce and measure the analogue of the Parisi overlap in independent
experimental realizations of the same disordered sample, and we find that the
distribution function yields evidence of a transition to a glassy light phase
compatible with a replica symmetry breaking.
PMID- 25588020
TI - Shelf-life of E-lysyl-3-(trimethylstannyl)benzamide immunoconjugates, precursors
for 211At labeling of antibodies.
AB - Astatine-211 is possibly the most promising radionuclide for targeted alpha
particle therapy when it comes to the treatment of occult disseminated cancer.
Preclinical research has proven effective, and patient studies have been
initiated based on these results. However, a lack of production capacity and the
complex radiochemistry of (211)At are major obstacles for research and
prospective clinical applications. In the present study, astatination of
immunoconjugates, already prepared well in advance before radiolabeling, was
performed to investigate the possibility of formulating a kit-like reagent for
the production of (211)At radiopharmaceuticals. The shelf-life of E-lysyl-3
(trimethylstannyl)benzamide immunoconjugates was evaluated, that is, the effect
of different storage times on the quality of the immunoconjugates. The quality
being referred to is the capacity to maintain a good radiochemical yield and good
cell-binding property after labeling with (211)At. The stability of the
conjugates was found to be pH dependent with high stability at pH>=7 and less
stability at pH<=5.5. The immunoconjugates (based on trastuzumab) could be kept
for more than 3 months in a phosphate buffered saline solution (pH 7.4) at 4
degrees C before labeling, without compromising the quality of the labeled
product. The conjugates are also unaffected by storage at -20 degrees C.
Conjugates with a good shelf-life compatible with distant shipping as well as
improved radiochemistry are important steps to facilitate further clinical
progress with (211)At.
PMID- 25588021
TI - Adherence to transfusion guidelines: are we prepared for the Smarter Medicine or
Choosing Wisely initiative?
AB - OBJECTIVE: To determine, whether a restrictive transfusion strategy is followed
in our hospital and to identify differences in activities within departments and
patient groups. METHOD: Over a period of 15 months, RBC transfusions were
prospectively recorded including the haemoglobin level prior to transfusion and
were grouped in the different departments of our hospital (internal medicine
ward, department of surgery, emergency room, intensive care unit, gynaecology
ward, medical outpatient clinic and oncology outpatient clinic). Indications and
co-morbidities were assessed retrospectively by reviewing the patient's charts.
RESULTS: There were 1,832 RBC products transfused in total. The overall mean
level of haemoglobin before transfusion was 7.61 g/dl (+/-1.1). These haemoglobin
levels differed significantly between the departments (p <0.001), with the lowest
threshold in the internal medicine ward (7.30 g/dl +/- 1.0) compared to the
surgery ward (7.73 g/dl +/- 1.0) and to the intensive care unit (7.82 g/dl +/-
0.9). In general, mean pre-transfusion haemoglobin levels did not differ
significantly between patients with coronary artery disease (CAD) and patients
without (7.64 g/dl +/- 1.0 vs 7.59 g/dl +/- 1.1, p = 0.48). In transfusions for
patients with acute coronary syndrome a tendency to a higher transfusion
threshold than in patients with stable CAD could be found (7.84 g/dl +/- 0.7 vs
7.58 g/dl +/- 1.0, p = 0.05). Patients with haematological disorders were
transfused at a higher threshold when compared to patients without (7.77 g/dl vs
7.56 g/dl, p = 0.006). CONCLUSION: All wards in our analysis are following the
current guidelines based on restrictive transfusion strategies. At the same time,
we were able to detect significant differences between different departments and
patient characteristics.
PMID- 25588022
TI - Three- and four-class classification models for P-glycoprotein inhibitors using
counter-propagation neural networks.
AB - P-glycoprotein (P-gp) is an ATP binding cassette (ABC) transporter that helps to
protect several certain human organs from xenobiotic exposure. This efflux pump
is also responsible for multi-drug resistance (MDR), an issue of the chemotherapy
approach in the fight against cancer. Therefore, the discovery of P-gp inhibitors
is considered one of the most popular strategies to reverse MDR in tumour cells
and to improve therapeutic efficacy of commonly used cytotoxic drugs. Until now,
several generations of P-gp inhibitors have been developed but they have largely
failed in preclinical and clinical studies due to lack of selectivity, poor
solubility and severe pharmacokinetic interactions. In this study, three models
(SION, SIO, SIN) to classify specific 'true' P-gp inhibitors as well as three
other models (CPBN, CPB1, CPN) to distinguish between P-gp inhibitors, CYP 3A
inhibitors and co-inhibitors of these proteins with rather high accuracy values
for the test set and the external set were generated based on counter-propagation
neural networks (CPG-NN). Such three and four-class classification models helped
provide more information about the bioactivities of compounds not only on one
target (P-gp), but also on a combination of multiple targets (P-gp, CYP 3A).
PMID- 25588023
TI - [Cough as a rare symptom of a pacemaker lead perforation].
AB - Cough is a common symptom in respiratory medicine. We report on a 60-year-old
patient, who developed cough after pacemaker implantation. Diagnostic work up
yielded malposition of the right-ventricular lead with penetration of the
myocardium. Revision of the lead resulted in complete cessation of cough.
CONCLUSION: Pacemaker dysfunction and/or malposition of pacemaker lead should be
considered in differential diagnosis of cough after pacemaker implantation.
PMID- 25588024
TI - Fusobacterium nucleatum endocarditis presenting as liver and brain abscesses in
an immunocompetent patient.
PMID- 25588025
TI - Global establishment risk of economically important fruit fly species
(Tephritidae).
AB - The global invasion of Tephritidae (fruit flies) attracts a great deal of
attention in the field of plant quarantine and invasion biology because of their
economic importance. Predicting which one in hundreds of potential invasive fruit
fly species is most likely to establish in a region presents a significant
challenge, but can be facilitated using a self organising map (SOM), which is
able to analyse species associations to rank large numbers of species
simultaneously with an index of establishment. A global presence/absence dataset
including 180 economically significant fruit fly species in 118 countries was
analysed using a SOM. We compare and contrast ranked lists from six countries
selected from each continent, and also show that those countries geographically
close were clustered together by the SOM analysis because they have similar fruit
fly assemblages. These closely clustered countries therefore represent greater
threats to each other as sources of invasive fruit fly species. Finally, we
indicate how this SOM method could be utilized as an initial screen to support
prioritizing fruit fly species for further research into their potential to
invade a region.
PMID- 25588026
TI - The heterogeneity of socially isolated older adults: a social isolation typology.
AB - Recent statistics show a growing number of older adults who are living alone and
are socially isolated. It is against this background that, in recent years, many
interventions have been developed to address social isolation among the elderly.
Evaluative studies show that most interventions are hardly effective, though. An
important reason for this is the heterogeneity of the socially isolated. This
article offers insight into this heterogeneity by presenting a typology with
different profiles of socially isolated older adults and the intervention
implications of this typology. The typology is derived from an extensive
qualitative study on socially isolated elderly individuals in the Netherlands.
The typology imposes some degree of order to a diversity of circumstances,
ambitions, and possibilities of the socially isolated elderly, thereby deepening
the understanding of the heterogeneity of this population. The definition of
social isolation used in this study starts from a societal angle of incidence,
namely the current policy context of Western European welfare states, in which
governments emphasize the importance of independence and self-reliance of their
citizens. Developed from that perspective, the typology provides a theoretical
basis for applying interventions aimed at increasing self-reliance of social
isolated elderly. This perspective on social isolation also has consequences for
the way in which the effectiveness of interventions to alleviate social isolation
is assessed.
PMID- 25588027
TI - Reactivity of the [M(PS)2](+) building block (M = Re(III) and (99m)Tc(III); PS =
phosphinothiolate) toward isopropylxanthate and pyridine-2-thiolate.
AB - The coordination properties of isopropylxanthate (i-Pr-Tiox) and pyridine-2
thiolate (PyS) toward the [M(PS)2](+) moiety (M = Re and (99m)Tc; PS =
phosphinothiolate) were investigated. Synthesis and full characterization of
[Re(PS2)2(i-Pr-Tiox)] (Re1), [Re(PSiso)2(i-Pr-Tiox)] (Re2), [Re(PS2)2(PyS)]
(Re3), and [Re(PSiso)2(PyS)] (Re4), where PS2 = 2
(diphenylphosphino)ethanethiolate and PSiso = 2
(diisopropylphosphino)ethanethiolate, and the structural X-ray analysis of
complex Re3 were carried out. (99m)Tc analogues of complexes Re2 ((99m)Tc2) and
Re4 ((99m)Tc4) were obtained in high radiochemical yield following a simple one
pot procedure. The chemical identity of the radiolabeled compounds was confirmed
by chromatographic comparison with the corresponding rhenium complexes and by
dual radio/UV HPLC analysis combined with ESI(+)-MS of (99g/99m)Tc complexes
prepared in carrier-added conditions. The two radiolabeled complexes were stable
with regard to trans chelation with cysteine, glutathione, and
ethylenediaminotetraacetic acid and in rat and human sera. This study highlights
the substitution-inert metal-fragment behavior of the [M(PS)2](+) framework,
which reacts with suitable bidentate coligands to form stable hexacoordinated
asymmetrical complexes. This feature makes it a promising platform on which to
develop a new class of Re/Tc complexes that are potentially useful in
radiopharmaceutical applications.
PMID- 25588028
TI - Optical drug monitoring: photoacoustic imaging of nanosensors to monitor
therapeutic lithium in vivo.
AB - Personalized medicine could revolutionize how primary care physicians treat
chronic disease and how researchers study fundamental biological questions. To
realize this goal, we need to develop more robust, modular tools and imaging
approaches for in vivo monitoring of analytes. In this report, we demonstrate
that synthetic nanosensors can measure physiologic parameters with photoacoustic
contrast, and we apply that platform to continuously track lithium levels in
vivo. Photoacoustic imaging achieves imaging depths that are unattainable with
fluorescence or multiphoton microscopy. We validated the photoacoustic results
that illustrate the superior imaging depth and quality of photoacoustic imaging
with optical measurements. This powerful combination of techniques will unlock
the ability to measure analyte changes in deep tissue and will open up
photoacoustic imaging as a diagnostic tool for continuous physiological tracking
of a wide range of analytes.
PMID- 25588029
TI - Guardian small RNAs and sex determination.
AB - The W chromosome of the silkworm Bombyx mori has been known to determine
femaleness for more than 80 years. However, the feminizing gene has not been
molecularly identified, because the B. mori W chromosome is almost fully occupied
by a large number of transposable elements. The W chromosome-derived feminizing
factor of B. mori was recently shown to be a female-specific PIWI-interacting RNA
(piRNA). piRNAs are small RNAs that potentially repress invading "non-self"
elements (e.g., transposons and virus-like elements) by associating with PIWI
proteins. Our results revealed that female-specific piRNA precursors, which we
named Fem, are transcribed from the sex-determining region of the W chromosome at
the early embryonic stage and are processed into a single mature piRNA (Fem
piRNA). Fem piRNA forms a complex with Siwi (silkworm Piwi), which cleaves a
protein-coding mRNA transcribed from the Z chromosome. RNA interference of this Z
linked gene, which we named Masc, revealed that this gene encodes a protein
required for masculinization and dosage compensation. Fem and Masc both
participate in the ping-pong cycle of the piRNA amplification loop by associating
with the 2 B. mori PIWI proteins Siwi and BmAgo3 (silkworm Ago3), respectively,
indicating that the piRNA-mediated interaction between the 2 sex chromosomes is
the primary signal for the B. mori sex determination cascade. Fem is a non
transposable repetitive sequence on the W chromosome, whereas Masc is a single
copy protein-coding gene. It is of great interest how the piRNA system recognizes
"self "Masc mRNA as "non-self" RNA.
PMID- 25588030
TI - Human-inspired sound environment recognition system for assistive vehicles.
AB - OBJECTIVE: The human auditory system acquires environmental information under
sound stimuli faster than visual or touch systems, which in turn, allows for
faster human responses to such stimuli. It also complements senses such as sight,
where direct line-of-view is necessary to identify objects, in the environment
recognition process. This work focuses on implementing human reaction to sound
stimuli and environment recognition on assistive robotic devices, such as robotic
wheelchairs or robotized cars. These vehicles need environment information to
ensure safe navigation. APPROACH: In the field of environment recognition, range
sensors (such as LiDAR and ultrasonic systems) and artificial vision devices are
widely used; however, these sensors depend on environment constraints (such as
lighting variability or color of objects), and sound can provide important
information for the characterization of an environment. In this work, we propose
a sound-based approach to enhance the environment recognition process, mainly for
cases that compromise human integrity, according to the International
Classification of Functioning (ICF). Our proposal is based on a neural network
implementation that is able to classify up to 15 different environments, each
selected according to the ICF considerations on environment factors in the
community-based physical activities of people with disabilities. MAIN RESULTS:
The accuracy rates in environment classification ranges from 84% to 93%. This
classification is later used to constrain assistive vehicle navigation in order
to protect the user during daily activities. This work also includes real-time
outdoor experimentation (performed on an assistive vehicle) by seven volunteers
with different disabilities (but without cognitive impairment and experienced in
the use of wheelchairs), statistical validation, comparison with previously
published work, and a discussion section where the pros and cons of our system
are evaluated. SIGNIFICANCE: The proposed sound-based system is very efficient at
providing general descriptions of the environment. Such descriptions are focused
on vulnerable situations described by the ICF. The volunteers answered a
questionnaire regarding the importance of constraining the vehicle velocities in
risky environments, showing that all the volunteers felt comfortable with the
system and its performance.
PMID- 25588031
TI - Public health interventions to control syphilis.
AB - Syphilis control strategies are old, but interventions have changed and there is
now a more scientific approach to evidence of effectiveness. We searched PubMed
using 'syphilis control' to identify papers that measured the effectiveness of
interventions. We also included novel approaches and comprehensive responses to
outbreaks. Few papers used high-quality research methodology and fewer evaluated
impact on prevalence or incidence; most assessed intermediate outcomes. Syphilis
can often be controlled by a combination of case finding, treatment and
education. However, outbreaks are unique and ongoing evaluation is needed to see
if interventions are producing intended intermediate outcomes at reasonable
costs.
PMID- 25588032
TI - Cost of abating greenhouse gas emissions with cellulosic ethanol.
AB - We develop an integrated framework to determine and compare greenhouse gas (GHG)
intensities and production costs of cellulosic ethanol derived from corn stover,
switchgrass, and miscanthus grown on high and low quality soils for three
representative counties in the Eastern United States. This information is
critical for assessing the cost-effectiveness of utilizing cellulosic ethanol for
mitigating GHG emissions and designing appropriate policy incentives to support
cellulosic ethanol production nationwide. We find considerable variations in the
GHG intensities and production costs of ethanol across feedstocks and locations
mostly due to differences in yields and soil characteristics. As compared to
gasoline, the GHG savings from miscanthus-based ethanol ranged between 130% and
156% whereas that from switchgrass ranged between 97% and 135%. The corresponding
range for GHG savings with corn stover was 57% to 95% and marginally below the
threshold of at least 60% for biofuels classified as cellulosic biofuels under
the Renewable Fuels Standard. Estimates of the costs of producing ethanol
relative to gasoline imply an abatement cost of at least $48 Mg(-1) of GHG
emissions (carbon dioxide equivalent) abated and can be used to infer the minimum
carbon tax rate needed to induce consumption of cellulosic ethanol.
PMID- 25588033
TI - HIV infection, cardiovascular disease risk factor profile, and risk for acute
myocardial infarction.
AB - BACKGROUND: Traditional cardiovascular disease risk factors (CVDRFs) increase the
risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants.
We assessed the association between HIV and incident AMI within CVDRF strata.
METHODS: Cohort-81,322 participants (33% HIV+) without prevalent CVD from the
Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched
HIV- veterans) participated in this study. Veterans were followed from first
clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date
(December 31, 2009). Predictors-HIV, CVDRFs (total cholesterol, cholesterol
lowering agents, blood pressure, blood pressure medication, smoking, diabetes)
used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal
CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome-Incident AMI
[defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9
(Medicare), and/or death certificates]. Statistics-Cox models adjusted for
demographics, comorbidity, and substance use. RESULTS: Of note, 858 AMIs (42%
HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was
<2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates.
Compared with HIV- veterans, AMI rates among HIV+ veterans with similar CVDRF
profiles were higher. Compared with HIV- veterans without major CVDRFs, HIV+
veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95%
confidence interval: 1.0 to 3.9; P = 0.044). CONCLUSIONS: The prevalence of
optimal cardiac health is low in this cohort. Among those without major CVDRFs,
HIV+ veterans have twice the AMI risk. Compared with HIV- veterans with high
CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing
CVDRF burden may reduce excess AMI risk among HIV+ people.
PMID- 25588034
TI - Berberine ameliorates nonbacterial prostatitis via multi-target metabolic network
regulation.
AB - Metabolomics has been increasingly applied to discovering biomarkers and
identifying perturbed pathways. Berberine has been shown to exhibit anti
inflammatory, antioxidant, and anticancer properties, but its mechanisms for
treating nonbacterial prostatitis (NBP) remain unclear completely. We developed
the untargeted metabolomics approach based on UPLC-Q-TOF-HDMS to profile the
metabolite changes in urine samples in order to discover novel potential
biomarkers to clarify mechanisms of berberine in treating a rat model of
capsaicin-induced nonbacterial prostatitis (NBP). The changes in metabolic
profiling were restored to their base-line values after berberine treatment
according to the principal component analysis (PCA) score plots. Fourteen
different potential biomarkers and five acutely perturbed metabolic pathways
contributing to the treatment of NBP were discovered and identified.
Specifically, the berberine-treated rats are located closer to the normal group,
indicating that the NBP-induced disturbances to the metabolic profile were
partially reversed by berberine treatment. After treatment with berberine, the
relative contents of 12 potential biomarkers were effectively regulated, which
suggested that the therapeutic effects of berberine on NBP may involve regulating
disturbances to the metabolism. Our results show that the protective effect of
berberine occurs in part through a reversal of the NBP-caused disturbances.
PMID- 25588035
TI - Evaluation of the efficacy and safety of fractional bipolar radiofrequency with
high-energy strategy for treatment of acne scars in Chinese.
AB - BACKGROUND: Fractional technology overcomes several problems of ablative lasers
such as a high incidence rate of post- inflammatory hyperpigmentation (PIH). A
new technology fractional radiofrequency, which induces deep dermal heating and
leaves the epidermal less affected results in less adverse effect in Chinese.
OBJECTIVE: To evaluate the efficacy, safety and tolerance of fractional bipolar
radiofrequency (RF) in the treatment of acne scars in Asian people with the
strategy of high energy. METHODS: Twenty-six healthy Asian patients with acne
scars received four monthly high energy (85-95mj/pin) treatments with a
fractional bipolar RF device. Improvement and tolerance were evaluated at each
treatment and a 4-week and 12-week follow-up visit. RESULTS: Twenty-three
patients completed the study. Acne score showed a significantly decrease at 4
week and 12-week follow-up visits. Patients' evaluation of global improvement and
satisfaction increased at the 12-week visit compared with baseline. Side effects
were limited to transient pain, erythema, dryness and low risk of PIH.
CONCLUSION: Treatment with high energy of fractional bipolar RF is safe and
effective for acne scars in Asian people. Common side effects such as PIH,
eschars are less than fractional lasers.
PMID- 25588036
TI - Allergic reaction to hyaluronidase use after hyaluronic acid filler injection.
AB - Hyaluronic acid (HA) is biocompatible, easy to use and reversible. HA fillers are
considered to be safe, although some complications can occur. At this time,
hyaluronidase is used off-label for correction. A 41-year-old woman presented to
our clinic for focal erythematous plaque on hyaluronidase injection site. She got
the injection for correction of HA filler excess. The skin lesion continued for 7
days. Histopathologic findings were nonspecific. On intradermal skin test,
allergic reaction to hyaluronidase were confirmed. Adverse effects of this
hyaluronidase are uncommon with local injection site reactions most frequently
reported. Allergy to hyaluronidase should be included in the differential
diagnosis when focal erythema and swelling occur after hyaluronidase injection.
PMID- 25588037
TI - Treatment of atrophic facial acne scars with fractional Er:Yag laser.
AB - BACKGROUND: Acne scars are often a permanent disfiguring sequel of acne vulgaris.
Although many treatment modalities are available, they are often non satisfactory
for all patients. OBJECTIVE: To determine the effectiveness and safety of
fractional 1540 nm erbium_glass laser treatment of facial acne scars in Iraqi
patients. PATIENTS AND METHODS: Twenty one patients were enrolled in this
prospective clinical study. Three sessions of the 1540 nm erbium glass laser were
applied at 2-week intervals. The patients were assessed at 1, 3, and 6 months
after the last session. The effect of treatment was assessed by objective
(Sharquie scoring system for grading acne scarring and visual analog scale) and
subjective (patient satisfaction) methods. RESULTS: Two patients were defaulted.
Eleven patients (57.9%) showed improvement from moderate to mild grade, and no
grade changes were detected in eight patients (42.1%). The mean score of the
visual analog scale prior to treatment was 8.61 +/- 0.86 and decreased to 6.15 +/
1.28 (P = 0.037). Ten patients were satisfied to varying degrees. No significant
side effects were noted. CONCLUSION: Non-ablative fractional 1540 nm erbium glass
laser is an effective and safe method to treat acne scars and represent good
alternative for patients who cannot use the ablative methods because of its
longer downtime.
PMID- 25588038
TI - Verruca vulgaris: novel treatment with a 1064 nm Nd:YAG laser.
AB - BACKGROUND: Verruca Vulgaris (VV) is common benign neoplasm. However, it can
present a therapeutic challenge. Previous studies have suggested that the Nd-YAG
laser may be beneficial in the management of warts. OBJECTIVE: To determine the
effectiveness and safety of a novel 100 microsecond pulsed 1064 nm Nd:YAG laser
for the treatment of VV. METHOD: A total of 25 adult subjects with a total of 63
hand verrucae were enrolled in the clinical trial to receive treatment with a low
energy (200 mjoule) 1064 nm Nd:YAG laser (PinPointe, NuvoLase, Inc.). Each
subject was eligible for 3 treatments administered at monthly intervals. All
verrucae were measured before each treatment session and at 6 months after the
final treatment. RESULTS: A complete response was seen in 19 subjects and in 41
verrucae. A complete response was defined as complete absence of verruca with the
presence of normal skin dermatoglyphics. All other lesions showed at least
partial response. A partial response was defined as a 50% or greater reduction in
verruca size. No adverse events were noted. CONCLUSION: Low-energy 1064 nm Nd:
YAG laser treatment may be a promising, safe, and effective therapeutic modality
for the treatment of VV. However, more treatment sessions may be needed for
complete clearance and increased efficacy in some subjects.
PMID- 25588039
TI - A rapid tattoo removal technique using a combination of pulsed Er:YAG and Q
Switched Nd:YAG in a split lesion protocol.
AB - BACKGROUND: Tattoo removal has evolved over the years and though Q-switched laser
is the 'workhorse' laser, it invariably requires multiple sittings, which are
dependent on numerous factors, including the skin colour, location of the tattoo,
age of the tattoo, colour of pigment used, associated fibrosis and the kind of
tattoo treated. Though ablative lasers, both pulsed CO2 and Er:YAG, have been
used for recalcitrant tattoos, very few studies have been done comparing them
with pigment-specific lasers. Our study was based on the premise that ablating
the epidermis overlying the tattoo pigment with Er:YAG could help in gaining
better access to the pigment which would enable the Q-switched laser to work
effectively with less beam scattering. OBJECTIVE: A study of rapid tattoo removal
(RTR) technique using a combination of pulsed Er:YAG and Q-Switched Nd:YAG in a
split lesion protocol. MATERIALS AND METHODS: This prospective study was
undertaken during 2010-13 at a laser Clinic in the Maulana Azad Medical College,
New Delhi. A total of 10 patients were recruited, 5 of amateur tattoo and 5 of
professional tattoo. After informed consent each tattoo was arbitrarily 'split'
into two parts. One part was treated with QS Nd:YAG laser(1064 nm) and the other
part with Er:YAG laser immediately followed by the QS Nd:YAG. The laser
treatments were repeated at 6-week intervals until the tattoo pigment had
cleared. On the combination side in subsequent sittings only the QS Nd:YAG was
used, to minimize repetitive ablation. To ensure consistency in the intervention
methods a trained dermatologist who was independent of the treatment delivery
randomly rated 10% of the procedures. RESULTS: The mean improvement achieved by
the Q-switched laser (2.93) was less than the combination laser (3.85) side (p =
0.001) and needed more sessions (3.8 vs. 1.6; p = 0.001). There was a
statistically significant difference in the improvement on the combination side
till the second session. On the combination side patients required a maximum of 2
sessions, while the Q-switched laser required 3-5 sessions for appreciable
lightening. CONCLUSION: From our study it was concluded that use of a pulsed
ablative laser may help in rapid removal of tattoos in conjunction with QS lasers
with minimal side effects and can be used as a RTR.
PMID- 25588040
TI - The next-generation ALK inhibitors.
AB - PURPOSE OF REVIEW: Crizotinib now is accepted as the standard first-line
treatment of ALK-rearranged lung adenocarcinomas. To overcome the problem of
crizotinib resistance, second-generation ALK inhibitors are in development. The
aim of this review is to give an overview on the mechanisms behind crizotinib
resistance and on the preclinical background and clinical development of these
compounds. RECENT FINDINGS: Based on phase I/II data, ceritinib has gained
accelerated FDA approval for the treatment of crizotinib-resistant ALK-rearranged
lung cancer. The clinical development of alectinib has already reached phase III.
With AP26113, ASP3026, TSR-011, X-396 and different heat shock protein 90
inhibitors, several other compounds led to promising early trial results. The
toxicity profile of these drugs seems manageable, although side-effects still
require attention and optimized supportive care. SUMMARY: Second-generation ALK
inhibitors have arrived as part of our daily clinical practice. Challenges for
the future will be to find the optimal place for these new drugs within the
treatment algorithms. To reach this goal, careful trial design with special
emphasis on genetically defined, homogeneous patient populations is imperative.
PMID- 25588041
TI - Cell cycle control as a promising target in melanoma.
AB - PURPOSE OF REVIEW: This review highlights recent clinical developments in the
therapeutic targeting of cell cycle control in melanoma with cyclin-dependent
kinase inhibitors, checkpoint kinases, MDM2, MDM4 and p53 inhibitors. RECENT
FINDINGS: The high prevalence of activating genetic aberrations along the p16
INK4A:cyclinD-CDK4/6:RB pathway in melanoma and increasing evidence that
alterations in this pathway are linked to melanomagenesis, make targeting the p16
INK4A:cyclinD-CDK4/6:RB pathway in melanoma logical and highly attractive. The
presence of elevated CDK4 activity appears to correlate with greater CDK4/6
inhibitor therapeutic activity, whereas the loss of RB1 has been linked to CDK
inhibitor resistance. Other novel compounds targeting cell cycle control via
reactivating wild-type p53 and checkpoint kinases are also currently under
investigation in melanoma. SUMMARY: Cell cycle control is a promising target in
the management of melanoma with early data reporting therapeutic benefit with
cyclin-dependent kinase inhibitors, MDM2, and p53 reactivation compounds. Many of
these drugs have entered phase I and II clinical trial development. Preliminary
data from these studies are discussed in this review along with future treatment
strategies for maximizing treatment outcomes in advanced melanoma. VIDEO
ABSTRACT: http://links.lww.com/COON/A12.
PMID- 25588044
TI - A highly sensitive and flexible pressure sensor with electrodes and elastomeric
interlayer containing silver nanowires.
AB - The next-generation application of pressure sensors is gradually being extended
to include electronic artificial skin (e-skin), wearable devices, humanoid
robotics and smart prosthetics. In these advanced applications, high sensing
capability is an essential feature for high performance. Although surface
patterning treatments and some special elastomeric interlayers have been applied
to improve sensitivity, the process is complex and this inevitably raises the
cost and is an obstacle to large-scale production. In the present study a simple
printing process without complex patterning has been used for constructing the
sensor, and an interlayer is employed comprising elastomeric composites filled
with silver nanowires. By increasing the relative permittivity, epsilonr, of the
composite interlayer induced by compression at high nanowire concentration, it
has been possible to achieve a maximum sensitivity of 5.54 kPa(-1). The
improvement in sensitivity did not sacrifice or undermine the other features of
the sensor. Thanks to the silver nanowire electrodes, the sensor is flexible and
stable after 200 cycles at a bending radius of 2 mm, and exhibits outstanding
reproducibility without hysteresis under similar pressure pulses. The sensor has
been readily integrated onto an adhesive bandage and has been successful in
detecting human movements. In addition to measuring pressure in direct contact,
non-contact pressures such as air flow can also be detected.
PMID- 25588045
TI - A radiographic scoring system to assess healing in congenital pseudarthrosis of
the tibia.
AB - The aim of this study was to determine whether an established radiographic union
scoring system for tibial fracture healing (RUST) is reliable when used in
neurofibromatosis (NF1) patients with congenital pseudarthrosis of the tibia
(CPT) treated by intramedullary fixation. Four individuals reviewed 36 sets of
radiographs from 12 NF1 patients with CPT (preoperative, and 6 months and 1 year
postoperative). Intraobserver reliability (kappa-value 0.89) and interobserver
reliability (kappa-value 0.76) were high. The modified RUST scoring system is a
useful tool when faced with the challenge of postoperative radiographic
evaluation of the tibia in NF1 patients with CPT.
PMID- 25588042
TI - The baculovirus-expressed binding region of Plasmodium falciparum EBA-140 ligand
and its glycophorin C binding specificity.
AB - The erythrocyte binding ligand 140 (EBA-140) is a member of the Plasmodium
falciparum DBL family of erythrocyte binding proteins, which are considered as
prospective candidates for malaria vaccine development. The EBA-140 ligand is a
paralogue of the well-characterized P. falciparum EBA-175 protein. They share
homology of domain structure, including Region II, which consists of two
homologous F1 and F2 domains and is responsible for ligand-erythrocyte receptor
interaction during invasion. In this report we describe, for the first time, the
glycophorin C specificity of the recombinant, baculovirus-expressed binding
region (Region II) of P. falciparum EBA-140 ligand. It was found that the
recombinant EBA-140 Region II binds to the endogenous and recombinant glycophorin
C, but does not bind to Gerbich-type glycophorin C, neither normal nor
recombinant, which lacks amino acid residues 36-63 of its polypeptide chain. Our
results emphasize the crucial role of this glycophorin C region in EBA-140 ligand
binding. Moreover, the EBA-140 Region II did not bind either to glycophorin D,
the truncated form of glycophorin C lacking the N-glycan or to desialylated GPC.
These results draw attention to the role of glycophorin C glycans in EBA-140
binding. The full identification of the EBA-140 binding site on glycophorin C
molecule, consisting most likely of its glycans and peptide backbone, may help to
design therapeutics or vaccines that target the erythrocyte binding merozoite
ligands.
PMID- 25588046
TI - The use of ultrasound in the management of septic arthritis of the hip.
AB - In the assessment of septic arthritis of the hip in a pediatric population,
ultrasound is a safe and easily conducted method to confirm an effusion. The need
for MRI to further evaluate the patient for adjacent infection before treatment
is debatable. Once an effusion is confirmed on ultrasonography, we have found
that septic arthritis of the hip does not need advanced imaging before arthrotomy
and debridement. Patients who fail to clinically respond to an initial hip
arthrotomy and appropriate antibiotics may benefit from an MRI for the
identification of concomitant infections that may require surgical intervention.
PMID- 25588043
TI - Ontology-based data integration between clinical and research systems.
AB - Data from the electronic medical record comprise numerous structured but uncoded
elements, which are not linked to standard terminologies. Reuse of such data for
secondary research purposes has gained in importance recently. However, the
identification of relevant data elements and the creation of database jobs for
extraction, transformation and loading (ETL) are challenging: With current
methods such as data warehousing, it is not feasible to efficiently maintain and
reuse semantically complex data extraction and trans-formation routines. We
present an ontology-supported approach to overcome this challenge by making use
of abstraction: Instead of defining ETL procedures at the database level, we use
ontologies to organize and describe the medical concepts of both the source
system and the target system. Instead of using unique, specifically developed SQL
statements or ETL jobs, we define declarative transformation rules within
ontologies and illustrate how these constructs can then be used to automatically
generate SQL code to perform the desired ETL procedures. This demonstrates how a
suitable level of abstraction may not only aid the interpretation of clinical
data, but can also foster the reutilization of methods for un-locking it.
PMID- 25588047
TI - Deformity correction in pediatric skeletal dysplasia: treatment challenges and
solutions.
AB - We reviewed our experience with limb-deformity correction in 54 children with
skeletal dysplasias. Our goal was to outline common treatment strategies
developed in our hospital to overcome the challenges associated with the
management of these conditions. Utilization of computer-assisted preoperative
planning, intraoperative monitoring of peripheral nerve function, individualized
bone segment stabilization using a modular circular external fixation system, and
a flexible distraction protocol improved the precision of angular deformity
correction in our practice, simplified external fixator assembly, diminished
postoperative frame modifications, enhanced the stability of fixation, and
reduced the rate of complications.
PMID- 25588048
TI - Tibial shaft fractures in adolescents: analysis of cast treatment successes and
failures.
AB - This study retrospectively analyzed cast treatment of 75 adolescent closed tibial
diaphyseal fractures. The average age was 13.3 years (range, 10-17.4 years). Of
the patients, 21% (16/75) required cast change/wedging in the clinic for loss of
reduction, and three patients (4%, 3/75) injured in vehicular collisions had
failure of cast treatment, requiring an unplanned surgical intervention. Initial
and immediate postreduction radiographic deformities were greater (P<0.05) in
patients who required cast change/wedging. Of the patients, 59% (44/75) required
over 3 months of cast immobilization. Casting is successful in the majority of
adolescent patients despite prolonged immobilization and the need for cast
change/wedging.
PMID- 25588049
TI - Evaluation of complications of treatment of severe Blount's disease by circular
external fixation using a novel classification scheme.
AB - Corrective osteotomy for recalcitrant varus deformity secondary to adolescent and
infantile Blount's disease can be challenging because of a combination of
severity of deformity, complexity of deformity, and frequent association with
patient obesity. We present here the outcome of treatment by osteotomy and
gradual deformity correction by circular external fixation in 31 patients with
either infantile or adolescent Blount's disease. We used a unique classification
scheme to quantify and qualify complications in this patient group: category I,
complications not requiring an alteration in the treatment plan, not involving
unplanned return to surgery, and not influencing outcome; category II,
complications requiring an alteration in the treatment plan, including unplanned
returns to surgery, but that did not influence outcome; category IIIA,
complications that resulted in a failure to achieve treatment goals; and category
IIIB, complications that resulted in a failure to achieve treatment goals and the
development of a new pathology or worsening of patient condition. All but one
patient in this group incurred at least one complication. However, despite the
complex nature of this patient population, 88% achieved satisfactory correction
without developing category IIIA or IIIB complications. Careful selection of
patients and vigilant postoperative management can result in excellent outcomes
with circular external fixation and gradual correction in this challenging
patient population.
PMID- 25588050
TI - Activation of G protein coupled estrogen receptor (GPER) promotes the migration
of renal cell carcinoma via the PI3K/AKT/MMP-9 signals.
AB - Renal cell carcinoma (RCC) is the third most frequent malignancy within
urological oncology. However, the mechanisms responsible for RCC metastasis are
still needed further illustration. Our present study revealed that a seven
transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly
detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The
activation of GPER by its specific agonist G-1 significantly promoted the in
vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the
expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP
9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration,
which suggested that MMP-9 is the key molecule mediating G-1 induced RCC
progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in
RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059),
significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC
2 cells. Generally, our data revealed that activation of GPER by its specific
agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals,
which might be a promising new target for drug discovery of RCC patients.
PMID- 25588051
TI - Low-temperature polymorphic phase transition in a crystalline tripeptide L-Ala-L
Pro-Gly.H2O revealed by adiabatic calorimetry.
AB - We demonstrate application of precise adiabatic vacuum calorimetry to observation
of phase transition in the tripeptide L-alanyl-L-prolyl-glycine monohydrate (APG)
from 6 to 320 K and report the standard thermodynamic properties of the
tripeptide in the entire range. Thus, the heat capacity of APG was measured by
adiabatic vacuum calorimetry in the above temperature range. The tripeptide
exhibits a reversible first-order solid-to-solid phase transition characterized
by strong thermal hysteresis. We report the standard thermodynamic
characteristics of this transition and show that differential scanning
calorimetry can reliably characterize the observed phase transition with <5 mg of
the sample. Additionally, the standard entropy of formation from the elemental
substances and the standard entropy of hypothetical reaction of synthesis from
the amino acids at 298.15 K were calculated for the studied tripeptide.
PMID- 25588052
TI - Herpes simplex virus 1 Us3 deletion mutant is infective despite impaired capsid
translocation to the cytoplasm.
AB - Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus bud at the
inner nuclear membrane into the perinuclear space, acquiring envelope and
tegument. In theory, these virions are de-enveloped by fusion of the envelope
with the outer nuclear membrane and re-enveloped by Golgi membranes to become
infective. Us3 enables the nucleus to cytoplasm capsid translocation.
Nevertheless, Us3 is not essential for the production of infective progeny
viruses. Determination of phenotype distribution by quantitative electron
microscopy, and calculation per mean nuclear or cell volume revealed the
following: (i) The number of R7041(?US3) capsids budding at the inner nuclear
membrane was significantly higher than that of wild type HSV-1; (ii) The mean
number of R7041(?US3) virions per mean cell volume was 2726, that of HSV-1
virions 1460 by 24 h post inoculation; (iii) 98% of R7041(?US3) virions were in
the perinuclear space; (iv) The number of R7041(?US3) capsids in the cytoplasm,
including those budding at Golgi membranes, was significantly reduced. Cell
associated R7041(?US3) yields were 2.37*10(8) and HSV-1 yields 1.57*10(8) PFU/mL
by 24 h post inoculation. We thus conclude that R7041(?US3) virions, which
acquire envelope and tegument by budding at the inner nuclear membrane into the
perinuclear space, are infective.
PMID- 25588054
TI - Emergency department visits by children and adolescents for antipsychotic drug
adverse events.
PMID- 25588055
TI - Synthetic chemically modified mrna-based delivery of cytoprotective factor
promotes early cardiomyocyte survival post-acute myocardial infarction.
AB - To extend the temporal window for cytoprotection in cardiomyocytes undergoing
apoptosis after hypoxia and myocardial infarction (MI), a synthetic chemically
modified mRNA (modRNA) was used to drive delivery of insulin-like growth factor-1
(IGF1) within the area at risk in an in vivo murine model of MI. Delivery of IGF1
modRNA, with a polyethylenimine-based nanoparticle, augmented secreted and cell
associated IGF1, promoting cardiomyocyte survival and abrogating cell apoptosis
under hypoxia-induced apoptosis conditions. Translation of modRNA-IGF1 was
sufficient to induce downstream increases in the levels of Akt and Erk
phosphorylation. Downregulation of IGF1 specific miRNA-1 and -133 but not miR-145
expression was also confirmed. As a proof of concept, intramyocardial delivery of
modRNA-IGF1 but not control modRNA-GFP significantly decreased the level of TUNEL
positive cells, augmented Akt phosphorylation, and decreased caspase-9 activity
within the infarct border zone 24 h post-MI. These findings demonstrate the
potential for an extended cytoprotective effect of transient IGF1 driven by
synthetic modRNA delivery.
PMID- 25588056
TI - Alternative one-pot synthesis of (trifluoromethyl)phenyldiazirines from
tosyloxime derivatives: application for new synthesis of optically pure
diazirinylphenylalanines for photoaffinity labeling.
AB - Alternative one-pot synthesis of 3-(trifluoromethyl)-3-phenyldiazirine
derivatives from corresponding tosyloximes is developed. The deprotonation of
intermediate diaziridine by NH2(-) is a new approach for construction of
diazirine. Moreover, a novel synthesis of optically pure
(trifluoromethyl)diazirinylphenylalanine derivatives was attempted involving
these methods.
PMID- 25588053
TI - KSHV reactivation and novel implications of protein isomerization on lytic switch
control.
AB - In Kaposi's sarcoma-associated herpesvirus (KSHV) oncogenesis, both latency and
reactivation are hypothesized to potentiate tumor growth. The KSHV Rta protein is
the lytic switch for reactivation. Rta transactivates essential genes via
interactions with cofactors such as the cellular RBP-Jk and Oct-1 proteins, and
the viral Mta protein. Given that robust viral reactivation would facilitate
antiviral responses and culminate in host cell lysis, regulation of Rta's
expression and function is a major determinant of the latent-lytic balance and
the fate of infected cells. Our lab recently showed that Rta transactivation
requires the cellular peptidyl-prolyl cis/trans isomerase Pin1. Our data suggest
that proline-directed phosphorylation regulates Rta by licensing binding to Pin1.
Despite Pin1's ability to stimulate Rta transactivation, unchecked Pin1 activity
inhibited virus production. Dysregulation of Pin1 is implicated in human cancers,
and KSHV is the latest virus known to co-opt Pin1 function. We propose that Pin1
is a molecular timer that can regulate the balance between viral lytic gene
expression and host cell lysis. Intriguing scenarios for Pin1's underlying
activities, and the potential broader significance for isomerization of Rta and
reactivation, are highlighted.
PMID- 25588057
TI - Mechanical platelet activation potential in abdominal aortic aneurysms.
AB - Intraluminal thrombus (ILT) in abdominal aortic aneurysms (AAA) has potential
implications to aneurysm growth and rupture risk; yet, the mechanisms underlying
its development remain poorly understood. Some researchers have proposed that ILT
development may be driven by biomechanical platelet activation within the AAA,
followed by adhesion in regions of low wall shear stress. Studies have
investigated wall shear stress levels within AAA, but platelet activation
potential (AP) has not been quantified. In this study, patient-specific
computational fluid dynamic (CFD) models were used to analyze stress-induced AP
within AAA under rest and exercise flow conditions. The analysis was conducted
using Lagrangian particle-based and Eulerian continuum-based approaches, and the
results were compared. Results indicated that biomechanical platelet activation
is unlikely to play a significant role for the conditions considered. No
consistent trend was observed in comparing rest and exercise conditions, but the
functional dependence of AP on stress magnitude and exposure time can have a
large impact on absolute levels of anticipated platelet AP. The Lagrangian method
obtained higher peak AP values, although this difference was limited to a small
percentage of particles that falls below reported levels of physiologic
background platelet activation.
PMID- 25588060
TI - Glutathione S-transferase M1/T1 genotype and melanoma in a Southern Italian
population: a case-control study.
AB - BACKGROUND: The aim of this study was to assess the frequency of GSTM1 and GSTT1
null genotype in melanoma patients and controls from Sicily and Calabria, two
regions of Southern Italy never investigated on this issue before, that present a
peculiar gene pool because of their geographical and historical characteristics.
METHODS: One hundred and twelve Caucasian melanoma patients and 150 age- and sex
matched healthy controls were examined; their GSTM1/GSTT1 genotype was defined by
polymerase chain reaction on a sample of oral mucosa cells obtained by buccal
swabs. RESULTS: Odds ratio for melanoma was increased not significantly in case
of fair hair/eye color, presence of many naevi or solar lentigines, or history of
actinic keratosis, skin cancer or sunburns; frequencies of GSTM1 null, GSTT1 null
and all their possible combinations were not significantly different between
patients and controls. CONCLUSIONS: Our results, in agreement with worldwide
literature, show that melanoma is apparently independent from genetic lack of
GSTM1/GSTT1. However, melanoma is notoriously linked to a history of sunburns,
and GSTM1/GSTT1 null are a significant risk factor for sunburns. We describe a
possible explanation of this apparent contradiction, taking into account the
different roles of the multiple components of human skin in photoprotection, and
their variable importance in different conditions of exposure to UV radiations.
Simultaneous evaluation of a larger number of components of the antioxidant
system, to assess their individual contribution to protection against melanoma,
is advisable and should be considered in future studies. This could allow to
better define risks for each patient and possibly to tailor preventive measures.
PMID- 25588059
TI - TRF2: TRansForming the view of general transcription factors.
AB - Transcriptional regulation is pivotal for development and differentiation of
organisms. Transcription of eukaryotic protein-coding genes by RNA polymerase II
(Pol II) initiates at the core promoter. Core promoters, which encompass the
transcription start site, may contain functional core promoter elements, such as
the TATA box, initiator, TCT and downstream core promoter element. TRF2 (TATA-box
binding protein-related factor 2) does not bind TATA box-containing promoters.
Rather, it is recruited to core promoters via sequences other than the TATA box.
We review the recent findings implicating TRF2 as a basal transcription factor in
the regulation of diverse biological processes and specialized transcriptional
programs.
PMID- 25588062
TI - Graphene/phase change material nanocomposites: light-driven, reversible
electrical resistivity regulation via form-stable phase transitions.
AB - Innovative photoresponsive materials are needed to address the complexity of
optical control systems. Here, we report a new type of photoresponsive
nanomaterial composed of graphene and a form-stable phase change material (PCM)
that exhibited a 3 orders of magnitude change in electrical resistivity upon
light illumination while retaining its overall original solid form at the
macroscopic level. This dramatic change in electrical resistivity also occurred
reversibly through the on/off control of light illumination. This was attributed
to the reversible phase transition (i.e., melting/recrystallization) behavior of
the microscopic crystalline domains present in the form-stable PCM. The
reversible phase transition observed in the graphene/PCM nanocomposite was
induced by a reversible temperature change through the on/off control of light
illumination because graphene can effectively absorb light energy and convert it
to thermal energy. In addition, this graphene/PCM nanocomposite also possessed
excellent mechanical properties. Such photoresponsive materials have many
potential applications, including flexible electronics.
PMID- 25588061
TI - Tuscan consensus on the diagnosis, treatment and follow-up of moderate-to-severe
psoriasis.
AB - BACKGROUND: Psoriasis is traditionally defined as an inflammatory chronic
relapsing disease of the skin. As widely demonstrated, this disease is also
associated with multiple comorbidities: arthropathy, inflammatory bowel disease,
metabolic, cardiovascular, ocular and psychological disorders. The disease also
has a significant impact on patients' quality of life, whose work ability
decreases considerably with clear consequences for the social costs. Therefore,
if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer
from psoriasis, it is of paramount importance focusing the attention on a
rational model of clinical and therapeutic management of the disease. All the
leading experts in Tuscany have come together with the aim of defining
unanimously accepted regional guidelines for the diagnosis, treatment, follow-up
and management of psoriasis, and of providing practical guidance/protocol on
diagnosis, treatment, follow-up and management of special cases of moderate-to
severe plaque psoriasis. METHODS: In a working group formed ad hoc, the main
topics have been discussed and approved by plenary vote. RESULTS: Diagnosis must
include a proper general health condition overview, a careful evaluation of skin
and joints, the assessment and management of other comorbidities and the
definition of disease severity. With regards to the therapy the best time to
start a systemic treatment, the therapeutic goal, the most appropriate drug and
blood tests to be performed in case of moderate severe-psoriasis have been taken
into account. During follow-up, proper monitoring of systemic therapy and its
management in the long term has also been suggested. Eventually, the experts have
addressed the problem of how to manage the disease in special conditions, such as
during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV).
CONCLUSIONS: The main aim of this Consensus was to find agreement on the criteria
for diagnosis, treatment and follow-up of psoriasis, shared by all the
Dermatologic Therapy Units of Tuscany. A need to create an easier way for the
patient to access specialized dermatology outpatient services, and to reduce the
waiting list and costs related to the management of psoriasis has been stressed.
Most importantly, during the Consensus all of the participants agreed on the
central role of the patient, and on the need of a multidisciplinary management of
the disease which requires communication among specialists and regional centers
in order to build on existing experience.
PMID- 25588063
TI - Poly(vinyl ester 1,2,3-triazolium)s: a new member of the poly(ionic liquid)s
family.
AB - A vinyl ester monomer carrying a pendant 1,2,3-triazole group is synthesized in
two steps and polymerized by cobalt-mediated radical polymerization. Subsequent
alkylation with N-methyl bis[(trifluoromethyl)sulfonyl]imide affords the
corresponding poly(vinyl ester 1,2,3-triazolium). This unprecedented example of
poly(vinyl ester ionic liquid) exhibits an ionic conductivity of 9.2 * 10(-7) S
cm(-1) at 30 degrees C.
PMID- 25588064
TI - Manipulations to the Alcohol and Sodium Content of Beer for Postexercise
Rehydration.
AB - The addition of 25 mmol.L(-1) sodium to low alcohol (2.3% ABV) beer has been
shown to enhance post exercise fluid retention compared with full strength (4.8%
ABV) beer with and without electrolyte modification. This investigation explored
the effect of further manipulations to the alcohol and sodium content of beer on
fluid restoration following exercise. Twelve male volunteers lost 2.03 +/- 0.19%
body mass (mean +/- SD) using cycling-based exercise. Participants were then
randomly allocated a different beer to consume on four separate occasions. Drinks
included low alcohol beer with 25 mmol.L-1 of added sodium [LightBeer+25], low
alcohol beer with 50 mmol.L(-1) of added sodium [LightBeer+50], midstrength beer
(3.5% ABV) [Mid] or midstrength beer with 25 mmol.L(-1) of added sodium [Mid+25].
Total drink volumes in each trial were equivalent to 150% of body mass loss
during exercise, consumed over a 1h period. Body mass, urine samples and
regulatory hormones were obtained before and 4 hr after beverage consumption.
Total urine output was significantly lower in the LightBeer+50 trial (1450 +/-
183 ml) compared with the LightBeer+25 (1796 +/- 284 ml), Mid+25 (1786 +/- 373
ml) and Mid (1986 +/- 304 ml) trials (all p < .05). This resulted in
significantly higher net body mass following the LightBeer+50 trial (-0.97 +/-
0.17 kg) compared with all other beverages (LightBeer+25 (-1.30 +/- 0.24 kg),
Mid+25 (-1.38 +/-0.33 kg) and Mid (-1.58 +/-0.29 kg), all p < .05). No
significant changes to aldosterone or vasopressin were associated with different
drink treatments. The electrolyte concentration of low alcohol beer appears to
have more significant impact on post exercise fluid retention than small changes
in alcohol content.
PMID- 25588065
TI - Assessing implicit mate preferences among Chinese and Japanese women by providing
love, sex, or money cues.
AB - Love, sex, and money are the most direct cues involved in the fundamental forms
of mate preferences. These fundamental forms are not mutually exclusive but are
interrelated. As a result, humans base their mate choices on multiple cues. In
this study, 62 undergraduate women (M age = 20.4 yr., SD = 1.4) from China and
Japan served as the participants. They performed a variation of the semantic
priming task, in which they were instructed to decide by means of a key-press
whether the target was human or non-human. The primes were images that portrayed
potent evolutionary factors for mate preference (i.e., love, sex, and money), and
the manipulation was based on whether the prime and target matched regarding
gender, independent of the target decision task (human vs non-human).
Participants gave faster responses to male targets than to female targets under
priming. The results generally supported the evolutionary premises that assume
mate preference is determined by fundamental forms of providing emotional (love),
material (money), and fertility support (sex). The money priming effect was
stronger in the Chinese women than in the Japanese women, suggesting that social
context may influence mate preferences.
PMID- 25588066
TI - Resource-independent negative effects of foreign language on analogical problem
solving.
AB - It has been shown that analogical problem solving is more difficult when a target
problem is written in a foreign language than in one's native language. Possible
resource-independence of this negative effect of a foreign language was
investigated. After reading an analog or a filler story, participants solved a
target problem written in their native or a foreign language. Those who read the
problem in their native language performed a concurrent task to reduce their
available processing resources. Nevertheless, they were better able to solve it
than those who read the problem in a foreign language after reading the analog.
This indicates that reading the problem in a foreign language decreases
analogical problem-solving ability in a resource-independent manner.
PMID- 25588067
TI - Effects of temporary intensive feed restriction on performance, nutrient
digestibility and carcass criteria of growing male Californian rabbits.
AB - The aim of the study was to evaluate the effect of a temporary quantitative feed
restriction on growth performance, nutrient digestibility and carcass criteria of
rabbits. A total of 80 weaned male Californian rabbits (30 d of age) were
randomly assigned to four treatments of 20 rabbits each. The Control group was
fed ad libitum during the whole experimental period (days 30-72 of age). For the
three restricted fed groups the feed intake was reduced by 15%, 30% and 45%
compared to the Control group, respectively. The feed restriction was applied
after weaning and lasted for 21 d. Thereafter, at 51 d of age, in all treatments
the feed supply returned to ad libitum intake till 72 d of age (AL period). The
feed restriction decreased the body weight gain of rabbits (during the
restriction period and the whole experimental period, p < 0.001) and improved
feed conversion ratio during all tested periods (p < 0.001). In the AL period,
the daily body weight gain of all groups was similar. After the AL period, the
digestibility of all measured nutrients was significantly higher for animals fed
restrictively. Furthermore, feed restrictions significantly decreased the
proportion of perirenal and scapular fat and increased relative weight and length
of the gastrointestinal tract. Therefore, it can be concluded that the applied
feed restriction improved feed conversion, nutrient digestibility and reduced fat
at the slaughter age of Californian rabbits, but the reduced body weight gain
could not be compensated by a subsequent ad libitum feeding for 3 weeks.
PMID- 25588068
TI - Different VanA Elements in E. faecalis and in E. faecium Suggest at Least Two
Origins of Tn1546 Among VRE in a Brazilian Hospital.
AB - In 2009 during surveillance in a Brazilian hospital, many patients were confirmed
to be colonized by vancomycin-resistant enterococci (VRE) and a few infection
cases occurred. Among 14 isolates of Enterococcus faecalis, most had the same
pulsotype, virulence profile (agg(+)elrA(+)gelE(+)), and were sequence type
(ST)103, indicating dissemination of a clone. The 47 Enterococcus faecium were
separated into four pulsotypes, the predominant virulence profile being
esp(+)acm(+). All of them harbored the hospital marker IS16, and three randomly
chosen isolates were ST412, belonging to the Clonal Complex 17. E. faecalis were
all susceptible to penicillin and ampicillin, while all E. faecium were resistant
to them. All isolates were susceptible to daptomycin and tigecycline. There were
no rep-family genes common to all VRE. The VanA element of all E. faecium lost
its left-side inverted repeat (IRL) region and had a specific IS insertion. On
the other hand, all E. faecalis presented intact Tn1546. The size of plasmids
containing the vanA gene as well as its rep-families varied between and within
species. The lack of a vanA plasmid common to all VRE, together with the
differences among VanA elements, despite the fact that some patients were
colonized by both species during their hospitalization, leads us to suggest at
least two different Tn1546 origins.
PMID- 25588069
TI - Individualizing oral busulfan dose after using a test dose in patients undergoing
hematopoietic stem cell transplantation: pharmacokinetic characterization.
AB - BACKGROUND: Busulfan is an alkylating agent used for conditioning patients
undergoing hematopoietic stem cell transplantation with a narrow therapeutic
range and highly variable pharmacokinetics. High concentrations induce toxicity,
especially hepatic veno-occlusive disease, also referred to as sinusoidal
obstruction syndrome. This study aimed to assess busulfan pharmacokinetic
variability in pretransplant conditioning regimens using an analytical method
validated by high-performance liquid chromatography coupled to diode array
detector (HPLC/PDA). METHODS: Eight patients who used the test dose (TD) of 1
mg/kg busulfan 10 days before conditioning were included, and 10 serial blood
samples were collected to determine: the elimination half-life (t1/2), total area
under the curve (AUCT), total clearance (Cl(T)/F), and plasma concentration at
steady state (C(ss)), using a monocompartmental model and first-order kinetics.
The instrumental conditions were: HPLC/PDA Shimadzu, column ACE C18 (150 mm * 4
mm); methanol/water/acetonitrile (65:20:15) eluent flow rate of 1 mL/min; 1,6-bis
(methanesulfonyloxy)-hexane; UV lambda = 276 nm; analysis time 17 minutes; and
derivatization with sodium diethylcarbamate. The dose was adjusted, and 4 blood
samples per day were collected at days 2, 3, and 4 of treatment for new plasma
determinations. RESULTS: Four patients needed higher doses; the mean dose
administered was 1.02 +/- 0.19 mg/kg. Mean results at TD: t1/2 = 2.88 +/- 0.5
hours; Cl(T)/F = 0.18 +/- 0.03 L . h(-1) . kg(-1); AUC(T) = 5461.00 +/- 961.15 ng
. mL(-1) . h(-1); and C(ss) = 911.3 +/- 159.8 ng/mL. Mean results of samples
collected during conditioning: t1/2 = 3.21 +/- 0.9 hours; Cl(T)/F = 0.13 +/- 0.02
L . h(-1) . kg(-1); AUC(T) = 7571 +/- 1705 ng . mL(-1) . h(-1); and C(ss) =
1262.0 +/- 284.3 ng/mL. CONCLUSIONS: High variability in the assessed
pharmacokinetic parameters was observed, with a 38% variation in C(ss) between TD
and conditioning regimen; Cl(T)/F decreased by 30%, suggesting drug accumulation
after multiple-dose regimen. Although being lower than reported in the
literature, this variation may be associated with toxicity of the proposed
treatment, justifying patient monitoring and enhancing validity of previous
pharmacokinetic evaluation using TD regimen.
PMID- 25588072
TI - A microporous metal-organic framework with rare lvt topology for highly selective
C2H2/C2H4 separation at room temperature.
AB - A new lvt-type metal-organic framework UTSA-60a with suitable pore channels and
open metal sites has been developed for highly selective separation of C2H2/C2H4
at room temperature.
PMID- 25588070
TI - Expert system for predicting reaction conditions: the Michael reaction case.
AB - A generic chemical transformation may often be achieved under various synthetic
conditions. However, for any specific reagents, only one or a few among the
reported synthetic protocols may be successful. For example, Michael beta
addition reactions may proceed under different choices of solvent (e.g.,
hydrophobic, aprotic polar, protic) and catalyst (e.g., Bronsted acid, Lewis
acid, Lewis base, etc.). Chemoinformatics methods could be efficiently used to
establish a relationship between the reagent structures and the required reaction
conditions, which would allow synthetic chemists to waste less time and resources
in trying out various protocols in search for the appropriate one. In order to
address this problem, a number of 2-classes classification models have been built
on a set of 198 Michael reactions retrieved from literature. Trained models
discriminate between processes that are compatible and respectively processes not
feasible under a specific reaction condition option (feasible or not with a Lewis
acid catalyst, feasible or not in hydrophobic solvent, etc.). Eight distinct
models were built to decide the compatibility of a Michael addition process with
each considered reaction condition option, while a ninth model was aimed to
predict whether the assumed Michael addition is feasible at all. Different
machine-learning methods (Support Vector Machine, Naive Bayes, and Random Forest)
in combination with different types of descriptors (ISIDA fragments issued from
Condensed Graphs of Reactions, MOLMAP, Electronic Effect Descriptors, and
Chemistry Development Kit computed descriptors) have been used. Models have good
predictive performance in 3-fold cross-validation done three times: balanced
accuracy varies from 0.7 to 1. Developed models are available for the users at
http://infochim.u-strasbg.fr/webserv/VSEngine.html . Eventually, these were
challenged to predict feasibility conditions for ~50 novel Michael reactions from
the eNovalys database (originally from patent literature).
PMID- 25588073
TI - Cross-dehydrogenative coupling of azoles with alpha-C(sp3)-H of ethers and
thioethers under metal-free conditions: functionalization of H-N azoles via C-H
activation.
AB - A metal-free cross-dehydrogenative coupling method for the synthesis of N
substituted azoles has been developed. The TBAI/TBHP system catalyzed the
coupling of azoles with ethers and thioethers via alpha-C(sp(3))-H activation.
Under the optimized conditions, a diverse range of un/substituted azoles such as
1H-benzimidazole, 9H-purine, 1H-benzotriazole, 1H-1,2,3-triazole, 1H-1,2,4
triazole, and 1H-pyrazole were successfully employed for coupling with various
ethers and thioethers such as tetrahydrofuran, tetrahydropyran, 1,4-dioxane,
diethyl ether, tetrahydrothiophene, and 1,3-dithiolane.
PMID- 25588075
TI - Validity of clinic blood pressure compared to ambulatory monitoring in
hypertensive patients in a primary care setting.
AB - AIMS: To determine the validity of the blood pressure (BP) measurement in a
primary care setting in comparison with the measurement obtained from 24-h
ambulatory blood pressure monitoring (ABPM). METHODS: Patients with hypertension
(n = 137) were studied in primary care. Immediately after a nurse took two
measurements of each patient's BP, the ABPM device was attached. Agreement was
determined using the Bland-Altman method and the Kappa index. The sensitivity,
specificity, predictive values and likelihood ratios were calculated for the
manual BP measurement in comparison with ABPM for the purpose of diagnosing
uncontrolled BP. RESULTS: The BP values from ABPM were lower than those obtained
in the examination room. The difference between the clinic measurement and the
ABPM was 18.07 +/- 14.6 mmHg (systolic blood pressure, SBP) and 6.3 +/- 9.2 mmHg
(diastolic blood pressure, DBP). The agreement between the clinic measurement and
24h-ABPM for the purpose of classifying control or uncontrolled BP was 64.2%
(Kappa = 0.311). In the case of ABPM, the sensitivity of the measurement in the
examination room for diagnosing uncontrolled BP was 80.36%, specificity was
53.09%, positive predictive value 54.22% and negative predictive value 70.63%.
CONCLUSIONS: Clinic measurements do not have sufficient sensitivity/specificity
to be recommended as a single method of BP control in primary care.
PMID- 25588076
TI - Criterion Validity and Practical Utility of the Minnesota Multiphasic Personality
Inventory-2-Restructured Form (MMPI-2-RF) in Assessments of Police Officer
Candidates.
AB - Minnesota Multiphasic Personality Inventory-2-Restructured Form scores for 145
male police officer candidates were compared with supervisor ratings of field
performance and problem behaviors during their initial probationary period.
Results indicated that the officers produced meaningfully lower and less variant
substantive scale scores compared to the general population. After applying a
statistical correction for range restriction, substantive scale scores from all
domains assessed by the inventory demonstrated moderate to large correlations
with performance criteria. The practical significance of these results was
assessed with relative risk ratio analyses that examined the utility of specific
cutoffs on scales demonstrating associations with performance criteria.
PMID- 25588077
TI - Does induction time of mild hypothermia influence the survival duration of septic
rats?
AB - The relationship between hypothermia induction time and survival duration
following sepsis was studied on 31 male Sprague-Dawley rats (median weight 311 g,
range 260-356 g). After anesthesia and when the target temperature was reached
(normothermia: 38 degrees C or mild induced hypothermia: 34 degrees C), sepsis
was induced by cecal ligation and perforation. Five experimental groups were
used. In groups 1 and 2, temperature of septic rats was maintained throughout the
experiment at 38 degrees C (seven rats) or 34 degrees C (six rats), respectively.
In groups 3, 4, and 5, septic rats (six per group) were maintained at 38 degrees
C for 1, 2, and 3 hours, respectively, and then placed in mild hypothermia (34
degrees C). For each group, the survival duration was determined and blood
samples were performed at the tail to measure tumor necrosis factor-alpha (TNF
alpha) plasma concentration. Whatever the experimental group, a decrease in
temperature from 38 degrees C to 34 degrees C significantly increased the
survival duration of septic rats compared with those maintained at 38 degrees C
throughout the experiment. The delay between the onset of sepsis and induction of
hypothermia was also crucial. Thus, hypothermia induced after 1 hour of sepsis at
38 degrees C significantly increased the survival duration of septic rats (12
hours 37 minutes+/-1 hour 4 minutes; group 3) compared with hypothermia induced
after 3 hours of sepsis (8 hours 56 minutes+/-1 h 20 minutes; group 5). Moreover,
except for group 5, survival duration improvement of septic rats observed in
hypothermia was related to a lower increase of TNF-alpha plasma concentration
compared with septic rats in normothermia. During sepsis, mild induced
hypothermia significantly increased the survival duration of septic rats. The
earlier hypothermia was applied, the longer the septic rats survived. According
to these results, hypothermia may therefore provide the necessary time to apply a
proper treatment.
PMID- 25588078
TI - An interplay between the p38 MAPK pathway and AUBPs regulates c-fos mRNA
stability during mitogenic stimulation.
AB - Mitogen-activated protein kinase (MAPK) pathways constitute key regulatory
elements linking extracellular stimuli to nuclear gene expression. Immediate
early responsive genes (IEGs) of the activator protein 1 (AP-1) family, such as
fos, achieve peak expression levels shortly after cells are stimulated with
growth factors and sharply decrease thereafter. Several AU-rich binding proteins
(AUBPs), including HuR (Hu-antigen R, Elav-like protein 1, ELAVL1) and KSRP (far
upstream element-binding protein 2, KHSRP) bind to a fos AU-rich element (ARE)
present in the 3'-UTR (untranslated region) of fos mRNA regulating its stability
by a still poorly defined mechanism. We show in the present study that, whereas
HuR binds and stabilizes transcribed reporter mRNAs bearing the fos 3'-UTR, KSRP
counteracts this effect. Furthermore, we found that fos mRNA stability and HuR
phosphorylation status are dependent on the activity of p38 MAPK in both
epithelial cells and fibroblasts upon proliferative stimulation. Analysing PPI
(protein-protein interaction) networks, we performed a thorough query of
interacting proteins for p38 MAPKs, HuR and other AUBPs upon growth factor
stimulation. This revealed novel HuR interactors including inhibitors of protein
phosphatase 2 (PP2A) activity. Over-expression of two of these interactors, pp32
and APRIL (acidic leucine-rich nuclear phosphoprotein 32 family member B, ANP32B)
and pharmacological inhibition of PP2A stabilized a fos reporter mRNA. Our
results indicate that p38 MAPK regulates fos mRNA decay by affecting the state of
phosphorylation of HuR while controlling yet to be fully elucidated PP regulatory
networks.
PMID- 25588080
TI - Chemical composition of essential oils from the vegetative and reproductive
structures of Copaifera langsdorffii Desf.
AB - GC/FID and GC-MS analysis revealed germacrene D, bicyclogermacrene, alpha-cadinol
and cubenol as major compounds from aril. Germacrene D, bicyclogermacrene, trans
caryophyllene and delta-elemene are major compounds in fruits. Germacrene D,
spathulenol, trans-caryophyllene and caryophyllene oxide are major compounds in
leaves. Furthermore, multivariate analysis revealed distinct groups between the
composition of essential oils from aril and fruit, when compared with terpene
production found in leaves. Lipid composition found in arils could be protected
by the presence of non-oxygenated sesquiterpenes, as germacrene D and
bicyclogermacrene. Chemical profiles of essential oils from the fruits, arils and
leaves of Copaifera langsdorffii Desf. revealed different compositions, which
could be related to environmental pressures. Thereby, non-oxygenated
sesquiterpenes can also work against herbivory, pathogens and predator's attack,
emphasising the importance of further studies among terpenes, ecology
interactions and plant physiology.
PMID- 25588079
TI - Timing of subsequent new tumors in patients who present with basal cell carcinoma
or cutaneous squamous cell carcinoma.
AB - IMPORTANCE: Patients with basal cell carcinoma (BCC) and cutaneous squamous cell
carcinoma (SCC) (often termed nonmelanoma skin cancer or keratinocyte carcinoma
[KC]) often develop new KCs, but information is limited on the frequency and
timing of these subsequent tumors. This information is crucial to guide follow-up
care. OBJECTIVE: To determine the timing of subsequent new KCs in patients who
present with KC. DESIGN, SETTING, AND PARTICIPANTS: We enrolled a consecutive
cohort of 1426 patients diagnosed as having biopsy-proven KC from January 1,
1999, through December 31, 2000, in a university dermatology practice and its
affiliated Department of Veterans Affairs dermatology service. After exclusion of
patients with basal cell nevus syndrome and immunocompromise, 1284 patients
(90.0%) were followed up prospectively for a mean of 5.7 (range, 0-12.3) years.
MAIN OUTCOMES AND MEASURES: We assessed the risks for subsequent KCs over time
using single-failure and multiple-failure models. We separately assessed outcomes
after first lifetime KCs and after nonfirst lifetime KCs. We also performed
secondary analyses of the risk for a subsequent BCC after a prior BCC diagnosis
and the risk for a subsequent SCC after a prior SCC diagnosis. RESULTS: The risk
for a subsequent KC was substantially lower after the first lifetime KC
diagnosis: 14.5% (95% CI, 11.9%-17.7%) at 1 year, 31.1% (95% CI, 27.3%-35.3%) at
3 years, and 40.7% (95% CI, 36.5%-45.2%) at 5 years, than after a nonfirst KC:
43.9% (95% CI, 42.0%-45.9%) at 1 year, 71.1% (95% CI, 69.1%-73.0%) at 3 years,
and 82.0% (95% CI, 80.2%-83.7%) at 5 years. Secondary analyses of the risks for a
subsequent BCC after a prior BCC diagnosis and of a subsequent SCC after a prior
SCC diagnosis yielded results consistent with the analyses for the pooled KC
sample. CONCLUSIONS AND RELEVANCE: Although all patients with KC are assumed to
be at high risk for subsequent tumors, a subset may not develop another KC after
their first tumor. Whether these findings are related to biological or behavioral
differences or to differences in health care services should be investigated
further to inform and improve care. Ongoing routine screening for subsequent KC
may not be indicated for all patients with KC. Skin cancer screening can be
improved with a better understanding of the course and frequency of subsequent KC
diagnoses.
PMID- 25588081
TI - Older persons' perceptions of general practitioner or specialist primary care
physicians: same point of view?
AB - BACKGROUND: Identification of a Primary Care Physician (PCP) by older patients is
considered as essential for the coordination of care, but the extent to which
identified PCPs are general practitioners or specialists is unknown. This study
described older patients' experiences with their PCP and tested the hypothesis of
differences between patients who identify a specialist as their PCP (SP PCP) and
those who turn to a general practitioner (GP PCP). METHODS: In 2012, a cross
sectional postal survey on care was conducted in the 68+ year old population of
the canton of Vaud. Data was provided by 2,276 participants in the ongoing
Lausanne cohort 65+ (Lc65+), a study of those born between 1934 and 1943, and by
998 persons from an additional sample drawn to include the population outside of
Lausanne or born before 1934. RESULTS: Participants expressed favourable
perceptions, at rates exceeding 75% for most items. However, only 38% to 51%
responded positively for out-of-hours availability, easy access and at home
visits, likelihood of prescribing expensive medication if needed, and doctors'
awareness of over-the-counter drugs. 12.0% had an SP PCP, in 95.9% specialised in
a discipline implying training in internal medicine. Bivariate and multivariate
analyses did not result in significant differences between GP and SP PCPs
regarding perceptions of accessibility/availability, doctor-patient relationship,
information and continuity of care, prevention, spontaneous use of the emergency
department or ambulatory care utilisation. CONCLUSIONS: Experiences of old
patients were mostly positive despite some lack in reported hearing, memory
testing, and colorectal cancer screening. We found no differences between GP and
SP PCP groups.
PMID- 25588082
TI - Serum endocan levels are correlated with the presence and severity of coronary
artery disease in patients with hypertension.
AB - BACKGROUND: Endothelial dysfunction is one of the most important early indicators
of atherosclerosis in hypertension (HT) patients. Endocan has been reported to
play a role in the pathophysiology of endothelial dysfunction. OBJECTIVE: We
sought to assess whether serum endocan levels are correlated with the presence
and severity of coronary artery disease (CAD) in patients with HT. METHODS: We
measured endocan levels in 164 patients with HT and in 55 controls. The severity
of CAD was assessed by the coronary atherosclerosis index scores. RESULTS: Serum
endocan levels were independently correlated with the presence and severity of
CAD in HT patients. CONCLUSION: Endocan might function as a useful biomarker for
monitoring the development and progression of CAD in HT patients.
PMID- 25588083
TI - Aflibercept: an update on recent milestones achieved.
AB - In the last decade, intravitreal medications targeted to vascular endothelial
growth factor (VEGF) such as pegaptanib, ranibizumab and bevacizumab have
revolutionized the treatment and significantly improved visual acuity outcomes in
patients with retinal vascular diseases such as age-related macular degeneration
(AMD), diabetic macula edema (DME) and retinal vein occlusion (RVO). In recent
years, aflibercept, an anti-VEGF drug that targets all isoforms of VEGF as well
as placenta growth factor, has shown similar effectiveness in recent clinical
trials. Aflibercept has firmly joined ranibizumab and bevacizu-mab as an
important therapeutic option in the management of neovascular AMD. More recently,
aflibercept appears to be contending with ranibizumab and bevacizumab as an
important therapeutic option in the management of DME and RVO.
PMID- 25588084
TI - Nivolumab.
AB - Until recently, a treatment for advanced melanoma with a tolerable side effect
profile has remained elusive. Therefore, despite its relatively rare occurrence,
melanoma continues to cause the majority of skin cancer deaths, with less than
15% of those affected with late-stage disease surviving 10 years or more.
Historically, the mainstay of treatment has been single-agent chemotherapy or
immunotherapy with the alkylating agent dacarbazine and interleukin-2 or
interferon. Cytotoxic chemotherapy with dacarbazine demonstrated poor response
rates and little or no survival benefit, whereas IL-2 and interferon, although
showing durable responses, are associated with poor side effect profiles (1, 2).
However, with the elucidation of the molecular biology and oncogenic pathways
involved in melanoma, agents targeted against mutations in the mitogen-activated
protein kinase (MAPK) pathway including BRAF and MEK inhibitors have demonstrated
prolonged survival and more manageable side effect profiles relative to
traditional chemotherapy. Simultaneously, an evolved understanding of the
immunologic basis for the development and regression of melanoma lead to the
discovery of immune checkpoint inhibitors, which confer a similar survival
benefit. Foremost among these was ipilimumab, a monoclonal antibody against the
negative regulatory checkpoint molecule cytotoxic T-lymphocyte protein 4 (CTLA
4), which was the first drug in the management of metastatic melanoma to confer a
survival benefit. However, treatment is complicated by a high rate of grade 3 and
4 immune-related adverse events and limited response. Nivolumab, a fully human
monoclonal antibody against programmed cell death protein 1 (PD-1), has shown a
survival benefit in an open-label phase II trial, and was the first PD-1
inhibitor to be approved worldwide. With a favorable side effect profile and
ongoing trials in combination with extant therapies, nivolumab shows substantial
potential to further augment the options for an effective treatment in malignant
melanoma.
PMID- 25588085
TI - Tamsulosin/solifenacin fixed-dose combination tablet for the treatment of male
lower urinary tract symptoms.
AB - Men reporting mixed storage and voiding lower urinary tract symptoms (LUTS) often
experience persisting storage LUTS after initial treatment. Combination therapy
of an alpha-adrenergic antagonist and an antimuscarinic is increasingly
recognized as a therapy option. Clinical trials have combined tamsulosin (0.4 mg)
with different doses of solifenacin. In the SATURN study, greater efficacy
benefits were observed for moderate to severe storage symptoms. Single tablet
administration may offer improved compliance. Accordingly, the NEPTUNE study
researched fixed-dose combination (FDC) therapy for mixed LUTS, using tamsulosin
(oral controlled administration system formulation), with solifenacin (6 or 9
mg). The FDC containing tamsulosin and solifenacin 6 mg improved storage and
voiding LUTS, with no additional benefit from the higher solifenacin dose. During
the open-label extension study, symptom improvement was maintained. Adverse
events reflected the known effects of the component therapies. Acute urinary
retention, an adverse event of special interest, was seen in only a small number
of treated men.
PMID- 25588086
TI - Technosphere inhaled insulin (Afrezza).
AB - Technosphere(r) insulin uses a unique carrier -fumaryl diketopiperazine (FDKP)-
which adsorbs insulin to form microparticles to permit delivery to the alveoli by
inhalation. Toxicity studies have been entirely negative. The pulmonary
absorption of insulin is very rapid, and the disappearance time is shorter than
for subcutaneously delivered rapid-acting insulins. As a result, after
inhalation, there is a rapid drop in glucose levels which subsequently return to
normal in a shorter time than after subcutaneous insulin administration.
Consequently, there is a lower incidence of hypoglycemic reactions. Pulmonary
function studies have shown a small, reversible decrease in FEV1, and pulmonary
imaging studies have shown no adverse effect. The inhalation of Technosphere
insulin can produce a cough in up to 27% of patients. The cough has resulted in
discontinuance in as many as 9% of users. Technosphere insulin has been approved
for use in type 1 and type 2 diabetes. Long-term studies of pulmonary safety and
surveillance for malignancy will be performed in the future. Studies to assess
the optimal time dosing regimen are needed.
PMID- 25588087
TI - A report from the 2014 American College of Rheumatology/Association of
Rheumatology Health Professionals Annual Meeting (November 14-19 - Boston,
Massachusetts, USA).
AB - With freezing cold temperatures outside but great excitement for new research
inside Boston's Convention and Exhibition Center, clinical research on recently
launched and investigational small molecular drugs and biologics as well as
preclinical research with novel compounds acting on new targets that are paving
the way to future developments in the therapeutic armamentarium against
rheumatoid arthritis and other bone and joint diseases focused the attention of
researchers and clinicians attending this year's scientific sessions of the
American College of Rheumatology. The conference started with a full-blast poster
session during which significant research advancements were disclosed, but
parallel abstract sessions were not far behind in attendance, hooking the
interest of attendees from across the world.
PMID- 25588088
TI - CE: Original research: hospital system barriers to rapid response team
activation: a cognitive work analysis.
AB - BACKGROUND: The goal of rapid response team (RRT) activation in acute care
facilities is to decrease mortality from preventable complications, but such
efforts have been only moderately successful. Although recent research has shown
decreased mortality when RRTs are activated more often, many hospitals have low
activation rates. This has been linked to various hospital, team, and nursing
factors. Yet there is a dearth of research examining how hospital systems shape
nurses' behavior with regard to RRT activation. Making systemic constraints
visible and modifying them may be the key to improving RRT activation rates and
saving more lives. PURPOSE: The purpose of this study was to use cognitive work
analysis to describe factors within the hospital system that shape medical
surgical nurses' RRT activation behavior. METHODS: Cognitive work analysis offers
a framework for the study of complex sociotechnical systems. This framework was
used as the organizing element of the study. Qualitative descriptive design was
used to obtain data to fill the framework's five domains: resources, tasks,
strategies, social systems, and worker competency. Data were obtained from
interviews with 12 medical-surgical nurses and document review. Directed content
analysis was used to place the obtained data into the framework's predefined
domains. RESULTS: Many system factors affected participants' decisions to
activate or not activate an RRT. Systemic constraints, especially in cases of
subtle or gradual clinical changes, included a lack of adequate information, the
availability of multiple strategies, the need to justify RRT activation, a
scarcity of human resources, and informal hierarchical norms in the hospital
culture. The most profound constraint was the need to justify the call.
Justification was based on the objective or subjective nature of clinical
changes, whether the nurse expected to be able to "handle" these changes, the
presence or absence of a physician, and whether there was an expectation of
support from the RRT team. The need for justification led to delays in RRT
activation. CONCLUSIONS: Although it's generally thought that RRTs are activated
without hesitation, this study found the opposite was true. All of the
aforementioned constraints increase the cognitive processing load on the nurse.
The value of the RRT could be increased by modifying these constraints-in
particular, by lifting the need to justify calls, improving protocols, and
broadening the range of culturally acceptable triggers-and by involving the RRT
earlier in patient cases through discussion, consultation, and collaboration.
PMID- 25588089
TI - CE: Long-term outcomes after repair of congenital heart defects: part 2.
AB - OVERVIEW: Many congenital heart defects can be repaired, but long-term monitoring
is often required to forestall possible complications. This two-part article
reviews 10 common congenital heart defects, their repairs, and their common long
term outcomes, along with the implications for nurses in cardiac and noncardiac
settings alike. Here, in part 2, the author reviews four defects: tetralogy of
Fallot, transposition of the great arteries, congenitally corrected transposition
of the great arteries, and single-ventricle defects.
PMID- 25588090
TI - A bold new vision for America's health care system.
PMID- 25588092
TI - Atom-economical transformation of diaryliodonium salts: tandem C-H and N-H
arylation of indoles.
AB - Arylation using diaryliodonium salts generates one equivalent of an iodoarene as
a side-product, a significant waste of atom economy. Here, we show that
diaryliodoniums can undergo Cu-catalyzed tandem C-H/N-H arylation, producing
novel indoles that incorporate both aryl groups from the reagent.
PMID- 25588091
TI - Muscle atrophy and metal-on-metal hip implants: a serial MRI study of 74 hips.
AB - BACKGROUND AND PURPOSE: Muscle atrophy is seen in patients with metal-on-metal
(MOM) hip implants, probably because of inflammatory destruction of the musculo
tendon junction. However, like pseudotumors, it is unclear when atrophy occurs
and whether it progresses with time. Our objective was to determine whether
muscle atrophy associated with MOM hip implants progresses with time. PATIENTS
AND METHODS: We retrospectively reviewed 74 hips in 56 patients (32 of them
women) using serial MRI. Median age was 59 (23-83) years. The median time post
implantation was 83 (35-142) months, and the median interval between scans was 11
months. Hip muscles were scored using the Pfirrmann system. The mean scores for
muscle atrophy were compared between the first and second MRI scans. Blood cobalt
and chromium concentrations were determined. RESULTS: The median blood cobalt was
6.84 (0.24-90) ppb and median chromium level was 4.42 (0.20-45) ppb. The median
Oxford hip score was 34 (5-48). The change in the gluteus minimus mean atrophy
score between first and second MRI was 0.12 (p = 0.002). Mean change in the
gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p =
0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean
pseudotumor grade increased by 0.18 (p = 0.02). INTERPRETATION: Worsening muscle
atrophy and worsening pseudotumor grade occur over a 1-year period in a
substantial proportion of patients with MOM hip implants. Serial MRI helps to
identify those patients who are at risk of developing worsening soft-tissue
pathology. These patients should be considered for revision surgery before
irreversible muscle destruction occurs.
PMID- 25588093
TI - Why do patients keep coming back? Results of a readmitted patient survey.
AB - Hospital readmissions can negatively impact cost and patient outcomes. Predictors
of 30-day readmissions have been primarily identified using medical claims data.
Reported here are results of a patient survey developed as part of regular
hospital quality assurance activities. Two-thirds of patients reported good
discharge experiences but were still readmitted. One-third of patients discharged
had a post-discharge doctor appointment scheduled; half were readmitted before
that scheduled appointment. Results suggest post-discharge experiences could be
improved, especially the timing of follow up doctor appointments. Identified
weaknesses in the survey process highlight need for engagement of survey
methodologists in efforts to understand patient experiences.
PMID- 25588094
TI - First childbirth and motherhood at post natural fertile age: a persistent and
intergenerational experience of personal and social anomaly?
AB - This study was aimed at understanding long-term psychosocial implications of
first childbirth at post natural fertile age following assisted reproductive
treatment. Twenty women, whose average age at childbirth was 45, participated.
Findings show that the sense of anomaly experienced prior to pregnancy and
childbirth related to infertility and advanced age continued during treatment,
pregnancy, and motherhood. Participants associated their advanced age as cause
for what they perceived as a similar sense of anomaly experienced by their
children. The issue of a continuing and intergenerational sense of anomaly should
be addressed when counseling women considering fertility treatment at advanced
age.
PMID- 25588095
TI - Medication adherence skills training for African-American breast cancer
survivors: the effects on health literacy, medication adherence, and self
efficacy.
AB - There are gaps in research regarding medication adherence, self-efficacy in
proper medication adherence, and health literacy among breast cancer survivors.
This pilot randomized controlled study was conducted to provide information
addressing health literacy with respect to medication adherence and self-efficacy
in African American breast cancer survivors. The study sample consisted of an
intervention group (n = 24) of medication adherence skills training (MST) and a
control group (n = 24), with a total sample population of 48 participants. The
MST workshop was a collaborative intervention between pharmacy and social work
and was designed to address issues that may be encountered while taking multiple
medications for various acute and chronic conditions, increase participant
confidence in accessing necessary resources for improved medication usage, and
enhance personal self-efficacy regarding health care. A statistically significant
relationship was detected between initial health literacy and medication
adherence, as well as initial health literacy and self-efficacy. These findings
indicated that individuals with higher health literacy were more likely to have
higher levels of self-efficacy and were more likely to adhere to medication
instructions. Analysis of the intervention and treatment groups did not show a
statistically significant effect on health literacy, medication adherence, or
self-efficacy from pre-test to post-test.
PMID- 25588096
TI - Barriers to cancer care, perceived social support, and patient navigation
services for Korean breast cancer patients.
AB - The present study aimed to examine the relationships among barriers to cancer
care, perceived social support, and patient navigation services (PNS) for Korean
breast cancer patients. For Korean breast cancer patients, PNS are comprised of
five services, including emotional, financial, information, transportation, and
disease management. The study findings demonstrated that transportation and
disease management barriers were directly associated with PNS, whereas emotional
and financial barriers were indirectly associated with PNS through perceived
social support. The current study provides a preliminary Korean patient
navigation model to identify how barriers to cancer care can be reduced through
social support and PNS.
PMID- 25588098
TI - Resilience, self-efficacy, coping styles and depressive and anxiety symptoms in
those newly diagnosed with multiple sclerosis.
AB - High levels of depressive and anxiety symptoms have been reported by individuals
with multiple sclerosis (MS). This study examined the associations between
resilience, self-efficacy and coping and depressive and anxiety symptoms and
whether resilience, self-efficacy and coping were predictors of depressive and
anxiety symptoms in patients newly diagnosed with MS. A sample of 129 individuals
newly diagnosed with MS participated in this cross-sectional study and completed
an online questionnaire assessing resilience, self-efficacy, coping and
depressive and anxiety symptoms. Results revealed that depressive and anxiety
symptoms were significantly associated with problem-focused, emotion-focused and
avoidance coping strategies, resilience and self-efficacy. Anxiety symptoms were
also significantly associated with employment status and level of disability.
Results from hierarchical multiple regression revealed that the resilience
subscale of personal competence, the avoidance coping style of substance use and
emotion-focused coping styles of venting predicted depressive symptoms and
uniquely accounted for 63.8% of the variance in the depression score, F (18, 124)
= 10.36, p = .000. Level of disability and employment status accounted for 13.2%
of the anxiety score and avoidance coping style of denial and emotion-focused
coping style of humour accounted for 36.4% of the variance in the anxiety symptom
score, F (15, 112) = 6.37, p = .000. Our findings suggest that resilience and
avoidance and emotion-focused coping strategies are predictive of depressive
symptoms and anxiety symptoms in those newly diagnosed with MS. Resilience and
coping styles may be another target for interventions aimed at managing
depressive and anxiety symptoms in those newly diagnosed with MS.
PMID- 25588097
TI - Low health literacy and older adults: meanings, problems, and recommendations for
social work.
AB - Many older adults struggle to manage their health care problems. Low health
literacy exacerbates such struggles and contributes to a variety of adverse
health behaviors and outcomes. Addressing how health literacy impinges on the
lives of older adults is a neglected area of social work practice and knowledge.
This article explores seven areas: defining health literacy, the problem and
prevalence of low health literacy among older adults, health inequalities and
health literacy, a brief literature review, neglected issues in the literature,
suggestions for macro and micro social work interventions to improve health
literacy for older adult populations, and conclusion.
PMID- 25588100
TI - Photophysical Properties and Electronic Structure of Chlorin-Imides: Bridging the
Gap between Chlorins and Bacteriochlorins.
AB - Efficient light harvesting for molecular-based solar-conversion systems requires
absorbers that span the photon-rich red and near-infrared (NIR) regions of the
solar spectrum. Reported herein are the photophysical properties of a set of six
chlorin-imides and nine synthetic chlorin analogues that extend the absorption
deeper (624-714 nm) into these key spectral regions. These absorbers help bridge
the gap between typical chlorins and bacteriochlorins. The new compounds have
high fluorescence quantum yields (0.15-0.34) and long singlet excited-state
lifetimes (4.2-10.9 ns). The bathochromic shift in Qy absorption is driven by
substituent-based stabilization of the lowest unoccupied molecular orbital, with
the largest shifts for chlorins that bear an electron-withdrawing, conjugative
group at the 3-position in combination with a 13,15-imide ring.
PMID- 25588101
TI - Bright, efficient, and color-stable violet ZnSe-based quantum dot light-emitting
diodes.
AB - In this paper, highly stable violet-blue emitting ZnSe/ZnS core/shell QDs have
been synthesized by a novel "low temperature injection and high temperature
growth" method. The resulting nearly monodisperse ZnSe/ZnS core/shell QDs exhibit
excellent characteristics such as a high color saturation (typical spectral full
width at half-maximum between 12 and 20 nm), good emission tunability in the
violet-blue range of wavelengths from 400 to 455 nm, a high absolute PL quantum
yield (up to 83%), and superior chemical and photochemical stability. By
employing ZnSe/ZnS core/shell quantum dots (QDs) as emitters with a fully
solution processable method, bright, efficient, and color-stable violet Cd-free
quantum dot-based light-emitting diodes (QD-LEDs) with maximum luminance up to
2632 cd m(-2) and a peak EQE of 7.83% have been demonstrated successfully.
Considering the factors of the photopic luminosity function, the brightness and
efficiency results of such violet QD-LEDs not only represent a 12-fold increase
in device efficiency and an extraordinary 100 times increase in luminance
compared with previous Cd-free QD-LEDs but also can be much superior to the best
performance (1.7%) of their Cd-based violet counterparts. These results
demonstrate significant progress in short-wavelength QD-LEDs and shed light on
the acceleration of commercial application of environmentally-friendly violet QD
based displays and lighting.
PMID- 25588099
TI - Functional chromatographic technique for natural product isolation.
AB - Natural product discovery arises through a unique interplay between
chromatographic purification and biological assays. Currently, most techniques
used for natural product purification deliver leads without a defined biological
action. We now describe a technique, referred to herein as functional
chromatography, that deploys biological affinity as the matrix for compound
isolation.
PMID- 25588102
TI - Rapid quantification of digitoxin and its metabolites using differential ion
mobility spectrometry-tandem mass spectrometry.
AB - This study focuses on the quantitative analysis of the cardiac glycoside drug
digitoxin and its three main metabolites digitoxigenin-bisdigitoxose,
digitoxigenin-monodigitoxose, and digitoxigenin using electrospray ionization
differential ion mobility spectrometry-tandem mass spectrometry (ESI-DMS-MS/MS).
Despite large molecular weight differences, gas-phase separation of the four
compounds in the DMS drift cell was not possible, even by utilizing additional
volatile chemical modifiers. Baseline separation was achieved after adduct
formation with alkali metal ions, however, and efficiency was shown to improve
with increasing size of the alkali ion, reaching optimum conditions for the
largest cesium ion. Subsequently, an assay was developed for quantification of
digitoxin and its metabolites from human serum samples and its analytical
performance assessed in a series of proof-of-concept experiments. The method was
applied to spiked human serum pools with concentration levels between 2 and 80
ng/mL. After a short reversed-phase chromatographic step for desalting the
sample, rapid DMS separation of the analytes was carried out, resulting in a
total run time of less than 1.5 min. The instrumental method showed good
repeatability; the calculated coefficients of variation ranged from 2% to 13%.
PMID- 25588103
TI - Photoprotective effects of oxyresveratrol and Kuwanon O on DNA damage induced by
UVA in human epidermal keratinocytes.
AB - Ultraviolet A not only plays a major part in photoaging and skin tanning but also
induces genetic damage and mutation in the epidermal basal layer of human skin.
The photoprotective effect of oxyresveratrol and kuwanon O, two phenolic
compounds from the root extract of Morus australis, in human primary epidermal
keratinocytes was investigated in this study. Both of them were nontoxic to cells
at a concentration less than 10 and 0.5 MUM, respectively. After pretreatment at
the concentrations of 5 and 10 MUM, oxyresveratrol increased cell viability,
exhibited significant suppressions on UVA- or H2O2-induced cellular ROS. UVA
enhanced nitrotyrosine was also reduced by post-treatment with oxyresveratrol at
theses concentrations. Kuwanon O presented similar inhibitions on cellular ROS
and nitrotyrosine with lower concentrations (0.25 and 0.5 MUM), but there is no
significant protection on cell survival after UVA irradiation. Their
photoprotective effects also involved the enhanced repair of 8-hydroxy-2'
deoxyguanosine (8-OHdG) and cyclobutane pyrimidine dimers (CPDs) as mediated by
the augment of p53 expression after UVA radiation.
PMID- 25588104
TI - Fatty Acids Induce a Pro-Inflammatory Gene Expression Profile in Huh-7 Cells That
Attenuates the Anti-HCV Action of Interferon.
AB - The pathogenesis of nonalcoholic steatohepatitis is primarily an immune-driven
disease and a known factor associated with treatment failure of chronic hepatitis
C with interferon (IFN) and ribavirin. We studied the hepatocyte response in a
model of steatosis at the transcriptome level and the antiviral action of IFN
against hepatitis C virus (HCV) in this setting. In this study, we have shown
that lipid loading (oleic acid and palmitic acid, OA:PA) of Huh-7 cells leads to
increased expression of classical interferon-stimulated genes (ISGs) and NF
kappabeta-dependent pro-inflammatory genes. A selective blocker of Toll-like
receptor (TLR)2 signaling suppressed NF-kappabeta promoter activity by OA:PA,
suggesting that free fatty acids (FFAs) act as a TLR2 pathogen-associated
molecular pattern. Furthermore, in the presence of OA:PA, IFN stimulation and HCV
infection (Jc1) increased ISG expression. Somewhat counterintuitive to the
increase in ISGs, the anti-HCV activity of IFN was attenuated in the presence of
OA:PA. Interestingly, the combination of OA:PA, HCV, and IFN-alpha stimulation
resulted in a significant increase in CXCL8 protein production, a cytokine known
to have anti-IFN modulating activity. Thus, in an in vitro model of steatosis,
the FFAs OA and PA drive an NF-kappabeta-dependent inflammatory and ISG gene
expression profile via TLR2 activation. Furthermore, FFA synergistically
increases IFN-driven gene expression that may account for HCV treatment failure
in vivo.
PMID- 25588105
TI - Time trend analysis of primary tumor resection for stage IV colorectal cancer:
less surgery, improved survival.
AB - IMPORTANCE: With the advent of effective modern chemotherapeutic and biologic
agents, primary tumor resection for patients with stage IV colorectal cancer
(CRC) may not be routinely necessary. OBJECTIVE: To evaluate the secular patterns
of primary tumor resection use in stage IV CRC in the United States. DESIGN,
SETTING, AND PARTICIPANTS: A retrospective cohort study using data from the
National Cancer Institute's Surveillance, Epidemiology, and End Results CRC
registry. Demographic and clinical factors were compared for 64,157 patients
diagnosed with stage IV colon or rectal cancer from January 1, 1988, through
December 31, 2010, who had undergone primary tumor resection and those who had
not. Rates of primary tumor resection and median relative survival were
calculated for each year. Joinpoint regression analysis was used to determine
when a significant change in trend in the primary tumor resection rate had
occurred. Logistic regression analysis was used to assess factors associated with
primary tumor resection. MAIN OUTCOMES AND MEASURES: Difference in primary tumor
resection rates over time. RESULTS: Of the 64,157 patients with stage IV CRC,
43,273 (67.4%) had undergone primary tumor resection. The annual rate of primary
tumor resection decreased from 74.5% in 1988 to 57.4% in 2010 (P<.001), and a
significant annual percentage change occurred between 1998-2001 and 2001-2010 (
0.41% vs -2.39%; P<.001). Factors associated with primary tumor resection were
age younger than 50 years, female sex, being married, higher tumor grade, and
presence of colon tumors. Median relative survival rate improved from 8.6% in
1988 to 17.8% in 2009 (P<.001); the annual percentage change was 2.18% in 1988
2001 and 5.43% in 1996-2009 (P<.001). CONCLUSIONS AND RELEVANCE: The majority of
patients with stage IV CRC had undergone primary tumor resection but, beginning
in 2001, a trend toward fewer primary tumor resections was seen. Despite the
decreasing primary tumor resection rate, patient survival rates improved.
However, primary tumor resection may still be overused, and current treatment
practices lag behind evidence-based treatment guidelines.
PMID- 25588106
TI - Metamorphosis of Galleria mellonella research.
PMID- 25588107
TI - [Psychological distress, need for advice and utilization of professional help
among students].
AB - As a consequence of earlier investigations, which have demonstrated that 20-25%
of the students report psychological distress, the knowledge of the need and the
utilization of help resulting from psychological or social problems have to be
improved. Data from 366 students were collected to determine the need for advice,
the utilization of help and the occurrence of psychological symptoms (SCL-27) and
interpersonal problems (IIP-C). Comparisons between students and the total
population as well as between students with and without need for advice were
made. 23,3% of the persons surveyed, expressed the wish to receive professional
help. In comparison to the total population, the students reported more
psychological symptoms and consulted less frequently a general practitioner or a
gynecologist. Students with need for advice experienced more psychological
distress. To encourage more of the distressed students to utilize professional
help, the access to professional help should be facilitated.
PMID- 25588108
TI - Signaling proteins and pathways affected by flavonoids in leukemia cells.
AB - Flavonoids are a class of plant secondary metabolites that are found ubiquitously
in plants and in the human diet. Our objective is to investigate the
antiproliferative effects of flavonoids (baicalein, luteolin, genistein,
apigenin, scutellarin, galangin, chrysin, and naringenin) toward leukemia cells
(HL-60, NB4, U937, K562, Jurkat) as well as the relationship between their
antileukemic potencies and molecular structures. At the proteomic level, we
evaluate the effects of different flavonoids on the expression levels of various
proteins using Protein Pathway Array (PPA) technology. Our results showed a dose
dependent cytotoxicity of flavonoids toward various types of leukemia cells. The
results of PPA illustrated that flavonoids, such as baicalein, genistein, and
scutellarin affected different proteins in different leukemia cell lines. Cell
cycle regulatory proteins, such as CDK4, CDK6, Cyclin D1, Cyclin B1, p-CDC2, and
p-RB were affected in different leukemia cells. Furthermore, we found that
baicalein suppresses CDK4 and activates p-ERK in most leukemia cells; genistein
mainly affects CDK4, p-ERK, p-CDC2, while scutellarin dysregulated the proteins,
cell division control protein 42, Notch4, and XIAP. Collectively, a wide variety
of dysregulation of key signaling proteins related to apoptosis and cell-cycle
regulation contributes to the antileukemic properties of these flavonoids.
PMID- 25588110
TI - Host-guest complexation of a pyrogallol[4]arene derivative at the air-water
interface.
AB - The host-guest properties of acetylated aryl pyrogallol[4]arene (AcPy) were
studied as a Langmuir monolayer at the air-water interface. The self-assembled
Langmuir monolayer properties and interactions with monovalent and divalent metal
cations were investigated using surface pressure- and surface potential-area
isotherms, compression-decompression cycles, stability, and infrared reflection
absorption spectroscopy (IRRAS). A favorable interaction is observed for
complexation between acetylated aryl pyrogallol[4]arene with divalent calcium and
cadmium cations, while no interaction is observed for monovalent sodium and
potassium cations. Spectroscopic techniques allow for discrimination between
cadmium and calcium complexation.
PMID- 25588109
TI - Electron transfer mediated electrochemical biosensor for microRNAs detection
based on metal ion functionalized titanium phosphate nanospheres at attomole
level.
AB - MicroRNAs (miRNAs) have emerged as new candidates as diagnostic and prognostic
biomarkers for the detection of a wide variety of cancers; thus, sensitive and
selective detection of microRNAs is significant for early-phase cancer diagnosis
and disease prevention. A novel and simple electrochemical miRNA biosensor was
developed using Cd(2+)-modified titanium phosphate nanoparticles as signal unit,
two DNA as capture probes, and Ru(NH3)6(3+) as electron transfer mediator. Large
quantities of cadmium ions were mounted in titanium phosphate spheres to output
the electrochemical signal. Because of the presence of Ru(NH3)6(3+) molecules
that interacted with DNA base-pairs as electron wire, the electrochemical signal
significantly increased more than 5 times. This approach achieved a wide dynamic
linear range from 1.0 aM to 10.0 pM with an ultralow limit detection of 0.76 aM,
exerting a substantial enhancement in sensitivity. Moreover, the proposed
biosensor was sufficiently selective to discriminate the target miRNAs from
homologous miRNAs and could be used for rapid and direct analysis of miRNAs in
human serum. Therefore, this strategy provides a new and ultrasensitive platform
for miRNA expression profiling in biomedical research and clinical diagnosis.
PMID- 25588113
TI - A multiplex fluorophore molecular beacon: detection of the target sequence using
large Stokes shift and multiple emission signal properties.
AB - We have developed a multiplex fluorophore molecular beacon () with fluorophores
located at its end to produce unique FRET (Fluorescence Resonance Energy
Transfer). It exhibited diverse fluorescence properties depending on the mixing
pattern, such as large Stokes shift emission and multiple colors, namely, blue,
green and red using one excitation wavelength. Our also worked in probing a
target perfect matched sequence with exonuclease III.
PMID- 25588115
TI - Nondestructive identification of dye mixtures in polyester and cotton fibers
using raman spectroscopy and ultraviolet-visible (UV-Vis) microspectrophotometry.
AB - Presented in this paper is an assessment of the applicability of Raman
spectroscopy and microspectrophotometry (MSP) in visible and ultraviolet light
(UV-Vis) in the examination of textile fibers dyed with mixtures of synthetic
dyes. Fragments of single polyester fibers, stained with ternary mixtures of
disperse dyes in small mass concentrations, and fragments of single cotton
fibers, dyed with binary or ternary mixtures of reactive dyes, were subjected to
the study. Three types of excitation sources, 514, 633, and 785 nm, were used
during Raman examinations, while the MSP study was conducted in the 200 to 800 nm
range. The results indicate that the capabilities for discernment of dye mixtures
are similar in the spectroscopic methods that were employed. Both methods have a
limited capacity to distinguish slightly dyed polyester fiber; additionally, it
was found that Raman spectroscopy enables identification of primarily the major
components in dye mixtures. The best results, in terms of the quality of Raman
spectra, were obtained using an excitation source from the near infrared. MSP
studies led to the conclusion that polyester testing should be carried out in the
range above 310 nm, while for cotton fibers there is no limitation or restriction
of the applied range. Also, MSP UV-Vis showed limited possibilities for
discriminatory analysis of cotton fibers dyed with a mixture of reactive dyes,
where the ratio of the concentration of the main dye used in the dyeing process
to minor dye was higher than four. The results presented have practical
applications in forensic studies, inter alia.
PMID- 25588112
TI - Association between pre-pregnancy depression/anxiety symptoms and hypertensive
disorders of pregnancy.
AB - BACKGROUND: Depression and anxiety symptoms have been linked with hypertensive
disorders during pregnancy, but these associations have not been fully
elucidated. Our objective was to consider hypertension in pregnancy and its
subtypes (chronic hypertension, gestational hypertension, preeclampsia) and
evaluate whether the proximity of psychological symptoms to pregnancy informs any
associations observed. METHODS: Pregnancy Outcomes and Community Health Study
participants who provided interview data at enrollment (16-27 weeks' gestation)
and whose hypertensive disorder status was abstracted from medical records were
eligible for inclusion (n=1371). Maternal history of depression/anxiety symptoms
at four time points in the life course were ascertained via self-report at
enrollment (i.e., lifetime history, 1 year prior to pregnancy, since last
menstrual period, and past week). Weighted logistic regression models were used
to examine depression/anxiety symptom measures in relation to hypertensive
disorders (overall) and subtype. RESULTS: Following adjustment for maternal
sociodemographic factors, smoking, and prepregnancy body mass index, prepregnancy
depression or anxiety symptoms (i.e., lifetime history and 1 year prior to
pregnancy) were associated with hypertensive disorders during pregnancy. Subtype
analyses revealed that these associations were driven primarily by chronic
hypertension (adjusted odds ratios=2.7-3.5). Preeclampsia accompanied by preterm
delivery was also linked to women's lifetime history of depression symptoms (odds
ratio=2.3, 95% confidence interval 1.0-5.2). CONCLUSION: Our results suggest that
the link between maternal chronic hypertension and depression/anxiety symptoms
precedes pregnancy. In addition, prepregnancy history of depression/anxiety
symptoms may be considered part of a risk profile for preterm preeclampsia.
PMID- 25588111
TI - Beyond the histone tale: HP1alpha deregulation in breast cancer epigenetics.
AB - Heterochromatin protein 1alpha (HP1alpha) encoded from the CBX5-gene is an
evolutionary conserved protein that binds histone H3 di- or tri-methylated at
position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an
essential role in forming higher order chromatin structures. HP1alpha has diverse
functions in heterochromatin formation, gene regulation, and mitotic progression,
and forms complex networks of gene, RNA, and protein interactions. Emerging
evidence has shown that HP1alpha serves a unique biological role in breast cancer
related processes and in particular for epigenetic control mechanisms involved in
aberrant cell proliferation and metastasis. However, how HP1alpha deregulation
plays dual mechanistic functions for cancer cell proliferation and metastasis
suppression and the underlying cellular mechanisms are not yet comprehensively
described. In this paper we provide an overview of the role of HP1alpha as a new
sight of epigenetics in proliferation and metastasis of human breast cancer. This
highlights the importance of addressing HP1alpha in breast cancer diagnostics and
therapeutics.
PMID- 25588116
TI - Silk macromolecules with amino acid-poly(ethylene glycol) grafts for controlling
layer-by-layer encapsulation and aggregation of recombinant bacterial cells.
AB - This study introduces double-brush designs of functionalized silk
polyelectrolytes based upon regenerated silk fibroin (SF), which is modified with
poly-L-lysine (SF-PLL), poly-L-glutamic acid (SF-PGA), and poly(ethylene glycol)
(PEG) side chains with different grafting architecture and variable amino acid
PEG graft composition for cell encapsulation. The molecular weight of poly amino
acids (length of side chains), molecular weight and degree of PEG grafting (D)
were varied in order to assess the formation of cytocompatible and robust layer
by-layer (LbL) shells on two types of bacterial cells (Gram-negative and Gram
positive bacteria). We observed that shells assembled with charged polycationic
amino acids adversely effected the properties of microbial cells while promoting
the formation of large cell aggregates. In contrast, hydrogen-bonded shells with
high PEG grafting density were the most cytocompatible, while promoting formation
of stable colloidal suspensions of individual cell encapsulates. The stability to
degradation of silk shells (under standard cell incubation procedure) was related
to the intrinsic properties of thermodynamic bonding forces, with shells based on
electrostatic interactions having stronger resistance to deterioration compared
to pure hydrogen-bonded silk shells. By optimizing the charge density of silk
polyelectrolytes brushes, as well as the length and the degree of PEG side
grafts, robust and cytocompatible cell coatings were engineered that can control
aggregation of cells for biosensor devices and other potential biomedical
applications.
PMID- 25588114
TI - Synthesis, stereochemical analysis, and derivatization of myricanol provide new
probes that promote autophagic tau clearance.
AB - We previously discovered that one specific scalemic preparation of myricanol (1),
a constituent of Myrica cerifera (bayberry/southern wax myrtle) root bark, could
lower the levels of the microtubule-associated protein tau (MAPT). The
significance is that tau accumulates in a number of neurodegenerative diseases,
the most common being Alzheimer's disease (AD). Herein, a new synthetic route to
prepare myricanol using a suitable boronic acid pinacol ester intermediate is
reported. An X-ray crystal structure of the isolated myricanol (1) was obtained
and showed a co-crystal consisting of (+)-aR,11S-myricanol (2) and (-)-aS,11R
myricanol (3) coformers. Surprisingly, 3, obtained from chiral separation from 1,
reduced tau levels in both cultured cells and ex vivo brain slices from a mouse
model of tauopathy at reasonable mid-to-low micromolar potency, whereas 2 did
not. SILAC proteomics and cell assays revealed that 3 promoted tau degradation
through an autophagic mechanism, which was in contrast to that of other tau
lowering compounds previously identified by our group. During the course of
structure-activity relationship (SAR) development, we prepared compound 13 by
acid-catalyzed dehydration of 1. 13 had undergone an unexpected structural
rearrangement through the isomyricanol substitution pattern (e.g., 16), as
verified by X-ray structural analysis. Compound 13 displayed robust tau-lowering
activity, and, importantly, its enantiomers reduced tau levels similarly.
Therefore, the semisynthetic analogue 13 provides a foundation for further
development as a tau-lowering agent without its SAR being based on chirality.
PMID- 25588117
TI - Perturbation factors in the clinical handling of a fiber-coupled Raman probe for
cutaneous in vivo diagnostic Raman spectroscopy.
AB - The application of fiber-coupled Raman probes for the discrimination of cancerous
and normal skin has the advantage of a non-invasive in vivo application, easy
clinical handling, and access to the majority of body sites, which would
otherwise be limited by stationary Raman microscopes. Nevertheless, including
optical fibers and miniaturizing optical components, as well as measuring in
vivo, involves the sensibility to external perturbation factors that could
introduce artifacts to the acquired Raman spectra and thereby potentially reduce
classification performance. In this study, typical perturbation factors of Raman
measurements with a Raman fiber probe, optimized for clinical in vivo
discrimination of skin cancer, were investigated experimentally. Measurements
were performed under standardized conditions in clinical settings in vivo on
human skin, as well as ex vivo on porcine ears. Raman spectra were analyzed in
the fingerprint region between 1150 and 1730 cm(-1) using principal component
analysis. The largest artifacts in the Raman spectra were found in measurements
performed under the influence of strong ambient light conditions as well as after
miscellaneous pre-treatments to the skin, such as use of a permanent marker or a
sunscreen. Minor influences were also found in measurements using H2O immersion
and when varying the probe contact force. The effect of reasonable variation of
the fiber-bending radius was found to be of negligible impact. The influence of
measurements on hairy or sun-exposed body sites, as well as inter-subject
variation, was also investigated. The presented results may serve as a guide to
avoid negative effects during the process of data acquisition and so avoid
misclassification in tumor discrimination.
PMID- 25588118
TI - Modeling nitrous oxide production and reduction in soil through explicit
representation of denitrification enzyme kinetics.
AB - An enzyme-explicit denitrification model with representations for pre- and de
novo synthesized enzymes was developed to improve predictions of nitrous oxide
(N2O) accumulations in soil and emissions from the surface. The metabolic model
of denitrification is based on dual-substrate utilization and Monod growth
kinetics. Enzyme synthesis/activation was incorporated into each sequential
reduction step of denitrification to regulate dynamics of the denitrifier
population and the active enzyme pool, which controlled the rate function.
Parameterizations were developed from observations of the dynamics of N2O
production and reduction in soil incubation experiments. The model successfully
reproduced the dynamics of N2O and N2 accumulation in the incubations and
revealed an important regulatory effect of denitrification enzyme kinetics on the
accumulation of denitrification products. Pre-synthesized denitrification enzymes
contributed 20, 13, 43, and 62% of N2O that accumulated in 48 h incubations of
soil collected from depths of 0-5, 5-10, 10-15, and 15-25 cm, respectively. An
enzyme activity function (E) was defined to estimate the relative concentration
of active enzymes and variation in response to environmental conditions. The
value of E allows for activities of pre-synthesized denitrification enzymes to be
differentiated from de novo synthesized enzymes. Incorporating explicit
representations of denitrification enzyme kinetics into biogeochemical models is
a promising approach for accurately simulating dynamics of the production and
reduction of N2O in soils.
PMID- 25588119
TI - Tree species composition affects the abundance of rowan (Sorbus aucuparia L.) in
urban forests in Finland.
AB - Recent studies have shown a considerable increase in the abundance of rowan
(Sorbus aucuparia) saplings in urban forests in Finland, yet the reasons for this
increase are not well understood. Here we investigated whether canopy cover or
tree species composition, i.e., the basal areas of different tree species in
Norway spruce dominated urban forests, affects the abundances of rowan seedlings,
saplings and trees. Altogether 24 urban forest patches were investigated. We
sampled the number of rowan and other saplings, and calculated the basal areas of
trees. We showed that rowan abundance was affected by tree species composition.
The basal area of rowan trees (>= 5 cm in diameter at breast height, dbh)
decreased with increasing basal area of Norway spruce, while the cover of rowan
seedlings increased with an increase in Norway spruce basal area. However, a
decrease in the abundance of birch (Betula pendula) and an increase in the broad
leaved tree group (Acer platanoides, Alnus glutinosa, Alnus incana, Amelanchier
spicata, Prunus padus, Quercus robur, Rhamnus frangula and Salix caprea)
coincided with a decreasing number of rowans. Furthermore, rowan saplings were
scarce in the vicinity of mature rowan trees. Although it seems that tree species
composition has an effect on rowan, the relationship between rowan saplings and
mature trees is complex, and therefore we conclude that regulating tree species
composition is not an easy way to keep rowan thickets under control in urban
forests in Finland.
PMID- 25588120
TI - Recovery of bulk proton magnetization and sensitivity enhancement in ultrafast
magic-angle spinning solid-state NMR.
AB - The sensitivity of solid-state NMR experiments is limited by the proton
magnetization recovery delay and by the duty cycle of the instrument. Ultrafast
magic-angle spinning (MAS) can improve the duty cycle by employing experiments
with low-power radio frequency (RF) irradiation which reduce RF heating. On the
other hand, schemes to reduce the magnetization recovery delay have been proposed
for low MAS rates, but the enhancements rely on selective transfers where the
bulk of the (1)H magnetization pool does not contribute to the transfer. We
demonstrate here that significant sensitivity enhancements for selective and
broadband experiments are obtained at ultrafast MAS by preservation and recovery
of bulk (1)H magnetization. We used [(13)C, (15)N]-labeled glutamine as a model
compound, spinning in a 1.3 mm rotor at a MAS frequency of 65 kHz. Using low
power (1)H RF (13.4 kHz), we obtain efficient (1)H spin locking and (1)H-(13)C
decoupling at ultrafast MAS. As a result, large amounts of (1)H magnetization,
from 35% to 42% of the initial polarization, are preserved after cross
polarization and decoupling. Restoring this magnetization to the longitudinal
axis using a flip-back pulse leads to an enhancement of the sensitivity, an
increase ranging from 14% to 21% in the maximal achievable sensitivity regime and
from 24% to 50% in the fast pulsing regime, and to a shortening of the optimal
recycling delay to 68% of its original duration. The analysis of the recovery and
sensitivity curves reveals that the sensitivity gains do not rely on a selective
transfer where few protons contribute but rather on careful conservation of bulk
(1)H magnetization. This makes our method compatible with broadband experiments
and uniformly labeled materials, in contrast to the enhancement schemes proposed
for low MAS. We tested seven different cross-polarization schemes and determined
that recovery of bulk (1)H magnetization is a general method for sensitivity
enhancement. The physical insight gained about the behavior of proton
magnetization sharing under spin lock will be helpful to break further
sensitivity boundaries, when even higher external magnetic fields and faster
spinning rates are employed.
PMID- 25588121
TI - Metabolic profiling of plant extracts using direct-injection electrospray
ionization mass spectrometry allows for high-throughput phenotypic
characterization according to genetic and environmental effects.
AB - In comparison to the exponential increase of genotyping methods, phenotyping
strategies are lagging behind in agricultural sciences. Genetic improvement
depends upon the abundance of quantitative phenotypic data and the statistical
partitioning of variance into environmental, genetic, and random effects. A
metabolic phenotyping strategy was adapted to increase sample throughput while
saving reagents, reducing cost, and simplifying data analysis. The chemical
profiles of stem extracts from maize plants grown under low nitrogen (LN) or
control trial (CT) were analyzed using optimized protocols for direct-injection
electrospray ionization mass spectrometry (DIESI-MS). Specific ions significantly
decreased or increased because of environmental (LN versus CT) or genotypic
effects. Biochemical profiling with DIESI-MS had a superior cost-benefit compared
to other standard analytical technologies (e.g., ultraviolet, near-infrared
reflectance spectroscopy, high-performance liquid chromatography, and gas
chromatography with flame ionization detection) routinely used for plant
breeding. The method can be successfully applied in maize, strawberry, coffee,
and other crop species.
PMID- 25588122
TI - Procedures for the Comparative Testing of Noninvasive Neuroassessment Devices.
AB - A sequential process for comparison testing of noninvasive neuroassessment
devices is presented. Comparison testing of devices in a clinical population
should be preceded by computational research and reliability testing with healthy
populations, as opposed to proceeding immediately to testing with clinical
participants. A five-step process is outlined as follows: 1. Complete a
preliminary literature review identifying candidate measures. 2. Conduct
systematic simulation studies to determine the computational properties and data
requirements of candidate measures. 3. Establish the test-retest reliability of
each measure in a healthy comparison population and the clinical population of
interest. 4. Investigate the clinical validity of reliable measures in
appropriately defined clinical populations. 5. Complete device usability
assessment (weight, simplicity of use, cost effectiveness, ruggedness) only for
devices and measures that are promising after steps 1 through 4 are completed.
Usability may be considered throughout the device evaluation process but such
considerations are subordinate to the higher priorities addressed in steps 1
through 4.
PMID- 25588124
TI - Modular and highly stereoselective approach to all-carbon tetrasubstituted
alkenes.
AB - A modular and completely stereoselective approach for the construction of all
carbon tetrasubstituted alkenes is described. It is based on the three-fold,
sequential metal-catalyzed, cross-coupling functionalization of simple
enolphosphate dibromide templates with carbon nucleophiles, affording
tetrasubstituted alkenes as single isomers.
PMID- 25588123
TI - Changes in drug coverage generosity and untreated serious mental illness:
transitioning from Medicaid to Medicare Part D.
AB - IMPORTANCE: More than 1 in 5 disabled people with dual Medicare-Medicaid
enrollment have schizophrenia or a bipolar disorder (ie, a serious mental
illness). The effect of their transition from Medicaid drug coverage, which
varies in generosity across states, to the Medicare Part D drug benefit is
unknown. Many thousands make this transition annually. OBJECTIVES: To determine
the effect of transitioning from Medicaid drug benefits to Medicare Part D on
medication use by patients with a serious mental illness and to determine the
influence of Medicaid drug caps. DESIGN, SETTING, AND PARTICIPANTS: In time
series analysis of continuously enrolled patient cohorts (2004-2007), we
estimated changes in medication use before and after transitioning to Part D,
comparing states that capped monthly prescription fills with states with no
prescription limits. We used Medicaid and Medicare claims from a 5% national
sample of community-dwelling, nonelderly disabled dual enrollees with
schizophrenia (n = 5554) or bipolar disorder (n = 3675). MAIN OUTCOMES AND
MEASURES: Psychotropic treatments included antipsychotics for schizophrenia and
antipsychotics, anticonvulsants, and lithium for bipolar disorder. We measured
monthly rates of untreated illness, intensity of treatment, and overall
prescription medication use. RESULTS: Prior to Part D, the prevalence of
untreated illness among patients with a bipolar disorder was 30.0% in strict-cap
states and 23.8% in no-cap states. In strict-cap states, the proportion of
untreated patients decreased by 17.2% (relatively) 1 year after Part D, whereas
there was no change in the proportion of untreated patients in no-cap states. For
patients with schizophrenia, the untreated rate (20.6%) did not change in strict
cap states, yet it increased by 23.3% (from 11.6%) in no-cap states. Overall
medication use increased substantially after Part D in strict-cap states:
prescription fills were 35.5% higher among patients with a bipolar disorder and
17.7% higher than predicted among schizophrenic patients; overall use in no-cap
states was unchanged in both cohorts. CONCLUSIONS AND RELEVANCE: The effects of
transitioning from Medicaid to Medicare Part D on essential treatment of serious
mental illness vary by state. Transition to Part D in states with strict drug
benefit limits may reduce rates of untreated illness among patients with bipolar
disorders, who have high levels of overall medication use. Access to
antipsychotic treatment may decrease after Part D for patients with a serious
mental illness living in states with relatively generous uncapped Medicaid
coverage.
PMID- 25588125
TI - Emergence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii ST2
Clinical Isolate in Algeria: First Case Report.
AB - AIM: The aim of this study was to investigate the prevalence and the mechanisms
of carbapenem and colistin resistance in Acinetobacter baumannii clinical
isolates in an Algerian hospital. RESULTS: Twelve isolates were collected between
October 2013 and March 2014. All isolates were resistant to almost all
antibiotics tested with a high-level resistance to imipenem (minimum inhibitory
concentrations [MICs] >32 mg/L) with one strain showing resistance to colistin
(MIC=16 mg/L). The results of the modified Hodge test and the modified Carba NP
test were positive for all isolates. Besides, the activity of beta-lactamases was
inhibited by EDTA in only two isolates. All the 12 isolates contained the
naturally occurring blaOXA-51-like gene. Ten of them harbored the OXA beta
lactamases: blaOXA-23 (six isolates) and blaOXA-24 (four isolates) genes, while
two isolates were positive for blaNDM-1 gene. The colistin-resistant isolate
producing OXA-24 enzyme harbored a single mutation in the pmrB gene. Multilocus
sequence typing demonstrated that the 12 isolates belonged to 2 clones: 10 to ST2
and 2 to ST85. CONCLUSIONS: Here, we describe the mechanisms of carbapenem
resistance and we report the first colistin and carbapenemase-producing A.
baumannii clinical isolate from a patient in Algeria.
PMID- 25588127
TI - Copper(I)-catalyzed regioselective amination of N-aryl imines using TMSN3 and
TBHP: a route to substituted benzimidazoles.
AB - A novel and efficient copper-catalyzed amination of N-aryl imines is described.
This one-pot, multicomponent reaction, in which imine acts as a directing group
by chelating to the metal center, affords a potential route for the
transformation of the commercial aryl amines, aldehydes, and azides into valuable
benzimidazole structural units with wide substrate scope and diversity. The
synthetic and mechanistic aspects are presented.
PMID- 25588126
TI - Fabrication and characterization of the nano-composite of whey protein
hydrolysate chelated with calcium.
AB - The nano-composites of whey protein hydrolysate (WPH) chelated with calcium were
fabricated in aqueous solution at 30 degrees C for 20 min, with the ratio of
hydrolysate to calcium 15 : 1 (w/w). UV scanning spectroscopy, fluorescent
spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering
and atomic force microscopy were applied to characterize the structure of the WPH
calcium chelate. The nano-composites showed the successful incorporation of
calcium into the WPH, indicating the interaction between calcium and WPH. The
chelation of calcium ions to WPH caused molecular folding and aggregation which
led to the formation of a WPH-calcium chelate of nanoparticle size, and the
principal sites of calcium-binding corresponded to the carboxyl groups and
carbonyl groups of WPH. The WPH-calcium chelate demonstrated excellent stability
and absorbability under both acidic and basic conditions, which was beneficial
for calcium absorption in the gastrointestinal tract of the human body. Moreover,
the calcium absorption of the WPH-calcium chelate on Caco-2 cells was
significantly higher than those of calcium gluconate and CaCl2 in vitro,
suggesting the possible increase in calcium bioavailability. The findings suggest
that the WPH-calcium chelate has the potential in making dietary supplements for
improving bone health of the human body.
PMID- 25588128
TI - Membrane bioreactor wastewater treatment plants reveal diverse yeast and protist
communities of potential significance in biofouling.
AB - The yeast community was studied in a municipal full-scale membrane bioreactor
wastewater treatment plant (MBR-WWTP). The unexpectedly high diversity of yeasts
indicated that the activated sludge formed a suitable environment for them to
proliferate, with cellular concentrations of 2.2 +/- 0.8 * 10(3) CFU ml(-1).
Sixteen species of seven genera were present in the biological reactor, with
Ascomycetes being the most prevalent group (93%). Most isolates were able to grow
in a synthetic wastewater medium, adhere to polyethylene surfaces, and develop
biofilms of variable complexity. The relationship between yeast populations and
the protists in the MBR-WWTP was also studied, revealing that some protist
species preyed on and ingested yeasts. These results suggest that yeast
populations may play a role in the food web of a WWTP and, to some extent,
contribute to membrane biofouling in MBR systems.
PMID- 25588129
TI - Efficient approach to improving the flame retardancy of poly(vinyl alcohol)/clay
aerogels: incorporating piperazine-modified ammonium polyphosphate.
AB - Ammonium polyphosphates (APP) modified with piperazine (PA-APP) was used to
improve the flame retardancy of poly(vinyl alcohol) (PVA)/montmorillonite (MMT)
aerogels, which were prepared via an environmentally friendly freeze-drying
method. The thermal stabilities of the samples were evaluated by
thermogravimetric analysis (TG); the flammability behaviors of samples were
investigated by limiting oxygen index (LOI), vertical burning test (UL-94) and
cone calorimeter (CC) tests. TG test results showed that the 5% weight loss
temperature (T5%) of PVA/MMT/PA-APP was 10 degrees C higher than that of
PVA/MMT/APP. In combustion testing, all of PVA/MMT/PA-APP aerogels achieved V-0
ratings and have a higher LOI values than the unmodified PVA/MMT aerogel.
Moreover, the aerogel with 1% PA-APP5, which means that the content of piperazine
is 5% in PA-APP, decreased the cone calorimetry THR value to 5.71 MJ/m(2), and
increased the char residue to 52%. The compressive modulus of PVA/MMT/PA-APP was
increased by 93.4% compared with PVA/MMT/APP because of the increase in
interfacial adhesion between matrix and PA-APP fillers. The densities of the
PVA/MMT/PA-APP samples were slightly lower than those of the unmodified aerogels
because of reduced shrinkage in the presence of PA-APP. All the tests results
indicated that the incorporation of PA-APP not only improved the thermal
stability and flame retardancy of aerogels but also maintained their mechanical
properties.
PMID- 25588132
TI - Introducing the medical care blog.
PMID- 25588131
TI - Fatty acid hydrolysis of acyl marinobactin siderophores by Marinobacter acylases.
AB - The marine bacteria Marinobacter sp. DS40M6 and Marinobacter nanhaiticus D15-8W
produce a suite of acyl peptidic marinobactin siderophores to acquire iron under
iron-limiting conditions. During late-log phase growth, the marinobactins are
hydrolyzed to form the marinobactin headgroup with release of the corresponding
fatty acid tail. The bntA gene, a homologue of the Pseudomonas aeruginosa
pyoverdine acylase gene, pvdQ, was identified from Marinobacter sp. DS40M6. A
bntA knockout mutant of Marinobacter sp. DS40M6 produced the suite of acyl
marinobactins A-E, without the usual formation of the marinobactin headgroup.
Another marinobactin-producing species, M. nanhaiticus D15-8W, is predicted to
have two pvdQ homologues, mhtA and mhtB. MhtA and MhtB have 67% identical amino
acid sequences. MhtA catalyzes hydrolysis of the apo-marinobactin siderophores as
well as the quorum sensing signaling molecule, dodecanoyl-homoserine lactone. In
contrast to hydrolysis of the suite of apo-marinobactins by MhtA, hydrolysis of
the iron(III)-bound marinobactins was not observed.
PMID- 25588130
TI - Effect of supplementation of water-soluble vitamins on oxidative stress and blood
pressure in prehypertensives.
AB - The objective of the study was to evaluate the effect of water-soluble vitamins
on oxidative stress and blood pressure in prehypertensives. Sixty
prehypertensives were recruited and randomized into 2 groups of 30 each. One
group received water-soluble vitamins and the other placebo for 4 months. Further
increase in blood pressure was not observed in the vitamin group which increased
significantly in the placebo group at the end of 4 months. Malonedialdehyde and
protein carbonylation were reduced during the course of treatment with vitamins
whereas in the placebo group there was an increase in the level of
malondialdehyde. In conclusion, supplementation of water-soluble vitamins in
prehypertension reduces oxidative stress and its progression to hypertension.
PMID- 25588133
TI - The cost-effectiveness of pay-for-performance: a multidimensional approach to
analysis.
PMID- 25588134
TI - How effective is health coaching in reducing health services expenditures?
AB - BACKGROUND: Health coaching interventions aim to identify high-risk enrollees and
encourage them to play a more proactive role in improving their health, improve
their ability to navigate the health care system, and reduce costs. OBJECTIVES:
Evaluate the effect of health coaching on inpatient, emergency room, outpatient,
and prescription drug expenditures. RESEARCH DESIGN: Quasiexperimental pre-post
design. Health coaching participants were identified over the 2-year time period
2009-2010. Propensity scores facilitated matching eligible participants and
nonparticipating controls on a one-to-one basis using nearest kernel techniques.
Difference in differences logistic and generalized linear models addressed the
impact of health coaching on the probability of incurring costs and levels of
inpatient, emergency room, outpatient, and prescription drug expenditures,
respectively. MEASURES: Administrative claims data were used to analyze health
services expenditures preparticipation and post health coaching participation
time periods. RESULTS: Of the 6940 health coaching participants, 1161
participated for at least 4 weeks and had a minimum of 6 months of claims data
preparticipation and postparticipation. Although the probability of incurring
costs and expenditure levels for emergency room services were not affected, the
probability of incurring inpatient expenditures and levels of outpatient and
total costs for health coaching participants fell significantly from
preparticipation to postparticipation relative to controls. Estimated outpatient
and total cost savings were $286 and $412 per person per month, respectively.
CONCLUSIONS: Health coaching led to significant reductions in outpatient and
total expenditures for high-risk plan enrollees. Future studies analyzing both
health outcomes and claims data are needed to assess the cost-effectiveness of
health coaching in specific populations.
PMID- 25588136
TI - A systematic review of intervention studies to prevent hospitalizations of
community-dwelling older adults with dementia.
AB - OBJECTIVES: To conduct a systematic literature review to determine if there were
any intervention strategies that had any measurable effect on acute-care
hospitalizations among community-dwelling adults with dementia. DESIGN: Studies
were identified by a professional research librarian and content experts.
SETTING: Community dwelling. PARTICIPANTS: Participants were diagnosed with
dementia, severity ranging from mild to severe, and were recruited from health
care and community agencies. MEASUREMENTS: A study met the inclusion criteria if
it: (a) was published in English; (b) included a control or comparison group; (c)
published outcome data from the intervention under study; (d) reported
hospitalization as one of the outcomes; (e) included community-dwelling older
adults; and (f) enrolled participants with dementia. Ten studies met all
inclusion criteria. RESULTS: Of the 10 studies included, most assessed health
services use (ie, hospitalizations) as a secondary outcome. Participants were
recruited from a range of health care and community agencies, and most were
diagnosed with dementia with severity ratings ranging from mild to severe. Most
intervention strategies consisted of face-to-face assessments of the persons
living with dementia, their caregivers, and the development and implementation of
a care plan. A significant reduction in hospital admissions was not found in any
of the included studies, although 1 study did observe a reduction in hospital
days. CONCLUSIONS: The majority of studies included hospitalizations as a
secondary outcome. Only 1 intervention was found to have an effect on
hospitalizations. Future work would benefit from strategies specifically designed
to reduce and prevent acute hospitalizations in persons with dementia.
PMID- 25588135
TI - The role of technical advances in the adoption and integration of patient
reported outcomes in clinical care.
AB - BACKGROUND: Patient-reported outcomes (PROs) are gaining recognition as key
measures for improving the quality of patient care in clinical care settings.
Three factors have made the implementation of PROs in clinical care more
feasible: increased use of modern measurement methods in PRO design and
validation, rapid progression of technology (eg, touchscreen tablets, Internet
accessibility, and electronic health records), and greater demand for measurement
and monitoring of PROs by regulators, payers, accreditors, and professional
organizations. As electronic PRO collection and reporting capabilities have
improved, the challenges of collecting PRO data have changed. OBJECTIVES: To
update information on PRO adoption considerations in clinical care, highlighting
electronic and technical advances with respect to measure selection, clinical
workflow, data infrastructure, and outcomes reporting. METHODS: Five practical
case studies across diverse health care settings and patient populations are used
to explore how implementation barriers were addressed to promote the successful
integration of PRO collection into the clinical workflow. The case studies
address selecting and reporting of relevant content, workflow integration,
previsit screening, effective evaluation, and electronic health record
integration. CONCLUSIONS: These case studies exemplify elements of well-designed
electronic systems, including response automation, tailoring of item selection
and reporting algorithms, flexibility of collection location, and integration
with patient health care data elements. They also highlight emerging logistical
barriers in this area, such as the need for specialized technological and
methodological expertise, and design limitations of current electronic data
capture systems.
PMID- 25588138
TI - Cesarean 10-group classification: a tool for clinical management of the delivery
ward.
AB - AIM: Aim of the present study was to evaluate 10-group Robson classification for
delivery ward clinical management. METHODS: To evaluate cesarean section (C
section) rate following the implementation firstly of recommendations, and then
of 10-group reporting and medical audit, a retrospective cohort study was
performed including all women who gave birth in the years 2001, 2006 and 2010.
Data were analyzed by means of 10-group classification. RESULTS: C-section rate
was 27.5% in 2001, 31.1% in 2006, and 30.5% in 2010. Ten-group analysis showed
that from 2001 to 2006 group 1-2 size increased from 27.6% to 42.5% (P<0.01), and
contribution to the overall cesarean rate from 22.3% to 29.9% (P<0.01), whereas
the group 1 C-section sub-rate was reduced from 19.6% to 13.5% (P<0.05). Previous
cesarean increased from 9.2% to 11.6% (P<0.05). Delivery ward 10-group monitoring
showed that from January to May 2010 the C-section rate was consistently above
30%. The audit was started and the causes were analyzed. Subsequently, C-section
rate dropped to the actual 30.5%. CONCLUSION: Ten-group analysis showed that the
2006 cesarean rate increase was related to a significant shift in obstetric
population toward groups 5 to 9 at higher risk of C-section, whereas after
recommendation implementation a significant reduction of C-section subrates was
observed in groups 1, 2a, 3, 4a, and 10 which represented more than 80% of the
hospital population. In 2010, 10-group monitoring of the cesarean subrates
stabilized the C-section rate. Ten-group analysis should be implemented in
clinical practice to control delivery ward clinical management. It only requires
the involvement of a clinical manager and of a midwife for data collection.
PMID- 25588137
TI - Increasing BCI communication rates with dynamic stopping towards more practical
use: an ALS study.
AB - OBJECTIVE: The P300 speller is a brain-computer interface (BCI) that can possibly
restore communication abilities to individuals with severe neuromuscular
disabilities, such as amyotrophic lateral sclerosis (ALS), by exploiting elicited
brain signals in electroencephalography (EEG) data. However, accurate spelling
with BCIs is slow due to the need to average data over multiple trials to
increase the signal-to-noise ratio (SNR) of the elicited brain signals.
Probabilistic approaches to dynamically control data collection have shown
improved performance in non-disabled populations; however, validation of these
approaches in a target BCI user population has not occurred. APPROACH: We have
developed a data-driven algorithm for the P300 speller based on Bayesian
inference that improves spelling time by adaptively selecting the number of
trials based on the acute SNR of a user's EEG data. We further enhanced the
algorithm by incorporating information about the user's language. In this current
study, we test and validate the algorithms online in a target BCI user
population, by comparing the performance of the dynamic stopping (DS) (or early
stopping) algorithms against the current state-of-the-art method, static data
collection, where the amount of data collected is fixed prior to online
operation. MAIN RESULTS: Results from online testing of the DS algorithms in
participants with ALS demonstrate a significant increase in communication rate as
measured in bits/min (100-300%), and theoretical bit rate (100-550%), while
maintaining selection accuracy. Participants also overwhelmingly preferred the DS
algorithms. SIGNIFICANCE: We have developed a viable BCI algorithm that has been
tested in a target BCI population which has the potential for translation to
improve BCI speller performance towards more practical use for communication.
PMID- 25588139
TI - Integrating the pathogenesis of spondyloarthritis: gut and joint united?
AB - PURPOSE OF REVIEW: The association between spondyloarthritis (SpA) and
inflammatory bowel disease (IBD) is well known. Additionally, about half of SpA
patients show microscopic gut inflammation. Substantial progress has been made in
understanding the pathogenesis of SpA and IBD, with new therapeutic targets for
either of them in clinical development. RECENT FINDINGS: Microscopic gut
inflammation was found in early forms of SpA in about 50% of cases and is
associated with age, sex, disease activity and degree of MRI inflammation on
sacroiliac joints. Although prospective follow-up data in men and murine animal
studies show a parallelism between gut and joint evolution in SpA, therapeutic
outcomes are not always the same in SpA and IBD. These differences can be
ascribed to differences in not only the cytokine pathways and cells involved in
disease, tissue localization and environmental factors but also in
pharmacokinetics and biodistribution. SUMMARY: A significant amount of data all
point in the direction of arthritis and gut inflammation being pathogenetically
closely linked in the SpA concept. However, when it comes to therapeutic
effectiveness, the gut and the joints do not always react in the same way. These
differences in therapeutic effect could be attributed to the different ways in
which cytokine pathways are involved in SpA and IBD.
PMID- 25588141
TI - Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in
vascular medicine.
AB - Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality
that complements and enhances standard vascular ultrasound imaging. Ultrasound
contrast agents are gas-filled microbubbles that are injected intravenously and
serve as intravascular tracers. Based on the properties to enhance and to
quantify the macro- and microcirculation down to the capillary perfusion level in
different vascular territories and organs, CEUS imaging has the potential to
improve the diagnostic performance in the detection and characterisation of
various vascular disorders reviewed in this article. In carotid atherosclerotic
disease, CEUS imaging provides additional information on plaque vulnerability by
illustrating the presence and extent of intraplaque neovascularisation. This new
imaging modality may be helpful for further risk stratification of
arteriosclerotic lesions and for detecting patients at risk for vascular events,
eventually leading to more specific individually tailored therapeutic
recommendations. CEUS imaging is also a helpful tool for the diagnosis and for
monitoring of inflammatory vascular diseases. It increases the diagnostic
performance of ultrasound in detecting inflammatory changes of the vessel wall
such as hypervascularisation and hyperaemia. Changes in vessel wall enhancement
may also reflect the response to anti-inflammatory therapy. Moreover, CEUS
imaging is also a valuable tool for the assessment of the microcirculation and
the tissue perfusion in solid organs including native and transplanted kidneys.
The technique provides more accurate information on perfusion deficits of the
parenchyma in patients with kidney infarction, necrosis or graft dysfunction.
CEUS also has great potential in the assessment of the microcirculation of the
skeletal muscle, particularly in patients with peripheral artery disease or
diabetic microangiopathy. In the future, the use of targeted on site microbubbles
could further enhance and expand the diagnostic capabilities of current vascular
ultrasound by assessing specific molecular processes that play a role in the
pathophysiology of vascular diseases. Furthermore, ultrasound-directed, site
specific drug and gene delivery using microbubble contrast agents could gain
great clinical value in the future. The combination of CEUS for diagnosis and
therapy will provide unique opportunities for vascular clinicians to image the
microcirculation and directly treat vascular diseases.
PMID- 25588140
TI - Guanidinium-rich, glycerol-derived oligocarbonates: a new class of cell
penetrating molecular transporters that complex, deliver, and release siRNA.
AB - A highly versatile and step-economical route to a new class of guanidinium-rich
molecular transporters and evaluation of their ability to complex, deliver, and
release siRNA are described. These new drug/probe delivery systems are prepared
in only two steps, irrespective of length or composition, using an
organocatalytic ring-opening co-oligomerization of glycerol-derived cyclic
carbonate monomers incorporating either protected guanidine or lipid side chains.
The resultant amphipathic co-oligomers are highly effective vehicles for siRNA
delivery, providing an excellent level of target protein suppression (>85%).
These new oligocarbonates are nontoxic at levels required for cell penetration
and can be tuned for particle size. Relative to the previously reported
methyl(trimethylene)carbonate (MTC) scaffold, the ether linkage at C2 in the new
transporters markedly enhances the stability of the siRNA/co-oligomer complexes.
Both hybrid co-oligomers, containing a mixture of glycerol- and MTC-derived
monomers, and co-oligomers containing only glycerol monomers are found to provide
tunable control over siRNA complex stability. On the basis of a glycerol and CO2
backbone, these new co-oligomers represent a rapidly tunable and biocompatible
siRNA delivery system that is highly effective in suppressing target protein
synthesis.
PMID- 25588142
TI - Synthetic peptides reproducing tissue transglutaminase-gliadin complex neo
epitopes as probes for antibody detection in celiac disease patients' sera.
AB - Celiac disease (CD) patients usually present high levels of circulating IgA
antibodies directed to different antigens, in particular tissue transglutaminase
(tTG), gliadin (Glia), and endomysium. A series of synthetic peptide constructs
containing cross-linked tTG and Glia deamidated peptides have been synthesized.
Peptides were tested in enzyme-linked immunosorbent assays against celiac disease
patients' sera versus normal blood donors, and their conformational features were
evaluated by molecular modeling techniques. Four peptides were recognized as
epitopes by autoantibodies (IgG class) circulating in CD patients' sera before
gluten-free diet. The peptide II, containing Ac-tTG(553-564)-NH2 sequence cross
linked with deamidated Ac-alpha2-Glia(63-71)-NH2, was able to identify specific
disease antibodies with a sensitivity of 50% and a specificity of 94.4%.
Structural conformations of the linear fragments Ac-tTG(553-564)-NH2 and Ac
alpha2-Glia(63-71)-NH2 and the corresponding cross-linked peptide II were
calculated by molecular modeling. Results showed that cross-linking is
determinant to assume conformations, which are not accessible to the linear
fragments.
PMID- 25588145
TI - Determining pH at elevated pressure and temperature using in situ 13C NMR.
AB - We have developed an approach for determining pH at elevated pressures and
temperatures by using (13)C NMR measurements of inorganic carbon species together
with a geochemical equilibrium model. The approach can determine in situ pH with
precision better than 0.1 pH units at pressures, temperatures, and ionic
strengths typical of geologic carbon sequestration systems. A custom-built high
pressure NMR probe was used to collect (13)C NMR spectra of (13)C-labeled CO2
reactions with NaOH solutions and Mg(OH)2 suspensions at pressures up to 107 bar
and temperatures of 80 degrees C. The quantitative nature of NMR spectroscopy
allows the concentration ratio [CO2]/[HCO3(-)] to be experimentally determined.
This ratio is then used with equilibrium constants calculated for the specific
pressure and temperature conditions and appropriate activity coefficients for the
solutes to calculate the in situ pH. The experimentally determined [CO2]/[HCO3(
)] ratios agree well with the predicted values for experiments performed with
three different concentrations of NaOH and equilibration with multiple pressures
of CO2. The approach was then applied to experiments with Mg(OH)2 slurries in
which the change in pH could track the dissolution of CO2 into solution, rapid
initial Mg(OH)2 dissolution, and onset of magnesium carbonate precipitation.
PMID- 25588144
TI - Structural vulnerabilities to HIV/STI risk among female exotic dancers in
Baltimore, Maryland.
AB - Female exotic dancers (FEDs) are an important, yet understudied group of women
who may engage in drug- and sex-related HIV/STI risk behaviors through their
work. The study objective was to identify co-occurring indicators of
vulnerability (e.g., housing, income, incarceration) associated with HIV/STI risk
behavior among FEDs in Baltimore, Maryland. Surveys administered during July 2008
February 2009 captured socio-demographic characteristics, drug use, and sexual
practices among dancers (N = 101) aged >=18 years. Multivariate logistic
regression was used to assess the relationship between vulnerability and risk
behavior. Dancers with a high vulnerability score (i.e., 2 or more indicators)
were more likely to report sex exchange (AOR: 10.7, 95% CIs: 2.9, 39.9) and
multiple sex partnerships (AOR: 6.4, 95% CIs: 2.3, 18.3), controlling for
demographics and drug use, compared to their less vulnerable counterparts.
Findings point to primacy of macro-level factors that need to be addressed in
HIV/STI prevention efforts targeting this and other high-risk populations.
PMID- 25588146
TI - Multiple orbital effects and magnetic ordering in a neutral radical.
AB - The alternating ABABAB pi-stacked architecture of the EtCN solvate of the iodo
substituted, oxobenzene-bridged bisdithiazolyl radical IBBO (space group Pnma)
gives rise to strong ferromagnetic exchange along the pi-stacks, and the material
orders as a spin-canted antiferromagnet with T(N) = 35 K, with a spontaneous
(canted) moment M(spont) = 1.4 * 10(-3) MUB and a coercive field H(c) = 1060 Oe
(at 2 K). The observation of spin-canting can only be understood in terms of
multiorbital contributions to both isotropic and anisotropic exchange
interactions, the magnitude of which are enhanced by spin-orbit effects arising
from the heavy-atom iodine substituent. Pseudodipolar interactions lead to a net
canted moment along the c-axis, while the sublattice magnetization is predicted
to possess an easy a-axis.
PMID- 25588147
TI - A Raman spectroscopic study of cell response to clinical doses of ionizing
radiation.
AB - The drive toward personalized radiation therapy (RT) has created significant
interest in determining patient-specific tumor and normal tissue responses to
radiation. Raman spectroscopy (RS) is a non-invasive and label-free technique
that can detect radiation response through assessment of radiation-induced
biochemical changes in tumor cells. In the current study, single-cell RS
identified specific radiation-induced responses in four human epithelial tumor
cell lines: lung (H460), breast (MCF-7, MDA-MB-231), and prostate (LNCaP),
following exposure to clinical doses of radiation (2-10 Gy). At low radiation
doses (2 Gy), H460 and MCF-7 cell lines showed an increase in glycogen-related
spectral features, and the LNCaP cell line showed a membrane phospholipid-related
radiation response. In these cell lines, only spectral information from
populations receiving 10 Gy or less was required to identify radiation-related
features using principal component analysis (PCA). In contrast, the MDA-MB-231
cell line showed a significant increase in protein relative to nucleic acid and
lipid spectral features at doses of 6 Gy or higher, and high-dose information
(30, 50 Gy) was required for PCA to identify this biological response. The
biochemical nature of the radiation-related changes occurring in cells exposed to
clinical doses was found to segregate by status of p53 and radiation sensitivity.
Furthermore, the utility of RS to identify a biological response in human tumor
cells exposed to therapeutic doses of radiation was found to be governed by the
extent of the biochemical changes induced by a radiation response and is
therefore cell line specific. The results of this study demonstrate the utility
and effectiveness of single-cell RS to identify and measure biological responses
in tumor cells exposed to standard radiotherapy doses.
PMID- 25588148
TI - Antioxidant activity and mechanism of the abietane-type diterpene ferruginol.
AB - The antioxidant activity of the abietane-type diterpene ferruginol was evaluated
by comparison with that of carnosic acid, ( +/- )-alpha-tocopherol and
dibutylhydroxytoluene using 2,2-diphenyl-1-picrylhydrazyl, beta-carotene
bleaching and linoleic acid assays. Ferruginol had the lowest antioxidant
activity of this group using the 2,2-diphenyl-1-picrylhydrazyl and beta-carotene
methods in polar solvent buffer. However, ferruginol exhibited stronger activity
than carnosic acid and alpha-tocopherol for linoleic acid oxidation under non
solvent conditions. Five peaks corresponding to ferruginol derivatives were
detected through GC-MS analysis of the reaction between ferruginol and methyl
linoleate. The three reaction products were identified as dehydroferruginol,
7beta-hydroxyferruginol and sugiol, and the other two peaks were assumed to be
7alpha-hydroxyferruginol and the quinone methide derivative of ferruginol. The
time course of the reaction suggests that the quinone methide was produced early
in the reaction and reacted further to produce dehydroferruginol, 7
hydroxyferruginol and sugiol. Thus, we inferred that quinone methide formation
was a key step in the antioxidant reaction of ferruginol.
PMID- 25588150
TI - Are two hands sensing the load better than one?
PMID- 25588151
TI - Enhancing ion yields in time-of-flight-secondary ion mass spectrometry: a
comparative study of argon and water cluster primary beams.
AB - Following from our previous Letter on this topic, this Article reports a detailed
study of time-of-flight-secondary ion mass spectrometry (TOF-SIMS) positive ion
spectra generated from a set of model biocompounds (arginine, trehalose, DPPC,
and angiotensin II) by water cluster primary ion beams in comparison to argon
cluster beams over a range of cluster sizes and energies. Sputter yield studies
using argon and water beams on arginine and Irganox 1010 have confirmed that the
sputter yields using water cluster beams lie on the same universal sputtering
curve derived by Seah for argon cluster beams. Thus, increased ion yield using
water cluster beams must arise from increased ionization. The spectra and
positive ion signals observed using cluster beams in the size range from 1,000 to
10,000 and the energy range 5-20 keV are reported. It is confirmed that water
cluster beams enhance proton related ionization over against argon beams to a
significant degree such that enhanced detection sensitivities from 1 MUm(2) in
the region of 100 to 1,000 times relative to static SIMS analysis with Ar2000
cluster beams appear to be accessible. These new studies show that there is an
unexpected complexity in the ionization enhancement phenomenon. Whereas optimum
ion yields under argon cluster bombardment occur in the region of E/n >= 10 eV
(where E is the beam energy and n the number of argon atoms in the cluster) and
fall rapidly when E/n < 10 eV; for water cluster beams, ion yields increase
significantly in this E/n regime (where n is the number of water molecules in the
cluster) and peak for 20 keV beams at a cluster size of 7,000 or E/n ~3 eV. This
important result is explored further using D2O cluster beams that confirm that in
this low E/n regime protonation does originate to a large extent from the water
molecules. The results, encouraging in themselves, suggest that for both argon
and water cluster beams, higher energy beams, e.g., 40 and 80 keV, would enable
larger cluster sizes to be exploited with significant benefit for ion yield and
hence analytical capability.
PMID- 25588149
TI - c-Jun gene-modified Schwann cells: upregulating multiple neurotrophic factors and
promoting neurite outgrowth.
AB - Genetically modified Schwann cells (SCs) that overexpress neurotrophic factors
(NFs), especially those that overexpress multiple NFs, hold great potential for
promoting nerve regeneration. Currently, only one NF can be upregulated in most
genetically modified SCs, and simultaneously upregulating multiple NFs in SCs
remains challenging. In this study, we found that the overexpression of c-Jun, a
component of the AP-1 transcription factor, effectively upregulated the
expression and secretion of multiple NFs, including glial cell line-derived
neurotrophic factor, brain-derived neurotrophic factor, artemin, leukemia
inhibitory factor, and nerve growth factor. The c-Jun gene-modified SCs showed a
normal morphology in scanning electron microscopy and fluorescent staining
analysis. In addition, the c-Jun-modified SCs showed enhanced proliferation and
migration abilities compared with vector control cells. We used transwell
chambers to establish coculture systems imitating the in vivo conditions in which
transplanted SCs might influence native SCs and neurons. We found that the c-Jun
modified SCs enhanced native SC migration and promoted the proliferation of
native SCs in the presence of axons. Further analysis revealed that in the c-Jun
group, the average length and the total area of neurites divided by the total
area of the explant body were MUm 1180+/-25 and 6.4+/-0.4, respectively, which
were significantly greater compared with the other groups. These findings raise
the possibility of constructing an optimal therapeutic alternative for nerve
repair using c-Jun-modified SCs, which have the potential to promote axonal
regeneration and functional recovery by upregulating multiple NFs. In addition,
these cells exhibit enhanced migration and proliferation abilities, enhance the
biological functions of native SCs, and promote neurite outgrowth.
PMID- 25588152
TI - BRAFV600E protein expression in primary cutaneous malignant melanomas and paired
metastases.
AB - IMPORTANCE: BRAFV600E mutations are present in approximately 50% of cutaneous
malignant melanomas (CMMs). The use of BRAFV600E mutation-specific monoclonal
antibody VE1 immunohistochemical analysis may facilitate rapid detection of
BRAFV600E mutations in CMMs and demonstrate heterogeneity among tumors.
OBJECTIVES: To characterize the pattern of BRAFV600E protein expression in
primary CMMs with matched metastases and to analyze the use of VE1
immunohistochemical analysis in clinical practice using formalin-fixed, paraffin
embedded tumor tissue. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective
cohort study performed at Karolinska University Hospital from September 2012 to
September 2013, we examined CMMs (124 primary tumors and 76 metastases) with VE1
immunohistochemical analysis, and results were compared with DNA mutation
analyses. MAIN OUTCOMES AND MEASURES: Determination of intratumoral and
intertumoral heterogeneity as well as the sensitivity and specificity of VE1
immunohistochemical analysis. RESULTS: Positive staining results with the VE1
antibody were detected in 94 of 200 tumors (47.0%). In general, VE1 staining was
homogeneous. However, VE1 staining intensity varied among the primary tumors and
corresponding metastases in 63 of 135 tumors (46.7%), but a change of mutational
status based on DNA analysis was found in only 4 matched tumors (3.0%).
Discordant findings between DNA mutation analysis and immunohistochemical
analysis were observed in 12 tumors. The overall sensitivity and specificity of
VE1 immunohistochemical analysis were 96.7% and 94.5%, respectively. A comparable
sensitivity was obtained for primary and metastatic CMMs. The specificity was
lower among primary CMMs (92.4%) compared with metastases (98.0%). CONCLUSIONS
AND RELEVANCE: We found VE1 immunohistochemical analysis to be a useful and rapid
assay for BRAFV600E mutations that may contribute to the detection of
intratumoral and intertumoral heterogenetic subclones. Tumors with positive
results, including strong staining, should be expedited for confirmatory BRAF
mutation testing. If this test result is negative, a false-negative result of the
mutation analysis should be considered. Validation of VE1 immunohistochemical
analysis in clinical practice is needed.
PMID- 25588153
TI - Depression CBT treatment gains among HIV-infected persons with a history of
injection drug use varies as a function of baseline substance use.
AB - Depression and substance use, the most common comorbidities with HIV, are both
associated with poor treatment outcomes and accelerated HIV disease progression.
Though previous research has demonstrated short-term and follow-up success for
cognitive behavioral therapy for adherence and depression (CBT-AD) on depression
outcomes among patients with HIV in care and among patients with HIV in active
substance abuse treatment for injection drug use (IDU), there is little
information regarding possible moderating effects of active use versus abstinence
on depression treatment gains. The present study aimed to examine recent
substance use at treatment initiation as a moderator of the acute and maintenance
effects of CBT-AD on depression. We used data from a two-arm, randomized
controlled trial (N = 89) comparing CBT-AD to enhanced treatment as usual in
individuals in treatment for IDU. To test whether depression at time of
presentation affected outcomes, repeated-measures ANOVAs were conducted for two
time frames: (1) acute phase (baseline to post-treatment) (acute) and (2)
maintenance phase (baseline to 12-month follow-up). To further examine
maintenance of gains, we additionally looked at post-treatment to 12-month follow
up. Depression scores derived from the clinical global impression for severity
and the Montgomery-Asberg depression rating scale (MADRS) served as the primary
outcome variables. Acute (baseline post treatment) moderation effects were found
for those patients endorsing active drug use at baseline in the CBT-AD condition,
who demonstrated the greatest reductions in MADRS scores at post-treatment
(F[1,76] = 6.78, p = .01) and follow-up (F[1,61] = 5.46, p = .023). Baseline
substance use did not moderate differences from post-treatment to 12-month follow
up as depression treatment gains that occurred acutely from baseline to post
treatment were maintained across both patients engaged in substance use and
abstainers. We conclude that CBT-AD for triply diagnosed patients (i.e. HIV,
depression, and substance dependence) is useful for treating depression for both
patients with a history of substance use, as well as patients currently engaged
in substance use.
PMID- 25588154
TI - Health risk assessment for exposure to benzene in petroleum refinery
environments.
AB - The health risk resulting from benzene exposure in petroleum refineries was
calculated using data from the scientific literature from various countries
throughout the world. The exposure data was collated into four scenarios from
petroleum refinery environments and plotted as cumulative probability
distributions (CPD) plots. Health risk was evaluated for each scenario using the
Hazard Quotient (HQ) at 50% (CEXP50) and 95% (CEXP95) exposure levels. Benzene
levels were estimated to pose a significant risk with HQ50 > 1 and HQ95 > 1 for
workers exposed to benzene as base estimates for petroleum refinery workers
(Scenario 1), petroleum refinery workers evaluated with personal samplers in
Bulgarian refineries (Scenario 2B) and evaluated using air inside petroleum
refineries in Bulgarian refineries (Scenario 3B). HQ50 < 1 were calculated for
petroleum refinery workers with personal samplers in Italian refineries (Scenario
2A), air inside petroleum refineries (Scenario 3A) and air outside petroleum
refineries (Scenario 4) in India and Taiwan indicating little possible adverse
health effects. Also, HQ95 was < 1 for Scenario 4 however potential risk was
evaluated for Scenarios 2A and 3A with HQ95 > 1. The excess Cancer risk (CR) for
lifetime exposure to benzene for all the scenarios was evaluated using the Slope
Factor and Overall Risk Probability (ORP) methods. The result suggests a
potential cancer risk for exposure to benzene in all the scenarios. However,
there is a higher cancer risk at 95% (CEXP95) for petroleum refinery workers (2B)
with a CR of 48,000 per 106 and exposure to benzene in air inside petroleum
refineries (3B) with a CR of 28,000 per 106.
PMID- 25588155
TI - Descriptive analysis of antibiotic-resistant patterns of methicillin-resistant
Staphylococcus aureus (MRSA) st398 isolated from healthy swine.
AB - BACKGROUND: Livestock-associated methicillin-resistant Staphylococcus aureus
(MRSA) such as the MRSA ST398 strain has spread all over the world and the most
worrying aspect of this fact appears to be its capacity to easily spread to
humans. The excessive use of antibiotics has made swine a reservoir of MRSA. The
aim of the present study was to determine the antibiotic resistance profile of
MRSA samples isolated from healthy swine of the island of Tenerife (Spain).
METHODS: A total of 256 MRSA isolates from swine samples and five MRSA isolates
from pig worker samples were investigated for MRSA antibiotic resistant patterns.
RESULTS: Analysis of the susceptibility status of MRSA pig isolates revealed that
39 isolates were resistant to one antibiotic, 71 isolates were resistant to two
antibiotics and 96 isolates were resistant to three or more antibiotics. SCCmec
typing revealed the presence of types IV and V. Isolates having SCCmec IV had an
increased resistance to the antimicrobial agents tested than those having SCCmec
V. We observed significant differences when comparing the most common resistance
patterns and SCCmec type. CONCLUSIONS: MRSA isolated from humans showed similar
resistance to those isolated from pigs, excepting erythromycin, since all the
workers' isolates were sensitive to this antibiotic. The evolution of new MRSA
clones has emphasized the need for infection control practices in animals and
humans in close contact.
PMID- 25588156
TI - Public health adaptation to climate change in Canadian jurisdictions.
AB - Climate change poses numerous risks to the health of Canadians. Extreme weather
events, poor air quality, and food insecurity in northern regions are likely to
increase along with the increasing incidence and range of infectious diseases. In
this study we identify and characterize Canadian federal, provincial, territorial
and municipal adaptation to these health risks based on publically available
information. Federal health adaptation initiatives emphasize capacity building
and gathering information to address general health, infectious disease and heat
related risks. Provincial and territorial adaptation is varied. Quebec is a
leader in climate change adaptation, having a notably higher number of adaptation
initiatives reported, addressing almost all risks posed by climate change in the
province, and having implemented various adaptation types. Meanwhile, all other
Canadian provinces and territories are in the early stages of health adaptation.
Based on publically available information, reported adaptation also varies
greatly by municipality. The six sampled Canadian regional health authorities (or
equivalent) are not reporting any adaptation initiatives. We also find little
relationship between the number of initiatives reported in the six sampled
municipalities and their provinces, suggesting that municipalities are adapting
(or not adapting) autonomously.
PMID- 25588157
TI - Work related stress, burnout, job satisfaction and general health of nurses.
AB - Gaps in research focusing on work related stress, burnout, job satisfaction and
general health of nurses is evident within developing contexts like South Africa.
This study identified the relationship between work related stress, burnout, job
satisfaction and general health of nurses. A total of 1200 nurses from four
hospitals were invited to participate in this cross-sectional study (75% response
rate). Participants completed five questionnaires and multiple linear regression
analysis was used to determine significant relationships between variables. Staff
issues are best associated with burnout as well as job satisfaction. Burnout
explained the highest amount of variance in mental health of nurses. These are
known to compromise productivity and performance, as well as affect the quality
of patient care. Issues, such as security risks in the workplace, affect job
satisfaction and health of nurses. Although this is more salient to developing
contexts it is important in developing strategies and intervention programs
towards improving nurse and patient related outcomes.
PMID- 25588158
TI - Describing the primary care actions of oral health teams in Brazil.
AB - OBJECTIVE: To describe the primary care actions performed by oral health teams
(OHTs) that participated in a large national survey led by the Ministry of Health
in 2012. METHODS: A total of 12,403 dentists from OHTs completed a set of survey
questions (response rate = 85.01%) on the organization of care, basic dental
procedures and oral health surveillance actions of OHTs. Descriptive and
hierarchical cluster analyses were developed. RESULTS: The majority of OHTs
(85.2%) reported that they performed "patient welcoming". The delivery of
services was based on a patient's identified disease risk (83.1%), and continuity
of care was ensured by 85.9% of OHTs. Individual preventive, restorative and
surgical procedures were performed by the majority of the teams; however,
screening for oral cancer and construction of dental prostheses/dentures occurred
less frequently. Cluster 1 was composed of OHTs with the lowest proportion of
oral healthcare actions related to oral cancer and dental prostheses/dentures,
and the Southeastern and Southern regions had higher proportions of OHTs from
cluster 2. CONCLUSIONS: OHTs adhere to some of the principles of primary care
organizations; however, the teams perform fewer actions related to oral cancer
treatment and rehabilitation with complete dentures. The geographical
distribution of the clusters was unequal in Brazil.
PMID- 25588159
TI - P-stereogenic PNP pincer-Pd catalyzed intramolecular hydroamination of amino-1,3
dienes.
AB - A new P-stereogenic PNP pincer-Pd complex was readily prepared from optically
pure 2,6-bis[(boranato(tert-butyl)methylphosphino)methyl]pyridine. It was used in
the asymmetric intramolecular hydroamination of amino-1,3-dienes, with the
desired products being obtained in good yields and with excellent
regioselectivities and up to moderate enantioselectivities. The absolute
configuration of one of the hydroamination products was determined by X-ray
crystallography studies. This simple and efficient procedure can be used for the
synthesis of allyl-type chiral pyrrolidine derivatives.
PMID- 25588160
TI - Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast
cancer cells through the PI3K/AKT-mTOR pathway.
AB - To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC)
cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and
MCF-7 cells were incubated with 0.1 MUmol/l gefitinib, 1 MUmol/l gefitinib, 10
MUmol/l gefitinib, 1 MUmol/l SF1126, 0.1 MUmol/l gefitinib+1 MUmol/l SF1126, 1
MUmol/l gefitinib+1 MUmol/l SF1126, and 10 MUmol/l gefitinib+1 MUmol/l SF1126.
Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2
thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The
apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the
mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors
were detected by western blot. For TNBC cells, cell viability or survival was not
significantly inhibited by gefitinib or SF1126 alone; however, marked cell
apoptosis was noted in the gefitinib and SF1126 combination groups, and this
effect was dose dependent. Also, the expressions of apoptosis markers, such as
cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126
combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6
kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination,
which may be responsible for the apoptosis. Gefitinib combined with SF1126 could
induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR
PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical
trials of TNBC therapy by the combination of gefitinib and SF1126.
PMID- 25588161
TI - N-Farnesyloxy-norcantharimide and N-farnesyl-norcantharimide inhibit the
progression of leukemia and increase survival days in a syngeneic mouse leukemia
model.
AB - This study investigated the anticancer effects of two newly synthesized
norcantharidin analogs, N-farnesyloxy-norcantharimide (NOC15) and N-farnesyl
norcantharimide (NC15), in L1210 cells and in a syngeneic mouse leukemia model
(L1210 cell line plus DBA/2 mice). We found that the half-maximal inhibitory
concentration (IC50) of NOC15 and NC15 on L1210 cells is 1.56 and 2.62 MUmol/l,
respectively, and that the IC50 of NOC15 and NC15 on human normal lymphoblast is
207.9 and 2569 MUmol/l, respectively. In cell cycle analysis, NOC15 could
increase the sub-G1 phase, whereas NC15 could induce G2/M arrest. Annexin-V
apoptosis assay indicated that both NOC15 and NC15 could induce cell apoptosis.
In the syngeneic mouse leukemia model, both NOC15 and NC15 could increase the
survival days of mice and decrease the tumor weight. Moreover, both NOC15 and
NC15 could retard the increase in peripheral blood leukocyte count due to L1210
cells. In the subcutaneous (s.c.) group, the treatment with NOC15 could retard
the decrease in the weight of the liver and the spleen caused by L1210 cells,
whereas the treatment with NC15 could retard the decrease in the weight of the
spleen caused by L1210 cells. We conclude that the new compounds NOC15 and NC15
have strong anticancer activity and low toxicity both in vitro and in vivo. NOC15
and NC15 may have the potential to be developed into anticancer agents in the
future.
PMID- 25588162
TI - The enhanced efficiency of graphene-silicon solar cells by electric field doping.
AB - The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as
one of the most low-cost candidates in photovoltaics due to its simple
fabrication process. However, the low Gr-Si Schottky barrier height largely
limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate
that electric field doping can be used to tune the work function of a Gr film and
therefore improve the photovoltaic performance of the Gr-Si solar cell
effectively. The electric field doping effects can be achieved either by
connecting the Gr-Si solar cell to an external power supply or by polarizing a
ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of
both of the device architecture designs showed that the power conversion
efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar
cells. Our study opens a new avenue for improving the performance of Gr-Si solar
cells.
PMID- 25588163
TI - Swept source optical coherence tomography Gabor fusion splicing technique for
microscopy of thick samples using a deformable mirror.
AB - We present a swept source optical coherence tomography (OCT) system at 1060 nm
equipped with a wavefront sensor at 830 nm and a deformable mirror in a closed
loop adaptive optics (AO) system. Due to the AO correction, the confocal profile
of the interface optics becomes narrower than the OCT axial range, restricting
the part of the B-scan (cross section) with good contrast. By actuating on the
deformable mirror, the depth of the focus is changed and the system is used to
demonstrate Gabor filtering in order to produce B-scan OCT images with enhanced
sensitivity throughout the axial range from a Drosophila larvae. The focus
adjustment is achieved by manipulating the curvature of the deformable mirror
between two user-defined limits. Particularities of controlling the focus for
Gabor filtering using the deformable mirror are presented.
PMID- 25588164
TI - Optical palpation in vivo: imaging human skin lesions using mechanical contrast.
AB - We demonstrate the first application of the recently proposed method of optical
palpation to in vivo imaging of human skin. Optical palpation is a tactile
imaging technique that probes the spatial variation of a sample's mechanical
properties by producing an en face map of stress measured at the sample surface.
This map is determined from the thickness of a translucent, compliant stress
sensor placed between a loading element and the sample and is measured using
optical coherence tomography. We assess the performance of optical palpation
using a handheld imaging probe on skin-mimicking phantoms, and demonstrate its
use on human skin lesions. Our results demonstrate the capacity of optical
palpation to delineate the boundaries of lesions and to map the mechanical
contrast between lesions and the surrounding normal skin.
PMID- 25588165
TI - Optical diagnosis of malaria infection in human plasma using Raman spectroscopy.
AB - We present the prediction of malaria infection in human plasma using Raman
spectroscopy. Raman spectra of malaria-infected samples are compared with those
of healthy and dengue virus infected ones for disease recognition. Raman spectra
were acquired using a laser at 532 nm as an excitation source and 10 distinct
spectral signatures that statistically differentiated malaria from healthy and
dengue-infected cases were found. A multivariate regression model has been
developed that utilized Raman spectra of 20 malaria-infected, 10 non-malarial
with fever, 10 healthy, and 6 dengue-infected samples to optically predict the
malaria infection. The model yields the correlation coefficient r(2) value of
0.981 between the predicted values and clinically known results of trainee
samples, and the root mean square error in cross validation was found to be 0.09;
both these parameters validated the model. The model was further blindly tested
for 30 unknown suspected samples and found to be 86% accurate compared with the
clinical results, with the inaccuracy due to three samples which were predicted
in the gray region. Standard deviation and root mean square error in prediction
for unknown samples were found to be 0.150 and 0.149, which are accepted for the
clinical validation of the model.
PMID- 25588166
TI - Cement-associated signs of inflammation: retrospective analysis of the effect of
excess cement on peri-implant tissue.
AB - PURPOSE: Excess cement left in the peri-implant sulcus after the placement of
prosthetic restorations risks inflammation in the peri-implant tissue. While many
current studies deal with the question of how to avoid undetected excess cement,
relatively little is known about the clinical consequences of this complication.
This study analyzed the clinical findings associated with excess cement. Further,
the influence of the sojourn time of undetected excess cement in the peri-implant
pocket on clinical findings was investigated. MATERIALS AND METHODS: Within the
scope of a retrospective clinical follow-up, the suprastructures that were
originally cemented with a methacrylate cement were revised in 93 patients (171
implants). The patients were split into two groups according to the time between
placement of the prosthetic restoration and revision. Group 1 (G1) had treatment
revisions within 2 years of restoration placement (71 patients with 126
implants); in group 2 (G2), treatment revisions were conducted at a later time
(22 patients with 45 implants). For the purpose of statistical analysis, both
groups were further analyzed based on the presence/absence of excess cement at
the time of revision. RESULTS: By definition, the average time to revision in G1
was shorter than in G2 (0.71 years versus 4.07 years). There was no significant
difference in the frequency of excess cement at revision between G1 (59.5%) and
G2 (62.2%). The clinical findings around the implants in G1 were significantly
less severe than in G2 (bleeding on probing: G1 without excess cement--17.6%, G1
with excess cement--80%, G2 without excess cement--94.1%, G2 with excess cement-
100%; suppuration: G1 without excess--0%, G1 with excess cement--21.3%, G2
without excess cement--23.3%, G2 with excess cement--89.3%). After removing the
excess cement, cleaning and disinfecting the implant abutment and restoration,
and using a different cement, significantly fewer signs of inflammation were
found at further follow-up in both groups. CONCLUSIONS: Within the limitations of
this retrospective observational study, excess cement was present in a high
number of cement-retained implant restorations. Signs of inflammation were
present in a large proportion of implants at short- to medium-term follow-up. At
the time of restoration revisions, the clinical observation of previously
undetected excess cement was associated with increased prevalence of
inflammation. Removal of excess cement significantly reduced the signs of
inflammation.
PMID- 25588167
TI - The influence of interimplant distance in mandibular overdentures supported by
two implants on patient satisfaction and quality of life.
AB - This study evaluates the influence of interimplant distance (ID) on patient
satisfaction and quality of life (QOL) of 55 patients who received mandibular
overdentures supported by two implants. IDs were measured over the residual ridge
crest and linearly on all of the patients' mandibular casts. The crestal detours
of all patients were determined by subtracting these two values from each other.
Higher IDs were associated with better QOL scores (P < .05), whereas higher
crestal detour values were associated with better general comfort, chewing, ease
of hygiene maintenance, esthetics, pain, and QOL scores (P < .05).
PMID- 25588168
TI - Retrievability of implant-supported crowns when using three different cements: a
controlled clinical trial.
AB - PURPOSE: The purpose of this study was to analyze the removal of implant
supported crowns retained by three different cements using an air-accelerated
crown remover and to evaluate the patients' response to the procedure. MATERIALS
AND METHODS: This controlled clinical trial was conducted with 21 patients (10
women, 11 men; mean age: 51 +/- 10.2 years) who had received a total of 74
implants (all placed in the posterior zone of the mandible). Four months after
implant surgery, the crowns were cemented on standard titanium abutments of
different heights. Three different cements (two temporary: Harvard TEMP and
Improv; and one definitive: Durelon) were used and randomly assigned to the
patients. Eight months later, one blinded investigator removed all crowns. The
number of activations of the instrument (CORONAflex, KaVo) required for crown
removal was recorded. The patients completed a questionnaire retrospectively to
determine the impact of the procedure and to gauge their subjective perception. A
linear regression model and descriptive statistics were used for data analysis.
RESULTS: All crowns could be retrieved without any technical complications or
damage. Both abutment height (P = .019) and cement type (P = .004) had a
significant effect on the number of activations, but the type of cement was more
important. An increased total number of activations had no or only a weak
correlation to the patients' perception of concussion, noise, pain, and
unwillingness to use the device. CONCLUSIONS: Cemented implant crowns can be
removed, and the application of an air-accelerated device is a practicable
method. A type of cement with appropriate retention force has to be selected. The
impact on the patients' subjective perception should be taken into account.
PMID- 25588169
TI - Randomized controlled trial comparing direct intraoral digitization and extraoral
digitization after impression taking.
AB - This study aimed to evaluate the correspondence of intraoral digitization (ID)
with extraoral digitization (ED) after impression taking. One-stage putty-and
wash impressions and ID were carried out in a randomized order for 10 subjects.
The impressions were used to make casts, which were then subjected to ED. ID
datasets were aligned to create computer-aided design reference models.
Deviations between ID and ED were calculated. The mean positive and negative
deviations were 37.7 and -48.4 um, respectively, for one quadrant. The results
showed that the ID system is well suited for the acquisition of single-tooth
restorations and is of limited suitability for the acquisition of small multiple
unit restorations.
PMID- 25588170
TI - Fixed full-arch implant-supported prostheses in a patient with epidermolysis
bullosa: a clinical case history report.
AB - Epidermolysis bullosa (EB) is a rare skin disorder characterized by blister
formation in response to minor trauma and accompanied by extracutaneous
manifestations. The use of endosseous implants to support fixed prostheses for
the rehabilitation of patients with recessive dystrophic EB might provide a
considerably better clinical treatment outcome than traditional prosthodontic
interventions. This case history report describes the clinical management of such
an afflicted patient. Implants were placed immediately following teeth
extractions and subsequently loaded with fixed full-arch prostheses. This
treatment option is proposed for patients with recessive dystrophic EB to
preclude mucosal irritation associated with wearing removable prostheses.
PMID- 25588171
TI - Adhesive strength of the luting technique for passively fitting screw-retained
implant-supported prostheses: an in vitro evaluation.
AB - PURPOSE: This in vitro study evaluated the adhesive strength of a technique to
lute implant cylinders to metal frameworks in implant-supported prostheses and
ensure a good passive fit. MATERIALS AND METHODS: Different height samples were
tested: In group 1, implant cylinders were 5 mm long; in group 2, they were 10 mm
long. A universal testing machine (Instron) was used to perform pullout tests.
RESULTS: The luting technique provided enough adhesive strength for clinical use
with greater adhesive strength in group 2 (mean pull-out strength: 2.85 kN in
group 1 versus 3.79 kN in group 2). CONCLUSIONS: The luting technique provides
enough adhesive strength for clinical use. Moreover, specimens with a larger
surface for adhesion demonstrated higher adhesive strength compared with shorter
specimens.
PMID- 25588172
TI - The effect of implant design and bone quality on insertion torque, resonance
frequency analysis, and insertion energy during implant placement in low or low-
to medium-density bone.
AB - PURPOSE: This study investigated the effect of implant design and bone quality on
insertion torque (IT), implant stability quotient (ISQ), and insertion energy
(IE) by monitoring the continuous change in IT and ISQ while implants were
inserted in artificial bone blocks that simulate bone of poor or poor-to-medium
quality. MATERIALS AND METHODS: Polyurethane foam blocks (Sawbones) of 0.16 g/cm3
and 0.32 g/cm3 were respectively used to simulate low density and low- to medium
density cancellous bone. In addition, some test blocks were laminated with a 1-mm
0.80 g/cm3 polyurethane layer to simulate cancellous bone with a thin cortical
layer. Four different implants (Nobel Biocare Mk III-3.75, Mk III-4.0, Mk IV-4.0,
and NobelActive-4.3) were placed into the different test blocks in accordance
with the manufacturer's instructions. The IT and ISQ were recorded at every 0.5
mm of inserted length during implant insertion, and IE was calculated from the
torque curve. The peak IT (PIT), final IT (FIT), IE, and final ISQ values were
statistically analyzed. RESULTS: All implants showed increasing ISQ values when
the implant was inserted more deeply. In contrast to the ISQ, implants with
different designs showed dissimilar IT curve patterns during the insertion. All
implants showed a significant increase in the PIT, FIT, IE, and ISQ when the test
block density increased or when the 1-mm laminated layer was present. Tapered
implants showed FIT or PIT values of more than 40 Ncm for all of the laminated
test blocks and for the nonlaminated test blocks of low to medium density.
Parallel-wall implants did not exhibit PIT or FIT values of more than 40 Ncm for
all of the test blocks. NobelActive-4.3 showed a significantly higher FIT, but a
significantly lower IE, than Mk IV-4.0. CONCLUSIONS: While the existence of
cortical bone or implant designs significantly affects the dynamic IT profiles
during implant insertion, it does not affect the ISQ to a similar extent. Certain
implant designs are more suitable than others if high IT is required in bone of
poor quality. The manner in which IT, IE, and ISQ represent the implant primary
stability requires further study.
PMID- 25588173
TI - Simplified edentulous treatment technique for edentulous hemimaxillectomy
patients: case history report.
AB - Technical difficulties in the construction of hard palate obturators following
oncologic surgery are due to the recording limitations of the entire defect area,
plus prosthesis base instability during recording of maxillomandibular
relationships. This article describes a time-saving technique that ensures stable
and precise recording bases. A light-polymerizing acrylic resin layer is used for
making the first impression of the defect, while simultaneously obtaining an
acrylic resin impression tray and base for recording maxillomandibular
relationships. Adhesive paper copies are used for the arrangement of the anterior
teeth.
PMID- 25588174
TI - Systematic review of current dental implant coating materials and novel coating
techniques.
AB - PURPOSE: Titanium dental implants have a high success rate; however, there are
instances when a modified surface may be desirable. The aim of this article was
to systematically review the different types of implant coatings that have been
studied clinically, in vivo and in vitro, and the coating techniques being
implemented. MATERIALS AND METHODS: The literature was searched electronically
and manually through The Cochrane Library, Medline, and PubMed databases to
identify articles studying dental implant surfaces and coating techniques. The
database search strategy revealed 320 articles, of which 52 articles were
considered eligible--40 in relation to implant coatings and 12 to the coating
technique. An additional 30 articles were retrieved by hand search. RESULTS:
Several materials were identified as possible candidates for dental implant
coatings; these include carbon, bisphosphonates, bone stimulating factors,
bioactive glass and bioactive ceramics, fluoride, hydroxyapatite (HA) and calcium
phosphate, and titanium/titanium nitride. HA coatings still remain the most
biocompatible coatings even though the more innovative bioglass suggests
promising results. The most common coating techniques are plasma spraying and
hydrocoating. More recent techniques such as the nanoscale technology are also
discussed. CONCLUSIONS: Several implant coatings have been proposed, and some
appear to give better clinical results and improved properties than others.
Clinical trials are still required to provide compelling evidence-based results
for their long-term successful outcomes.
PMID- 25588175
TI - Perception of dental esthetics: influence of restoration type, symmetry, and
color in four different countries.
AB - In this study, the influence of restoration type, symmetry, and color on the
perception of dental appearance was evaluated. An esthetic questionnaire was
completed by 29 patients before and after esthetic rehabilitation. In addition,
94 dentists from four countries (Germany, the United Kingdom [UK], China, and
Switzerland) evaluated the influence of the above factors using before-and-after
rehabilitation pictures. The most invasive treatment was recommended by Chinese
dentists, while German, Swiss, and UK dentists recommended comparable treatment
options. As for restorative symmetry, restoration type, and color, significant
differences could be found among and within the dentists of the four countries (P
+/- .05).
PMID- 25588176
TI - In situ evaluation of the microbial adhesion on a hard acrylic resin and a soft
liner used in removable prostheses.
AB - PURPOSE: The purpose of this study was to evaluate, in situ, the initial adhesion
of microorganisms to as well as the surface roughness and chemical composition of
ProBase Hot (Ivoclar Vivadent), a hard acrylic resin, and Vertex Soft (Vertex
Dental), an acrylic-based soft liner, used in removable dental prostheses.
MATERIALS AND METHODS: Equal sized disks of ProBase Hot and Vertex Soft were
prepared and polished according to the recommended procedures for clinical use.
Two disks of each material were mounted in individual oral splints and exposed
for 4 hours to the oral cavities of 15 participants. The microbial adhesion to
each material's surface was measured with the pour plate technique using rich and
selective growth media. Statistical analysis was performed using the Student t
test. Scanning electron microscopy and chemical composition analyses obtained
through electron probe radiographic microanalysis of sample disks also were
performed. RESULTS: In comparison to ProBase Hot, Vertex Soft presented higher
microbial adhesion, namely regarding total aerobes, anaerobes, streptococci, and
mutans streptococci (P < .05). Also, Vertex Soft presented higher surface
roughness. Differences in the chemical composition of the two materials also were
found. CONCLUSIONS: The Vertex Soft liner has been found to be more susceptible
to microbial adhesion than the acrylic resin ProBase Hot, probably due to its
greater surface roughness. The application of Vertex Soft liner to a hard denture
base may lead to a higher risk of oral and systemic infections for patients,
highlighting a greater need for plaque control, especially for more susceptible
individuals.
PMID- 25588177
TI - Hormonal fluctuations intensify temporomandibular disorder pain without impairing
masticatory function.
AB - PURPOSE: The influence of hormonal fluctuations on pain and mastication was
evaluated in patients with painful temporomandibular disorder (TMD) symptoms.
MATERIALS AND METHODS: Fifty women were assigned to menstrual cycle and oral
contraceptive groups (n = 25). Their TMD was diagnosed by Research Diagnostic
Criteria for Temporomandibular Disorders. Pain levels, maximum oclusal force
(MOF), and masticatory performance (MP) were measured in all menstrual cycle
phases. RESULTS: A lower pain level was observed in the ovulatory phase when
compared to menstrual and luteal phases (P = .02). No differences were found
regarding MOF (P = .20) or MP (P = .94). CONCLUSIONS: Hormonal fluctuations
intensify pain in women with symptomatic TMD without impairing mastication.
PMID- 25588178
TI - Reliability and failure modes of two Y-TZP abutment designs.
AB - Fracture strength and accelerated fatigue reliability of two zirconia abutment
systems were tested. Thirty-six implants with a Morse taper (MT; n = 18) or cone
(C; n = 18) design were restored with metallic crowns. Loads were applied as
single load to failure (SLF) or mouth-motion cycles using a step-stress
accelerated life testing (SALT) method. SLF mean values were 690 +/- 430 N and
209 +/- 25 for MT and C groups, respectively. In terms of the SALT results, 8
specimens survived (50,000 cycles) and 7 failed (maximum load 400 N) in the MT
group; whereas for the C group all abutments failed before the maximum number of
cycles. Failure mode was fracture of the Y-TZP abutments for both groups. Higher
reliability for a mission of 50,000 cycles at 175 N for MT versus C designs was
determined, and significant differences in fracture modes were observed.
PMID- 25588179
TI - Electromyographic evaluation of masticatory muscles in dentate patients versus
conventional and implant-supported fixed and removable denture wearers- a
preliminary report comparing model foods.
AB - PURPOSE: To evaluate differences in masticatory muscle function during chewing of
model foods designed to differ in fracture strength between dentate subjects (n =
5, ages 59 to 68 years) versus patients treated with a maxillary conventional
complete denture opposing natural dentition or one of the following types of
mandibular complete dentures: conventional, implant-supported overdenture,
implant-supported fixed denture (n = 20, ages 45 to 83 years). The authors
hypothesized that denture wearers would differ in duration of chewing, frequency
of chewing, and masticatory muscle activity while preparing a bolus for
swallowing. MATERIALS AND METHODS: Surface electromyography was recorded
bilaterally from the masseter, anterior temporalis, and anterior digastric.
Masticatory muscle activity was evaluated using scaled values of the area under
the electromyographic curve, while subjects chewed agar-based model foods with
different fracture strengths. Chewing duration and frequency also were calculated
from electromyographic recordings. Mixed model analysis of variance with
"subject" as a random factor was used during statistical analysis. Logarithmic
transformation was required to achieve normalization of residuals for the
duration of chewing and the relative masticatory muscles activity, but not for
the chewing frequency. RESULTS: Relative masticatory muscle activity was 2.57
times higher for the denture wearers than for the dentate subjects during chewing
of model foods (P < .0001). The reduction in masticatory muscle activity from the
1st to the 10th chewing cycle was proportionally less in magnitude and occurred
more gradually for denture wearers compared to dentate subjects. While chewing
sequence duration increased with food fracture strength, it did not differ
significantly in treatment versus dentate groups. Chewing cycle frequency did not
differ between groups or with food fracture strength. CONCLUSIONS: The observed
increases in relative masticatory muscle activity for denture wearers compared to
the dentate subjects during oral food processing likely reflect supplemental
mechanical efforts to accommodate the use of dentures for preparing a bolus for
swallowing.
PMID- 25588180
TI - Highly active and stable hybrid catalyst of cobalt-doped FeS2 nanosheets-carbon
nanotubes for hydrogen evolution reaction.
AB - Hydrogen evolution reaction (HER) from water through electrocatalysis using cost
effective materials to replace precious Pt catalysts holds great promise for
clean energy technologies. In this work we developed a highly active and stable
catalyst containing Co doped earth abundant iron pyrite FeS(2) nanosheets
hybridized with carbon nanotubes (Fe(1-x)CoxS(2)/CNT hybrid catalysts) for HER in
acidic solutions. The pyrite phase of Fe(1-x)CoxS(2)/CNT was characterized by
powder X-ray diffraction and absorption spectroscopy. Electrochemical
measurements showed a low overpotential of ~0.12 V at 20 mA/cm(2), small Tafel
slope of ~46 mV/decade, and long-term durability over 40 h of HER operation using
bulk quantities of Fe(0.9)Co(0.1)S(2)/CNT hybrid catalysts at high loadings (~7
mg/cm(2)). Density functional theory calculation revealed that the origin of high
catalytic activity stemmed from a large reduction of the kinetic energy barrier
of H atom adsorption on FeS(2) surface upon Co doping in the iron pyrite
structure. It is also found that the high HER catalytic activity of
Fe(0.9)Co(0.1)S(2) hinges on the hybridization with CNTs to impart strong
heteroatomic interactions between CNT and Fe(0.9)Co(0.1)S(2). This work produces
the most active HER catalyst based on iron pyrite, suggesting a scalable, low
cost, and highly efficient catalyst for hydrogen generation.
PMID- 25588181
TI - Chemical and toxicological characterization of halobenzoquinones, an emerging
class of disinfection byproducts.
AB - Halobenzoquinones (HBQs), a new class of disinfection byproducts (DBPs), occur
widely in treated drinking water and recreational water. The main concern
regarding human exposure to DBPs stems from epidemiological studies that have
consistently linked the consumption of chlorinated drinking water with an
increased risk of developing bladder cancer. The U.S. Environmental Protection
Agency and Health Canada have set regulations on the amount of DBPs in drinking
water to minimize the risk. However, these regulated DBPs do not account for the
increased risk of bladder cancer because they have different target organs or
lower magnitudes of risk based on animal carcinogenesis studies. Because of the
pervasive exposure to DBPs, identification of DBPs relevant to human health has
become one of the important research targets to address DBP-associated health
concerns. Quantitative structure-toxicity relationship (QSTR) analysis has
predicted HBQs to be potential bladder carcinogens. Therefore, this perspective
focuses on the chemical and toxicological characterization of HBQs. In vitro
cytotoxicity experiments have shown that HBQs induce greater cytotoxicity and/or
greater developmental toxicity than most of the regulated DBPs. Cellular
mechanistic studies indicate that HBQs are capable of producing reactive oxygen
species (ROS) either within cells or in solution, depleting cellular glutathione
levels, and influencing cellular antioxidant enzymes, which further induces
oxidative stress and oxidative damage to cellular proteins and DNA. Oxidative
damage to DNA was demonstrated in the form of significant increases in cellular
levels of 8-hydroxydeoxyguanosine (8-OHdG), DNA strand breaks, and
apurinic/apyrimidinic (AP) sites. HBQs can also form DNA adducts, affect genome
wide DNA methylation, and inhibit DNA repair enzymes. These findings demonstrate
that HBQs are highly cytotoxic and potentially genotoxic and carcinogenic,
although in vivo data corroborating this is not available. To fully understand
the potential adverse health effects and cancer risk due to HBQ exposure,
multidisciplinary research is required regarding human exposure, health risk
assessment, and toxicological mechanisms of HBQs.
PMID- 25588182
TI - Capturing heterogeneous nucleation of nanoscale pits and subsequent crystal
shrinkage during Ostwald ripening of a metal phosphate.
AB - It has been generally accepted that crystal shrinkage during Ostwald ripening can
be understood simply as a reverse process of crystal growth, and as a result,
little attention has been paid to shrinkage behavior. The entire microstructure
of polycrystalline materials, however, forms as a consequence of both growing and
shrinking crystals. Thus, scrutiny of shrinking characteristics in addition to
growth aspects is essential for a complete understanding of the evolution of
microstructure during Ostwald ripening. By capturing real-time in situ high
resolution electron micrographs at high temperature, we herein demonstrate the
shrinkage behavior of nanocrystals embedded in a solid crystalline matrix during
the ripening process of a metal phosphate. Unlike typical crystal growth behavior
based on two-dimensional homogeneous nucleation, heterogeneous types of
nucleation with nanoscale pits at solid-solid interfaces (or crystal edges) are
observed to dominantly occur during shrinkage of the crystals. The findings of
this study suggest that crystal shrinkage proceeds with a lower activation energy
barrier than that of crystal growth, although both crystal growth and shrinkage
take place at the same time during Ostwald ripening.
PMID- 25588184
TI - "When I'm rushing on my run" - novel psychoactive substances.
PMID- 25588183
TI - A checklist-based intervention to improve surgical outcomes in Michigan:
evaluation of the Keystone Surgery program.
AB - IMPORTANCE: Previous studies of checklist-based quality improvement interventions
have reported mixed results. OBJECTIVE: To evaluate whether implementation of a
checklist-based quality improvement intervention--Keystone Surgery--was
associated with improved outcomes in patients in a large statewide population
undergoing general surgery. DESIGN, SETTING, AND EXPOSURES: A retrospective
longitudinal study examined surgical outcomes in 64,891 Michigan patients in 29
hospitals using Michigan Surgical Quality Collaborative clinical registry data
from 2006 through 2010. Multivariable logistic regression and difference-in
differences analytic approaches were used to evaluate whether Keystone Surgery
program implementation was associated with improved surgical outcomes following
general surgery procedures, apart from existing temporal trends toward improved
outcomes during the study period. MAIN OUTCOMES AND MEASURES: Risk-adjusted rates
of superficial surgical site infection, wound complication, any complication, and
30-day mortality. RESULTS: Implementation of Keystone Surgery in 14 participating
centers was not associated with improvements in surgical outcomes during the
study period. Adjusted rates of superficial surgical site infection (3.2% vs
3.2%, P=.91), wound complication (5.9% vs 6.5%, P=.30), any complication (12.4%
vs 13.2%, P=.26), and 30-day mortality (2.1% vs 1.9%, P=.32) at participating
hospitals were similar before and after implementation. Difference-in-differences
analysis accounting for trends in 15 nonparticipating centers and sensitivity
analysis excluding patients receiving surgery in the first 6 or 12 months after
program implementation yielded similar results. CONCLUSIONS AND RELEVANCE:
Implementation of a checklist-based quality improvement intervention did not
affect rates of adverse surgical outcomes among patients undergoing general
surgery in participating Michigan hospitals. Additional research is needed to
understand why this program was not successful prior to further dissemination and
implementation of this model to other populations.
PMID- 25588186
TI - The In vitro and In vivo Evaluation of Fenofibrate with a Self-microemulsifying
Formulation.
AB - Fenofibrate is virtually insoluble in water and is highly lipophilic, which leads
to poor oral bioavailability. The purpose of this approach is to develop self
microemulsifying drug delivery system (SMEDDS) for oral bioavailability
enhancement of fenofibrate. The in vitro dissolution test and pharmacokinetic
behavior in beagle dogs were conducted to assess the formulation of fenofibrate
in self-microemulsifying systems. The concentrations of fenofibrate were
determined by HPLC. A crossover fashion study was performed in six fasted beagle
dogs with SMEDDS formulation and commercial capsules. The results showed that
SMEDDS formulation provide a good drug release with more than 90% of fenofibrate
dissoluted from self-emulsifying formulations while less than 10% from the
commercial capsules was released within 20min. The mean particle size of SMEDDS
formulation after dispersion was about 33.7nm In pharmacokinetic parameters of
SMEDDS formulation, the area under the plasma concentration-time curve (AUC) was
significantly higher and was approximately 7-fold greater than that obtained when
commercial capsule of the same dose of fenofibrate was administered. Also, the
maximum absorption was advanced (2h to 1.25h) with SMEDDS formulation. The self
microemulsifying drug delivery systems can significantly increase fenofibrate
dissolution in vitro and absorption in vivo.
PMID- 25588185
TI - [S3-Guideline: Recommendations for intra-aortic balloon pumping in cardiac
surgery].
AB - Although intra-aortic balloon pumping (IABP) is the most frequently used
mechanical cardiac assist device in cardiothoracic surgery, there are only
guidelines for substantive sections of aortic counterpulsation including
prophylactic and postoperative use. In contrast, evidence-based recommendations
are still lacking concerning intraoperative use, management, contraindication and
other relevant issues. According to international surveys, important aspects of
IABP usage show a wide variation in clinical practice. The results of a national
questionnaire performed before initiation of this guideline confirmed these
findings and demonstrated a clear need for the development of a consensus-based
guideline. Therefore, the presented multidisciplinary S-3-guideline was developed
under the direction of the German Society for Thoracic and Cardiovascular Surgery
(Deutsche Gesellschaft fur Thorax-, Herz- und Gefabetachirurgie, DGTHG) to make
evidence-based recommendations for the usage of aortic counterpulsation after
cardiothoracic surgery according to the requirements of the Association of the
Scientific Medical Societies in Germany (AWMF) and the Medical Centre for Quality
(Arztliches Zentrum fur Qualitat - (AZQ)). Main topics discussed in this
guideline involve IABP support in the prophylactic, preoperative, intraoperative
and postoperative setting as well as the treatment of right heart failure,
contraindications, anticoagulation, monitoring, weaning, and limitations of IABP
therapy. The presented 15 key messages of the guideline were approved after two
consensus meetings under moderation of the AWMF with participation of the German
Society of Cardiology (DGK), German Society of Anaesthesiology and Intensive Care
Medicine (DGAI), German Interdisciplinary Association for Intensive Care (DIVI)
and the German Society for Cardiovascular Engineering (DGfK).
PMID- 25588187
TI - Stabilizing electrochemical carbon capture membrane with Al2O3 thin-film
overcoating synthesized by chemical vapor deposition.
AB - Development of high-efficiency and cost-effective carbon capture technology is a
central element of our effort to battle the global warming and climate change.
Here we report that the unique high-flux and high-selectivity of electrochemical
silver-carbonate dual-phase membranes can be retained for an extended period of
operation by overcoating the surfaces of porous silver matrix with a uniform
layer of Al2O3 thin-film derived from chemical vapor deposition.
PMID- 25588188
TI - Nonsevere acute pulmonary embolism: prognostic CT pulmonary angiography findings.
AB - PURPOSE: To retrospectively evaluate the prognostic parameters of computed
tomography (CT) pulmonary angiographic findings in nonsevere (hemodynamically
stable) pulmonary embolism (PE) patients and to assess the predictive value of
these parameters for mortality within 1 month of the initial diagnosis. MATERIALS
AND METHODS: Retrospectively, 67 consecutive patients (28 men, 39 women; mean
age, 63.25 +/- 18 years) from 2 centers with nonsevere PE diagnosed using CT and
a clinical evaluation were included in the current study. Using consensus
reading, 2 readers blinded to the patients' clinical outcomes quantified the
right ventricle short axis to left ventricle short axis ratio in the axial plane,
vascular measurements, reflux of contrast medium into the inferior vena cava and
azygos vein, ventricular septal bowing, and clot load using the Qanadli scoring
system. The Simplified Pulmonary Embolism Severity Index (sPESI) and pulmonary
parenchymal findings were also evaluated. All CT pulmonary angiographic
parameters were compared with the risk of death within 1 month using logistic
regression analysis. RESULTS: Fifty-nine patients survived (88.1%), and 8
patients (11.9%) died because of PE. The sPESI and 2 parenchymal findings
(multiple wedge-shaped opacities or consolidation accompanied by a wedge-shaped
opacity) were significantly related to mortality. In the univariate analysis,
neither the cardiovascular CT parameters nor the clot burden was significant
between the survivors and nonsurvivors (P > 0.05). CONCLUSIONS: In clinically
nonsevere PE patients, the sPESI and significant parenchymal findings were the CT
parameters related to 1-month mortality.
PMID- 25588189
TI - Predicting outcome of substance abuse treatment in a feedback study: Can recovery
curves be improved upon?
AB - OBJECTIVE: The goal of the study was to evaluate whether enhanced normative
feedback recovery curves are needed for treatment of substance use problems.
METHOD: Patient predictors of outcome were examined using data from four
substance abuse treatment clinics. RESULTS: Baseline severity of
symptoms/functioning, employment, and craving were found to be associated with
rate of change in symptoms/functioning. Several other variables were associated
with rate of change in alcohol use, although in the opposite direction than found
in efficacy trials. CONCLUSIONS: The results point to the complexity of designing
feedback systems using normative recovery curves for those with substance use
problems and highlight the important differences between real-world treatment of
those with substance use problems compared to data from efficacy trials.
PMID- 25588191
TI - Determination of free electron density in sequentially doped InxGa1-xAs by Raman
spectroscopy.
AB - The advent and exponential growth of mobile computing has spurred greater
emphasis on the adoption of III-V compound semiconductors in device
architectures. The introduction of high charge carrier densities within InxGa1
xAs and the development of metrologies to quantitate the extent of doping have
thus emerged as an urgent imperative. As an amphoteric dopant, Si begins to
occupy anionic sites at high concentrations, thereby limiting the maximum carrier
density that can be obtained upon Si doping of III-V semiconductors. Here, we
present Raman results on sequentially doped In0.53Ga0.47As wherein sulfur
monolayer doping is used to introduce additional carrier density to Si-doped
samples. The sequential doping of Si and S allows for high carrier concentrations
of up to 1.3 * 10(19) cm(-3) to be achieved without damaging the III-V lattice.
The coupling of the plasmon in the doped samples to the longitudinal optic
phonons allows Raman spectroscopy to serve as an excellent probe of the extent of
dopant activation, charge carrier density, and the surface depletion region. In
particular, the energy position of a high-frequency coupled mode (HFCM) that is
detected above 400 cm(-1) is used to extract the free electron density in these
samples. The extracted free electron densities are well correlated with measured
sheet resistance values and the carrier densities deduced from Hall measurements.
PMID- 25588190
TI - VEGF mRNA and protein concentrations in the developing human eye.
AB - BACKGROUND: Vascular endothelial growth factor (VEGF), a well-characterized
regulator of angiogenesis, has been mechanistically implicated in retinal
neovascularization and in the pathogenesis of retinopathy of prematurity.
However, the ontogeny of VEGF expression in the human fetal retina is not well
known. Because retinal vasculature grows with gestational maturation, we
hypothesized that VEGF expression also increases in the midgestation human fetal
eye as a function of gestational age. METHODS: To identify changes in VEGF gene
expression during normal human development, we measured VEGF mRNA by quantitative
PCR and measured VEGF protein by enzyme-linked immunosorbent assay and western
blots in 10-24 wk gestation fetal vitreous, retina, and serum. RESULTS: VEGF mRNA
expression in the retina increased with gestational age. VEGF isoform A,
particularly its VEGF121 splice variant, contributed to this positive
correlation. Consistent with these findings, we detected increasing VEGF121
protein concentrations in vitreous humor from fetuses of 10-24 wk gestation,
while VEGF concentrations decreased in fetal serum. CONCLUSION: VEGF121 mRNA and
protein concentrations increase with increasing gestational age in the developing
human retina. We speculate that VEGF plays an important role in normal retinal
vascular development, and that preterm delivery affects production of this
vascular growth factor.
PMID- 25588192
TI - Theoretical insight into the structural mechanism for the binding of vinblastine
with tubulin.
AB - Vinblastine (VLB) is one of vinca alkaloids with high cytotoxicity toward cancer
cells approved for clinical use. However, because of drug resistance, toxicity,
and other side effects caused from the use of VLB, new vinca alkaloids with
higher cytotoxicity toward cancer cells and other good qualities need to develop.
One strategy is to further study and better understand the essence why VLB
possesses the high cytotoxicity toward cancer cells. In present work, by using
molecular simulation, molecular docking, density functional calculation, and the
crystal structure of alpha,beta-tubulin complex, we find two modes labeled in
catharanthine moiety (CM) and vindoline moiety (VM) modes of VLB bound with the
interface of alpha,beta-tubulin to probe the essence why VLB has the high
cytotoxicity toward cancer cells. In the CM mode, nine key residues B-Ser178, B
Asp179, B-Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, C-Lys336, and C-Lys352
from the alpha,beta-tubulin complex are determined as the active sites for the
interaction of VLB with alpha,beta-tubulin. Some of them such as B-Ser178, B
Glu183, B-Tyr210, B-Asp226, C-Lys326, C-Asp327, and C-Lys336 are newly identified
as the active sites in present work. The affinity between VLB and the active
pocket within the interface of alpha,beta-tubulin is -60.8 kJ mol(-1) in the CM
mode. In the VM mode, that is a new mode established in present paper, nine
similar key residues B-Lys176, B-Ser178, B-Asp179, B-Glu183, B-Tyr210, B-Asp226,
C-Lys326, C-Asp327, and C-Lys336 from the alpha,beta-tubulin complex are found as
the active sites for the interaction with VLB. The difference is from one key
residue C-Lys352 in the CM mode changed to the key residue B-Lys176 in the VM
mode. The affinity between VLB and the active pocket within the interface of
alpha,beta-tubulin is -96.3 kJ mol(-1) in the VM mode. Based on the results
obtained in present work, and because VLB looks like two faces, composed of CM
and VM both to have similar polar active groups, to interact with the active
sites, we suggest double-faces sticking mechanism for the binding of VLB to the
interface of alpha,beta-tubulin. The double-faces sticking mechanism can be used
to qualitatively explain high cytotoxicity toward cancer cells of vinca alkaloids
including vinblastine, vincristine, vindestine, and vinorelbine approved for
clinical use and vinflunine still in a phase III clinical trial. Furthermore,
this mechanism will be applied to develop novel vinca alkaloids with much higher
cytotoxicity toward cancer cells.
PMID- 25588193
TI - Characterization of hazardous and odorous volatiles emitted from scented candles
before lighting and when lit.
AB - Scented candles are known to release various volatile organic compounds (VOCs)
including both pleasant aromas and toxic components both before lighting (off)
and when lit (on). In this study, we explored the compositional changes of
volatiles from scented candles under various settings to simulate indoor use.
Carbonyl compounds and other VOCs emitted from six different candle types were
analyzed under 'on/off' conditions. The six candle types investigated were: (1)
Clean cotton (CT), (2) Floral (FL), (3) Kiwi melon (KW), (4) Strawberry (SB), (5)
Vanilla (VN), and (6) Plain (PL). Although a large number of chemicals were
released both before lighting and when lit, their profiles were noticeably
distinguishable. Before lighting, various esters (n = 30) showed the most
dominant emissions. When lit, formaldehyde was found to have the highest emission
concentration of 2098 ppb (SB), 1022 ppb (CT), and 925 ppb (PL). In most lit
scented candles, there was a general tendency to show increased concentrations of
low boiling point compounds. For some scented candle products, the emission of
volatiles occurred strongly both before lighting and when lit. For instance, in
terms of TVOC (ppbC), the highest concentrations were observed from the KW
product with their values of 12,742 (on) and 2766 ppbC (off). As such, the
results suggest that certain scented candle products should act as potent sources
of VOC emission in indoor environment, regardless of conditions--whether being
lit or not.
PMID- 25588195
TI - The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a
mouse model of diet induced obesity.
AB - A diet rich in polyphenols can ameliorate some metabolic alterations associated
with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in
isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this
research was to determine the metabolic effect of an OFI extract on a mouse model
of diet-induced obesity and in isolated pancreatic islets. OFI extract was added
to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to
C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract
gained less body weight and exhibited significantly lower circulating total
cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF
diet alone. The HF-OFI diet fed mice presented lower glucose and insulin
concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended
to have higher insulin concentration than control mice. The OFI extract
stimulated insulin secretion in vitro, associated with increased glucose
transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma
(PPARgamma) mRNA content. Furthermore, the OFI extract improved glucose
tolerance, and additionally increased energy expenditure. These metabolic
improvements were associated with reduced adipocyte size, increased hepatic IRS1
tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also
diminished the hepatic lipid content associated with reduced mRNA expression of
the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA
expression of genes related to fatty acid oxidation. Overall, the OFI extract
prevented the development of metabolic abnormalities associated with diet-induced
obesity.
PMID- 25588194
TI - A multimodal analysis of antipsychotic effects on brain structure and function in
first-episode schizophrenia.
AB - IMPORTANCE: Recent data suggest that treatment with antipsychotics is associated
with reductions in cortical gray matter in patients with schizophrenia. These
findings have led to concerns about the effect of antipsychotic treatment on
brain structure and function; however, no studies to date have measured cortical
function directly in individuals with schizophrenia and shown antipsychotic
related reductions of gray matter. OBJECTIVE: To examine the effects of
antipsychotics on brain structure and function in patients with first-episode
schizophrenia, using cortical thickness measurements and administration of the AX
version of the Continuous Performance Task (AX-CPT) during event-related
functional magnetic resonance imaging. DESIGN, SETTING, AND PARTICIPANTS: This
case-control cross-sectional study was conducted at the Imaging Research Center
of the University of California, Davis, from November 2004 through July 2012.
Participants were recruited on admission into the Early Diagnosis and Preventive
Treatment Clinic, an outpatient clinic specializing in first-episode psychosis.
Patients with first-episode schizophrenia who received atypical antipsychotics
(medicated patient group) (n = 23) and those who received no antipsychotics
(unmedicated patient group) (n = 22) and healthy control participants (n = 37)
underwent functional magnetic resonance imaging using a 1.5-T scanner. MAIN
OUTCOMES AND MEASURES: Behavioral performance was measured by trial accuracy,
reaction time, and d'-context score. Voxelwise statistical parametric maps tested
differences in functional activity during the AX-CPT, and vertexwise maps of
cortical thickness tested differences in cortical thickness across the whole
brain. RESULTS: Significant cortical thinning was identified in the medicated
patient group relative to the control group in prefrontal (mean reduction [MR],
0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P =
.001), and occipital (MR, 0.24 mm; P = .001) cortices. The unmedicated patient
group showed no significant cortical thickness differences from the control group
after clusterwise correction. The medicated patient group showed thinner cortex
compared with the unmedicated patient group in the dorsolateral prefrontal cortex
(DLPFC) (MR, 0.26 mm; P = .001) and temporal cortex (MR, 0.33 mm; P = .047).
During the AX-CPT, both patient groups showed reduced DLPFC activity compared
with the control group (P = .02 compared with the medicated group and P < .001
compared with the unmedicated group). However, the medicated patient group
demonstrated higher DLPFC activation (P = .02) and better behavioral performance
(P = .02) than the unmedicated patient group. CONCLUSIONS AND RELEVANCE: These
findings highlight the complex relationship between antipsychotic treatment and
the structural, functional, and behavioral deficits repeatedly identified in
schizophrenia. Although short-term treatment with antipsychotics was associated
with prefrontal cortical thinning, treatment was also associated with better
cognitive control and increased prefrontal functional activity. This study adds
important context to the growing literature on the effects of antipsychotics on
the brain and suggests caution in interpreting neuroanatomical changes as being
related to a potentially adverse effect on brain function.
PMID- 25588196
TI - Application of Molecular Diagnostics in Primary Detection of ESBL Directly from
Clinical Specimens.
AB - The infections caused by extended-spectrum beta-lactamase (ESBL)-producing
organisms are associated with increased mortality. The real-time polymerase chain
reaction (PCR) method, which enables detection of ESBLs directly from patients'
clinical material, was developed. This study focused on blaCTX-M and blaSHV
determination in endotracheal aspirates. Each sample was identified with standard
microbiological procedures and simultaneously analyzed for the presence of
nucleic acids, which encode CTX-M and SHV ESBL enzymes using real-time PCR. A
total of 341 samples were investigated. In the set, 27 ESBL-positive samples were
identified by phenotypic methods, while 60 positive samples were identified by
the PCR method. Of the 60 PCR-positive samples, 58 were positive for the blaCTX
M. In two samples, the ESBL blaSHV-ESBL gene was detected. One phenotypically
positive sample was PCR negative. The real-time PCR assay does not require a
cultivation step and therefore enables detection of ESBL in 6 hours. The rapid
method is necessary for early and adequate antimicrobial treatment.
PMID- 25588198
TI - Wavelength- and efficiency-tunable plasmon-induced charge separation by the use
of Au-Ag alloy nanoparticles.
AB - TiO2 electrodes loaded with Au-Ag alloy nanoparticles, Ag content of which is
about 0.25-0.90, exhibit stable anodic photocurrents due to plasmon-induced
charge separation (PICS) in the presence of an electron donor. The PICS
wavelength is blueshifted and the PICS efficiency is enhanced by increasing the
Ag content in the nanoparticles.
PMID- 25588199
TI - Analysis of impurity effects on the coloration of corundum by laser-induced
breakdown spectroscopy (LIBS).
AB - Corundum was analyzed using laser-induced breakdown spectroscopy (LIBS) for
impurity effects in their multiple colorings. Qualitative measurements were
attained for impurities of chromium, magnesium, iron, and titanium in red,
yellow, and blue samples. Moreover, treatment with a beryllium diffusion, which
can modify corundum to obtain an attractive color, was tested in the yellow
sample. In this work, most of the measurements were acquired using a laser pulse
energy of 5 mJ and impurity emissions were appreciable. The signal-to-noise
ratios were 11, 6.5, 10, and 4 for the Cr 425.44 nm, Fe 404.58 nm, Be 313.04 nm,
and Mg 285.21 nm lines, respectively, for five laser shots. The amount of damage
to the corundum samples was also monitored by measuring the craters after laser
analysis. It was found that the crater size was about 30 MUm after 10 laser
shots. As such, the damage to corundum sample is almost imperceptible after the
LIBS analysis.
PMID- 25588197
TI - Functional near infrared spectroscopy as a potential biological assessment of
addiction recovery: preliminary findings.
AB - BACKGROUND: Addiction science has primarily utilized self-report, continued
substance use, and relapse factors to explore the process of recovery. However,
the entry into successful abstinence substantially reduces our assessment
abilities. Advances in neuroscience may be the key to objective understanding,
treating, and monitoring long-term success in addiction recovery. OBJECTIVES: To
explore functional near infrared spectroscopy (fNIR) as a viable technique in the
assessment of addiction-cue reactivity. Specifically, prefrontal cortex (PFC)
activation to alcohol cues was explored among formally alcohol-dependent
individuals, across varying levels of successful abstinence. The aim of the
investigation was to identify patterns of PFC activation change consistent with
duration of abstinence. METHODS: A total of 15 formally alcohol-dependent
individuals, with abstinence durations ranging from 1 month to 10 years, viewed
alcohol images during fNIR PFC assessment. Participants also subjectively rated
the same images for affect and arousal level. RESULTS: Subjective ratings of
alcohol cues did not significantly correlate with duration of abstinence. As
expected, days of abstinence did not significantly correlate with neutral cue
fNIR reactivity. However, for alcohol cues, fNIR results showed increased days of
abstinence was associated with decreased activation within the dorsolateral and
dorsomedial prefrontal cortex regions. CONCLUSIONS: The present results suggest
that fNIR may be a viable tool in the assessment of addiction-cue reactivity.
RESULTS also support previous findings on the importance of dorsolateral and
dorsomedial PFC in alcohol-cue activation. The findings build upon these past
results suggesting that fNIR-assessed activation may represent a robust
biological marker of successful addiction recovery.
PMID- 25588200
TI - Clinical competency evaluation of Brazilian chiropractic interns.
AB - OBJECTIVE: This study compares the results of an objective structured clinical
examination (OSCE) between 2 groups of students before an internship and after 6
months of clinical practice in an internship. METHODS: Seventy-two students
participated, with 36 students in each cohort. The OSCEs were performed in the
simulation laboratory before the participants' clinical practice internship and
after 6 months of the internship. Students were tested in 9 stations for clinical
skills and knowledge. The same procedures were repeated for both cohorts. The t
test was used for unpaired parametric samples and Fisher's exact test was used
for comparison of proportions. RESULTS: There was no difference in the mean final
score between the 2 groups (p = .34 for test 1; p = .08 for test 2). The
performance of the students in group 1 was not significantly different when
performed before and after 6 months of clinical practice, but in group 2 there
was a significant decrease in the average score after 6 months of clinical
practice. CONCLUSIONS: There was no difference in the cumulative average score
for the 2 groups before and after 6 months of clinical practice in the
internship. There were differences within the cohorts, however, with a
significant decrease in the average score in group 2. Issues pertaining to test
standardization and student motivation for test 2 may have influenced the scores.
PMID- 25588201
TI - PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes
and low charge densities.
AB - OBJECTIVE: The aim of this study was to compare two different microelectrode
materials--the conductive polymer composite poly-3,4-ethylenedioxythiophene
(PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)--at activating spikes in
retinal ganglion cells in whole mount rat retina through stimulation of the local
retinal network. Stimulation efficacy of the microelectrodes was analyzed by
comparing voltage, current and transferred charge at stimulation threshold.
APPROACH: Retinal ganglion cell spikes were recorded by a central electrode (30
MUm diameter) in the planar grid of an electrode array. Extracellular stimulation
(monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using
constant voltage pulses applied to the eight surrounding electrodes. The
stimulation electrodes were equally spaced on the four sides of a square (400 *
400 MUm). Threshold voltage was determined as the pulse amplitude required to
evoke network-mediated ganglion cell spiking in a defined post stimulus time
window in 50% of identical stimulus repetitions. For the two electrode materials
threshold voltage, transferred charge at threshold, maximum current and the
residual current at the end of the pulse were compared. MAIN RESULTS: Stimulation
of retinal interneurons using PEDOT-CNT electrodes is achieved with lower
stimulation voltage and requires lower charge transfer as compared to TiN. The
key parameter for effective stimulation is a constant current over at least 0.5
ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to
its faradaic charge transfer mechanism. SIGNIFICANCE: In neuroprosthetic
implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a
safe voltage regime and lower energy-consumption. Our study also indicates, that
the charge transferred at threshold or the charge injection capacity per se does
not determine stimulation efficacy.
PMID- 25588202
TI - The emerging role of radiotherapy for desmoplastic melanoma and implications for
future research.
AB - The National Comprehensive Cancer Network (NCCN) 2014 guidelines are unclear
about the role of radiotherapy in the management of desmoplastic melanoma. The
guidelines specify that radiotherapy can be 'considered' for select patients with
desmoplastic melanoma with narrow surgical margins. Patient selection criteria,
including margins, are not well defined, causing considerable differences in
practice patterns across the country. There are also several conflicting reports
about the role of radiotherapy in improving postsurgical outcomes when other
adverse pathological risks factors, such as increased Clark level, head and neck
involvement, perineural invasion, positive margins, or recurrent disease, are
also present. Recent data provide further clarification and insights into the
role of radiotherapy. Thus, in light of the NCCN guidelines and the recently
published series, we critically review the role of radiotherapy for desmoplastic
melanoma. In our review, we highlight the published risk factors that predict for
increased risk of recurrence after surgery. We also provide a comparison of
surgical and radiation outcomes data, and then address areas for further
research.
PMID- 25588203
TI - Let-7b overexpression leads to increased radiosensitivity of uveal melanoma
cells.
AB - Uveal melanoma (UM) is an intraocular malignant tumor in adults that is
characterized by rapid progression and recurrence. Irradiation has become the
primary therapy for UM patients who are not candidates for surgery. However,
after large-dose fraction irradiation treatment, some patients undergo subsequent
enucleation because of radiotherapy-related complications. This situation has
raised concerns on how to optimize the effectiveness of radiation treatment.
Recent investigations of microRNAs are changing our understanding of UM tumor
biology and are helping to identify novel targets for radiotherapy. The
radioresistant UM cell lines OM431 and OCM1 were selected and exposed to
irradiation, and let-7b was found to be downregulated after exposure. We then
confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo.
More specifically, transfection with let-7b mimics markedly resensitized OCM1 and
OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1
plays a vital role in cell cycle arrest, which is induced by let-7b
overexpression. Cyclin D1 is also a target of let-7b and its expression is
suppressed by upregulation of let-7b. Collectively, our results indicate that let
7b overexpression can in turn downregulate cyclin D1 expression and enhance the
radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker
for radiosensitivity and could enhance the therapeutic benefit of UM cell
irradiation.
PMID- 25588205
TI - The supportive roles of religion and spirituality in end-of-life and palliative
care of patients with cancer in a culturally diverse context: a literature
review.
AB - PURPOSE OF REVIEW: This is a literature review of the supportive roles of
religion and spirituality (R/S) in end-of-life (EoL) and palliative care of
patients with cancer in a culturally diverse context. This review examines 26
noteworthy articles published between August 2013 and August 2014 from five well
supported databases. RECENT FINDINGS: Current evidence shows that R/S evokes in
patients the sources to find the necessary inner strengths, which includes
perspective thinking, rituals for transcending immediate physical condition and
modalities of coping with their oncological illnesses. R/S are not a
monolithically experience for they always manifest themselves in diverse cultural
settings. As such, R/S provide the individual and their families with a practical
context and social memory, which includes traditions and social family practices
for maintaining meaning and well-being. Nonetheless, although various dimensions
of R/S show a link between cancer risk factors and well being in cancer patients,
more specific dimensions of R/S need to be studied taking into account the
individuals' particular religious and cultural contexts, so that R/S variables
within that context can provide a greater integrative structure for understanding
and to move the field forward. SUMMARY: Behavioral, cognitive and psychosocial
scientists have taken a more in-depth look at the claims made in the past,
suggesting that a relationship between R/S, cultural diversity and health exists.
Case in point are the studies on EoL care, which have progressively considered
the role of cultural, religion and spiritual diversity in the care of patients
with oncological terminal illnesses. Beyond these facts, this review also shows
that EoL supportive and palliative care providers could further enhance their
practical interventions by being sensitive and supportive of cultural diversity.
VIDEO ABSTRACT: http://links.lww.com/COSPC/A10
PMID- 25588204
TI - The central role of meaning in adjustment to the loss of a child to cancer:
implications for the development of meaning-centered grief therapy.
AB - PURPOSE OF REVIEW: This review describes research on meaning and meaning-making
in parents who have lost a child to cancer, suggesting the need for a meaning
centered therapeutic approach to improve their sense of meaning, purpose, and
identity and help with management of prolonged grief symptoms. RECENT FINDINGS:
Several studies have demonstrated that parents bereaved by cancer experience
unique meaning-related challenges associated with the caregiving and illness
experience, including struggles with making sense of their loss, benefit-finding,
their sense of identity and purpose, disconnection from sources of meaning, and
sustaining a sense of meaning in their child's life. Meaning-centered grief
therapy, adapted from meaning-centered psychotherapy, directly addresses these
issues, highlighting the choices parents have in how they face their pain, how
they honor their child and his/her living legacy, the story they create, and how
they live their lives. SUMMARY: Given the important role that meaning plays in
adjustment to the loss of a child to cancer, a meaning-focused approach such as
meaning-centered grief therapy may help improve parents' sense of meaning and
grief symptoms. It seems particularly appropriate for parents who lost a child to
cancer because it does not pathologize their struggles and directly targets
issues they frequently face.
PMID- 25588206
TI - Palliative care issues in heart transplant candidates.
AB - PURPOSE OF REVIEW: Heart failure is a serious condition and equivalent to
malignant disease in terms of symptoms burden and mortality. Presently, only a
comparatively small number of heart failure patients receive specialized
palliative care. A literature search was conducted with the terms, palliative
care and heart failure, using the electronic databases of PubMed and MEDLINE.
RECENT FINDINGS: Nine-hundred and five articles were reviewed and of those, 78
articles discussed clinical trials in palliative care and heart failure. A
complex set of management tools and strategies were used and recommended,
including but not limited to lifestyle modification, exercise programs, pain and
sleep disorder management, and support in end-of-life care. Limited data are
available of using palliative care in heart transplant candidates prior to
transplant surgery. SUMMARY: Diminishing quality of life prevails throughout the
course of chronic heart failure. Therefore, palliative care should be integrated
into heart failure management. Heart transplant candidates may benefit from early
palliative care involvement independent of the clinical course and outcome.
Because of gaps in current scientific literature on palliative care, end-of-life
care, and hospice care and the services rendered, further research is necessary
to encourage healthcare professionals to introduce palliative care as an early
resource in chronic disease progression.
PMID- 25588207
TI - Parenting challenges in the setting of terminal illness: a family-focused
perspective.
AB - PURPOSE OF REVIEW: In the advanced stages of illness, families with dependent
children experience disruption across all dimensions of family life. The need for
family support during palliative care is well recognized, yet little is
understood about how parents and their children navigate these difficult
circumstances. This review summarizes the current body of research on parenting
challenges in advanced cancer. RECENT FINDINGS: To date, the study of parental
cancer has focused predominantly on the early stages of disease and its impact on
children and adolescents. Less is known about how families with minor children
prepare for parental loss. Evidence suggests that having dependent children
influences parents' treatment decisions at the end of life, and that a central
concern for children and parents is optimizing time spent together. Parents may
feel an urgency to engage in accelerated parenting, and maintaining normalcy
remains a consistent theme for the ill and healthy parent alike. There is a
growing evidence base affirming the importance of responsive communication prior
to death. SUMMARY: Advancing knowledge about the parenting experience at the end
of life is critical for ensuring effective support to the entire family, as it
accommodates and prepares for the loss of a vital member.
PMID- 25588208
TI - Burden of caring: risks and consequences imposed on caregivers of those living
and dying with advanced heart failure.
AB - PURPOSE OF REVIEW: To summarize the latest research on the risks and consequences
of the burden that may be imposed on informal carers of persons living and dying
with advanced heart failure. RECENT FINDINGS: A systematic search in PubMed over
the period 2013-2014 ultimately revealed 24 original articles included in this
review. From this research update it can be concluded that the body of knowledge
increased with more studies focusing on caregivers of patients with advanced
heart failure. SUMMARY: Caregivers are important partners in care and their lives
are seriously affected by the condition of advanced heart failure. Studies on the
longitudinal effects of the caregiving role on caregiver's quality of life and on
caregiver contributions to patient outcomes is still scarce. Focus of current
research is moving towards relationship aspects. Dyadic-care typologies and the
concept of incongruence within dyads in terms of conflicting perspectives on how
to manage the heart failure are new and important concepts presented in studies
presented in this review. Heart failure patients and their caregivers still lack
sufficient palliative care and communication on prognosis and end-of-life care.
More research is needed to determine the optimal time to start palliative
interventions to support caregivers of patients with advanced heart failure.
PMID- 25588211
TI - Getting a grasp of theories of sensorimotor control of the hand: identification
of underlying neural mechanisms.
PMID- 25588209
TI - Treatment with apixaban in a patient with recent chronic subdural haematoma: a
case report.
PMID- 25588210
TI - Approximating the detection limit of an infrared spectroscopic imaging microscope
operating in an attenuated total reflection (ATR) modality: theoretical and
empirical results for an instrument using a linear array detector and a 1.5
millimeter germanium hemisphere internal reflection element.
AB - Theoretical and empirical detection limits have been estimated for aripiprazole
(analyte) in alpha lactose monohydrate (matrix model pharmaceutical formulation)
using a micro-attenuated total reflection Fourier transform infrared (ATR FT-IR)
spectroscopic imaging instrument equipped with a linear array detector and a 1.5
mm germanium hemisphere internal reflection element (IRE). The instrument yielded
a theoretical detection limit of 0.0035% (35 parts per million (ppm)) when
operating under diffraction-limited conditions, which was 49 times lower than
what was achieved with a traditional macro-ATR instrument operating under
practical conditions (0.17%, 1700 ppm). However, these results may not be
achievable for most analyses because the detection limits will be particle size
limited, rather than diffraction limited, for mixtures with average particle
diameters greater than 8.3 MUm (most pharmaceutical samples). For example, a
theoretical detection limit of 0.028% (280 ppm) was calculated for an experiment
operating under particle size-limited conditions where the average particle size
was 23.4 MUm. These conditions yielded a detection limit of 0.022% (220 ppm) when
measured empirically, which was close to the theoretical value and only eight
times lower than that of a faster, more simplistic macro-ATR instrument.
Considering the longer data acquisition and processing times characteristic of
the micro-ATR imaging approach (minutes or even hours versus seconds), the cost
benefit ratio may not often be favorable for the analysis of analytes in matrices
that exhibit only a few overlapping absorptions (low-interfering matrices such as
alpha lactose monohydrate) using this technique compared to what can be achieved
using macro-ATR. However, the advantage was significant for detecting analytes in
more complex matrices (those that exhibited several overlapping absorptions with
the analyte) because the detection limit of the macro-ATR approach was highly
formulation dependent while that of the micro-ATR imaging technique was not. As a
result, the micro-ATR imaging technique is expected to be more valuable than
macro-ATR for detecting analytes in high-interfering matrices and in products
with unknown ingredients (e.g., illicit tablets, counterfeit tablets, and unknown
powders).
PMID- 25588212
TI - Byproduct promoted regioselective sulfenylation of indoles with sulfinic acids.
AB - An unprecedented method to synthesise 3-sulfenylindoles is demonstrated via
byproduct promoted sulfenylation of indoles with sulfinic acids in the absence of
an external catalyst. The reaction selectively afforded structurally diverse
indole thioethers in good to excellent yields in 1,2-dichloroethane at 80
degrees C.
PMID- 25588214
TI - TiO2 immobilized on Manihot carbon: optimal preparation and evaluation of its
activity in the decomposition of indigo carmine.
AB - Applications of carbon-TiO2 materials have attracted attention in nanotechnology
due to their synergic effects. We report the immobilization of TiO2 on carbon
prepared from residues of the plant Manihot, commercial TiO2 and glycerol. The
objective was to obtain a moderate loading of the anatase phase by preserving the
carbonaceous external surface and micropores of the composite. Two preparation
methods were compared, including mixing dry precursors and immobilization using a
glycerol slurry. The evaluation of the micropore blocking was performed using
nitrogen adsorption isotherms. The results indicated that it was possible to use
Manihot residues and glycerol to prepare an anatase-containing material with a
basic surface and a significant SBET value. The activities of the prepared
materials were tested in a decomposition assay of indigo carmine. The TiO2/carbon
eliminated nearly 100% of the dye under UV irradiation using the optimal
conditions found by a Taguchi L4 orthogonal array considering the specific
surface, temperature and initial concentration. The reaction was monitored by UV
Vis spectrophotometry and LC-ESI-(Qq)-TOF-MS, enabling the identification of some
intermediates. No isatin-5-sulfonic acid was detected after a 60 min
photocatalytic reaction, and three sulfonated aromatic amines, including 4-amino
3-hydroxybenzenesulfonic acid, 2-(2-amino-5-sulfophenyl)-2-oxoacetic acid and 2
amino-5-sulfobenzoic acid, were present in the reaction mixture.
PMID- 25588213
TI - Ponicidin induces apoptosis via JAK2 and STAT3 signaling pathways in gastric
carcinoma.
AB - Ponicidin has a variety of biological effects such as immunoregulatory and anti
inflammatory functions as well as anti-viral functions especially in the upper
respiratory tract infection. This study was aimed to elucidate the antitumor
effect of ponicidin in gastric carcinoma MKN28 cells and the possible molecular
mechanism involved. Cell viability was measured by the Cell Count Kit-8 (CCK8).
Cell apoptosis was assessed by flow cytometry as well as cell cycle and reactive
oxygen species (ROS) analysis. Western blot analysis was used to detect the
active form of caspase-3 as well as Bax and B-cell lymphoma-2 (Bcl-2) expressions
after cells were treated with different concentrations of ponicidin. The results
revealed that ponicidin could inhibit the growth of MKN28 cells significantly in
both a time- and dose-dependent manner. The cell cycle was blocked and ROS
generation was increased after the cells were treated with ponicidin. Bcl-2
expression was down-regulated remarkably while Bax expression and the active form
of caspase-3 were increased after apoptosis occurred. We therefore conclude that
ponicidin exhibited significant growth inhibition of gastric carcinoma cell line
MKN28 and induced apoptosis of MKN28 cells via the signaling pathway regulated by
Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3
(STAT3). Ponicidin may serve as a potential therapeutic agent for gastric
carcinoma.
PMID- 25588215
TI - Acetic acid can catalyze succinimide formation from aspartic acid residues by a
concerted bond reorganization mechanism: a computational study.
AB - Succinimide formation from aspartic acid (Asp) residues is a concern in the
formulation of protein drugs. Based on density functional theory calculations
using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the
possibility that acetic acid (AA), which is often used in protein drug
formulation for mildly acidic buffer solutions, catalyzes the succinimide
formation from Asp residues by acting as a proton-transfer mediator. The proposed
mechanism comprises two steps: cyclization (intramolecular addition) to form a
gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps
are catalyzed by an AA molecule, and the first step was predicted to be rate
determining. The cyclization results from a bond formation between the amide
nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part
of an extensive bond reorganization (formation and breaking of single bonds and
the interchange of single and double bonds) occurring concertedly in a cyclic
structure formed by the amide NH bond, the AA molecule and the side-chain C=O
group and involving a double proton transfer. The second step also involves an AA
mediated bond reorganization. Carboxylic acids other than AA are also expected to
catalyze the succinimide formation by a similar mechanism.
PMID- 25588216
TI - Caution is required in interpretation of mutations in the voltage sensing domain
of voltage gated channels as evidence for gating mechanisms.
AB - The gating mechanism of voltage sensitive ion channels is generally considered to
be the motion of the S4 transmembrane segment of the voltage sensing domains
(VSD). The primary supporting evidence came from R -> C mutations on the S4
transmembrane segment of the VSD, followed by reaction with a
methanethiosulfonate (MTS) reagent. The cys side chain is -SH (reactive form -S
); the arginine side chain is much larger, leaving space big enough to
accommodate the MTS sulfonate head group. The cavity created by the mutation has
space for up to seven more water molecules than were present in wild type, which
could be displaced irreversibly by the MTS reagent. Our quantum calculations show
there is major reorientation of three aromatic residues that face into the cavity
in response to proton displacement within the VSD. Two phenylalanines reorient
sufficiently to shield/unshield the cysteine from the intracellular and
extracellular ends, depending on the proton positions, and a tyrosine forms a
hydrogen bond to the cysteine sulfur with its side chain -OH. These could produce
the results of the experiments that have been interpreted as evidence for
physical motion of the S4 segment, without physical motion of the S4 backbone.
The computations strongly suggest that the interpretation of cysteine
substitution reaction experiments be re-examined in the light of these
considerations.
PMID- 25588219
TI - RETRACTION: Barkhordari A, et al. The glycoprofile patterns of endothelial cells
in usual interstitial pneumonia. Int J Occup Environ Med 2014;5:201-7.
PMID- 25588217
TI - Protection of retina by mini-alphaA in NaIO3-induced retinal pigment epithelium
degeneration mice.
AB - BACKGROUND: Studies have shown that mini-alphaA can protect retinal pigment
epithelium (RPE) cells from apoptosis. However, no in vivo study concerning the
anti-apoptotic function of mini-alphaA has been conducted yet. METHODS: MTT
assay, HE staining and TUNEL assay were used to assess levels of cells, and an
animal model was established to examine the protective effects of mini-alphaA
against NaIO3-induced RPE cell apoptosis. Western blot analysis and RT-qPCR were
performed to explore the possible mechanism of mini-alphaA's protective function
against NaIO3-induced RPE cell apoptosis. RESULTS: RESULTS from in vivo and
animal experiments showed that mini-alphaA antagonized NaIO3-induced RPE cell
apoptosis. Further investigation into how mini-alphaA provided protection against
NaIO3-induced RPE cell apoptosis showed that mini-alphaA reduced NaIO3-induced
RPE cell apoptosis and autophagy. In addition, unfolded protein response was also
involved in the protective effects of mini-alphaA against NaIO3-induced RPE cell
apoptosis. CONCLUSIONS: mini-alphaA can antagonize RPE cell apoptosis induced by
NaIO3. A possible mechanism is by inhibition of apoptosis by repressing autophagy
and endoplasmic reticulum stress.
PMID- 25588220
TI - Why is redundant publication a problem?
PMID- 25588218
TI - Activation of the ubiquitin proteasome pathway by silk fibroin modified chitosan
nanoparticles in hepatic cancer cells.
AB - Silk fibroin (SF) is a protein with bulky hydrophobic domains and can be easily
purified as sericin-free silk-based biomaterial. Silk fibroin modified chitosan
nanoparticle (SF-CSNP), a biocompatible material, has been widely used as a
potential drug delivery system. Our current investigation studied the bio-effects
of the SF-CSNP uptake by liver cells. In this experiment, the characterizations
of SF-CSNPs were measured by particle size analysis and protein assay. The
average size of the SF-CSNP was 311.9 +/- 10.7 nm, and the average zeta potential
was +13.33 +/- 0.3 mV. The SF coating on the SF-CSNP was 6.27 +/- 0.17 MUg/mL.
Moreover, using proteomic approaches, several proteins involved in the ubiquitin
proteasome pathway were identified by analysis of differential protein
expressions of HepG2 cell uptake the SF-CSNP. Our experimental results have
demonstrated that the SF-CSNP may be involved in liver cancer cell survival and
proliferation.
PMID- 25588221
TI - Attitude of medical students towards occupational safety and health: a multi
national study.
AB - BACKGROUND: Work-related diseases contribute immensely to the global burden of
diseases. Better understanding of attitudes of health care workers towards
occupational safety and health (OSH) is important for planning. OBJECTIVE: To
assess the attitude of medical students towards OSH around the globe. METHODS: A
questionnaire assessing the attitude towards OSH was administered to medical and
paramedical students of 21 Medical Universities across the globe. In the current
study 1895 students, aged 18-36 years, from 17 countries were included. After
having performed a principal components analysis, the associations of interest
between the identified components and other socio demographic characteristics
were assessed by multivariate linear regression. RESULTS: Principal component
analysis revealed 3 components. Students from lower and lower-middle-income
countries had a more positive attitude towards OSH, but the importance of OSH was
still rated higher by students from upper-income countries. Although students
from Asian and African continents showed high interest for OSH, European and
South-Central American students comparatively rated importance of OSH to be
higher. Paramedical students had more positive attitude towards OSH than medical
students. CONCLUSION: The attitude of students from lower-income and lower-middle
income towards importance of OSH is negative. This attitude could be changed by
recommending modifications to OSH courses that reflect the importance of OSH.
Since paramedical students showed more interest in OSH than medical students,
modifications in existing health care system with major role of paramedics in OSH
service delivery is recommended.
PMID- 25588222
TI - Effects of long-term exposure to hydrogen sulfide on human red blood cells.
AB - BACKGROUND: Hydrogen sulfide (H2S) exhibits both physiological and toxicological
roles in the biological systems. Acute exposure to high levels of H2S is life
threatening while long-term exposure to ambient levels of H2S elicits human
health effects. OBJECTIVE: To study the harmful effects of long-term exposure to
low levels of H2S on human blood cells. METHODS: 110 adult workers from Iran who
were occupationally exposed to 0-90 ppb H2S for 1-30 years were studied. The
participants aged between 18 and 60 years and were exposed directly or indirectly
to sulfur compounds (exposed group). The origin of H2S was natural gas processing
plants. A control group consisting of 110 males who were not in contact with H2S
was also studied. For all participants, hematological profile including total
hemoglobin and red blood cell count and sulfhemoglobin, methemoglobin levels were
measured. RESULTS: Among all parameters evaluated in this study the mean
methemoglobin and sulfhemoglobin levels were significantly higher among workers
who were exposed to sulfur compounds than the control group. Major differences
throughout the study period for sulfhemoglobinemia among exposed groups were
observed. CONCLUSION: Long-term exposure to even low levels of H2S in workplaces
may have potential harmful effects on human health.
PMID- 25588223
TI - Benchmarking of percutaneous injuries at the Ministry of Health hospitals of
Saudi Arabia in comparison with the United States hospitals participating in
Exposure Prevention Information Network (EPINetTM).
AB - BACKGROUND: Exposure to blood-borne pathogens from needle-stick and sharp
injuries continues to pose a significant risk to health care workers. These
events are of concern because of the risk to transmit blood-borne diseases such
as hepatitis B virus, hepatitis C virus, and the human immunodeficiency virus.
OBJECTIVE: To benchmark different risk factors associated with needle-stick
incidents among health care workers in the Ministry of Health hospitals in the
Kingdom of Saudi Arabia compared to the US hospitals participating in Exposure
Prevention Information Network (EPINetTM). METHODS: Prospective surveillance of
needle-stick and sharp incidents carried out during the year 2012 using EPINetTM
ver 1.5 that provides uniform needle stick and sharp injury report form. RESULTS:
The annual percutaneous incidents (PIs) rate per 100 occupied beds was 3.2 at the
studied MOH hospitals. Nurses were the most affected job category by PIs (59.4%).
Most PIs happened in patients' wards in the Ministry of Health hospitals (34.6%).
Disposable syringes were the most common cause of PIs (47.20%). Most PIs occurred
during use of the syringes (36.4%). CONCLUSION: Among health care workers, nurses
and physicians appear especially at risk of exposure to PIs. Important risk
factors of injuries include working in patient room, using disposable syringes,
devices without safety features. Preventive strategies such as continuous
training of health care workers with special emphasis on nurses and physicians,
encouragement of reporting of such incidents, observation of sharp handling,
their use and implementation of safety devices are warranted.
PMID- 25588224
TI - Metabolic syndrome: a common problem among office workers.
AB - BACKGROUND: Metabolic syndrome (MSx) is associated with several health problems.
Workers are an important part of any organization. OBJECTIVE: To determine the
prevalence of MSx and related variables among office workers. METHODS: This cross
sectional study evaluated 1488 office workers in Qom province, Central Iran, by
using a multi-stage cluster sampling. Diagnosis of MSx was based on blood HDL
cholesterol, triglyceride, and fasting blood sugar (FBS) levels and waist
circumference, and blood pressure. RESULTS: The overall prevalence of MSx was
35.9% (95% CI 33.5% to 38.3%), higher in men (37.2%) than in women (20.6%), and
increased with age. The most common laboratory findings of MSx were
hypertriglyceridemia (45.9%) and low HDL-cholesterol level (45.5%). Office
workers with MSx had a significantly (p<0.001) higher body mass index than those
without MSx. Lack of regular leisure time physical activity (p=0.003), and low
intake of fruits (p=0.02) were associated with MSx. CONCLUSION: The prevalence of
MSx was very high among office workers. Workplace health improvement programs
through identifying and preventing MSx are necessary for improvement of staff's
health.
PMID- 25588225
TI - Respiratory disorders associated with occupational inhalational exposure to
bioaerosols among wastewater treatment workers of petrochemical complexes.
AB - BACKGROUND: Workers in wastewater treatment plants are exposed to a wide range of
chemicals as well as biological contaminants. OBJECTIVE: To ascertain whether
exposure to bio-aerosols under the normal working conditions in wastewater
treatment plants is associated with any significant changes in the prevalence of
respiratory symptoms and lung function capacities. METHODS: 198 employees of
wastewater treatment plants and 99 unexposed persons were studied. American
thoracic society (ATS) standard respiratory symptom questionnaire was used to
determine the prevalence of respiratory symptoms. Pulmonary function tests were
conducted for each participant. RESULTS: The prevalence of respiratory symptoms
among exposed persons was significantly higher than that of unexposed people.
Mean values of most pulmonary function test parameters were significantly lower
in the exposed compared to the comparison group persons. CONCLUSION: Increased
prevalence of respiratory symptoms and decrements in pulmonary function test
parameters may be attributed to exposure to bio-aerosols released from wastewater
treatment plants.
PMID- 25588226
TI - Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function
in lead-exposed workers from lead-acid battery manufacturing process.
AB - BACKGROUND: The interaction between serum neuron-specific enolase (NSE), biogenic
amino-acids and neurobehavioral function with blood lead levels in workers
exposed to lead form lead-acid battery manufacturing process was not studied.
OBJECTIVE: To evaluate serum NSE and biogenic amino-acids (dopamine and
serotonin) levels, and neurobehavioral performance among workers exposed to lead
from lead-acid storage battery plant, and its relation with blood lead levels
(BLLs). METHODS: In a cross-sectional study, we performed biochemical and
neurobehavioral function tests on 146 workers exposed to lead from lead-acid
battery manufacturing process. BLLs were assessed by an atomic absorption
spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA.
Neurobehavioral functions were assessed by CDC-recommended tests---simple
reaction time (SRT), symbol digit substitution test (SDST), and serial digit
learning test (SDLT). RESULTS: There was a significant correlation (r 0.199,
p<0.05) between SDST and BLL. SDLT and SRT had also a significant positive
correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05)
with serotonin level. Multiple linear regression analysis revealed that both SRT
and SDST had positive significant associations with BLL. SRT also had a positive
significant association with age. CONCLUSION: Serum NSE cannot be used as a
marker for BLL. The only domain of neurobehavioral function tests that is
affected by increased BLL in workers of lead-acid battery manufacturing process
is that of the "attention and perception" (SDST).
PMID- 25588229
TI - Guest editorial: pittcon 2015.
PMID- 25588230
TI - Meet the new president: Diane Parry.
PMID- 25588227
TI - Knowledge and attitude towards asbestos hazards among asbestos workers in India.
PMID- 25588231
TI - Analysis of pure tar substances (polycyclic aromatic hydrocarbons) in the gas
stream using ultraviolet visible (UV-Vis) spectroscopy and multivariate curve
resolution (MCR).
AB - The analysis of tar, mostly characterized as polycyclic aromatic hydrocarbons
(PAHs), describes a topic that has been researched for years. An online analysis
of tar in the gas stream in particular is needed to characterize the tar
conversion or formation in the biomass gasification process. The online analysis
in the gas is carried out with ultraviolet-visible (UV-Vis) spectroscopy (190-720
nm). This online analysis is performed with a measuring cell developed by the
Fraunhofer Institute for Chemical Technology (ICT). To this day, online tar
measurements using UV-Vis spectroscopy have not been carried out in detail.
Therefore, PAHs are analyzed as follows. The measurements are split into
different steps. The first step to prove the online method is to vaporize single
tar substances. These experiments show that a qualitative analysis of PAHs in the
gas stream with the used measurement setup is possible. Furthermore, it is shown
that the method provides very exact results, so that a differentiation of various
PAHs is possible. The next step is to vaporize a PAH mixture. This step consists
of vaporizing five pure substances almost simultaneously. The interpretation of
the resulting data is made using a chemometric interpretation method, the
multivariate curve resolution (MCR). The verification of the calculated results
is the main aim of this experiment. It has been shown that the tar mixture can be
analyzed qualitatively and quantitatively (in arbitrary units) in detail using
the MCR. Finally it is the main goal of this paper to show the first steps in the
applicability of the UV-Vis spectroscopy and the measurement setup on online tar
analysis in view of characterizing the biomass gasification process. Due to that,
the gasification plant (at the laboratory scale), developed and constructed by
the Fraunhofer ICT, has been used to vaporize these substances. Using this
gasification plant for the experiments enables the usage of the measurement setup
also for the spectroscopic analysis of the tar formation during the biomass
gasification.
PMID- 25588233
TI - Festschrift in honour of David Smith.
PMID- 25588232
TI - Ionizing radiation induces structural and functional damage on the molecules of
rat brain homogenate membranes: a Fourier transform infrared (FT-IR)
spectroscopic study.
AB - Humans can be exposed to ionizing radiation, due to various reasons, whose
structural effects on biological membranes are not well defined. The current
study aims to understand the ionizing radiation-induced structural and functional
alterations in biomolecules of brain membranes using Fourier transform infrared
(FT-IR) spectroscopy using rat animal models. For this purpose, 1000 cGy of
ionizing radiation was specifically directed to the head of Sprague Dawley rats.
The rats were decapitated after 24 h. The results revealed that the lipid-to
protein ratio decreased and that irradiation caused lipid peroxidation and
increases in the amounts of olefinic =CH, carbonyl, and methylene groups of
lipids. In addition, ionizing radiation induced a decrease in membrane fluidity,
disordering of membrane lipids, strengthening of the hydrogen bonding of the
phosphate groups of lipid head-groups, and weakening in the hydrogen bonding of
the interfacial carbonyl groups of lipids. Radiation further caused significant
decrements in the alpha-helix and turns, and significant increments in the beta
sheet and random coil contents in the protein structure. Hierarchical cluster
analyses, performed in the whole region (3030-1000 cm(-1)), lipid (3030-2800 cm(
1)), and protein (1700-1600 cm(-1)) regions separately, successfully
differentiated the control and irradiated groups of rat brain membranes and
showed that proteins in the membranes are affected more than lipids from the
damages induced with ionizing radiation. As a result, the current study showed
that FT-IR spectroscopy can be used successfully as a novel method to monitor
radiation-induced alterations on biological membranes.
PMID- 25588234
TI - How states are expanding Medicaid to low-income adults through Section 1115
waiver demonstrations.
AB - In the wake of the Supreme Court's 2012 decision making state expansion of
Medicaid to more adults optional under the Affordable Care Act, several states
have received approval to combine such expansion with broader Medicaid reforms.
They are doing so under Section 1115 of the Social Security Act, which authorizes
Medicaid demonstrations that further program objectives. State demonstrations
approved so far combine expanded adult coverage with changes in that coverage and
in how the states deliver and pay for health care. These states have focused
especially on expanding the use of private health insurance, requiring
beneficiaries to pay premiums, and incentivizing them to choose cost-effective
care. By enabling states to link wider program reforms to the adult expansion,
Section 1115 has allowed them to better align Medicaid with local political
conditions while extending insurance to more than 1 million adults who would
otherwise lack a pathway to coverage.
PMID- 25588235
TI - Implementing the Affordable Care Act: state approaches to premium rate reforms in
the individual health insurance market.
AB - The Affordable Care Act protects people from being charged more for insurance
based on factors like medical history or gender and establishes new limits on how
insurers can adjust premiums for age, tobacco use, and geography. This brief
examines how states have implemented these federal reforms in their individual
health insurance markets. We identify state rating standards for the first year
of full implementation of reform and explore critical considerations weighed by
policymakers as they determined how to adopt the law's requirements. Most states
took the opportunity to customize at least some aspect of their rating standards.
Interviews with state regulators reveal that many states pursued implementation
strategies intended primarily to minimize market disruption and premium shock and
therefore established standards as consistent as possible with existing rules or
market practice. Meanwhile, some states used the transition period to strengthen
consumer protections, particularly with respect to tobacco rating.
PMID- 25588236
TI - [Epidemiology of chronic bronchopulmonary diseases II].
PMID- 25588237
TI - [The antalgic and antiinflammatory effect of the total extract from Helleborus
species (the Boicil product), in rat].
PMID- 25588238
TI - [[100 years from the discovery of the Koch's bacillus].
PMID- 25588239
TI - [Possibilities and limitations in the esophageal cancer surgery].
PMID- 25588240
TI - [Mediastinal giant cystic dysembrioma].
AB - A 42 years old man with evident distortion in the lower 2/3 of the right
hemithorax, area in which he presents a compression syndrome and radiologically a
bulky opacity with tumoral aspect that shifts the heart and mediastinum to the
left, is presented. The thoracotomy reveals a giant cystic formation containing
approximatively 7 l. of rough magma into which hair, cartilaginous and bone
tissue are identified. After their removal the cystic wall (1 cm thick) is
excised except for an implantation area of 4/8 cm adherent to the large vessels
and pericardium. The postoperative evolution is uneventful. The histopathological
examination confirms the diagnostis of MCD identifying derivatives from all 3
embryonic sheets.
PMID- 25588241
TI - [Preleukaemia].
PMID- 25588242
TI - [Ways of bacterial attachment to mucous surfaces and possibilities of preventing
the infections].
PMID- 25588243
TI - [Investigations of the left ventricular dynamics in stable-angina pectoris (AP)].
AB - The investigations were carried out in 78 patients with stable AP without
myocardiaI infarction in their case history and in 30 controls all distributed in
three series: I = 37 patients with AP and marked alterations of ventricular
repolarization (ST depression >= 52 mm and T negative waves >= 2 mm); II = 41
patients with AP and normal ECG and III = 30 controls, clinically and ECG normal,
of similar age with the patients in the I and II series. The investigations of
the left ventricular systole periods also rendered evident in the patients with
AP important alterations of ventricular repolarization (Ist series): prolonged
preejection period (PEP) due to the izovolumetric contraction time (IVCT),
shortening of the ejection time (LVET) and decrease of PEP/LVET ratio as well as
the significant increase of S(IV)/S(I) ratio. Although slightly shortened in this
series, the electromechanic systole (QS(II)) does not present statistically
significant alterations, the prolonged PEP being partially counter-balaced by the
shortened LVET. The most sensitive index seems to be the PEP/LVET ratio. The
alterations' of the left ventricular systole periods become evident late in the
course of the disease, when significant ischemic lesions are present this the
method has no value in determining an early diagnosis. On the other hand this
type of investigation is an useful quantitative method for estimating the
functional state of the cardiac muscle in the patients with the diagnosis of AP
(stage diagnosis of AP) and subsequent evolution (repeated records).
PMID- 25588245
TI - [Bordeline states and their significance in psychiatry].
AB - The authors critically analyse the tendency of conceptualizing some difficult to
classify psycho-pathological states, the symptoms and clinical dynamics of which
would be characteristic, in a psycho-analytical interpretation, to a
nosologically distinct category termed "bordeline states". The authors'
orientation and clinical observations related to the data in the literature lead
to the specification of those situations in which this term can be used in the
psychiatric diagnosis, preferably under its original lexical form and with the
specification of the substantiating concept. Due to the looseness and ununitary
interpretation of the "bordeline states" situations, for the clinical cases that
correspond to the diagnostic criteri, it is prefered the term of psychopathy,
which although controversial, has a more statutory use in psychiatry.
PMID- 25588244
TI - [Benign solitary thyroid nodule (BSTN)].
AB - Out of a series of 210 patients (193 women and 17 men) with BSTN, 62% presented
an warm nodule, 25.2% a hot nodule and 11.9% a cold nodule. The highest incidence
of the nodule was noticed round the age of 40-50 years. The most common site was
the middle and lower area of the right thyroid lobe. The thyroid scintigram
provided orientative data regarding the nature of BSTN, the treatment indication
being the surgical intervention. Histopathologically, polymorphic aspects ranging
from anizofollicular adenoma, adenomatous proliferations areas and
hyperfunctional aspect to degenerative sclerous alterations and
lymphoplasmocitary infiltrations were noticed. The current hypotheses regarding
the etiopathogeny of nodule forming process are discussed. Based on some data in
the literature, we consider the nodularization of the thyroid gland as a
reactional zone functional desynchronization in the conditions of some great
variations of the iodate intaxe.
PMID- 25588246
TI - [Possibilities of employing the extracts from Bulbus cepae in dermopreparations].
PMID- 25588247
TI - [Gastric stump cancer].
AB - The cases of gastric stump cancer recorded at the III-rd Surgical Clinic of Iaoi
during the last 5 years are analysed. Based upon the personal experience and data
in the literature 7 cases are discussed. Out of the 7 cases, in 3 an initial
resection for gastric ulcer and in 4 for duodenal ulcer was performed 17-40 years
previously (with an average of 26 years). All the patients presented Bilroth II
anastomoses. The diagnosis was determined by radiological, endoscopic and
endobioptic examinations after a mean interval of 10 month since the occurence of
the clinical symptoms. The site of the lesion was the following: in 3 cases on
the anastomosis line and in 4 on the reminder of the stump. Out of the 7 cases, 5
were operable and in 4 the resection was completed. Two days post-operatively a
death was recorded. The conclusions of this paper insist upon the fact that the
occurance of the tumor on the gastric resection stump mainly depends on the
initial lesion (gastric lesion) and less on the type of anastomosis. The long
term surveillance of the gastric resection patients is thus essential.
PMID- 25588248
TI - [On tihe diagnosis, treatment and late results in prostatic carcinoma].
AB - 209 cases of prostatic carcinoma out of which 112 with coexistance adenoma-cancer
and 97 true carcinomas are analysed. The diagnosis was determined by histological
examination of adenomectomy or transrectal or perineal needle biopsy specimens.
Out of the 112 adenoma-cancer cases in 65 the existence of a single or multiple
nodule, having a more firm consistency, was noticed and in 47 the rendering
evident of the malignant lesion was a histological surprise of the adenomectomy
specimens. The age distribution is the following: 42.7% between the age of 71 and
80, 31.5% between 61 and 70, 13% between 51 and 60, 70% between 45 and 50, 5.8%
above 80. The treatments employed were: 112 adenomectomies, 50 removals of the
pelviprostatic capsular ligament associated with bilateral castration and
hormonotherapy and 47 estrogen hormonotherapies. The importance of the
histological examination of the surgical specimens (in the case of adenomectomy)
and biopsy for specifying the malignant nature of the prostatic alterations is
emphasized.
PMID- 25588250
TI - [Methodolgy and interpretation in the study of the complement system in chronic
hepatitis].
AB - The determination of the total hemolitic serum complement, as a screening test
for investigating the activity of the entire complement system and the
measurement of the C3 fraction consumption, has now gained a peculiar importance
due to its contribution to the clearing up of some problems regarding the
pathogeny an diagnosis of chronic hepatitis. The correlation of these values
alterations with the presence of antiglobulinic antigens orientatively suggests
the presence of immune complexes taking part in the maintainance of the
inflammatory hepatic process.
PMID- 25588249
TI - [Cerebellar contusive syndrome].
AB - As part of the localized encephalic contusions, the cerebellar contusion, by its
etiopathogenic, clinic, paraclinic, therapeutic and prognostic aspects represents
a distinct individuality. Studying a series of 30 cases of cerebellar contusions
the authors notice the increased incidence in children (28 cases), the cerebellar
vulnerability in children being explained by the high site and increased
elasticity of the occipital bone as well as by the nape muscles thinness. The
clinical syndrome, more common of archicerebellar type, can occur alone or
associated with a minor or mild diffuse mental shock. The paraclinic
investigation is reduced to lombar puncture, cranial radiography and EEG. The
evolution, especially in children, is towards healing in 2-3 weeks of
conservative treatment.
PMID- 25588251
TI - [Professionally conditioned pathology].
AB - The existence of some differences between the indices of morbidity with temporary
disablement in some working sectors in which do work persons having similar sex
and age features determined the authors to adopt the term of professionally
conditioned pathology for the affections in the etiology of which favouring
factors of professional nature do interpose. In the modern society, as the
manifest professional pathology is diminishing, the industrial medicine, as a
scientific discipline, is changing its sphere and content, increasingly orienting
itself towards the investigation of the professionally conditioned pathology and
its implications in the medical practice. The prioritary orientation towards the
prevalent diseases of the modern society is a main task for the present and
future industrial medicine.
PMID- 25588252
TI - [New parameters of electrocardiotachographic (EKT) evaluation of the
organovegetative reactivity].
AB - The analysis of some EKT lines evolution obtained by some investigations on the
organovegetative reactivity carried out in the Laboratory of physiology
correlated with the different experimental stages led to the formulation of some
original cardiotachographic (KTG) parameters which seem to have a peculiar
usefulness within the framework of the investigation methods. Except for the
routine KTG parameters under the form of instantaneous cardiac rhythm (ICR) and
mean cardiac rhythm (MCR) another 5 indices can now be used: 1) frequency of the
rhythm fluctuations (FRF); 2) vegetative lability index (VLI); 3) mean rhythm
fluctuation (MRF); 4) latency of rhythm fluctuation (LRF) and 5) amplitude of
rhythm fluctuation (ARF). Their introduction as part of the investigation methods
for the neurovegetative system would permit a better outline both of the relative
relationship. between the component parts of the reactive system (normotonic or
distonic) and its receptivity and promptitute to the different neurohumoral or
somato-viscero-motor interferences.
PMID- 25588253
TI - Mechanisms of the neuromuscular blocking activity of the aminoglycoside
antibiotic streptomycin.
AB - While increasing the spontaneous quantal transmitter release in frog
neuromuscular junctions, streptomycin blocked the evoked transmitter release by
decreasing the quantal content (m). The quantal parameter of release n (number of
release sites) was significantly decreased, while p (probability of release
through transmitter activation) increased. Streptomycin competes with calcium
ions for the membrane release sites while the intracellular mechanisms of release
remain unaffected. The data show a good fit to the two-step hypothesis of quantal
transmitter release recently developed on the basis of ouabain actions.
PMID- 25588254
TI - [Visceral arterial embolization (VAE). Note I. VAE in renal cancer. Experimental
study and preliminary clinical results].
AB - After a short history of the VAE, a new method in the intervention radiology, the
authors present the technique and results of the experimental renal VAE performed
on dogs, with autologous clot, Gelaspon and Isobutyl-2-cyanoacrylat. The
favourable results of the experimental investigations permitted for the first
time in our country the use of VAE in inoperable renal cancers. The paper
presents the clinico-therapeutical results of VAE as well as the control
angiographic and echotomographic aspects after embolization. The conclusions
support the need of using VAE both preoperatively and in the inoperable cases of
renal cancer, suggesting the possibility of extending the use of this method to
other visceral cancers with selective arterial catheterizations approach.
PMID- 25588255
TI - [Rotaviruses and their implications in pathology].
PMID- 25588256
TI - [Considerations on the crown restoration in youngsters and teenagers].
AB - The crown restorations in young people and teenagers represents a priority in the
current dental practice. After presenting plurifactorially the etiology of the
odontal lesions, the different methods of treatment employed currently in our
clinic are analysed. In order to avoid some confusion in the use of some already
accepted terms and to select the best treatment, the most common therapeutic
means of crown restoration are described and analysed.
PMID- 25588257
TI - [Some oral manifestations in blood disorders].
AB - The authors present their own experience regarding the detection of hemopathies
based upon the alterations of oral and tongue mucosae. The blood test confirmed
the suspicion of hemopathy.
PMID- 25588258
TI - [Digestive pathology in the elderly].
AB - Some etiopathogenic, physiopathologic, clinic, evolutive and therapeutic
peculiarities of the most common digestive affections encountered in the old aged
patients are presented.
PMID- 25588259
TI - [Is pain a symptom in placenta praevia?].
PMID- 25588260
TI - [2-R-mercapto-1, 3, 4-thyadiazol derivates having biological activity. Note I].
AB - The importance of 1,3,4-thyadiazol nucleus is illustrated by the fact that it
enters the structure of many compounds having different biological activities. In
this paper the results of some investigations for obtaining new derivates of
1,3,4-thydiazol 2,5 distributed are presented. Based upon the presented diagram
13 2-R-5-mercapto-1,3,4-thyadiazols, analysed both physico-chemically and
biologically were synthetized.
PMID- 25588261
TI - [Investigations for obtaining compounds with potential antiinflammatory action,
carboxymethylic ethers of some oximes].
AB - In this paper the synthesis of 5 etheric derivates of some aromatic oxymes: p
metoxy-benz-(sin)-aldoxyme, p-chlorine-benz-(sin)-aldoxyme, sin-piperonal-oxyme,
2,4-di- chlorinebenzaldoxyme and 3,4-dichlor-benzaldoxyme were described. In view
of a subsequent study on the antiinflammatory action a simple method for
obtaining these compounds based on the reaction between the sodium salt of the
monochloracetic acid and the sodium derivates of the corresponding oxymes. The
structure of the newly obtained products was confirmed by the elementary
quantitative chemical analysis and the spectral analysis in IR.
PMID- 25588262
TI - [Studies regarding the fixing of the zinc from ADH through some azopyrazolone].
AB - The mechanism of reaction-between the zinc atom of alcohol dehydrogenase and 6
pyrazolone and azopyrazolone compounds, type 1-(4'-carboxyphenyl)-3-methyl
4(1"azo-4"-ethoxy-phenyl)-5-pyrazolone, synthetized by the authors, is studied.
For elucidating the "in vivo" phenomenon, the complexes of these compounds were
synthetized with zinc atoms, the IR specters and quantitative chemical analyses
being followed. Based on these, the possibilities of complexing the zinc from the
ADH molecule by these compounds are discussed.
PMID- 25588263
TI - [Pharmacological trial of a glucose acetylate derivative].
AB - Toxicological and pharmacokinetic data regarding a glucose acetylate derivative,
conventionally termed PAG, are presented.
PMID- 25588264
TI - [Recording of pH of the lower part of esophagus].
PMID- 25588266
TI - [Surgical acute abdomen].
PMID- 25588265
TI - [Aspects of progress in toxicology].
PMID- 25588267
TI - [Medical acute abdomen].
PMID- 25588268
TI - The influence of cyclooxygenase inhibitors on morphine addiction.
PMID- 25588269
TI - [Possibilities and limitations in the surgical treatment of subdiaphragmatic
digestive tract cancer].
PMID- 25588271
TI - Detecting letters and words in prose passages: a test of alternative theoretical
accounts of the missing letter effect.
AB - College students searched for either h or the in prose passages in which every h
occurred in the test word the. In Experiment 1, passage versions differed in that
the critical noun phrases were either the alone (i.e., in citation form as a noun
referring to itself) or "the definite article." Many more detection errors
occurred for letter than word target items, especially with "the definite
article." In Experiment 2, passage versions differed in that a given noun phrase
containing the test word the occurred as a subject in one version and an object
in the other. Again, many more detection errors occurred when the target item was
the letter h than when it was the letter sequence the. Also, with letter but not
letter sequence targets, more detection errors occurred for object than subject
noun phrases. In Experiment 3, passages were presented either in regular format
or with all capital letters. Students made more detection errors with the regular
than with the capitals format, many more errors occurred when participants
searched for letters than for letter sequences, and the effect of target item was
larger with regular than with capitals format. These findings suggest that
accounts of detection errors in reading must include the influence of unitization
and processing time or attentional allocation.
PMID- 25588270
TI - Improvements in perception of maximum reaching height transfer to increases or
decreases in reaching ability.
AB - Perception of affordances for a given behavior reflects not only a person's
current action capabilities but also impending changes to his or her action
capabilities. This experiment investigated perception of affordances for reaching
when the means of performing the reaching task would increase or decrease
reaching ability. The results showed that in both cases perception of maximum
reaching height reflected the person's anthropometric properties (i.e., standing
height) and the future means of reaching, and improvements in perception of
maximum reaching height transferred to unpracticed reaching tasks. The results
highlight the role of action in the perception of affordances and are discussed
in the context of a description of perceptual systems as smart perceptual
devices.
PMID- 25588272
TI - A possible correction of the face inversion effect: a methodological commentary.
AB - The face inversion effect is based on 2 phenomena: Recognition of faces presented
upright (hair above, chin below) is better than that of faces presented inverted
(chin above, hair below), and inversion impairs recognition of faces more than of
nonfacial objects (buildings, cars). Based on theoretical and empirical
considerations, this article suggests that in many cases the size of the second
phenomenon is overestimated, because it is influenced by recognition of upright
faces being higher than recognition of upright objects (i.e., a baseline-level
effect). A mathematically based correction is suggested for the baseline-level
effect. It rests on the assumption that recognition of inverted faces depends on
recognition of upright faces. Theoretical and empirical support is offered for
this assumption. Also, an empirical base for the proposed correction is provided.
PMID- 25588273
TI - Effects of gender, imagery ability, and sports practice on the performance of a
mental rotation task.
AB - Mental rotation is one of the main spatial abilities necessary in the spatial
transformation of mental images and the manipulation of spatial parameters.
Researchers have shown that mental rotation abilities differ between populations
depending on several variables. This study uses a mental rotation task to
investigate effects of several factors on the spatial abilities of 277
volunteers. The results demonstrate that high and low imagers performed equally
well on this tasks. Athletes outperformed nonathletes regardless of their
discipline, and athletes with greater expertise outperformed those with less
experience. The results replicate the previously reported finding that men
exhibit better spatial abilities than women. However, with high amounts of
practice, the women in the current study were able to perform as well as men.
PMID- 25588274
TI - Working memory, situation models, and synesthesia.
AB - Research on language comprehension suggests a strong relationship between working
memory span measures and language comprehension. However, there is also evidence
that this relationship weakens at higher levels of comprehension, such as the
situation model level. The current study explored this relationship by comparing
10 grapheme-color synesthetes who have additional color experiences when they
read words that begin with different letters and 48 normal controls on a number
of tests of complex working memory capacity and processing at the situation model
level. On all tests of working memory capacity, the synesthetes outperformed the
controls. Importantly, there was no carryover benefit for the synesthetes for
processing at the situation model level. This reinforces the idea that although
some aspects of language comprehension are related to working memory span scores,
this applies less directly to situation model levels. This suggests that theories
of working memory must take into account this limitation, and the working memory
processes that are involved in situation model construction and processing must
be derived.
PMID- 25588275
TI - The importance of source and cue type in time-based everyday prospective memory.
AB - We examined the effects of the source of a prospective memory task (provided or
generated) and the type of cue (specific or general) triggering that task in
everyday settings. Participants were asked to complete both generated and
experimenter-provided tasks and to send a text message when each task was
completed. The cue/context for the to-be-completed tasks was either a specific
time or a general deadline (time-based cue), and the cue/context for the texting
task was the completion of the task itself (activity-based cue). Although
generated tasks were completed more often, generated cues/contexts were no more
effective than provided ones in triggering the intention. Furthermore, generated
tasks were completed more often when the cue/context comprised a specific time,
whereas provided tasks were completed more often when the cue/context comprised a
general deadline. However, texting was unaffected by the source of the
cue/context. Finally, emotion modulated the effects. Results are discussed within
a process-driven framework.
PMID- 25588276
TI - Monetary and affective judgments of consumer goods: modes of evaluation matter.
AB - Participants who evaluated 2 positively valued items separately reported more
positive attraction (using affective and monetary measures) than those who
evaluated the same two items as a unit. In Experiments 1-3, this separate/unitary
evaluation effect was obtained when participants evaluated products that they
were purchasing for a friend. Similar findings were obtained in Experiments 4 and
5 when we considered the amount participants were willing to spend to purchase
insurance for items that they currently owned. The averaging/summation model was
contrasted with several theoretical perspectives and implicated averaging and
summation integration processes in how items are evaluated. The procedural and
theoretical similarities and differences between this work and related research
on unpacking, comparison processes, public goods, and price bundling are
discussed. Overall, the results support the operation of integration processes
and contribute to an understanding of how these processes influence the
evaluation and valuation of private goods.
PMID- 25588277
TI - Ethics under uncertainty: the morality and appropriateness of utilitarianism when
outcomes are uncertain.
AB - Real-life moral dilemmas inevitably involve uncertainty, yet research has not
considered how uncertainty affects utilitarian moral judgments. In addition, even
though moral dilemma researchers regularly ask respondents, "What is
appropriate?" but interpret it to mean, "What is moral?," little research has
examined whether a difference exists between asking these 2 types of questions.
In this study, 140 college students read moral dilemmas that contained certain or
uncertain consequences and then responded as to whether it was appropriate and
whether it was moral to kill 1 to save many (a utilitarian choice). Ratings of
the appropriateness and morality of the utilitarian choice were lower under
uncertainty than certainty. A follow-up experiment found that these results could
not be explained entirely by a change in the expected values of the outcomes or a
desire to avoid the worst-case scenario. In addition, the utilitarian choice to
kill 1 to save many was rated as more appropriate than moral. The results imply
that moral decision making may depend critically on whether uncertainties in
outcomes are admitted and whether people are asked about appropriateness or
morality.
PMID- 25588278
TI - Goals, styles, and decisions: changes and interactions during the first year of
college.
AB - First-year undergraduates participated in a short-term longitudinal study of goal
setting and decision making over their first 14 months of college. First,
students wrote a mission statement, listed their goals for the upcoming year, and
filled out several individual difference style measures. In subsequent sessions,
students were surveyed about different decisions pertaining to their choice of
college major, course selection, housing, and summer plans. At the beginning of
their second year, participants were shown their previously listed goals and
surveyed about their progress, their satisfaction with their progress, and their
retrospective view of their goals. Additionally, participants responded again to
the individual difference measures. A moderate degree of stability was found in
the individual difference measures, yet there were several significant changes
over the year. Goal evaluation scores correlated with specific individual
difference measures, and self-reported descriptions of reactions to how specific
decisions were made, but not with behavioral measures of decision making.We
speculate on ways in which stylistic measures become part of a construction of a
more general narrative identity, shaped in significant ways by the college
environment that selectively reinforces some analytic habits of mind.
PMID- 25588279
TI - Identifying at-risk drinkers in primary care.
PMID- 25588280
TI - Improving outcomes for chronic pain in primary care.
AB - Although the patient's goal is often complete pain relief, this is rarely a
realistic outcome, so the role of the physician in managing chronic pain involves
optimising pain relief as far as possible. Careful explanation and education may
be needed to enable the focus to shift from cure to better management of pain,
and improvement of function and quality of life. Chronic pain is defined as pain
continuing beyond the normal time for tissue healing. Pain may be broadly
classified on the basis of mechanism, as neuropathic, nociceptive or mixed. A
thorough biopsychosocial assessment is essential so that an individualised
multidisciplinary approach to management can be developed. The aims of assessment
of chronic pain are to rule out any underlying serious pathology, identify the
pain mechanism and identify and evaluate risk factors that contribute to
chronicity. SIGN emphasises the need for a multidisciplinary team approach to
improve outcomes, and highlights five broad categories of care: supported self
management, drug treatment, psychologically-based interventions, physical
therapies and complementary therapies. Exercise, regardless of its type and the
source of pain, is recommended for the management of chronic pain. In chronic low
back pain, exercise therapy can improve strength and range of motion across
joints, cardiorespiratory fitness and sense of wellbeing. Pain management
programmes reduce anxiety and depressive symptoms, increase function and improve
mood. They may be considered in patients with poor functional capacity, pain
related social and occupational problems and in cases where other management
strategies have failed.
PMID- 25588281
TI - Migraine is underdiagnosed and undertreated.
AB - Migraine is a common neurovascular disorder characterised by attacks of head pain
that are typically unilateral and often described as severe and throbbing in
association with nausea and sensitivity to sensory input, i.e. light, sound and
head movement. The headaches typically last 4-72 hours, up to 31% of migraineurs
have aura on some occasions. Migraine is commonly episodic. With an increasing
intake of painkillers, patients often complain of an escalation of migraine
attacks or a transformation to a chronic daily background pain with
exacerbations. Acute painkiller use, both prescription and OTC, should be
enquired about in all cases and medication overuse headache suspected and managed
if patients are taking any acute painkiller excessively. Migraineurs should be
encouraged to have regular habits. Regular sleep, exercise, meals, work habits
and relaxation will be rewarded by a reduction in headache frequency. NICE
guidelines recommend adopting the stepped-down approach to management. They
suggest a combination of a triptan, NSAID or paracetamol, and an anti-emetic
taken as early as possible during the headache. The decision to commence a
preventative agent should depend on a combination of attack frequency, duration
and severity, as well as response to abortive therapy and patient preference.
PMID- 25588282
TI - Preventing avoidable asthma deaths.
AB - The UK has one of the highest death rates in Europe from asthma, with more than
20 people dying from the disease each week. Across the UK there is a five-fold
variation in the number of hospital admissions for asthma almost certainly
explained in part by variations in delivery, uptake and organisation of care.
Deaths from asthma are frequently avoidable the findings from the National Review
of Asthma Deaths have confirmed. A total of 276 cases were considered by the
confidential enquiry panels and 195 confirmed as asthma deaths. Major avoidable
factors were judged to be present in 60% of cases. Key findings from the report
include: Almost half the patients (45%) died without seeking medical help or
before help could be provided; 10% died within 28 days of discharge from
hospital; 21% had attended A&E with asthma in the previous year; and only 23% had
a personal asthma action plan. Over-prescription of short-acting bronchodilators
and under-prescription of preventer inhalers was common. Every general practice
should have a designated, named clinical lead for asthma services. Patients with
asthma should be referred to a specialist asthma service if they have required
more than two courses of systemic corticosteroids, oral or injected, in the
previous 12 months or management using BTS steps 4 or 5 to achieve control. Any
patient admitted to hospital or attending A&E with asthma should be reviewed, and
control optimised, within a week of discharge. All asthma patients should have a
written personal asthma action plan and should have a structured review by a
healthcare professional with training. in asthma at least annually.
PMID- 25588283
TI - Conditions in children.
PMID- 25588285
TI - The changing face of general practice.
PMID- 25588284
TI - Autotherapy in the prevention and cure of purulent infections. 1914.
PMID- 25588286
TI - Neuroimaging of Ethiopian patients with epilepsy: a retrospective review.
AB - BACKGROUND: Epilepsy is arguably the most common neurological condition
encountered by neurologists in Africa. Neuroimaging (CT and MRI) represents the
most important recent contribution to the diagnosis, classification and
management of the patient with epilepsy. OBJECTIVE: To describe the role of
neuroimaging in the evaluation of Ethiopian patients with epilepsy, by
identifying intracranial pathology, and formulating syndromic and etiological
diagnoses. METHODS: We performed a retrospective review of neuroimaging in 181
patients with epilepsy presenting to a specialized referral hospital (Addis Ababa
University Tikur Anbessa Teaching Hospital) and a private clinic (Yehuleshet
Higher Clinic) in Addis Ababa, Ethiopia between September 2008 and August 2010.
Each patient had an interictal EEG recording. RESULTS: Neuroimaging demonstrated
abnormal intracranial structural lesions in 65 of 181 or 35.9% of epileptic
patients (31% with CT; 38% with MRI). Brain lesions were single in 28 (42.8%) and
multiple in 23 (35.4%) patients. The lesions were lateralized in 35 patients
(53.8%), with 23 (35.4%) on the left add 12 (18.5%) on the right. Twenty seven
(41.5%) of these lesions originated in or involved the temporal or frontal lobes.
Over one third of the lesions were lobar equally divided among temporal, frontal
and parietal regions. The imaging findings demonstrated intracranial space
occupying lesions (ICSOL) in 17 (9.4%) patients (with 64.7% brain tumors),
cerebral infarctions in 15 (8.3%), cortical atrophy in 9 (5.0%), and gliosis in
7(3.9%). The interictal EEG recordings revealed epileptiform abnormalities in
60/181 patients (33.1%). CONCLUSION: Neuroimaging detected intracranial pathology
in more than one third of Ethiopian patients with epilepsy. A significant
proportion of the cases demonstrated focal epileptiform discharges and non
epileptiform features with abnormal intracranial pathologies. Further prospective
neuroimaging studies are recommended. Brain scan and EEG did help in the
diagnosis, classification and treatment of epileptics.
PMID- 25588287
TI - Microscopic transphneoidal surgery experence from christian Medical Center Addis
Abeba Ethiopia.
AB - BACKGROUND: The transphneoidal approach to the pituitary gland using the
microscope has undergone continuous modification since its introduction by Hardy
over 50 years ago. It is one of the most effective and safest of major
neurosurgical procedures with excellent outcomes and low complication rates.
OBJECTIVE: To describe the experience of Endonasal microscopic transsphenoidal
surgery at Myungsung Christian Medical Center during three-years period. PATIENTS
AND METHODS: This is a hospital based retrospective review of patients with
pituitary tumor for whom microscopic transsphenoidal surgery was done in
Myungsung Christian Medical Center, Addis Ababa, Ethiopia in the period between
September 2010 and August 2014. Patients' demographic data, type of symptoms,
hormonal profile, imaging modality, complications and outcomes were recorded in
apre-formed questionnaire. Frequencies and means were computed for description of
the various variables and presented in prose form and graphs. The association
between categorical variables was calculated using Chi-square test. RESULTS:
sixteen (53.3%) patients were males, 14 (46.7%) females. The mean age was 33.77,
+/- 10.85 years (rang 14 - 53). The most common presentation were headache in 28
(93.3%) patients and visual disturbances in 26 (86.7%), while 18 (60%) had
bitemporal hemianopia. prolactin levels were elevated in 4 (13.3%) of them having
hyperprolactinemia, cortisol levels revealed hypercortisolemia with clinical
evidence Cushing disease in 5 (16.7%). Three ((10%) had elevated growth hormone
levels with acromegalic features. All patients included in the study had a MRI;
tumors were with suprasellar extension in all (100%) patients, involvement of
floor ofsella in 18 (60%), extension to sphenoid sinus in 8 (26.7%) and with
parasellar extension in 5 (16.7%). Twenty-seven (90%) were done through direct
transnasal, 2 (6.7%) transseptal transphneoidal approach; in one patient the
approach was translabial. Early complication and mortality rate was 18 (60%) and
2 (6.7%) respectively. At one-year follow-up period, 22 (73.3%) patients had good
functional outcome, while 6 (20% 0 were in the same status as in the preoperative
period, 2(6.7%) had residual/recurrent tumor. CONCLUSION: Our patients were
relatively advanced cases with suprasellar and parasellar extensions. Direct
transnasal approach, is straightforward, quick and does not require dissection of
nasal mucosa or removal of septal cartilage and that the procedure can be done by
neurosurgeon with some experience in the procedure without an increased risk of
complications. High early complication rate was tolerable and manageable.
Acceptable mortality and good functional outcome during follow up period is
encouraging and compares favorably with African and other similar studies.
PMID- 25588288
TI - Review of morbidity and mortality among patients adimitted to the Surgical
Intensive Care Unit at Tikur Anbessa Specialized Teaching Hospital, Ethiopia.
AB - BACKGROUND: Caring for the critically ill is a challenge in developing country
including Ethiopia, where heath needs often outstrip available resources. There
is scarce data available on morbidity and mortality of surgical intensive care
unit patients in Ethiopia. OBJECTIVE: To describe mortality, morbidity and
outcomes of patients under the care of surgical intensive care unit team between
September 2010 and August 2011. PATIENTS AND METHODS: This is a hospital based
retrospective review of morbidity and mortality among surgical patients admitted
to Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia in the period
between September 2010 and August 2011. RESULTS: The study reviewed 441 surgical
intensive care unit admissions over one- year period Age ranged from 10 to 90
years mean 37.55 +/- 16.56 years. Mortality was high in 21-30 years age group,
9.1%. The highest admission was from cardiothoracic surgery unit, 37.4%, the
average length of hospital stay was 4.52 days (range 1 to 87 days). Significant
number 52 (33.3%) of patients who died under surgical ICU care belongs to General
surgery unit. Two Hundred eighty (63.5%) patients had an uneventful course, while
156 (35.4%) and 161 (36.5%) died and developed complications respectively. Age of
the patient at the time of admission, mode of admission, and post admission
complications were significantly and positively associated with mortality (p =
0.0001) while gender did not show any association with mortality at SICU (p =
0.528).CCONCLUSION:The highest admission was from department of cardiothoracic
surgery, while mortality rate was high-st from general surgery side. There are
significant and positive associations ofa ge, urgency ofa dmission, and
complications with mortality while gender did not show any association.
PMID- 25588289
TI - Tuberculosis of the cervix mimicking cervical cancer.
AB - Tuberculosis of the cervix is a rare disease and accounts for 0.1-0.65% of all
cases of tuberculosis. We present an unusual case of a 57 years old female who
presented with chief complaints of Serosaguineous vaginal discharge of one year
duration and irregular firm cervix with contact bleeding and was clinically
diagnosed to have cervical cancer. Histopathology revealed typical findings of
cervical tuberculosis. Cervical tuberculosis should be considered as a
differential diagnosis of cervical malignancy. The clinical presentation and
diagnosis of cervical tuberculosis is reviewed.
PMID- 25588290
TI - Adrenocortical carcinoma in a 3% years old girl with hetro-sexual precocity.
AB - Adrenocortical carcinoma is a rare neoplasm in children. Hetro-sexual precocious
puberty could be the initial presentation of a rare adrenocortical neoplasm in
the pediatric age group. Features of hetro-sexual precocious puberty in a girl
should alert the possibility of such a rare disease. We report a rare case of
adrenocortical carcinoma in a three years and six months old girl who presented
with hetro-sexual precocious puberty of two years duration. Left adrenalectomy
was done and histopathology revealed adrenocortical carcinoma.
PMID- 25588291
TI - Parosteal lipoma with hyperostosis: case report.
AB - Parosteal lipoma is an extremely rare benign tumor that is composed mainly of
mature adipose tissue and has an intimate relationship to the underlying
periosteal bone. We present a case of parosteal lipoma of humerus combined with
hyperostosis. Standard radiography demonstrated a radiolucent mass surrounding an
exostosis. CT showed a fat density, lobulated mass surrounding the larger osseous
excrescence and cortex. The patient underwent surgery. Intraoperative examination
found a well encapsulated, homogenous, yellowish, fatty tissue attached by a
stalk to the underlying bone. The pathology specimen showed mature adipose tissue
consistent with the intraoperative finding.
PMID- 25588292
TI - Severe hospital acquired pneumonia and septicemia due TO methicillin resistant
Staphylococcus lugdunensis in a newborn in Northwestern Ethiopia.
AB - Staphylococcus lugdunensis can cause virulent infections in immunosuppressed
individuals. This report describes the first known case of hospital acquired
pneumonia and septicemia due to methicillin-resistant Staphylococcus lugdunensis
in a newborn at Felege Hiwot Referral Hospital, North Western Ethiopia. The
strain was simultaneously resistant to trimethoprim-sulfamethoxazole,
tetracycline (30 ug), chloramphenicol (30 ug), gentamycin (10ug) and
ciprofloxacin (5ug) but sensitive to erythromycin (15ug) and clindamycin (10ug).
PMID- 25588293
TI - Importance of national context in the translation of personalised treatments for
smoking cessation.
PMID- 25588295
TI - Electrophysiologic characteristics of ventricular arrhythmias arising from the
aortic mitral continuity - potential role of the conduction system.
PMID- 25588296
TI - Effects of huwentoxin-I on catecholamines in cultured PC12 cells.
AB - The measurement of catecholamines in biological samples remains a current
analytical challenge in the study on neurotransmitter release, although much
effort has been devoted toward the relevant methodology. Here we first
established a fluoresence-based method for the quantitative determination of
catecholamines and then applied it to the investigation of effects of huwentoxin
I (HWTX-I), a peptide neurotoxin, on catecholamines in cultured PC12 cells. The
results showed that treatment with HWTX-I at different concentrations (10, 50,
100 and 1000 nM) for 20 min significantly increased dopamine (DA) content in the
culture medium (p < 0.01), with ~1.6-fold increase compared with that of the
control at the highest concentration tested. Within 20 min, DA content in the
medium increased with increasing the treatment time. In contrast, HWTX-I
decreased norepinephrine (NE) content in the medium. However, after the PC12
cells were treated with HWTX-I, the intracellular contents of both DA and NE were
kept at a relatively constant level. These data suggest that HWTX-I
differentially affects the DA and NE of the neuroendocrine cells, with enhancing
the actions of DA and weakening those of NE.
PMID- 25588297
TI - Feature confirmation in object perception: Feature integration theory 26 years on
from the Treisman Bartlett lecture.
AB - The Treisman Bartlett lecture, reported in the Quarterly Journal of Experimental
Psychology in 1988, provided a major overview of the feature integration theory
of attention. This has continued to be a dominant account of human visual
attention to this day. The current paper provides a summary of the work reported
in the lecture and an update on critical aspects of the theory as applied to
visual object perception. The paper highlights the emergence of findings that
pose significant challenges to the theory and which suggest that revisions are
required that allow for (a) several rather than a single form of feature
integration, (b) some forms of feature integration to operate preattentively, (c)
stored knowledge about single objects and interactions between objects to
modulate perceptual integration, (d) the application of feature-based inhibition
to object files where visual features are specified, which generates feature
based spreading suppression and scene segmentation, and (e) a role for attention
in feature confirmation rather than feature integration in visual selection. A
feature confirmation account of attention in object perception is outlined.
PMID- 25588294
TI - Use of the nicotine metabolite ratio as a genetically informed biomarker of
response to nicotine patch or varenicline for smoking cessation: a randomised,
double-blind placebo-controlled trial.
AB - BACKGROUND: Substantial variability exists in therapeutic response and adverse
effects with pharmacotherapies for tobacco dependence. Biomarkers to optimise
treatment choice for individual smokers might improve treatment outcomes. We
tested whether a genetically informed biomarker of nicotine clearance, the
nicotine metabolite ratio (NMR; 3'-hydroxycotinine:cotinine), predicts response
to nicotine patch or varenicline for smoking cessation. METHODS: We undertook NMR
stratified multicentre, randomised, placebo-controlled clinical trial from Nov
16, 2010, to Sept 12, 2014, at four sites. Smokers seeking treatment were
randomly assigned by baseline NMR status and study site, in blocks of 12 patients
(1:1:1 ratio), to 11 weeks of placebo (placebo pill plus placebo patch), nicotine
patch (active patch plus placebo pill), or varenicline (active pill plus placebo
patch), plus behavioural counselling. Participants and investigators were masked
to group allocation and NMR status. An intention-to-treat analysis was done.
Participants were followed up for 12 months after the target quit date. The
primary endpoint was biochemically verified 7 day point prevalence abstinence at
the end of treatment to estimate the pharmacological effect of treatment by NMR.
The trial is registered at ClinicalTrials.gov, number NCT01314001. FINDINGS: 1246
participants (662 slow metabolisers of nicotine, 584 normal metabolisers of
nicotine) were enrolled and randomly assigned to the three interventions (408
placebo, 418 nicotine patch, 420 varenicline). At end of treatment, varenicline
was more efficacious than nicotine patch in normal metabolisers (OR 2.17, 95% CI
1.38-3.42; p=0.001), but not in slow metabolisers (OR 1.13, 0.74-1.71; p=0.56).
In the longitudinal model including all timepoints, the NMR-by-treatment
interaction was significant (ratio of odds ratios [ORR] 1.96, 95% CI 1.11-3.46;
p=0.02). An NMR-by-treatment interaction showed that slow (vs normal)
metabolisers reported greater overall side-effect severity with varenicline
versus placebo (beta=-1.06, 95% CI -2.08 to -0.03; p=0.044). INTERPRETATION:
Treating normal metabolisers with varenicline and slow metabolisers with nicotine
patch could optimise quit rates while minimising side-effects. FUNDING: National
Institutes of Health, Canadian Institutes of Health Research, Abramson Cancer
Center, Centre for Addiction and Mental Health Foundation, and Pennsylvania
Department of Health.
PMID- 25588298
TI - Editorial Note to the last issue of Hereditas.
PMID- 25588299
TI - A tale of two papers.
AB - Two papers published in HEREDITAS between 1921 and 1939 show how the attitude
towards race biology changed in the course of the interwar period in the Nordic
countries. In the early 1920s race biology was seen to constitute a legitimate
science. Ordinary human genetics prevailed, however, over race biology already in
the very beginning on the pages of HEREDITAS. Population thinking was introduced
into the study of human heredity around the year 1930. It effectively
contradicted the concept of the race. Interestingly, HEREDITAS does not carry a
single paper on eugenics and sterilization. In 1939 we see a final repudiation of
the doctrines on race. Times had changed and the National Socialists had usurped
the doctrines of race in Germany.
PMID- 25588300
TI - Strange history: the fall of Rome explained in Hereditas.
AB - In 1921 Hereditas published an article on the fall of Rome written by the famous
classical scholar Martin P:son Nilsson. Why was a paper on this unexpected topic
printed in the newly founded journal? To Nilsson, the demise of the Roman Empire
was explained by the "bastardization" occurring between "races" from different
parts of the realm. Offspring from mixed couples were of a less stable "type"
than their parents, due to the breaking up by recombination of the original
hereditary dispositions, which led to a general loss of competence to rule and
govern. Thus, the "hardness" of human genes, together with their recombination,
was - according to Nilsson - the main cause of the fall of Rome. Nilsson's
argument is not particularly convincingly presented. Human "races" are taken to
have the same genetic structure as inbred crop strains, and Nilsson believes in a
metaphysical unity between the individual and the race to which it belongs.
However, in my view, Martin P:son Nilsson and his friend Herman Nilsson-Ehle had
wider aims with the article than to explain a historical event. The article can
be read as indicating strong support from the classical human sciences to the
ambitious new science of genetics. Support is also transferred from genetics to
the conservative worldview, where the immutability and inflexibility of the
Mendelian genes are used to strengthen the wish for greater stability in politics
and life. The strange article in Hereditas can, thus, be read as an early
instance in the - still ongoing - tug-of-war between the conservative and the
liberal ideological poles over how genetic results best are socially interpreted.
PMID- 25588301
TI - Association analysis of the GRM8 gene with schizophrenia in the Uygur Chinese
population.
AB - GRM8 is a schizophrenia candidate gene that is also thought to be involved in the
glutamate pathway, which is very important in the pathogenesis of schizophrenia.
In this study, we aim to investigate the association between GRM8 and
schizophrenia in the Uygur Chinese population. Rs2237748 and rs2299472, located
in the GRM8 gene, were selected for genotyping in a set of Uygur Chinese case
control samples, which included 723 cases and 561 controls, using TaqMan assays
and capillary sequencing. The statistical analysis was carried out using the
online software program SHEsis, and a meta-analysis was carried out to identify
other relevant studies using Review Manager 5. We found that the rs2299472
genotype was significantly associated with schizophrenia (P = 0.015, P = 0.030,
after Bonferroni correction). The frequency of the CC genotype was higher in the
schizophrenic patients (P = 0.008), and the frequency of the AC genotype was
lower (P = 0.008). Furthermore, the meta-analysis incorporating the previous and
current studies also showed that rs2299472 is associated with schizophrenia. This
study indicates that the GRM8 gene may play an important role in the pathogenesis
of schizophrenia.
PMID- 25588302
TI - Genetic diversity and population structure of leafy kale and Brassica rupestris
Raf. in south Italy.
AB - Local varieties of leafy kales (Brassica oleracea L.) are grown in home gardens
in Calabria and Sicily for self-consumption, in the same area where the wild
relative Brassica rupestris Raf. also grows. With the use of AFLP markers,
comparisons were made of the genetic diversity and population structure of ten
wild and 22 cultivated populations, as well as of a hybrid population and of four
commercial cultivars of different B. oleracea crops. The level of genetic
diversity was higher in leafy kales than in wild populations and this diversity
was mainly distributed within populations. Wild populations remained distinct
from cultivated material. Additionally, most wild populations were distinctively
isolated from each other. On the other hand, it was not possible to molecularly
distinguish even geographically distant leafy kale populations from each other or
from different B. oleracea crops. It was possible to detect inter-crossing
between leafy kales and B. rupestris. Findings from this study illustrate the
existing level of genetic diversity in the B. oleracea gene pool. Individual
populations (either wild or leafy kales) with higher levels of genetic diversity
have been identified and suggestions are given for an informed conservation
strategy. Domestication hypotheses are also discussed.
PMID- 25588303
TI - Deletion mapping in the Enhancer of split complex.
AB - The Enhancer of split complex [E(spl)-C] comprises twelve genes of different
classes. Seven genes encode proteins of with a basic-helix-loop-helix-orange
(bHLH-O) domain that function as transcriptional repressors and serve as
effectors of the Notch signalling pathway. They have been named E(spl)m8-, m7-,
m5-, m3-, mbeta-, mgamma- and mdelta-HLH. Four genes, E(spl)m6-, m4-, m2- and
malpha-BFM are intermingled and encode Notch repressor proteins of the Bearded
family (BFM). The complex is split by a single gene of unrelated function,
encoding a Kazal-type protease inhibitor (Kaz-m1). All members within a family,
bHLH-O or BFM, are very similar in structure and in function. In an attempt to
generate specific mutants, we have mobilised P-element constructs residing next
to E(spl)m7-HLH and E(spl)mgamma-HLH, respectively. The resulting deletions were
mapped molecularly and by cytology. Two small deletions affected only E(spl)m7
HLH and E(spl)mdelta. The deficient flies were viable without apparent phenotype.
Larger deletions, generated also by X-ray mutagenesis, uncover most of the E(spl)
C. The phenotypes of homozygous deficient embryos were analysed to characterize
the respective loss of Notch signalling activity.
PMID- 25588304
TI - Wild Estonian and Russian sea trout (Salmo trutta) in Finnish coastal sea trout
catches: results of genetic mixed-stock analysis.
AB - For responsible fisheries management of threatened species, it is essential to
know the composition of catches and the extent to which fisheries exploit weak
wild populations. The threatened Estonian, Finnish and Russian sea trout
populations in the Gulf of Finland are targets of mixed-stock fisheries. The fish
may originate from rivers with varying production capacities, from different
countries, and they may also have either a wild or hatchery origin. In order to
resolve the composition of Finnish coastal sea trout catches, we created a
standardized baseline dataset of 15 DNA microsatellite loci for 59 sea trout
populations around the Gulf of Finland and tested its resolution for mixed-stock
analysis of 1372 captured fish. The baseline dataset provided sufficient
resolution for reliable mixture analysis at regional group level, and also for
most of the individual rivers stocks. The majority (76-80%) of the total catch
originated from Finnish sea trout populations, 6-9% came from Russian and 12-15%
from Estonian populations. Nearly all Finnish trout in the catch were of hatchery
origin, while the Russian and Estonian trout were mostly of wild origin. The
proportion of fish in the Finnish catches that originated from rivers with
natural production was at least one fifth (22%, 19-23%). Two different spotting
patterns were observed among the captured trout, with a small and sparsely
spotted form being markedly more common among individuals of Russian (28%) and
Estonian origin (22%) than among fish assigned to a Finnish origin (0.7%).
PMID- 25588305
TI - An improved MALDI-TOF mass spectrometry procedure and a novel DNA marker for
identifying over-expressed Bx7 glutenin protein subunit in wheat.
AB - Wheat bread-making quality is mainly determined by glutenin proteins in the
grain, which exist in a wide range of variable alleles with differential
influence on processing attributes. A recently identified allele, Bx7 over
expression (Bx7(oe) ), has been showing highly significant positive effects on
wheat dough strength over the normally expressed Bx7 allele. SDS-PAGE and normal
RP-HPLC procedures failed to separate the two alleles. In the current study, an
extensively optimised MALDI-TOF based procedure and a refined DNA based marker
for efficiently differentiating Bx7(oe) from normal Bx7 allele were established.
Results indicated that the MALDI-TOF procedure is cost effective, high
throughput, and proven reliable, while the refined PCR marker only amplifies
Bx7(oe) allele, a clear advantage over the previously developed codominant
marker.
PMID- 25588306
TI - Genetic polymorphism of 15 Y chromosomal STR loci and haplotypes of Henan Han
population.
AB - We studied and established a DNA database of 15 Y-STRs (DYS438, DYS446, DYS391,
DYS390, DYS458, DYS534, DYS426, DYS626, DYS504, DYS505, DYS576, DYS532, DYS594,
DYS522, DYS540) in a population sample of 102 unrelated, healthy, male
individuals of Henan Han population. Allelic frequencies and statistical
parameters of Han population were calculated. Totally 90 alleles were observed,
with the corresponding allelic frequencies ranging from 0.0098 to 0.9020. 102
haplotypes were found in the studied group, the haplotype diversity for 15 Y-STR
loci was 1. The results of present study were valuable for human identification
and paternity tests routine forensic applications in the region.
PMID- 25588307
TI - Analysis of the interaction between human RITA and Drosophila Suppressor of
Hairless.
AB - Notch signalling mediates intercellular communication, which is effected by the
transcription factor CSL, an acronym for vertebrate CBF1/RBP-J, Drosophila
Suppressor of Hairless [Su(H)] and C. elegans Lag1. Nuclear import of CBF1/RBP-J
depends on co-activators and co-repressors, whereas the export relies on RITA.
RITA is a tubulin and CBF1/RBP-J binding protein acting as a negative regulator
of Notch signalling in vertebrates. RITA protein is highly conserved in
eumatazoa, but no Drosophila homologue was yet identified. In this work, the
activity of human RITA in the fly was addressed. To this end, we generated
transgenic flies that allow a tissue specific induction of human RITA, which was
demonstrated by Western blotting and in fly tissues. Unexpectedly, overexpression
of RITA during fly development had little phenotypic consequences, even when
overexpressed simultaneously with either Su(H) or the Notch antagonist Hairless.
We demonstrate the in vivo binding of human RITA to Su(H) and to tubulin by co
immune precipitation. Moreover, RITA and tubulin co-localized to some degree in
several Drosophila tissues. Overall our data show that human RITA, albeit binding
to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in
the fly, suggesting that a nuclear export mechanism of Su(H), if existent in
Drosophila, does not depend on RITA.
PMID- 25588308
TI - Identification of fruit related microRNAs in cucumber (Cucumis sativus L.) using
high-throughput sequencing technology.
AB - MicroRNAs (miRNAs) are approximately 21 nt noncoding RNAs that influence the
phenotypes of different species through the post-transcriptional regulation of
gene expression. Although many miRNAs have been identified in a few model plants,
less is known about miRNAs specific to cucumber (Cucumis sativus L.). In this
study, two libraries of cucumber RNA, one based on fruit samples and another
based on mixed samples from leaves, stems, and roots, were prepared for deep
sequencing. A total of 110 sequences were matched to known miRNAs in 47 families,
while 56 sequences in 46 families are newly identified in cucumber. Of these, 77
known and 44 new miRNAs were differentially expressed, with a fold-change of at
least 2 and p-value < 0.05. In addition, we predicted the potential targets of
known and new miRNAs. The identification and characterization of known and new
miRNAs will enable us to better understand the role of these miRNAs in the
formation of cucumber fruit.
PMID- 25588309
TI - Relatedness and diversity of nine Swedish local chicken breeds as indicated by
the mtDNA D-loop.
AB - In this study part of the mitochondrial D-loop was sequenced in a total of 40
samples from nine Swedish local chicken breeds. Among our 40 samples we observed
15 segregating sites and seven different haplotypes. The most common haplotype
was present in all investigated individuals in five breeds and together with
other haplotypes in three breeds. This haplotype is common in domestic chickens
and has been found in both local and commercial breeds in many parts of the
world. The breed Olandshona was most different from the other Swedish breeds with
all three individuals sharing a haplotype that differed from the most common
haplotype at nine of the 15 segregating sites.
PMID- 25588311
TI - Retrospective study of the prevalence of Pseudoloma neurophilia shows male sex
bias in zebrafish Danio rerio (Hamilton-Buchanan).
PMID- 25588312
TI - Ionic interaction of positive amino acid residues of fungal hydrophobin RolA with
acidic amino acid residues of cutinase CutL1.
AB - Hydrophobins are amphipathic proteins secreted by filamentous fungi. When the
industrial fungus Aspergillus oryzae is grown in a liquid medium containing the
polyester polybutylene succinate co-adipate (PBSA), it produces RolA, a
hydrophobin, and CutL1, a PBSA-degrading cutinase. Secreted RolA attaches to the
surface of the PBSA particles and recruits CutL1, which then condenses on the
particles and stimulates the hydrolysis of PBSA. Here, we identified amino acid
residues that are required for the RolA-CutL1 interaction by using site-directed
mutagenesis. We quantitatively analyzed kinetic profiles of the interactions
between RolA variants and CutL1 variants by using a quartz crystal microbalance
(QCM). The QCM analyses revealed that Asp142, Asp171 and Glu31, located on the
hydrophilic molecular surface of CutL1, and His32 and Lys34, located in the N
terminus of RolA, play crucial roles in the RolA-CutL1 interaction via ionic
interactions. RolA immobilized on a QCM electrode strongly interacted with CutL1
(K(D) = 6.5 nM); however, RolA with CutL1 variants, or RolA variants with CutL1,
showed markedly larger KD values, particularly in the interaction between the
double variant RolA-H32S/K34S and the triple variant CutL1-E31S/D142S/D171S (K(D)
= 78.0 nM). We discuss a molecular prototype model of hydrophobin-based enzyme
recruitment at the solid-water interface.
PMID- 25588313
TI - A call for better reporting of conservation research data for use in meta
analyses.
PMID- 25588310
TI - Differences in the distribution, phenotype and gene expression of subretinal
microglia/macrophages in C57BL/6N (Crb1 rd8/rd8) versus C57BL6/J (Crb1 wt/wt)
mice.
AB - BACKGROUND: Microglia/macrophages (MG/MPhi) are found in the subretinal space in
both mice and humans. Our goal was to study the spatial and temporal
distribution, the phenotype, and gene expression of subretinal MG/MPhi in mice
with normal retinas and compare them to mice with known retinal pathology.
METHODS: We studied C57BL/6 mice with (C57BL/6N), or without (C57BL/6J) the rd8
mutation in the Crb1 gene (which, in the presence of yet unidentified
permissive/modifying genes, leads to a retinal degeneration), and documented
their fundus appearance and the change with aging. Immunostaining of retinal
pigment epithelium (RPE) flat mounts was done for 1) Ionized calcium binding
adaptor (Iba)-1, 2) FcgammaIII/II Receptor (CD16/CD32, abbreviated as CD16), and
3) Macrophage mannose receptor (MMR). Reverse-transcription quantitative PCR (RT
qPCR) was done for genes involved in oxidative stress, complement activation and
inflammation. RESULTS: The number of yellow fundus spots correlated highly with
subretinal Iba-1+ cells. The total number of subretinal MG/MPhi increased with
age in the rd8 mutant mice, but not in the wild-type (WT) mice. There was a
centripetal shift in the distribution of the subretinal MG/MPhi with age. Old rd8
mutant mice had a greater number of CD16+ MG/MPhi. CD16+ cells had morphological
signs of activation, and this was most prominent in old rd8 mutant mice (P < 1 *
10(-8) versus old WT mice). Subretinal MG/MPhi in rd8 mutant mice also expressed
iNOS and MHC-II, and had ultrastructural signs of activation. Finally, rd8 mutant
mouse RPE/ MG/MPhi RNA isolates showed an upregulation of Ccl2, CFB, C3, NF
kbeta, CD200R and TNF-alpha. The retinas of rd8 mutant mice showed upregulation
of HO-1, C1q, C4, and Nrf-2. CONCLUSIONS: When compared to C57BL/6J mice,
C57BL/6N mice demonstrate increased accumulation of subretinal MG/MPhi,
displaying phenotypical, morphological, and gene-expression characteristics
consistent with a pro-inflammatory shift. These changes become more prominent
with aging and are likely due to the combination of the rd8 mutation and yet
unidentified permissive/modulatory genes in the C57BL/6N mice. In contrast, aging
leads to a scavenging phenotype in the C57BL/6J subretinal microglia/macrophages.
PMID- 25588314
TI - Using text mining for study identification in systematic reviews: a systematic
review of current approaches.
AB - BACKGROUND: The large and growing number of published studies, and their
increasing rate of publication, makes the task of identifying relevant studies in
an unbiased way for inclusion in systematic reviews both complex and time
consuming. Text mining has been offered as a potential solution: through
automating some of the screening process, reviewer time can be saved. The
evidence base around the use of text mining for screening has not yet been pulled
together systematically; this systematic review fills that research gap. Focusing
mainly on non-technical issues, the review aims to increase awareness of the
potential of these technologies and promote further collaborative research
between the computer science and systematic review communities. METHODS: Five
research questions led our review: what is the state of the evidence base; how
has workload reduction been evaluated; what are the purposes of semi-automation
and how effective are they; how have key contextual problems of applying text
mining to the systematic review field been addressed; and what challenges to
implementation have emerged? We answered these questions using standard
systematic review methods: systematic and exhaustive searching, quality-assured
data extraction and a narrative synthesis to synthesise findings. RESULTS: The
evidence base is active and diverse; there is almost no replication between
studies or collaboration between research teams and, whilst it is difficult to
establish any overall conclusions about best approaches, it is clear that
efficiencies and reductions in workload are potentially achievable. On the whole,
most suggested that a saving in workload of between 30% and 70% might be
possible, though sometimes the saving in workload is accompanied by the loss of
5% of relevant studies (i.e. a 95% recall). CONCLUSIONS: Using text mining to
prioritise the order in which items are screened should be considered safe and
ready for use in 'live' reviews. The use of text mining as a 'second screener'
may also be used cautiously. The use of text mining to eliminate studies
automatically should be considered promising, but not yet fully proven. In highly
technical/clinical areas, it may be used with a high degree of confidence; but
more developmental and evaluative work is needed in other disciplines.
PMID- 25588315
TI - Estimation of the Binding Free Energy of AC1NX476 to HIV-1 Protease Wild Type and
Mutations Using Free Energy Perturbation Method.
AB - The binding mechanism of AC1NX476 to HIV-1 protease wild type and mutations was
studied by the docking and molecular dynamics simulations. The binding free
energy was calculated using the double-annihilation binding free energy method.
It is shown that the binding affinity of AC1NX476 to wild type is higher than not
only ritonavir but also darunavir, making AC1NX476 become attractive candidate
for HIV treatment. Our theoretical results are in excellent agreement with the
experimental data as the correlation coefficient between calculated and
experimentally measured binding free energies R = 0.993. Residues Asp25-A, Asp29
A, Asp30-A, Ile47-A, Gly48-A, and Val50-A from chain A, and Asp25-B from chain B
play a crucial role in the ligand binding. The mutations were found to reduce the
receptor-ligand interaction by widening the binding cavity, and the binding
propensity is mainly driven by the van der Waals interaction. Our finding may be
useful for designing potential drugs to combat with HIV.
PMID- 25588317
TI - Comparison of Newcastle disease vaccine administered as powder or liquid in
relation to the serum antibody response and adverse vaccinal reactions in
broilers.
AB - Liquid spray and aerosol mass vaccination of poultry have several drawbacks, such
as uncontrolled deposition of vaccine particles in the respiratory tract and
vaccine virus inactivation by formation and evaporation of droplets. These may be
addressed by using dry powder vaccines with defined particle size distribution
targeting the upper (primary vaccination) or the entire respiratory tract
(booster vaccination). Therefore, a coarse Newcastle disease (LZ58 strain) powder
vaccine was administered to specified pathogen free (SPF) broiler hens to compare
the antibody response and adverse vaccinal reactions with those induced by a
coarse liquid spray and a fine liquid aerosol. Groups of 40 broilers each housed
in isolators were vaccinated at 4 days of age and intratracheally inoculated with
Escherichia coli (strain 506) at 11 days of age. Adverse vaccinal reactions were
evaluated by measuring body weight gain and mortality between 4 and 11 days of
age and between 11 and 18 days of age, and by recording colibacillosis lesions at
18 days of age. The antibody serum response was measured at 18 days of age by the
haemagglutination inhibition test. Despite the relative low initial vaccine virus
loss and narrow particle size distribution of the powder vaccines in comparison
with their liquid counter parts, no significant differences (P > 0.05) regarding
adverse vaccinal reactions and antibody response were observed between broilers
vaccinated with the powder vaccines or with their liquid counterparts.
PMID- 25588318
TI - Protective Effects of Glycyrrhizic Acid and 18beta-Glycyrrhetinic Acid against
Cisplatin-Induced Nephrotoxicity in BALB/c Mice.
AB - The clinical use of antineoplastic drug cisplatin (CP) is commonly complicated by
nephrotoxic side effects that limit its application and therapeutic efficiency.
This study used a model of CP-induced renal injury in male BALB/c mice to
investigate the protective effects of the active components of licorice,
glycyrrhizic acid (GA), and 18beta-glycyrrhetinic acid (18betaGA) against CP
induced nephrotoxicity, and the chemoprotectant, amifostine, was used as a
control. Oral administration of GA or 18betaGA significantly reduced CP-induced
increases in the levels of blood urea nitrogen, creatinine, and lactate
dehydrogenase. Hematoxylin and eosin staining revealed that GA and 18betaGA
delayed the progression of renal injury, including tubular necrosis, hyaline
casts, and tubular degeneration in response to CP exposure. Oxidative status and
inflammatory responses in CP-treated mice were restored to near-normal levels by
treatment with GA or 18betaGA. These protective effects might be associated with
upregulation of nuclear factor E2-related protein (Nrf2) and downregulation of
nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappaB) in the
kidney. Notably, we demonstrated that GA and 18betaGA rendered renal cells
resistant to CP-induced HMGB1 cytoplasmic translocation and release. These
findings suggest that GA and 18betaGA might be act as the chemoprotectants
against CP-induced nephrotoxicity.
PMID- 25588319
TI - Delayed tracheobronchial rupture after caustic ingestion.
PMID- 25588320
TI - Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A
activity in humans.
AB - AIM: We aimed to establish a method to assess systemic and pre-systemic
cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam.
METHODS: In an open, one sequence, crossover study, 16 healthy participants
received intravenous and oral midazolam at microgram (0.001 mg intravenous and
0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to
assess the linearity of plasma and urine pharmacokinetics. RESULTS: Dose
normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng
ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1,
42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was
253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for
intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1)
[95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose
was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular
dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI
0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for
milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]).
CONCLUSION: The pharmacokinetics of an intravenous midazolam microdose is linear
to the applied regular doses and can be used to assess safely systemic CYP3A
activity and, in combination with oral microdoses, pre-systemic CYP3A activity.
PMID- 25588321
TI - Highly precise detection, discrimination, and removal of anionic surfactants over
the full pH range via cationic conjugated polymer: an efficient strategy to
facilitate illicit-drug analysis.
AB - A water-soluble cationic conjugated polyelectrolyte (CPE), poly(1,4-bis(6-(1
methylimidazolium)-hexyloxy)-benzene bromide) (PMI) displays extraordinary
stability over the full pH range of 1-14 as well as in seawater, brine, urine,
and other solutions and carries out efficient detection, discrimination, and
removal of moderately dissimilar anionic surfactants (viz., sodium dodecyl
benzenesulfonate (SDBS) and sodium dodecyl sulfate (SDS)) at very low levels
(31.7 and 17.3 parts per billion (ppb), respectively). PMI formed stable
hydrogels in the presence of SDS that remained unaffected by strong acids/bases,
heating, ultrasonication, or exposure to light, whereas SDBS formed precipitate
with PMI as a result of its different interpolymer cofacial arrangement via
Columbic attraction. The complex-forming ability of PMI with SDS and SDBS
facilitated their elimination from water or drug-doped urine samples without the
use of any organic solvent, chromatographic technique, or solid support. This
protocol, the first of its kind for the removal of anionic surfactants at very
low concentrations from any type of solution and competitive environments,
demonstrates an original application using a CPE. The surfactant-free sample
solutions could be precisely analyzed for the presence of illicit drugs by any
standard methods. Using PMI, a newly developed CPE, a rapid and practical method
for the efficient detection, discrimination, and removal of SDS and SDBS at ppb
levels from water and urine, under harsh conditions, and in natural chemical
environments is demonstrated.
PMID- 25588316
TI - Metabolic vs. hedonic obesity: a conceptual distinction and its clinical
implications.
AB - Body weight is determined via both metabolic and hedonic mechanisms. Metabolic
regulation of body weight centres around the 'body weight set point', which is
programmed by energy balance circuitry in the hypothalamus and other specific
brain regions. The metabolic body weight set point has a genetic basis, but
exposure to an obesogenic environment may elicit allostatic responses and upward
drift of the set point, leading to a higher maintained body weight. However, an
elevated steady-state body weight may also be achieved without an alteration of
the metabolic set point, via sustained hedonic over-eating, which is governed by
the reward system of the brain and can override homeostatic metabolic signals.
While hedonic signals are potent influences in determining food intake, metabolic
regulation involves the active control of both food intake and energy
expenditure. When overweight is due to elevation of the metabolic set point
('metabolic obesity'), energy expenditure theoretically falls onto the standard
energy-mass regression line. In contrast, when a steady-state weight is above the
metabolic set point due to hedonic over-eating ('hedonic obesity'), a persistent
compensatory increase in energy expenditure per unit metabolic mass may be
demonstrable. Recognition of the two types of obesity may lead to more effective
treatment and prevention of obesity.
PMID- 25588322
TI - Role of the kidney in the fetal programming of adult cardiovascular disease: an
update.
AB - It is well established that an adverse in utero environment can impinge upon
fetal development and place the offspring on a track leading to future
cardiovascular disease. Significantly, this may occur in the absence of any
outward manifestations at birth. In this brief review, we focus on potential
renal mechanisms that lead to adaptations in glomerular and tubular function that
initiate hypertension of developmental origin and examine potential therapeutic
interventions. This report updates recent data in this field.
PMID- 25588323
TI - In vitro anti-lithogenic activity of lime powder regimen (LPR) and the effect of
LPR on urinary risk factors for kidney stone formation in healthy volunteers.
AB - Hypocitraturia, hypokaliuria, and increased oxidative stress are common
lithogenic risk factors found in nephrolithiasis patients, especially in
Thailand. We previously developed lime powder regimen (LPR), and demonstrated
that LPR delivered citraturic, alkalinizing, and antioxidative effects in kidney
stone patients. In this study, in vitro anti-lithogenic activity, in vivo acute
toxicity, and crossover-designed phase 1 trial (in 13 healthy volunteers) of LPR
were investigated. LPR inhibited the growth of calcium oxalate monohydrate (COM)
crystals in dose-dependent manner, and inhibited the intracellular production of
reactive oxygen species (ROS) in COM-treated HK-2 cells. LPR did not
significantly alter viability of HK-2 cells. No acute toxicity was detected in
mice orally fed with LPR (10 g/kg). No adverse effect and complaint of LPR
ingestion (5 g/dose) were observed in the tested volunteers. Plasma citrate was
elevated at 30 min after LPR load, which was higher than the water load control.
Plasma potassium was significantly elevated at 30 min after LPR load and remained
high for 2 h, and at 2 h, it was significantly higher than the water load.
Urinary citrate was significantly increased at 1 h after LPR load and remained
high for 2 h, and at 2 h, it was significantly higher than the water load.
Urinary potassium was significantly increased at 1 h after LPR load and remained
high for 3 h, and its levels at 1, 2, and 3 h were significantly higher than the
water load. Urinary total antioxidant status was significantly increased at 2 h
after LPR load. In conclusion, LPR had an inhibitory effect on COM growth and
exerted as antioxidant to attenuate ROS production in the COM-treated renal
tubular cells. LPR provided citraturic, kaliuric, and antioxidative responses in
healthy individuals without any adverse events. This suggests that LPR is well
tolerated and safe for daily consumption.
PMID- 25588325
TI - Primary hepatic myopericytoma with rhabdoid-like cells: Report of the first case
and review of Literature.
PMID- 25588324
TI - [Treatment of localized prostate cancer with high-intensity focused ultrasound].
AB - BACKGROUND: High-intensity focused ultrasound (HIFU) is an alternative technique
in the treatment of prostate cancer (PC). Despite proven oncologic efficacy, HIFU
is still not establish as a standard therapy for PC in Germany due to
insufficient clinical studies. OBJECTIVES: HIFU can be performed as primary whole
gland treatment, primary focal treatment, or salvage treatment in patients with
local recurrence after external radiation therapy (RT) or seeds (BT). This paper
provides an overview of the current significance of HIFU therapy in Germany.
RESULTS: Primary whole gland HIFU treatment showed approximately similar
oncologic efficacy and side effects when compared to radical prostatectomy (RP)
and RT or BT but results were not better than standard therapies. Between the
priorities of the active standard therapies, on the one hand, and active
surveillance, on the other, primary focal HIFU treatment may offer a new
therapeutic approach for patients with low- and early intermediate-risk diseases.
Diagnostic uncertainties and the lack of validated oncological outcome data are
currently strong limitations to the results of primary focal treatment. Salvage
treatment may offer intermediate-term disease-free survival for patients with
local recurrence after RT or BT, although it may be accompanied by increased side
effects. CONCLUSION: Currently, there is only little need for an alternative
whole gland treatment besides RP and RT/BT. The number of patients with low- and
early intermediate-risk diseases continues to grow. Some of these patients may
benefit from primary focal HIFU treatment. Prospective multicentric clinical
trials are needed to validate the oncologic efficacy of primary focal HIFU
treatment.
PMID- 25588327
TI - Erratum to: Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their
Basic and Clinical Pharmacology.
PMID- 25588326
TI - Superior radiation-resistant nanoengineered austenitic 304L stainless steel for
applications in extreme radiation environments.
AB - Nuclear energy provides more than 10% of electrical power internationally, and
the increasing engagement of nuclear energy is essential to meet the rapid
worldwide increase in energy demand. A paramount challenge in the development of
advanced nuclear reactors is the discovery of advanced structural materials that
can endure extreme environments, such as severe neutron irradiation damage at
high temperatures. It has been known for decades that high dose radiation can
introduce significant void swelling accompanied by precipitation in austenitic
stainless steel (SS). Here we report, however, that through nanoengineering,
ultra-fine grained (UFG) 304 L SS with an average grain size of ~100 nm, can
withstand Fe ion irradiation at 500 degrees C to 80 displacements-per-atom (dpa)
with moderate grain coarsening. Compared to coarse grained (CG) counterparts,
swelling resistance of UFG SS is improved by nearly an order of magnitude and
swelling rate is reduced by a factor of 5. M(23)C(6) precipitates, abundant in
irradiated CG SS, are largely absent in UFG SS. This study provides a
nanoengineering approach to design and discover radiation tolerant metallic
materials for applications in extreme radiation environments.
PMID- 25588328
TI - Primary malignant mixed Mullerian tumor of the fallopian tube after subtotal
hysterectomy: a case report and literature review.
PMID- 25588329
TI - Distinct demographic factors influence the acceptance of vaccination against HPV.
AB - PURPOSE: To investigate the possible effect of demographic factors on HPV
vaccination acceptance in Greece. METHODS: Analysis was performed on data from
the "LYSISTRATA" project, a prospective, cross-sectional study, focusing on
questions regarding the acceptance of HPV vaccination among Greek women for
themselves, and their 13-year-old daughter or son. In total, 5,379 women
participated in the study, between 2005 and 2011. RESULTS: Women born and raised
in Greece were more likely to accept HPV vaccination for themselves (aOR = 4.1,
95 % CI 2.9-5.8), their daughter (aOR = 3.3, 95 % CI 2.3-4.7) and son (aOR = 3.3,
95 % CI 2.3-4.8), compared with immigrants. Similarly, women who had a
Papanicolaou's test were more likely to accept vaccination for themselves (aOR =
1.8, 95 % CI 1.4-2.3), their daughter (aOR = 1.5, 95 % CI 1.2-1.9) and son (aOR =
1.4, 95 % CI 1.1-1.7) than those never tested. Smokers were less likely to accept
HPV vaccination for themselves (aOR = 0.8, 95 % CI 0.6-0.9); however, such an
association was not documented concerning their children. Educational level had a
rather inconsistent impact on HPV vaccination acceptance. The effect of womens'
age, monthly income, residence, profession and marital status on HPV vaccination
acceptance for themselves was different than that for their daughters, and even
more for their sons. CONCLUSIONS: There are distinct demographic factors that
influence HPV vaccination acceptance. Women's perception that male vaccination is
not as necessary may lead to lower acceptance of HPV vaccination for young boys
and men.
PMID- 25588331
TI - [Laboratory assessment of deformational features in thermoplastic materials for
removable dentures].
AB - The paper presents the results of laboratory tests of base thermoplastic
materials Acry F711 and Flexi N512 in comparison with the traditional acrylic
base material Ftoracs to study their deformational properties when loaded by
repetitive forces close to the functional chewing loads.
PMID- 25588332
TI - [Harmonic imaging analysis for assessment of morphological changes in mini-pig
alveolar bone by normal and increased functional load].
AB - The aim of the study was to reveal the mastication forces effect on the
microstructure of mandible bone tissue of mini-pigs by Fouirier harmonic imaging
analysis of bone sections images of back scattered electrons and assessment of
calcium and phosphorous distribution maps obtained by roentgenofluorescence
technique. The results showed that by higher functional loads not only the total
content of mineral elements in the bone matrix increased but also the of the low
frequency harmonics in the image spectrum indicating structural heterogeneity
decrease in bone mineralization.
PMID- 25588330
TI - Does metabolic syndrome increase the risk of infective complications after
prostate biopsy? A critical evaluation.
AB - PURPOSE: To evaluate the possible association between metabolic syndrome (MetS)
and infectious complications after prostate biopsy. METHODS: A total of 480 men
underwent prostatic biopsy due to elevated prostate-specific antigen levels
and/or abnormal digital rectal examination. Patients were divided into two
subgroups with respect to the presence or absence of MetS. Patients in both
groups were closely followed with respect to infectious complications after
biopsy and the possible effect of MetS as a certain risk factor on these
complications was evaluated with a multivariate analysis. RESULTS: Infectious
complications were observed in 33 cases (6.8%), while urinary tract infection
(UTI) was detected in 30 (6.2%) cases, sepsis occurred in three (0.6%) cases. The
percentage of the cases with infectious complications was 11.0 and 3.4% in men
with and without MetS, respectively (p = 0.002). These rates were 3.7 versus
1.5%, respectively, for UTI (p < 0.003) and 0.9 versus 0.4%, respectively, for
sepsis in both groups (p = 0.594). Multivariate analysis of the data confirmed
that MetS was associated with an increased risk of infective complications (odds
ratio 3.44 and 95% CI 1.56-7.58, p < 0.002) after this procedure. CONCLUSIONS:
MetS could pose a certain increased risk for infectious complications after
prostate biopsy. Patients with MetS should be considered as risk cases for this
procedure, and they should be evaluated and followed in a very close manner with
respect to these complications.
PMID- 25588334
TI - [Methods of complex diagnostics of oral leukoplakia].
AB - The problem of diagnostic of various forms of leukoplakia of the oral mucosa is
reviewed IT is introduced a set of methods for diagnosis of the disease,
including a clinical check up, evaluation of the data of optical coherence
tomography, classical histological and immunohistochemical study to determine the
neoplastic cell transformation of oral mucosa in the early stages of its
development.
PMID- 25588333
TI - [Antimicrobial efficacy of systemic antibiotics of different groups in the
complex treatment of patients with chronic periodontal disease].
AB - Among microorganisms found in the oral cavity there are several kinds of
periodontopathogenic bacteria having higher adhesive, invasive and toxic
properties. Eighty patients with moderate and severe chronic generalized
periodontitis were included in the study. The choice of treatment regimen
depended on real-time PCR values of pathogenic microorganisms in periodontal
pockets. Data on composition of periodontal pockets microflora by moderate and
severe periodontal disease allow prompt target antimicrobial therapy.
PMID- 25588335
TI - [Hemodynamic features assessment in submental and facial arteries in patients
with early atherosclerotic disease of brachycephalic arteries].
AB - By ultrasonicduplex scanning nature estimated haemodynamics in the
arteriessubmentalis and facial of patients with early signs of atherosclerotic
changes in the brakhiotsefalarteries and periodontal pathology of different
stages - for perfection of prophylaxis of periodontal diseases by the means of
investigation of prophylaxis vascular diseases. It was established, that
influence of risk factors is more important than the age of patients.
PMID- 25588336
TI - [Comparative study of bacterial flora in patients with chronic periodontal
disease assessed by various microbiological methods (preliminary study)].
AB - Periodontal pockets microflora features by aggressive and chronic periodontal
disease were studied by means of polymerase chain reaction (PCR) and mass
spectrometry. The study included 14 patients aged 25-70 years without somatic
pathology. The pilot study has shown the high prevalence rate in obligate
periodontal pathogens in periodontal pockets revealed by PCR diagnostics, at the
same time mass spectrometry has revealed the presence of other pathogens which
had not been primarily included into PRC diagnosis. Periodontal disease,
periodontal pathogenes, mass spectrometry, PCR diagnostics, periodontal pockets,
microbiological flora.
PMID- 25588337
TI - [Method of root canal retreatment using computer simulation].
AB - The paper describes a method of root canal retreatment that enables by means of
CT data, laser surface scanning of teeth and a number of software to create
plastic templates making possible successful retreatment with minimal risk of
complications. The effectiveness of the method was evaluated in vitro on 10
extracted teeth. Application of the method in clinical practice enables the
highest degree of accuracy and security of the procedure.
PMID- 25588338
TI - [Efficiency and safety of local anesthesia in teeth with mild and moderate
periodontal disease].
AB - The rationale for the choice of local anesthesia in teeth with mild to moderate
periodontal disease was formulated based on a comparative analysis of the
effectiveness and safety of different local anesthesia methods with 4% articaine.
Effectiveness of anesthesia was assessed using objective values of electric study
of pulp sensitivity and registration of microcirculation in dental pulp. Safety
analysis was based on changes in periodontal tissues microcirculation assessed by
laser Doppler flowmetry, as well as of central hemodynamics rates.
PMID- 25588339
TI - [Surgical treatment of patients with drug abuse and mandible necrosis].
AB - The article describes clinical and radiological classification of osteonecrosis
of the mandible in patients with drug dependence, surgical options presented on
the basis of classification proposed. Clinical case of simultaneous application
of individual plate of nikelid titanium in patient with osteonecrosis of the
mandible is presented.
PMID- 25588340
TI - [PCR rationale for use of oral cephalosporins by oral surgery procedures].
AB - The article presents the experience of PCR detection of DNA of pathogenic germs
inducing odontogenic inflammation. Pus samples of 48 patients aged 18 to 68 years
undergoing oral surgery because of apical periodontal lesions and pericoronitis.
The results showed microorganisms associations revealed by PCR are sensitive to
III generation cephalosporins. Effective oral regimen included 400 mg Ceftibuten
once daily. The PCR results thus served as a rationale for use of oral
cephalosporins by oral surgery procedures proved by clinical and immunological
data in postoperative period.
PMID- 25588342
TI - [Mandibular condyle fractures fixation via intraoral approach with endoscopic
assistance].
AB - The aim of the study was to evaluate the effectiveness of mandibular condyle
fractures fixation via intraoral approach with endoscopic assistance. Thirty-nine
patients with low mandibular condyle fractures with lateral (34 patients) or
medial (5 patients) displacement were included in the study. The paper contains
detailed description of operation technique considering displacement type. This
minimally invasive procedure resulted in stable fixation of the fracture so that
maxillomandibular splinting was limited to 9-14 days after operation. The
patients were discharged 4 to 7 days postoperatively. The study revealed no cases
of facial palsies and all patients were highly satisfied with the absence of
visible scars.
PMID- 25588341
TI - [Choice of cystotomy method in patients with cysts of maxillary frontal region
according to resorption grade of adjacent bony structures].
PMID- 25588343
TI - [Use of elastopositioner for treatment of masticator muscles discoordination in
patients with TMJ dysfunction].
AB - The paper presents the analysis of functional changes in patients with TMJ
dysfunction before and after the use of elastopositioner. Analysis has shown that
at the initial stages the device provide relief from pain and masticatory muscles
hypertension, reduced the bioelectric activity of the muscles. Normalization of
the lower jaw movements when opening and closing the mouth and reduction of noise
events in TMJ were also noted.
PMID- 25588344
TI - [Stabilometric features of vertical stability in healthy individuals by short
time bite change].
AB - The aim of the study was to evaluate vertical stability changes according to
stabilometric findings under artificial short-time disturbed occlusion. Twelve
individuals were included in the study and vertical stability was assessed in
stability platform before and under short-time bite change. The registered
changes might be connected with an approximate reaction and random reasons. There
is a possibility of bias by mechanical transfer of the stabilometric study
results on the diagnosis of dental status.
PMID- 25588345
TI - [The experience of complex treatment of children with bilateral cleft lip and
palate].
AB - Three grades of premaxilla deformation were revealed in children with bilateral
cleft lip and palate. All patients with grade I and some children with grade II
deformation received early orthopedic treatment by Sharova appliance while in
patients with grade III deformation orthodontic devices with bone fixation with
microimplants were used or microimplants alone for orthodontic anchorage. This
approach allowed achieving full side contact of premaxilla and maxillary
fragments in 1-2 months thus creating favorable conditions for surgical
procedure.
PMID- 25588347
TI - Retraction. Breast cancer surgery in elderly patients: postoperative
complications and survival.
PMID- 25588346
TI - Investigation of mosquito oviposition pheromone as lethal lure for the control of
Aedes aegypti (L.) (Diptera: Culicidae).
AB - BACKGROUND: The trend in chemical insecticide development has focused on
improving the efficacy against mosquitoes while reducing the environmental
impact. Lethal lures apply an "attract-and-kill" strategy that draws the insect
to the killing agent rather than bringing the killing agent to the insect.
METHODS: In this study, the mosquito oviposition pheromone was extracted from the
eggs of Aedes aegypti (L.) and further investigated with a combination of
pheromone and granular temephos as a lethal lure. RESULTS: The compound caproic
acid attracted significantly more egg-laying mosquitos at 1 ppm (660.83 +/-
91.61) than the control (343.83 +/- 56.24), which consisted of solvent only
(Oviposition Activity Index: 0.316). Further investigation of the combination of
caproic acid with granular temephos as a lethal lure attracted significantly more
gravid female Ae. aegypti to oviposit their eggs than the temephos treated water
and control. CONCLUSIONS: This indicated the ability of caproic acid in acting as
an attractant and counters the repellency effect of temephos. Additionally, the
presence of temephos in the lethal lure also restricted the hatching of the eggs
and killed any larvae that hatched.
PMID- 25588348
TI - An optopneumatic piston for microfluidics.
AB - We demonstrate an optopneumatic piston based on glass capillaries, a mixture of
PDMS-carbon nanopowder, silicone and mineral oil. The fabrication method is based
on wire coating techniques and surface tension-driven instabilities, and allows
for the assembly of several pistons from a single batch production. By coupling
the photothermal response of the PDMS-carbon mixture with optical excitation via
an optical fiber, we demonstrate that the piston can work either as a valve or as
a reciprocal actuator. The death volume of the pistons was between 0.02 and 1.56
MUL and the maximum working frequency was around 1 Hz. Analysis of the motion
during the expansion/contraction of the piston shows that this machine can be
described by a phenomenological equation analogous to the Kelvin-Voight model
used in viscoelasticity, having elastic and viscous components.
PMID- 25588349
TI - Aggregation behavior of a gemini surfactant with a tripeptide spacer.
AB - A peptide gemini surfactant, 12-G(NH2)LG(NH2)-12, has been constructed with two
dodecyl chains separately attached to the two terminals of a glutamic acid-lysine
glutamic acid peptide and the aggregation behavior of the surfactant was studied
in aqueous solution. The 12-G(NH2)LG(NH2)-12 molecules form fiber-like
precipitates around pH 7.0, and the precipitation range is widened on increasing
the concentration. At pHs 3.0 and 11.0, 12-G(NH2)LG(NH2)-12 forms soluble
aggregates because each molecule carries two positively charged amino groups at
the two ends of the peptide spacer at pH 3.0, while each molecule carries one
negatively charged carboxyl group in the middle of the peptide spacer at pH 11.0.
12-G(NH2)LG(NH2)-12 displays a similar concentration-dependent process at these
two pHs: forming small micelles above the critical micelle concentration and
transferring to fibers at pH 3.0 or twisted ribbons at pH 11.0 above the second
critical concentration. The fibers formed at pH 3.0 tend to aggregate into
bundles with twisted structure. Both the twisted fibers at pH 3.0 and the twisted
ribbons at pH 11.0 contain beta-sheet structure formed by the peptide spacer.
PMID- 25588350
TI - Novel FGG variant (gamma339C->S) confirms importance of the gamma326-339
disulphide bond for plasma expression of newly synthesised fibrinogen.
PMID- 25588352
TI - The strain rate effect on the buckling of single-layer MoS2.
AB - The Euler buckling theory states that the buckling critical strain is an inverse
quadratic function of the length for a thin plate in the static compression
process. However, the suitability of this theory in the dynamical process is
unclear, so we perform molecular dynamics simulations to examine the
applicability of the Euler buckling theory for the fast compression of the single
layer MoS2. We find that the Euler buckling theory is not applicable in such
dynamical process, as the buckling critical strain becomes a length-independent
constant in the buckled system with many ripples. However, the Euler buckling
theory can be resumed in the dynamical process after restricting the theory to an
individual ripple in the buckled structure.
PMID- 25588353
TI - Long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal
gel: an open-label extension of the double-blind pivotal study in advanced
Parkinson's disease patients.
AB - BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) is delivered continuously
via intrajejunal percutaneous gastrostomy tube. OBJECTIVE: To examine long-term
safety, efficacy and quality of life of LCIG in an open-label extension study.
METHODS: Patients received 52 weeks of open-label LCIG treatment following a 12
week double-blind, double-dummy trial in which they were randomized to either
LCIG or immediate-release oral levodopa-carbidopa. Patient cohort designation was
by receipt of LCIG in the preceding trial randomization (continuing-LCIG vs. LCIG
naive patients). RESULTS: Sixty-two of 66 subjects in the double-blind proceeded
to the open-label extension. Most subjects (95%) reported >=1 adverse event (AE);
only 3 subjects (4.8%) discontinued due to AEs. AE incidence declined gradually
over 52 weeks. Serious AEs were reported by 23%. LCIG-naive patients (N = 29)
showed a decrease in "Off" time and an increase in "On" time without troublesome
dyskinesia (change from baseline to final visit in mean [SD] hours = -2.34 [2.78]
P < 0.001 and 2.19 [3.70] P = 0.005, respectively), while continuing-LCIG
patients (N = 33) showed sustained "Off" time duration and further improvement in
"On" time without troublesome dyskinesia (-0.42 [2.67] P = 0.377 and 1.00 [2.58]
P = 0.036, respectively). The majority of patients in both groups (LCIG-naive,
continuing-LCIG, respectively) were rated 'Much Improved' or 'Very Much Improved'
at final visit on the Clinical Global Impression-Improvement scale (69.0%,
69.7%). CONCLUSIONS: Continuing-LCIG patients continued to derive benefit from
LCIG while the magnitude of improvement among LCIG-naive patients was similar to
that observed for patients on LCIG in the preceding double-blind study. The
overall AE profile was consistent with previous phase 3 clinical trials involving
the LCIG system.
PMID- 25588355
TI - Sleep correlates of trait executive function and memory in Parkinson's disease.
AB - BACKGROUND: Sleep disturbance and cognitive impairment are correlated in non
diseased populations, but their association in Parkinson's disease (PD) is
uncertain. Prior studies examining measures of cognition in relation to sleep
have used either self-report or actigraphically measured sleep and have produced
conflicting findings. OBJECTIVE: In this descriptive study, we correlated
measurements of sleep in PD patients derived from the gold-standard measurement,
in-lab polysomnography, with an extensive battery of cognitive measures. We
hypothesized that poorer sleep would be related to relatively more impaired
cognition. METHODS: Idiopathic PD patients (n = 34) completed a cognitive battery
encompassing three broad domains (executive function, immediate memory and
delayed memory), and underwent PSG for two nights. Scores for each domain from
individual cognitive measures were converted to z-scores and then averaged to
produce a composite score. We used second night PSG data and quantified measures
of sleep architecture, sleep continuity, sleep apnea and nocturnal movement
(periodic leg movements, PLMS). RESULTS: Lower executive function was associated
with higher PLMS after controlling for chronological age, mini-mental state
examination scores, and UPDRS motor subscale scores. These results were
independent from psychomotor speed. There was a marginally significant positive
correlation between the proportion of time spent in REM and immediate recall
ability. Measures of sleep continuity and sleep apnea were unrelated to cognition
in these patients. CONCLUSIONS: PLMS, known to be a frequent feature of PSG
measured sleep in PD, may be an important correlate of impaired executive
function in PD. Whether treating this disorder of sleep results in improvement in
cognition remains to be determined.
PMID- 25588356
TI - Social Cognition Impairments in Mice Overexpressing Alpha-Synuclein Under the
Thy1 Promoter, a Model of Pre-manifest Parkinson's Disease.
AB - BACKGROUND: Patients with Parkinson's disease (PD) may exhibit deficits in
"Theory of Mind", the ability to read others' mental states and react
appropriately, a prerequisite for successful social interaction. Alpha-synuclein
overexpression is widely distributed in the brain of patients with sporadic PD,
suggesting that it may contribute to the non-motor deficits observed in PD
patients. Mice over-expressing human wild-type alpha-synuclein under the Thy1
promoter (Thy1-aSyn mice) have synaptic deficits in the frontostriatal pathway,
low cortical acetylcholine, and high level of expression of mGluR5 receptors,
which have all been implicated in social recognition deficits. OBJECTIVE: To
determine whether Thy1-aSyn mice present alterations in their response to social
stimuli. METHODS: We have submitted Thy1-aSyn mice to tests adapted from autism
models. RESULTS: At 7-8 month of age Thy1-aSyn mice explored their conspecifics
significantly less than did wild-type littermates, without differences in
exploration of inanimate objects, and pairs of Thy1-aSyn mice were involved in
reciprocal interactions for a shorter duration than wild-type mice at this age.
These deficits persisted when the test animal was enclosed in a beaker and were
not present at 3-4 months of age despite the presence of olfactory deficits at
that age, indicating that they were not solely caused by impairment in olfaction.
CONCLUSION: Thy1-aSyn mice present progressive deficits in social recognition,
supporting an association between alpha-synuclein overexpression and Theory of
Mind deficits in PD and providing a useful model for identifying mechanisms and
testing novel treatments for these deficits which impact patients and caretakers
quality of life.
PMID- 25588357
TI - Participatory design in Parkinson's research with focus on the symptomatic
domains to be measured.
AB - BACKGROUND: There is a growing interest in the objective assessment of health
related outcomes using technology providing quality measurements to be applied
not only in daily clinical practice, but also in scientific research. Differences
in the understandings of the condition and the terminology used between people
with Parkinson's (PwPs), clinicians and technical developers may influence the
progress of a participatory design process. OBJECTIVE: This paper reports on a
participatory design process to achieve a consensus among PwPs, clinicians and
technologists over the selection of a set of symptomatic domains to be
continuously assessed, in order to provide results relevant to both PwPs and
clinicians. METHODS: The methods used were a Web based user survey, end-user
focus groups, ranking by combined methods, a Delphi process performed among
clinicians and scientists, and prioritization of the results in a concertation
workshop for PwPs, clinicians and technologists. RESULTS: The following
symptomatic domains were commonly agreed by PwPs and clinicians to be of central
importance in a system of continuous assessment: hypokinesia/bradykinesia,
tremor, sway, gait, sleep and cognition. This list satisfied both the needs of
the PwPs and the concerns of the clinicians regarding the means of advancing new
strategies in assessment and interventions in PD. CONCLUSIONS: A participatory
design strategy allowed the definition of a consensual list of symptomatic
domains. Both the strategy and the achieved results may be of relevance for
similar interdisciplinary approaches in the field of PD using a participatory
design involving patients, clinicians and technologists.
PMID- 25588358
TI - Using lanthanide ions in molecular bioimaging.
AB - Trivalent lanthanide ions offer remarkable opportunities in the design of
bioimaging agents: this review presents an accessible discussion of their
application in both optical and magnetic resonance imaging. Aspects of molecular
design, control over key physical properties and biological compatibility are
discussed in this context, together with developments and opportunities as
responsive probes and in multimodal imaging.
PMID- 25588359
TI - Response to: A rapid skeletal turnover in radiographic mimic of osteopetrosis
might be secondary to systemic mastocytosis.
PMID- 25588354
TI - Role of alpha-synuclein in inducing innate and adaptive immunity in Parkinson
disease.
AB - Alpha-synuclein (alpha-syn) is central to the pathogenesis of Parkinson disease
(PD). Gene duplications, triplications and point mutations in SNCA1, the gene
encoding alpha-syn, cause autosomal dominant forms of PD. Aggregated and post
translationally modified forms of alpha-syn are present in Lewy bodies and Lewy
neurites in both sporadic and familial PD, and recent work has emphasized the
prion-like ability of aggregated alpha-syn to produce spreading pathology.
Accumulation of abnormal forms of alpha-syn is a trigger for PD, but recent
evidence suggests that much of the downstream neurodegeneration may result from
inflammatory responses. Components of both the innate and adaptive immune systems
are activated in PD, and influencing interactions between innate and adaptive
immune components has been shown to modify the pathological process in animal
models of PD. Understanding the relationship between alpha-syn and subsequent
inflammation may reveal novel targets for neuroprotective interventions. In this
review, we examine the role of alpha-syn and modified forms of this protein in
the initiation of innate and adaptive immune responses.
PMID- 25588361
TI - Experimental and theoretical charge density distribution in Pigment Yellow 101.
AB - The charge density distribution in 2,2'-dihydroxy-1,1'-naphthalazine (Pigment
Yellow 101; P.Y.101) has been determined using high-resolution X-ray diffraction
and multipole refinement, along with density functional theory calculations.
Topological analysis of the resulting densities highlights the localisation of
single/double bonds in the central C=N-N=C moiety of the molecule in its ground
state. The density in the N-N is examined in detail, where we show that very
small differences between experiment and theory are amplified by use of the
Laplacian of the density. Quantification of hydrogen bonds highlights the
importance of the intramolecular N-H...O interaction, known to be vital for
retention of fluorescence in the solid state, relative to the many but weak
intermolecular contacts located. However, a popular method for deriving H-bond
strengths from density data appears to struggle with the intramolecular N-H...O
interaction. We also show that theoretical estimation of anisotropic
displacements for hydrogen atoms brings little benefit overall, and degrades
agreement with experiment for one intra-molecular contact.
PMID- 25588360
TI - The role of postoperative chemoradiation for oropharynx carcinoma: a critical
appraisal of the published literature and National Comprehensive Cancer Network
guidelines.
AB - The National Comprehensive Cancer Network (NCCN) describes the presence of
extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an
indication for the addition of chemotherapy to postoperative radiation. The
guideline's category 1 consensus is based on what they term high-level evidence.
For this study, the authors performed a critical appraisal of the research upon
which the NCCN guideline is based and assessed its relevance in the era of human
papillomavirus (HPV)/p16-positive OPC. Multiple shortcomings were identified,
including patient exclusion after randomization and the use of unplanned subgroup
analyses without multivariate adjustment, which undermined internal validity.
Indeterminate HPV/p16 status limited external validity. Given the unique biology
of HPV/p16-positive tumors and the problems of internal and external validity,
the authors concluded that the literature upon which the recommendation for the
addition of chemotherapy to adjuvant radiation was based does not generate high
level evidence, and its relevance for the postoperative management of patients
with HPV/p16-positive OPC remains unknown.
PMID- 25588363
TI - Erratum to: Comparative assessment of surgeons' task performance and surgical
ergonomics associated with conventional and modified flank positions: a
simulation study.
PMID- 25588362
TI - National outcomes of laparoscopic Heller myotomy: operative complications and
risk factors for adverse events.
AB - INTRODUCTION: Laparoscopic Heller myotomy (LHM) has supplanted an open approach
due to decreased operative morbidity. Our goal was to quantify the incidence of
peri-operative complications and identify risk factors for adverse outcomes in
LHM. METHODS: All LHM were queried from 2005 to 2011 from the National Surgical
Quality Improvement Program database. Adverse outcomes were identified, and
univariate and stepwise logistic regression (MVR) was then performed to quantify
association. RESULTS: There were 1,237 LHM in the study period. Patient averages
were: age 51.9 +/- 16.8 years, BMI 27.3 +/- 6.6 kg/m(2), Charlson comorbidity
index (CCI) 0.2 +/- 0.6. 15.3 % had >10 % body mass loss in the preoperative 6
months. During surgery, 10.2 % underwent concomitant EGD, and mean operative time
was 141.6 +/- 63.4 min. There were 7(0.06 %) wound complications, 22(1.8 %)
general complications, and 30(2.4 %) major complications. Average length of stay
(LOS) was 2.8 +/- 5.5 days. The rate of readmission and reoperation were 3.1 and
2.3 %, respectively, and there were 4(0.03 %) deaths. General and major
complications were associated with alcohol use, pack-years of smoking, weight
loss, history of stroke, radiation therapy, and longer operative times (p <
0.05); however, these factors did not remain significant on MVR (p > 0.05).
Operative time was found to be significantly longer by 35.3 min for inpatients,
43.1 min in functionally dependent patients, 50.0 min in preoperative septic
patients, and 17.2 min with concomitant EGD (p < 0.01 for all). LOS was found to
be longer by 1.9 days for inpatients, 1.8 days in ASA category >=3, and 1.2 days
per one point increase in CCI (p < 0.001 for all). CONCLUSION: LHM is being
performed nationally with a low incidence of operative complications and
mortality. General and major complications following LHM are associated with
patient alcohol use, pack-years of smoking, weight loss, history of stroke,
radiation therapy, and longer operative times. Additionally, independent
predictors of longer operative time and LOS were identified.
PMID- 25588364
TI - Biliary metal stents for proximal esophageal or hypopharyngeal strictures.
AB - INTRODUCTION: Endoscopic dilation is the standard of care for stenoses of the
cervical esophagus, but refractory strictures require some form of stenting. Most
endoscopists avoid the placement of metal stents near the upper esophageal
sphincter as they can cause major problems like severe cervical pain and globus
sensation. We report our results with the use of biliary SEMS in the upper
esophagus, which have a smaller diameter than regular esophageal stents and
therefore exert less expansive force. MATERIAL AND METHODS: We retrospectively
reviewed all patients in our center between July 2011 and June 2014 who received
a biliary metal stent because of a refractory stricture in the cervical
esophagus. We implanted biliary SEMS (Wallflex, Boston Scientific) with a
diameter of 1 cm and length of 6-8 cm. Technical and clinical success, adverse
events and duration of stenting were evaluated. RESULTS: Ten patients were
treated with biliary SEMS in the upper esophagus. Strictures were located between
10 and 19 cm from incisor teeth. Stent placement was successful in all (10/10)
patients. One stent had to be extracted because of pain and globus sensation.
Apart from that stent tolerability was good. All remaining patients (9/9)
reported improvement of dysphagia with a decrease in mean dysphagia score from
3.2 to 1.78. Mean duration of stenting was 68 days. DISCUSSION: Because of a high
clinical success rate and good tolerability, biliary metal stents are a
reasonable alternative for difficult strictures in the cervical esophagus,
especially in the palliative setting.
PMID- 25588366
TI - The improvement of the dissolution rate of ziprasidone free base from solid oral
formulations.
AB - This work aims at increasing solubility and dissolution rate of ziprasidone free
base-Biopharmaceutics Classifaction System (BCS) class II compound. The authors
describe a practical approach to amorphization and highlight problems that may
occur during the development of formulations containing amorphous ziprasidone,
which was obtained by grinding in high-energy planetary ball mills or cryogenic
mills. The release of ziprasidone free base from the developed formulations was
compared to the reference drug product containing crystalline ziprasidone
hydrochloride-Zeldox(r) hard gelatin capsules. All preparations were investigated
using compendial tests (USP apparatuses II and IV) as well as novel, biorelevant
dissolution tests. The novel test methods simulate additional elements of
mechanical and hydrodynamic stresses, which have an impact on solid oral dosage
forms, especially during gastric emptying. This step may prove to be particularly
important for many formulations of BCS class II drugs that are often
characterized by narrow absorption window, such as ziprasidone. The dissolution
rate of the developed ziprasidone free base preparations was found to be
comparable or even higher than in the case of the reference formulation
containing ziprasidone hydrochloride, whose water solubility is about 400 times
higher than its free base.
PMID- 25588365
TI - A gastrointestinal transit study on amphotericin B-loaded solid lipid
nanoparticles in rats.
AB - The gastrointestinal (GI) transit behavior of and absorption from an amphotericin
B (AmB) solid lipid nanoformulation (SLN) in rats was investigated. We aimed to
estimate the gastric emptying time (GET) and cecal arrival time (CAT) of AmB SLN
in rats as animal models. From these two parameters, an insight on the absorption
window of AmB was ascertained. Three types of SLNs, AmB, paracetamol (PAR), and
sulfasalazine (SSZ), were similarly formulated using beeswax/theobroma oil
composite as the lipid matrix and characterized with regard to size, viscosity,
density, migration propensity within agarose gel, in vitro drug release,
morphology, gastrointestinal transit, and in vivo absorption. The GET and CAT
were estimated indirectly using marker drugs: PAR and sulfapyridine (SP). All
three types of SLNs exhibited identical properties with regard to z-average,
viscosity, relative density, and propensity to migrate. PAR was absorbed rapidly
from the small intestine following emptying of the SLNs giving the T50E (time for
50% absorption of PAR) to be 1.6 h. SP was absorbed after release and microbial
degradation of SSZ from SLN in the colon with a lag time of 2 h post
administration, serving as the estimated cecal arrival time of the SLNs. AmB
within SLN was favorably absorbed from the small intestine, albeit slowly.
PMID- 25588367
TI - A non-invasive method for the determination of liquid injectables by Raman
spectroscopy.
AB - Drug safety has become a very important subject, and more countries have joined
in the fight against counterfeit drugs. This study demonstrated a non-invasive
Raman spectroscopy method that could be utilized for screening liquid injectable
drugs for spurious/falsely-labeled/falsified/counterfeit medical products
(SFFCs). Two problems were solved to remove the blocks in identification and
quantitation: one problem was the weak API signal extraction from the non
invasive Raman spectra and the other was the problem of Raman absolute
measurement. Principal component analysis (PCA) and classical least square (CLS)
algorithms were performed to establish the models. Water was chosen as the
"internal standard" to normalize the spectra to solve the problem of Raman
absolute measurement. The results showed that the 11 positive samples and 66
negative samples were all well identified with a threshold of 0.95. One of the
positive samples contained the excipient propylene glycol, which was identified
successfully at the same time. The accuracy of quantitative results was
approximately 5% for doxofylline liquid injectables and about 10% for the low
concentration and big glass bottle-containers of Levofloxacin Lactate and Sodium
Chloride Injections as compared to the results using an HPLC method, this is
satisfactory for fast screening of SFFCs. In conclusion, with the development of
a database of identification and quantitation models, this method may determine
liquid injectable drugs in a fast and non-invasive way and become one of the most
powerful weapons against SFFCs. Graphical Abstract ?.
PMID- 25588368
TI - The fate of NHC-stabilized dicarbon.
AB - The attempted synthesis of NHC-stabilized dicarbon (NHC=C=C=NHC) through
deprotonation of a doubly protonated precursor ([NHC-CH=CH-NHC](2+) ) is
reported. Rather than deprotonation, a clean reduction to NHC=CH-CH=NHC is
observed with a variety of bases. The apparent resistance towards deprotonation
to the target compound led to a reinvestigation of the electronic structure of
NHC->C?C<-NHC, which showed that the highest occupied molecular orbital/lowest
unoccupied molecular orbital (HOMO/LUMO) gap is likely too small to allow for
isolation of this species. This is in contrast to the recent isolation of the
cyclic alkylaminocarbene analogue (cAAC=C=C=cAAC), which has a large HOMO-LUMO
gap. A detailed theoretical study illuminates the differences in electronic
structures between these molecules, highlighting another case of the potential
advantages of using cAAC rather than NHC as a ligand. The bonding analysis
suggests that the dicarbon compounds are well represented in terms of donor
acceptor interactions L->C2 <-L (L=NHC, cAAC).
PMID- 25588369
TI - Clinical evaluation of Moro (Citrus sinensis (L.) Osbeck) orange juice
supplementation for the weight management.
AB - In the last years, several studies have recently evaluated the beneficial effects
of red orange juice (Citrus sinensis (L.) Osbeck) and its active components in
weight management and obesity. Moro orange is a cultivar of red orange,
particularly rich in active compounds such as anthocyanins, hydroxycinnamic
acids, flavone glycosides and ascorbic acid, which displays anti-obesity effects
in in vitro and in vivo studies. In this clinical study, the effect of a Moro
juice extract (Morosil((r)), 400 mg/die) supplementation was evaluated in
overweight healthy human volunteers for 12 weeks. Results showed that Moro juice
extract intake was able to induce a significant reduction in body mass index
(BMI) after 4 weeks of treatment (p < 0.05). Moreover, in subjects treated with
Moro extract, body weight, BMI, waist and hip circumference were significantly
different from the placebo group (p < 0.05). In conclusion, it could be suggested
that the active compounds contained in Moro juice have a synergistic effect on
fat accumulation in humans and Moro juice extract can be used in weight
management and in the prevention of human obesity.
PMID- 25588370
TI - The lack of efficacy of oxytocin and NSAIDs.
PMID- 25588371
TI - Relationship between cigarette smoking and radiographic knee osteoarthritis in
Chinese population: a cross-sectional study.
AB - The purpose of this paper was to estimate the cross-sectional association between
cigarette smoking and radiographic knee Osteoarthritis (OA) in Chinese
population. A total of 3,789 subjects (1,796 females and 1,993 males)
participated in this study. A subject was diagnosed with radiographic knee OA if
Kellgren-Lawrence (K-L) grade >=2 in at least one leg. The smoking status was
classified into four levels based on the daily smoking habit: (1) 0/day; (2) 1
10/day; (3) 11-20/day; and (4) >20/day. Linear trend and multivariable logistic
regression were conducted for statistical analysis. The prevalence of
radiographic knee OA was 28.4 % among the subjects of this study. An inverse
association was observed between cigarette smoking and radiographic knee OA in
the linear trend test. Such association remained valid after adjusting the
factors of age, gender, body mass index, betel quilt chewing status, physical
activity, alcohol drinking status, mean total energy intake and educational level
in the multivariable logistic regression. This study suggested a negative
association between cigarette smoking and radiographic knee OA in the Chinese
population. The findings of this study need to be confirmed by further
prospective research.
PMID- 25588372
TI - Current cigarette use in rheumatoid arthritis patients: associated factors and a
limited mediating role of depression.
AB - Some newly published studies revealed that current smoking was associated with
accelerated disease progression in diagnosed rheumatoid arthritis (RA) patients.
The major aims of this study were to analyze the associated factors of current
smoking in RA patients and explore the mediating role of depression in the
associations between identified factors and smoking. RA patients were selected
from NHANES databases 2005-2012. Current smoking was determined by race-specific
serum cotinine levels. Depression was measured by the Depression Screener
questionnaire. Totally, 848 RA patients were identified and included into final
analysis. Logistic regression model founds that age, race, and socioeconomic
status (SES) were associated with current smoking in RA patients: the odds ratios
(ORs) of smoking were 0.29 (95 % CI 0.17, 0.49) and 0.39 (95 % CI 0.24, 0.62) in
patients over 60 years old and of higher SES, respectively; non-Hispanic white
patients with a pre-RA smoking history had an OR of 3.48 (95 % CI 1.35, 5.18)
when compared with patients of other race with no pre-RA smoking history.
Structural equation model identified a weak mediating role of depression, only
accounted for 5 % of the total SES-smoking association. In this sample of
diagnosed RA patients, age, SES, ethnicity, but not depression, were
significantly associated with current smoking.
PMID- 25588373
TI - Opioid and chemokine receptor crosstalk: a promising target for pain therapy?
AB - Chemokines and opioids are important regulators of immune, inflammatory and
neuronal responses in peripheral and central pain pathways. Recent studies have
provided insights into the functional interactions between chemokine receptors
and opioid receptors, and their role in pain modulation. In this Progress
article, we discuss how crosstalk between these two systems might provide a
molecular and cellular framework for the development of novel analgesic therapies
for the management of acute and/or chronic pain.
PMID- 25588381
TI - Scotland's evidence based outcomes framework for problem drug use.
PMID- 25588380
TI - Psychological treatments are effective for depression in primary care, study
shows.
PMID- 25588382
TI - "Frustrated," "depressed," and "devastated" pediatric trainees: US academic
medical centers fail to provide adequate workplace breastfeeding support.
AB - BACKGROUND: Exclusive breastfeeding (EBF) is recommended until about 6 months of
age. Pediatricians are at the forefront of encouraging mothers to achieve this
goal, yet pediatricians who parent during their training may face substantial
barriers in achieving their own breastfeeding goals. OBJECTIVES: This study aimed
to assess breastfeeding support available to US pediatricians in training and the
effect of trainees' personal experiences on their attitude toward breastfeeding.
METHODS: An online survey was emailed to American Academy of Pediatrics Section
on Medical Students, Residents, and Fellowship Trainees members. RESULTS: There
were 927 respondents, of which 421 had children and 346 breastfed their children.
Almost 80% agreed that 6 months is the ideal duration for EBF. One in 4 did not
have access to or were not aware of a private room to express milk or breastfeed.
Forty percent needed to extend the duration of their training for a longer
maternity leave, with breastfeeding a factor for longer leave among 44%. One in 4
did not meet their breastfeeding duration goal, and 1 in 3 did not meet their
goal for EBF. Negative emotions were common among those not meeting goals. Ninety
two percent felt that their or their partner's experience with breastfeeding
affected their clinical interaction with patients' mothers. CONCLUSION: A
majority of respondents cited problems with breastfeeding support during
training, and many failed to meet their intended goals. Not meeting personal
breastfeeding goals was associated with negative emotions and influenced how they
counsel about breastfeeding as a result of personal and often negative attitudes.
PMID- 25588383
TI - The relationship between deprivation and alcohol-related presentation at Accident
and Emergency (A&E) over a three-month period.
AB - OBJECTIVES: To identify any relationship between deprivation and the level of
presentation to Accident and Emergency with alcohol-related conditions in a busy
East Coast teaching hospital in Scotland. METHODS: Over an 87-day-period initial
screening to determine whether alcohol played a part in each presentation was
conducted at triage. These patients were then streamed according to their
Paddington Alcohol Test (Pat) score into Pat +ve and Pat -ve groups. The postcode
of each patient was recorded before they were assigned deprivation levels using
the DepCat scoring system. This information was then compiled in Microsoft Excel
2003 and a graph showing the differences in the number of presentations across
the social spectrum was constructed. RESULTS: Nine hundred and forty four
patients were screened as attending due to alcohol with 43.86% being Pat +ve and
56.14% being Pat -ve. Overall 66.42% of the Pat +ve group and 54.42% of Pat -ve
were from deprived or very deprived areas. CONCLUSIONS: The use of electronic
based screening was effective at highlighting patients presenting to Accident and
Emergency with alcohol-related problems, and these presentations highlighted a
direct link between the level of deprivation and attendances.
PMID- 25588379
TI - Integrated PK-PD and agent-based modeling in oncology.
AB - Mathematical modeling has become a valuable tool that strives to complement
conventional biomedical research modalities in order to predict experimental
outcome, generate new medical hypotheses, and optimize clinical therapies. Two
specific approaches, pharmacokinetic-pharmacodynamic (PK-PD) modeling, and agent
based modeling (ABM), have been widely applied in cancer research. While they
have made important contributions on their own (e.g., PK-PD in examining
chemotherapy drug efficacy and resistance, and ABM in describing and predicting
tumor growth and metastasis), only a few groups have started to combine both
approaches together in an effort to gain more insights into the details of drug
dynamics and the resulting impact on tumor growth. In this review, we focus our
discussion on some of the most recent modeling studies building on a combined PK
PD and ABM approach that have generated experimentally testable hypotheses. Some
future directions are also discussed.
PMID- 25588384
TI - Impact of nutrition on ageing the process. Bridging the gap: the animal
perspective.
AB - In pets, as in humans, there is increasing interest in interventions that promote
'health and well-being' into later life and extend these beyond their current
limits. The purpose of this review was to assess the relevance of current
knowledge of ageing in humans, described in a companion paper, as well as
reviewing recent research on ageing in pet populations. The role of diet and
other factors that influence the ageing process and ultimately lifespan in pets
are highlighted in this review; in addition, future opportunities and challenges
to further our understanding of the ageing process in pets are identified.
Advancing knowledge of the fundamental biology of ageing will be key for the
development and evaluation of strategies that extend both the quality and the
quantity of lifespan in human and pet populations.
PMID- 25588378
TI - Spreading of pathology in neurodegenerative diseases: a focus on human studies.
AB - The progression of many neurodegenerative diseases is thought to be driven by the
template-directed misfolding, seeded aggregation and cell-cell transmission of
characteristic disease-related proteins, leading to the sequential dissemination
of pathological protein aggregates. Recent evidence strongly suggests that the
anatomical connections made by neurons - in addition to the intrinsic
characteristics of neurons, such as morphology and gene expression profile -
determine whether they are vulnerable to degeneration in these disorders.
Notably, this common pathogenic principle opens up opportunities for pursuing
novel targets for therapeutic interventions for these neurodegenerative
disorders. We review recent evidence that supports the notion of neuron-neuron
protein propagation, with a focus on neuropathological and positron emission
tomography imaging studies in humans.
PMID- 25588385
TI - Maternal depression, stress and feeding styles: towards a framework for theory
and research in child obesity.
AB - Against the background of rising rates of obesity in children and adults in the
USA, and modest effect sizes for obesity interventions, the aim of the present
narrative review paper is to extend the UNICEF care model to focus on childhood
obesity and its associated risks with an emphasis on the emotional climate of the
parent-child relationship within the family. Specifically, we extended the UNICEF
model by applying the systems approach to childhood obesity and by combining
previously unintegrated sets of literature across multiple disciplines including
developmental psychology, clinical psychology and nutrition. Specifically, we
modified the extended care model by explicitly integrating new linkages (i.e.
parental feeding styles, stress, depression and mother's own eating behaviour)
that have been found to be associated with the development of children's eating
behaviours and risk of childhood obesity. These new linkages are based on studies
that were not incorporated into the original UNICEF model, but suggest important
implications for childhood obesity. In all, this narrative review offers
important advancements to the scientific understanding of familial influences on
children's eating behaviours and childhood obesity.
PMID- 25588386
TI - Efficacy of sustained combination therapy for at least 6 months with thiopurines
and infliximab in patients with ulcerative colitis in clinical remission: a
retrospective multicenter French experience.
AB - BACKGROUND AND AIMS: Long-term benefits of combination therapy (combotherapy)
with infliximab (IFX) and azathioprine (AZA) have been less studied in ulcerative
colitis (UC) than in Crohn's disease. The aim of the present study was to
determine UC disease activity in patients who received at least 6 months of
combotherapy, and whether cotreatment for more than 6 months was useful in these
patients. METHODS: A retrospective multicenter study was conducted in seven
French academic centers from January 2010 to September 2012, including all UC
patients having received at least 6 months of combotherapy in prolonged remission
off steroids. During the follow-up period, which was divided into trimesters,
scheduled IFX was continued as maintenance and AZA could be withdrawn. Assessment
of UC activity by trimester was based on the following events: disease relapse
defined by clinical relapse requiring a change of treatment, IFX failure, and
colectomy. RESULTS: Eighty-two patients were included (mean age 38 years;
male:female ratio 1:1) and followed up for a median of 22.3+/-14.0 months.
Comparing 393 trimesters of combotherapy with 282 trimesters of IFX alone, fewer
clinical relapses were observed with combotherapy (p = 0.049). Similar results
were observed for IFX failure (p = 0.048). No difference was observed for
colectomy. Duration of combotherapy longer than 9 months was inversely associated
with clinical relapse (hazard ratio = 0.32 [95% confidence interval 0.15-0.70]).
CONCLUSIONS: UC patients treated with combotherapy should maintain IFX and AZA
for at least 9 months. Further studies are required to determine the optimal
duration of combotherapy before stopping AZA in this situation.
PMID- 25588387
TI - Better duplicate detection for systematic reviewers: evaluation of Systematic
Review Assistant-Deduplication Module.
AB - BACKGROUND: A major problem arising from searching across bibliographic databases
is the retrieval of duplicate citations. Removing such duplicates is an essential
task to ensure systematic reviewers do not waste time screening the same citation
multiple times. Although reference management software use algorithms to remove
duplicate records, this is only partially successful and necessitates removing
the remaining duplicates manually. This time-consuming task leads to wasted
resources. We sought to evaluate the effectiveness of a newly developed
deduplication program against EndNote. METHODS: A literature search of 1,988
citations was manually inspected and duplicate citations identified and coded to
create a benchmark dataset. The Systematic Review Assistant-Deduplication Module
(SRA-DM) was iteratively developed and tested using the benchmark dataset and
compared with EndNote's default one step auto-deduplication process matching on
('author', 'year', 'title'). The accuracy of deduplication was reported by
calculating the sensitivity and specificity. Further validation tests, with three
additional benchmarked literature searches comprising a total of 4,563 citations
were performed to determine the reliability of the SRA-DM algorithm. RESULTS: The
sensitivity (84%) and specificity (100%) of the SRA-DM was superior to EndNote
(sensitivity 51%, specificity 99.83%). Validation testing on three additional
biomedical literature searches demonstrated that SRA-DM consistently achieved
higher sensitivity than EndNote (90% vs 63%), (84% vs 73%) and (84% vs 64%).
Furthermore, the specificity of SRA-DM was 100%, whereas the specificity of
EndNote was imperfect (average 99.75%) with some unique records wrongly assigned
as duplicates. Overall, there was a 42.86% increase in the number of duplicates
records detected with SRA-DM compared with EndNote auto-deduplication.
CONCLUSIONS: The Systematic Review Assistant-Deduplication Module offers users a
reliable program to remove duplicate records with greater sensitivity and
specificity than EndNote. This application will save researchers and information
specialists time and avoid research waste. The deduplication program is freely
available online.
PMID- 25588388
TI - A flowering integrator, SOC1, affects stomatal opening in Arabidopsis thaliana.
AB - Stomatal movements are regulated by multiple environmental signals. Recent
investigations indicate that photoperiodic flowering components, such as CRY, GI,
CO, FT and TSF, are expressed in guard cells and positively affect stomatal
opening in Arabidopsis thaliana. Here we show that SOC1, which encodes a MADS box
transcription factor and integrates multiple flowering signals, also exerts a
positive effect on stomatal opening. FLC encodes a potent repressor of FT and
SOC1, and FRI acts as an activator of FLC. Thus, we examined stomatal phenotypes
in FRI-Col, which contains an active FRI allele of accession Sf-2 by
introgression. We found higher expression of FLC and lower expression of FT, SOC1
and TSF in guard cells from FRI-Col than in those from Col. Light-induced
stomatal opening was significantly suppressed in FRI-Col. Interestingly,
vernalization of FRI-Col partially restored light-induced stomatal opening,
concomitant with a decrease of FLC and increase of FT, SOC1 and TSF. Furthermore,
we observed the constitutive open-stomata phenotype in transgenic plants
overexpressing SOC1-GFP (green fluorescent protein) in guard cells (SOC1-GFP
overexpressor), and found that light-induced stomatal opening was significantly
suppressed in a soc1 knockout mutant. RNA sequencing using epidermis from the
SOC1-GFP overexpressor revealed that the expression levels of several genes
involved in stomatal opening, such as BLUS1 and the plasma membrane H(+)-ATPases,
were higher than those in background plants. From these results, we conclude that
SOC1 is involved in the regulation of stomatal opening via transcriptional
regulation in guard cells.
PMID- 25588389
TI - RNAi screening identifies the armadillo repeat-containing kinesins responsible
for microtubule-dependent nuclear positioning in Physcomitrella patens.
AB - Proper positioning of the nucleus is critical for the functioning of various
cells. Actin and myosin have been shown to be crucial for the localization of the
nucleus in plant cells, whereas microtubule (MT)-based mechanisms are commonly
utilized in animal and fungal cells. In this study, we combined live cell
microscopy with RNA interference (RNAi) screening or drug treatment and showed
that MTs and a plant-specific motor protein, armadillo repeat-containing kinesin
(kinesin-ARK), are required for nuclear positioning in the moss Physcomitrella
patens. In tip-growing protonemal apical cells, the nucleus was translocated to
the center of the cell after cell division in an MT-dependent manner. When
kinesin-ARKs were knocked down using RNAi, the initial movement of the nucleus
towards the center took place normally; however, before reaching the center, the
nucleus was moved back to the basal edge of the cell. In intact (control) cells,
MT bundles that are associated with kinesin-ARKs were frequently observed around
the moving nucleus. In contrast, such MT bundles were not identified after
kinesin-ARK down-regulation. An in vitro MT gliding assay showed that kinesin-ARK
is a plus-end-directed motor protein. These results indicate that MTs and the MT
based motor drive nuclear migration in the moss cells, thus showing a
conservation of the mechanism underlying nuclear localization among plant, animal
and fungal cells.
PMID- 25588391
TI - [The rat submandibular lymph node after introduction in mandibular bone defect
ultipotent mesenchymal cells adsorbed on polyhydroxyalkanoate scaffold].
AB - The reactions of rat regional lymph nodes, caused by implantation of the
autologous multipotent mesenchymal stromal cells of a bone marrow origin
(AMMSCBM) for acceleration of bone defect regeneration in bottom jaw experiment
were studied by methods of fluorescent light microscopy. After introduction in an
injury site of a bottom jaw bone of polyhydroxyalkanoate with adsorbed AMMSCBM
with a transfected GFP gene the numerous large macrophages with a set of oval
fluorescent inclusions in cytoplasm appear in lymph nodules of submandibular
lymph nodes. The number of such macrophages increases within 2 weeks after
operation, and further starts decreasing. Probably, entered via such way the
AMMSCBM partially are phagocytized by macrophages. At destruction of the
structures created from AMMSCBM, debris also are phagocytized by macrophages. In
that and other case these macrophages appear in the germinative centers of lymph
nodules in lymph nodes where initiation of immunity reactions against DNA and
same GFP isn't excluded.
PMID- 25588390
TI - Impact and cost-effectiveness of chlamydia testing in Scotland: a mathematical
modelling study.
AB - BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection
in Scotland, and is associated with potentially serious reproductive outcomes,
including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in
women. Chlamydia testing in Scotland is currently targeted towards symptomatic
individuals, individuals at high risk of existing undetected infection, and young
people. The cost-effectiveness of testing and treatment to prevent PID and TFI in
Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of
chlamydia infection in 15-24 year olds in Scotland was developed. The model was
used to estimate the impact of a change in testing strategy from baseline (16.8%
overall testing coverage; 0.4 partners notified and tested/treated per treated
positive index) on PID and TFI cases. Cost-effectiveness calculations informed by
best-available estimates of the quality-adjusted life years (QALYs) lost due to
PID and TFI were also performed. RESULTS: Increasing overall testing coverage by
50% from baseline to 25.2% is estimated to result in 21% fewer cases in young
women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would
result in 20% more PID (669 additional) and TFI (84 additional) cases occurring
annually. The cost per QALY gained of current testing activities compared to no
testing is L40,034, which is above the L20,000-L30,000 cost-effectiveness
threshold. However, calculations are hampered by lack of reliable data. Any
increase in partner notification from baseline would be cost-effective
(incremental cost per QALY gained for a partner notification efficacy of 1
compared to baseline: L5,119), and would increase the cost-effectiveness of
current testing strategy compared to no testing, with threshold cost
effectiveness reached at a partner notification efficacy of 1.5. However, there
is uncertainty in the extent to which partner notification is currently done, and
hence the amount by which it could potentially be increased. CONCLUSIONS: Current
chlamydia testing strategy in Scotland is not cost-effective under the
conservative model assumptions applied. However, with better data enabling some
of these assumptions to be relaxed, current coverage could be cost-effective.
Meanwhile, increasing partner notification efficacy on its own would be a cost
effective way of preventing PID and TFI from current strategy.
PMID- 25588392
TI - [Comparative analysis of the various instrumental diagnostics methods to the
assessment of tooth supporting structure].
AB - The tooth resonance frequency method for periodontal condition diagnostics was
compared with apparatus measurement of the tooth mobility in vivo. Tooth natural
frequency and tooth mobility were correlated with clinical condition of tooth
supporting structure. According to the condition of tooth supporting structure
stability zones were indentified. The squared dependence between tooth natural
frequency and the value of tooth mobility was revealed. The resonance frequency
method is more exact for clinical assessment of periodontal tissues in comparison
with instrumental measurement of the tooth mobility.
PMID- 25588393
TI - [The main aspects of the multidisciplinary dispensary dental care to elderly and
senile population].
AB - In the article presents the characteristics of the organization of dispensary
work with patients older than 60 years. The main directions and objectives
dispensary. The features of clinical supervision of dental patients belonging to
the category of persons decreed by the elderly, senile age from the perspective
of interaction professionals in a multidisciplinary clinic.
PMID- 25588394
TI - [Clinical efficiency of short and long-term adjuvant therapy of chronic
periodontal disease with azithromycin].
AB - The purpose of the study was to compare the clinical response to two regimes of
azithromycin use in the complex of non-surgical periodontal therapy. After
initial periodontal therapy of chronic generalized periodontitis (CGP), 60
patients were randomly assigned to 3 groups. In group 2 and 3 azithromycin was
administered: 500 mg 1 time per day, 3 days, and by 500 mg 1 time per day, 7
days, followed by 500 mg 1 time per week for 12 weeks. Clinical indexes were
record before treatment and after 1, 3, 6 and 12 months. After 3 months 13
patients in group 1st had the exacerbation of CGP, and only 1 and 2 patients
(p<0.05) in the 2nd and 3rd groups, respectively. After 12 months, significantly
fewer patients on the 3rd group (as compared with the 1st (p=0.0015) and the 2nd
(p=0.0040) had clinical exacerbation. Unscheduled visits were significantly less
in the 3rd group as compared with the 1st (chi(2)=8.03; p=0.0046). The long-term
adjunctive azithromycin results in a significantly clinical benefit of 80%
patients for 1 year with satisfactory tolerance.
PMID- 25588395
TI - [Identification of key markers of normal and pathogenic microbiota determining
health of periodontium by NGS-sequencing 16S-rDNA libraries of periodontal
swabs].
AB - By using NGS-sequencing libraries of DNA from periodontal swabs with primers
specific to V6 region of 16S rDNA prevalence of bacterial genera and species in
periodontal microbiota of patients with aggressive periodontitis and healthy
donors was analyzed. Six genera of putative periodontal protectors and eight
periodontal pathogens were identified with respect to aggressive (but not
chronic) periodontitis. Statistically relevant over-colonization by general
Porphyromonas, Treponema, Synergistes, Tannerella, Filifactor, Ruminococcus,
Parvimonas and Mycoplasma was found to be associated with the condition. From
these, only three genera Porphyromonas, Treponema and Tannerella are
traditionally considered as periodontal pathogens. Statistically confidential
over-colonization by genus Veillonella was found in healthy patients. This genus
should be considered as a relevant marker of a healthy periodontium. Genera
Streptococcus, Bergeyella, Granulicatella, Kingella and Corynebacterium may be
considered as putative periodontal protectors. Comparison of data of NGS
sequencing and real-time PCR demonstrated a good agreement if different PCR
efficiency using independent primer pairs is taken into account.
PMID- 25588396
TI - [Audiodiagnostics in examination of patients with internal TMJ derangement].
AB - The aim of the study was to assess the efficacy of audiodiagnostics in
dysfunctional TMJ disorders. Thirty-four patients were included in the study. The
analysis of phonograms revealed correlation of adverse sound effects with varying
degrees of internal TMJ-disorder seen by MRI imaging. The study results confirm
the advantages of electronic registration of TMJ sound phenomena.
PMID- 25588398
TI - [Evaluation of changes in periodontal status of patients with diabetes mellitus
type II in surgical in-patient department after using Parodontax Extra Fresh
toothpaste].
AB - Inflammatory periodontal disease in patients with type II diabetes mellitus are
characterized by a more severe course. Properly organized oral hygiene can
effectively prevent and treat inflammation of periodontal tissues. The choice of
therapeutic-prophylactic toothpaste, as one of the main means of personal
hygiene, is especially important in patients with diabetes in surgical in-patient
department. The study revealed high need in dental care (90%) in 20 patients with
diabetes mellitus type II admitted to purulent surgery unit. After a week of
using toothpaste Parodontax Extra Fresh oral hygiene index improved 1.8 times and
BOP index reduced twice-folds. Decrease of tissue swelling and tartar formation
was also seen.
PMID- 25588397
TI - [New method of conduction anesthesia in the maxilla].
AB - There was the research aimed at improving the effeciency of intraosseous
anesthesia in the maxilla by blocking the infraorbital nerve conduction along its
entire length. In the experimental part of the needle puncture defined place and
character of the spreading of contrast medium into the upper jaw. In the clinical
part of the study shows the advantages of the proposed method of intraosseous
anesthesia.
PMID- 25588399
TI - [TMJ disc displacement as a cause of changes in facial skeletal morphology].
AB - OBJECTIVE: To evaluate an efficiency of TMJ open disc repositioning surgery with
use of bone anchors. MATERIAL AND METHODS: TMJ open disc repositioning surgery
was indicated for patients with TMJ anterior disc displacement without reduction
and skeletal class II or asymmetric forms of dysgnathia related to condyle
resorption. Surgery was performed on 9 patients divided into two groups: the
first one (5 patients) consisted of patients that were seeking help for bite
problems, the second one (4 patients) consisted of patients with signs of TMJD,
such as decreased mouth opening and pain in TMJ area. RESULTS: The first group
patients underwent open disc repositioning and orthognathic surgery with
counterclockwise rotation of occlusal plane. All the patients showed stability in
skeletal and occlusal elements at 6 months follow-up period. The second group
patients underwent disc-repositioning surgery only. In all the cases pain was
completely eliminated but there was no sufficient improvement in MIO at 6 months
follow-up period. Open TMJ disc repositioning surgery can be used for prevention
of relapse after orthognathic surgery in patients with TMJ internal derangements
such as anterior disc displacement without reduction.
PMID- 25588400
TI - [Total excision of parotid salivary gland saving ramus of n. facialis in the case
of pharyngeal processus tumor].
AB - The article describes the method of surgical treatment of patients with huge
tumors of pharyngeal processus of parotid gland saving ramus of n. facialis. The
method allows avoiding mandibular osteotomy without relapse risk it supposes the
total excision of the gland.
PMID- 25588401
TI - [Recurrent mixed parotid tumor localized in pharyngeal processus].
AB - Tumors of pleomorhic adenoma parapharingeal space of the parotid gland amount for
less than 20% of all salivary gland tumors. In most cases these tumors are
benign, and pleomorphic (polymorphous) adenomas prevail among them (up to 80
90%). The frequency of their malignization varies from 3.6 to 30%. Pleomorphic
adenoma of parapharingeal space of the parotid gland was removed from patient S.,
aged 23 years, in head and neck department of RROI. Tumors of superficial part of
the parotid gland were removed from the patient 5 times during the last 10 years
maintaining the integrity of the facial nerve. Each time the tumor was
pleomorphic adenoma morphologically. After physical and x-ray (CT, MRI, MRI with
angiography of neck vessels) examinations a tumor -- pleomorphic adenoma -- was
removed with submandibular method. The control MRI check showed continued growth.
Radiation therapy was prescribed, after which the pronounced therapeutic effect
was noted. The patient has been observed for 8 months without recurrence.
PMID- 25588402
TI - [Impact of various second-stage implant surgery methods on adjacent gingival
tissues microcirculation].
AB - The paper presents the rezults of laser doppler flowmetry (LDF) studies of
microcirculation in gingival tissues around dental implants disclosed by
different methods. Microhemodynamics in gingival tissues when using a scalpel
recovered after 14 days, carbon dioxide laser -- 7 days and erbium laser -- 3
days, which may be important in the choice of the operation tactics.
PMID- 25588403
TI - [Comprehensive treatment of patient with class III malocclusion complicated by
partial teeth absence].
AB - The article presents the results of planning and comprehensive treatment of a
patient with class III malocclusion complicated by partial teeth absence. Split
osteotomy of the mandible improved the relationship of dental arches facilitating
complete oral restorative rehabilitation with adequate functional load
distribution and esthetic harmony.
PMID- 25588404
TI - Authors' response: Importance of defining loss of response before therapeutic
drug monitoring.
PMID- 25588405
TI - The natural course of serrated lesions: a difficult enigma to resolve.
PMID- 25588406
TI - Small-molecule inhibitors prevent the genotoxic and protumoural effects induced
by colibactin-producing bacteria.
AB - OBJECTIVE: Colorectal cancers (CRCs) are frequently colonised by colibactin toxin
producing Escherichia coli bacteria that induce DNA damage in host cells and
exhibit protumoural activities. Our objective was to identify small molecules
inhibiting the toxic effects induced by these colibactin-producing bacteria.
DESIGN: A structural approach was adopted for the identification of a putative
ligand for the ClbP enzyme involved in the synthesis of colibactin. Intestinal
epithelial cells and a CRC mouse model were used to assess the activity of the
selected compounds in vitro and in vivo. RESULTS: Docking experiments identified
two boron-based compounds with computed ligand efficiency values (-0.8 and -0.9
kcal/mol/atom) consistent with data expected for medicinal chemistry leads. The
crystalline structure of ClbP in complex with the compounds confirmed that the
compounds were binding to the active site of ClbP. The two compounds (2 mM)
suppressed the genotoxic activity of colibactin-producing E coli both in vitro
and in vivo. The mean degree of suppression of DNA damage for the most efficient
compound was 98+/-2% (95% CI). This compound also prevented cell proliferation
and colibactin-producing E coli-induced tumourigenesis in mice. In a CRC murine
model colonised by colibactin-producing E coli, the number of tumours decreased
by 3.5-fold in animals receiving the compound in drinking water (p<0.01).
CONCLUSIONS: These results demonstrate that targeting colibactin production
controls the genotoxic and protumoural effects induced by this toxin.
PMID- 25588407
TI - Validation of AD-CSF-Index in Chinese patients with Alzheimer's disease and
nondemented controls.
AB - Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), especially
Abeta42/t-tau and Abeta42/p-tau, showed high diagnostic sensitivities and
specificities. But significant interassay and interlaboratory variabilities
hinder the widespread clinical applications of CSF biomarkers. The objective of
this study was to validate the diagnostic accuracy of AD-CSF-Index in our local
Chinese patients with AD compared to nondemented controls. A total of 36
patients, which included 24 patients with AD and 12 nondemented controls, were
recruited. Chinese patients with AD showed higher mean AD-CSF-Indices than
nondemented controls (AD = 1.25-1.3, normal = 0.62-0.63; P < .001). The AD-CSF
indices have a high sensitivity and specificity of 86.4% to 90.9% and 83.3%,
respectively, in differentiating patients with AD from nondemented controls.
After selecting the patients with "pure AD" and "pure normal" controls, the AD
CSF-indices have a high sensitivity and specificity of 94.1% and 90%,
respectively, in differentiating patients with AD from nondemented controls. Most
importantly, our AD-CSF-indices cutoff was highly similar to that reported in
Western studies.
PMID- 25588408
TI - The effectiveness of reality orientation in the treatment of Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most frequent cause of dementia. This work aims
to assess the effectiveness of reality orientation (RO), a traditional,
extensively documented cognitive enhancement technique, when combined with
acetylcholinesterase inhibitors in the treatment of AD. Fourteen patients with AD
having mild to moderate dementia receiving standard treatment with donepezil were
randomly assigned to control and treatment groups. Patients in the treatment
group were submitted to weekly RO sessions for 6 months. Cognitive outcomes were
assessed based on scores in the Consortium to Establish a Registry for
Alzheimer's Disease (CERAD) neuropsychological battery and the Clock Drawing Test
(CDT). Mean CERAD neuropsychological battery, Mini-Mental State Examination
(MMSE), and CDT scores improved in the treatment group and worsened in the
control group. A number of CERAD neuropsychological battery and MMSE scores were
statistically significant. Our findings suggest that RO is a valuable long-term
complementary intervention for dementia in AD.
PMID- 25588409
TI - Serum sEPCR levels are elevated in patients with Alzheimer's disease.
AB - Blood-brain barrier impairment and endothelial cell dysfunction have both been
implicated in the pathogenesis of Alzheimer's disease (AD). The presence of
vascular risk factors is also known to increase the risk of AD. Soluble
endothelial protein C receptor (sEPCR) should thus produce procoagulant and
proinflammatory effects. Serum sEPCR levels have been found to be associated with
several diseases. To date, no reports have been published regarding serum sEPCR
levels in AD. In this study, we found that serum sEPCR levels were significantly
increased in patients with AD when compared to control participants (P = .0005).
There was no significant difference between patients with mild cognitive
impairment (MCI) and healthy controls (P = .055) or between patients with AD and
MCI (P = .054). Importantly, our results also indicate that the degree of
cognitive impairment is significantly correlated with serum sEPCR levels in all
patients and healthy controls. These findings suggest that serum sEPCR levels
could be a potential candidate for a biomarker panel for AD diagnosis.
PMID- 25588410
TI - The midwifery initiated oral health-dental service protocol: an intervention to
improve oral health outcomes for pregnant women.
AB - BACKGROUND: Evidence is emerging that women's poor oral health and health
practices during pregnancy are associated with poor oral health in their children
and potentially an increased risk of pre-term or low-birth weight infants.
METHODS/DESIGN: The Midwifery Initiated Oral Health-Dental Service (MIOH-DS)
trial is a three arm multicentre randomised controlled trial which will recruit
women from three metropolitan hospitals aimed at improving women's oral health
and service access and indirectly reducing perinatal morbidity. All three arms of
the trial will deliver oral health promotion material, although a midwife oral
assessment and referral to private/public/health fund dental services pathway
(Intervention Group 1) and the midwife oral assessment and referral to local free
public dental services pathway (Intervention Group 2) will be compared to the
control group of oral health promotional material only. Midwives will undergo
specific oral health education and competency testing to undertake this novel
intervention. DISCUSSION: This efficacy trial will promote a new partnership
between midwives and dentists focused on enhancing the oral health of women and
their infants. Should the intervention be found effective, this intervention,
with existing on-line educational program for midwives, can be easily transferred
into practice for large metropolitan health services within and beyond Australia.
Further cost-benefit analysis is proposed to inform national health policy. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12612001271897.
PMID- 25588412
TI - Does the prepotential truly reflect the activation preceding the development of
ventricular arrhythmias?
PMID- 25588413
TI - Volatile composition and aroma activity of guava puree before and after thermal
and dense phase carbon dioxide treatments.
AB - Volatiles from initially frozen, dense phase carbon dioxide (DPCD)- and thermally
treated guava purees were isolated by solid phase microextraction (SPME),
chromatographically separated and identified using a combination of gas
chromatography-mass spectrometry (GC-MS), GC-olfactometry (GC-O), and GC-pulsed
flame photometric detector (GC-PFPD, sulfur mode). Fifty-eight volatiles were
identified using GC-MS consisting of: 6 aldehydes, 2 acids, 15 alcohols, 6
ketones, 21 esters, and 8 terpenes. Eleven volatiles were newly identified in
guava puree. Hexanal was the most abundant volatile in all 3 types of guava
puree. Ten sulfur compounds were identified using GC-PFPD of which 3 possessed
aroma activity and 3 were not previously reported in guava puree. Both treatments
profoundly reduced total sulfur peak areas and produced different peak patterns
compared to control. Thermal treatment reduced total sulfur peak area 47.9%
compared to a loss of 34.7% with DPCD treatment. Twenty-six volatiles possessed
aroma activity. (Z)-3-Hexenyl hexanoate was the major contributor to the aroma of
the freshly thawed and DPCD-treated guava puree. DPCD treatment reduced total MS
ion chromatogram (MS TIC) peak area 35% but produced a GC-O aroma profile very
similar to control. Whereas thermal treatment reduced total TIC peak area only
8.7% compared to control but produced a 35% loss in total GC-O peak intensities.
PMID- 25588411
TI - Concurrent occurrence of renal cell carcinoma with rhabdoid features in a married
couple: a case report.
AB - BACKGROUND: Renal cell carcinoma (RCC) with rhabdoid features is a rare histology
and exhibits clinically aggressive behavior. We report a case of a married couple
in whom RCC with rhabdoid features concurrently occurred. The rarity of this
event suggests that environmental factors may contribute to the etiology of RCC
with rhabdoid features. CASE PRESENTATION: A 76-year-old Japanese woman was
diagnosed with a hypervascular mass in the right kidney and tumor thrombus
extending into the right atrium by enhanced computed tomography (CT). She
underwent radical nephrectomy and tumor thrombectomy following systemic therapy
with the tyrosine kinase inhibitor sunitinib. The histological evaluation denoted
clear cell RCC with rhabdoid features. The patient died of cancer 12 months
postoperatively. A 76-year-old man, her husband, presented with gross hematuria 2
weeks after his wife had undergone surgery. He had a long history of asbestos
exposure. An abdominal CT scan revealed a hypervascular mass in the right kidney
and tumor thrombus extending into the inferior vena cava. He also underwent
radical nephrectomy and tumor thrombectomy. The histological evaluation also
showed clear cell RCC with rhabdoid features. Bone metastasis occurred 12 months
postoperatively, but he died of an unrelated cause 18 months after surgery.
CONCLUSION: Concurrent occurrence of RCC with rhabdoid features may not to be
coincidental. Although further studies are warranted, asbestos exposure may
contribute to the etiology of clear cell RCC with rhabdoid features.
PMID- 25588414
TI - Development and validation of a real-time PCR assay for the detection of
anguillid herpesvirus 1.
AB - Anguillid herpesvirus 1 (AngHV1) causes a haemorrhagic disease with increased
mortality in wild and farmed European eel, Anguilla anguilla (L.) and Japanese
eel Anguilla japonica, Temminck & Schlegel). Detection of AngHV1 is currently
based on virus isolation in cell culture, antibody-based typing assays or
conventional PCR. We developed, optimized and concisely validated a diagnostic
TaqMan probe based real-time PCR assay for the detection of AngHV1. The primers
and probe target AngHV1 open reading frame 57, encoding the capsid protease and
scaffold protein. Compared to conventional PCR, the developed real-time PCR is
faster, less labour-intensive and has a reduced risk of cross-contamination. The
real-time PCR assay was shown to be analytically sensitive and specific and has a
high repeatability, efficiency and r(2) -value. The diagnostic performance of the
assay was determined by testing 10% w/v organ suspensions and virus cultures from
wild and farmed European eels from the Netherlands by conventional and real-time
PCR. The developed real-time PCR assay is a useful tool for the rapid and
sensitive detection of AngHV1 in 10% w/v organ suspensions from wild and farmed
European eels.
PMID- 25588415
TI - Race-ethnicity and gender differences in VA health care service utilization among
U.S. veterans of recent conflicts.
AB - OBJECTIVE: The purpose of this study was to compare health care utilization
patterns by race-ethnicity and gender among veterans returning from Iraq and
Afghanistan. METHODS: A retrospective analysis was conducted with records from
U.S. service members and veterans returning from Iraq and Afghanistan who
enrolled in health care through the Veterans Health Administration, who received
a psychiatric diagnosis, and who had used primary or mental health outpatient
care between October 7, 2001, and December 31, 2012 (N=309,050). Racial-ethnic
minority groups were first collapsed together and compared with whites and then
separated by racial-ethnic group. Gender was also tested as a moderator of
utilization. RESULTS: Although rates of mental health outpatient care, primary
care, and emergency service utilization were relatively similar for racial-ethnic
minority groups and whites, minority groups were admitted to psychiatric
inpatient care at lower rates than whites. When veterans were separately
categorized by specific racial-ethnic groups, some differences in utilization
rates emerged; most notably, only black and Hispanic men were admitted less
frequently to psychiatric inpatient care, and male and female Asian/Pacific
Islander veterans used emergency services less, than their white counterparts.
Gender moderated the association between race-ethnicity and mental health
outpatient use, such that American Indian and Hispanic women used mental health
outpatient services less than white women, but American Indian and Hispanic men
showed the opposite pattern. Furthermore, black men were more likely than white
men to use mental health outpatient services, but there was no difference between
these women. CONCLUSIONS: Although service utilization rates between minority
groups and whites were similar when minority groups were combined, examination of
utilization by racial-ethnic groups and by men and women separately yielded more
robust findings.
PMID- 25588416
TI - Evolution of general practitioners' preferences for antipsychotics in France,
2003-2010.
AB - OBJECTIVE: The study examined changes in French general practitioners' (GPs)
antipsychotic preferences between 2003 and 2010, a period when evidence
challenging the superiority and safety of second-generation antipsychotics was
introduced. METHODS: Data from the IMS Health Disease Analyzer database for a
cohort of 347 GPs (with 12 or more antipsychotic prescriptions in 2003 and in
2010) were used. For each year and GP, preferred antipsychotic was defined as the
drug most frequently prescribed at the patient level. Trends in mean number of
prescriptions, preferred drug, and changes in preferred antipsychotic class were
documented. RESULTS: The mean annual number of antipsychotic prescriptions
increased over the period (p<.001). The percentage of GPs who preferred a second
generation antipsychotic tripled, from 16% in 2003 to 50% in 2010. In 2010, 42%
of GPs who preferred first-generation antipsychotics in 2003 had switched their
preference to second-generation antipsychotics. CONCLUSIONS: GPs' preferences for
antipsychotics changed dramatically between 2003 and 2010.
PMID- 25588417
TI - The costs and benefits of reducing racial-ethnic disparities in mental health
care.
AB - OBJECTIVE: Previous studies have found that timely mental health treatment can
result in savings in both mental health and general medical care expenditures.
This study examined whether reducing racial-ethnic disparities in mental health
care offsets costs of care. METHODS: Data were from a subsample of 6,206
individuals with probable mental illness from the 2004-2010 Medical Expenditure
Panel Survey (MEPS). First, disparities in mental health treatment were analyzed.
Second, two-year panel data were used to determine the offset of year 1 mental
health outpatient and pharmacy treatment on year 2 mental and general medical
expenditures. Third, savings were estimated by combining results from steps 1 and
2. RESULTS: Compared with whites, blacks and Latinos with year 1 outpatient
mental health care spent less on inpatient and emergency general medical care in
year 2. Latinos receiving mental health care in year 1 spent less than others on
inpatient general medical care in year 2. Latinos taking psychotropic drugs in
year 1 showed reductions in inpatient general medical care. Reducing racial
ethnic disparities in mental health care and in psychotropic drug use led to
savings in acute medical care expenditures. CONCLUSIONS: Savings in acute care
expenditures resulting from eliminating disparities in racial-ethnic mental
health care access were greater than costs in some but not all areas of acute
mental health and general medical care. For blacks and Latinos, the potential
savings from eliminating disparities in inpatient general medical expenditures
are substantial (as much as $1 billion nationwide), suggesting that financial and
equity considerations can be aligned when planning disparity reduction programs.
PMID- 25588419
TI - Assessment of two different types of sample for the early detection and isolation
of thermophilic Campylobacter in broiler farms.
AB - In order to assess the optimal method for the early detection and isolation of
thermophilic Campylobacter in broilers at farm level, two types of samples were
compared: caecal contents obtained by necropsy and cloacal swabs transported in
charcoal Amies medium. The study was conducted in five batches of broilers from
five different farms, where weekly samples (caecal contents and cloacal swabs)
from 30 birds were obtained. Samples were plated onto selective agar (modified
charcoal cefoperazone desoxycholate agar, mCCDA) for Campylobacter isolation.
Four out of five batches were positive for Campylobacter. No marked differences
in sensitivity of both sample types were observed. However, a higher percentage
of positive birds were detected when cloacal swabs were used. The results show
that cloacal swab samples are adequate, and in some cases even better than caecal
samples for the early detection of Campylobacter in broiler flocks at farm level.
Also, this sample avoids sacrificing birds to test Campylobacter, which not only
allows saving time in sample collection, transportation and processing at the
laboratory, but also improves bird welfare and cost of sampling.
PMID- 25588418
TI - Duration of Untreated Psychosis in Community Treatment Settings in the United
States.
AB - OBJECTIVE: This study is the first to examine duration of untreated psychosis
(DUP) among persons receiving care in community mental health centers in the
United States. METHODS: Participants were 404 individuals (ages 15-40) who
presented for treatment for first-episode psychosis at 34 nonacademic clinics in
21 states. DUP and individual- and site-level variables were measured. RESULTS:
Median DUP was 74 weeks (mean=193.5+/-262.2 weeks; 68% of participants had DUP of
greater than six months). Correlates of longer DUP included earlier age at first
psychotic symptoms, substance use disorder, positive and general symptom
severity, poorer functioning, and referral from outpatient treatment settings.
CONCLUSIONS: This study reported longer DUP than studies conducted in academic
settings but found similar correlates of DUP. Reducing DUP in the United States
will require examination of factors in treatment delay in local service settings
and targeted strategies for closing gaps in pathways to specialty FEP care.
PMID- 25588420
TI - Synthetic cannabinoid withdrawal: a new demand on detoxification services.
AB - INTRODUCTION AND AIMS: Synthetic cannabinoid dependence and withdrawal are not
well described in the literature. We aimed to report on the characteristics and
treatment course of clients attending a detoxification service for support with
synthetic cannabinoid withdrawal in Auckland, New Zealand. DESIGN AND METHODS: A
retrospective audit of electronic and paper files for clients presenting for
treatment in association with problematic synthetic cannabinoid use between May
2013 and May 2014 was conducted. Demographic information, reported synthetic
cannabinoid use, other substance use, reported adverse effects, withdrawal
symptoms and treatment information were recorded using a piloted template.
Descriptive statistics were used to summarise the characteristics of the audit
sample. RESULTS: In the 12 month period, 47 people presented to detoxification
services reporting problems withdrawing from synthetic cannabinoids. Twenty
clients were admitted for medical management within an inpatient setting.
Coexisting substance dependence apart from nicotine dependence was low. The most
common withdrawal symptoms were agitation, irritability, anxiety and mood swings.
Withdrawal symptoms were managed with diazepam and quetiapine. DISCUSSION AND
CONCLUSIONS: The harm associated with use of synthetic cannabinoids has had a
direct impact on the utilisation of specialist alcohol and drug services in
Auckland, New Zealand. Many clients with synthetic cannabinoid withdrawal
symptoms required intensive support including medication and admission to an
inpatient detoxification unit. Clients withdrawing from synthetic cannabinoids
were the third largest group of clients admitted to inpatient detoxification
services in Auckland, New Zealand, between May 2013 and May 2014.
PMID- 25588421
TI - When the light begins to fade.
PMID- 25588422
TI - What influences doctors to work in rural locations?
PMID- 25588423
TI - Childhood food allergy and anaphylaxis: an educational priority.
PMID- 25588424
TI - Can Australia's clinical practice guidelines be trusted?
PMID- 25588426
TI - What can we do to help Australians die the way they want to?
PMID- 25588427
TI - Antenatal care for asylum seekers.
PMID- 25588428
TI - Inappropriate pathology ordering and pathology stewardship.
PMID- 25588429
TI - Ethical challenges for doctors working in immigration detention.
PMID- 25588430
TI - Ethical challenges for doctors working in immigration detention.
PMID- 25588432
TI - Rural emergency departments supplement general practice care.
PMID- 25588431
TI - Ethical challenges for doctors working in immigration detention.
PMID- 25588434
TI - The importance of surgeons teaching anatomy, especially by whole-body dissection.
PMID- 25588433
TI - Reporting rural workforce outcomes of rural-based postgraduate vocational
training.
PMID- 25588435
TI - Cardiopulmonary arrest and mortality trends, and their association with rapid
response system expansion.
PMID- 25588436
TI - Cardiopulmonary arrest and mortality trends, and their association with rapid
response system expansion.
PMID- 25588437
TI - Cardiopulmonary arrest and mortality trends, and their association with rapid
response system expansion.
PMID- 25588438
TI - Renal replacement therapy associated with lithium nephrotoxicity in Australia.
PMID- 25588440
TI - Preventing type 2 diabetes: scaling up to create a prevention system.
AB - About 2 million Australians have prediabetes and are at high risk of developing
type 2 diabetes. Type 2 diabetes is a fast-growing epidemic and the economic
costs are estimated to be $14.6 billion per year in Australia. Strong evidence
from randomised controlled trials shows type 2 diabetes can be prevented in up to
58% of people at high risk, through structured lifestyle intervention. Good
evidence and experience obtained from translational studies in Australia shows we
can deliver effective community-based prevention programs. To be effective, a
national strategy for prevention of type 2 diabetes should involve two concurrent
approaches - a targeted approach aimed at those most at risk (ie, with
prediabetes) combined with an environments, systems and behaviour approach for
the entire population. Australia's current efforts in both these areas are not
nationwide, not large scale and often not sustained.
PMID- 25588439
TI - Chronic suppurative lung disease and bronchiectasis in children and adults in
Australia and New Zealand Thoracic Society of Australia and New Zealand
guidelines.
PMID- 25588441
TI - Comparing non-sterile to sterile gloves for minor surgery: a prospective
randomised controlled non-inferiority trial.
AB - OBJECTIVE: To compare the incidence of infection after minor surgery conducted
using non-sterile clean boxed gloves with surgery conducted using sterile gloves.
DESIGN: Prospective randomised controlled single-centre trial testing for non
inferiority in infection rates. SETTING: Primary care regional centre,
Queensland, Australia. PARTICIPANTS: Consecutive patients presenting to
participating general practitioners for a minor skin excision, between 30 June
2012 and 28 March 2013, were eligible to participate. INTERVENTION: The use of
non-sterile clean boxed gloves was compared with normal treatment using sterile
gloves in the control group. MAIN OUTCOME MEASURES: Wound infection, assessed at
the time of removal of sutures, and other adverse events. RESULTS: Four hundred
and ninety-three consecutive patients presenting for minor skin excisions were
randomly allocated to the two treatment groups: non-sterile clean boxed gloves (n
= 250) or sterile gloves (n = 243). Four hundred and seventy-eight patients
contributed data for analysis (241 non-sterile, 237 sterile gloves). The
incidence of infection in the non-sterile gloves group (8.7%; 95% CI, 4.9%-12.6%)
was significantly non-inferior compared with the incidence in the control group
(9.3%; 95% CI, 7.4%-11.1%). The two-sided 95% CI for the difference in infection
rate (- 0.6%) was - 4.0% to 2.9%, and did not reach the predetermined margin of
7% which had been assumed as the non-inferiority limit. RESULTS of the intention
to-treat analysis were confirmed by per-protocol and sensitivity analyses. There
were no important adverse effects. CONCLUSION: Our study suggests that in regard
to wound infection, non-sterile clean boxed gloves are not inferior to sterile
gloves for minor skin excisions in general practice. TRIAL REGISTRATION:
ACTRN12612000698875.
PMID- 25588442
TI - Estimating the current and future prevalence of atrial fibrillation in the
Australian adult population.
AB - OBJECTIVE: To estimate the current and future prevalence of atrial fibrillation
(AF) in the Australian adult population according to age and sex. DESIGN:
Application of international AF prevalence statistics to Australian adult
population data (for people >= 55 years) to estimate population prevalence; use
of population projections to estimate potential future prevalence of AF. MAIN
OUTCOME MEASURES: Estimated prevalence of AF in 2014 and future prevalence
projected to 2034. RESULTS: We estimated that at 30 June 2014 there would be
328,562 cases of AF among people aged >= 55 years (a prevalence of 5.35%; 95% CI,
3.79%-7.53%), comprising 174,986 men (prevalence, 5.97%; 95% CI, 4.11%-8.54%) and
153,576 women (prevalence, 4.79%; 95% CI, 3.50%-6.60%). Without significant
changes to the natural history of AF, by 2034 this figure is projected to rise to
over 600,000 (prevalence, 6.39%; 95% CI, 4.56%-8.90%), with a prevalence of 7.22%
among men (95% CI, 4.99%-10.28%) and 5.64% (95% CI, 4.18%-7.64%) among women. The
greatest projected regional increase in prevalence between 2014 and 2034 is
expected in Queensland, with a likely twofold increase (from 61,613 cases to
123,142 cases), although New South Wales cases will remain predominant, with a
1.7-fold increase (from 110 892 to 191 578). We also predicted that between 2014
and 2034 the number of AF cases would double among older age groups (from 200 638
to 414 377 individuals aged >= 75 years) and would increase 2.5-fold among men
aged >= 85 years (from 29 370 to 71 582). CONCLUSIONS: These data are indicative
of a largely underappreciated AF prevalence in Australia. They mandate a more
systematic effort to both understand and respond to an evolving AF burden.
PMID- 25588444
TI - Availability of highly sensitive troponin assays and acute coronary syndrome
care: insights from the SNAPSHOT registry.
AB - OBJECTIVES: To examine differences in care and inhospital course of patients with
possible acute coronary syndrome (ACS) in Australia and New Zealand based on
whether a highly sensitive (hs) troponin assay was used at the hospital to which
they presented. DESIGN, SETTING AND PATIENTS: A snapshot study of consecutive
patients presenting to hospitals in Australia and New Zealand from 14 to 27 May
2012 with possible ACS. MAIN OUTCOME MEASURES: Rates of major adverse cardiac
events (inhospital death, new or recurrent myocardial infarction, stroke, cardiac
arrest or worsening heart failure); association between assay type and outcome
(via propensity score matching and a generalised estimating equation [GEE];
averages of the predicted outcomes among patients who were treated with and
without the availability of an hs assay (via inverse probability-weighting [IPW]
with regression-adjusted estimators). RESULTS: 4371 patients with possible ACS
were admitted to 283 hospitals. Over half of the hospitals (156 [55%]) reported
using the hs assay and most patients (2624 [60%]) had hs tests (P = 0.004). Use
of the hs assay was independent of hospital coronary revascularisation
capability. Patients tested with the hs assay had more non-invasive
investigations (exercise tests, stress echocardiography, stress nuclear scans,
and computed tomography coronary angiography) than those tested with the
sensitive assay. However, there were no differences between the groups in rates
of angiography or revascularisation. All adjusted analyses showed a consistently
lower rate of inhospital events, including recurrent heart failure in patients
for whom the hs assay was used (GEE odds ratio, 0.75; 95% CI, 0.60-0.94; P =
0.014); IPW analysis showed a 2.3% absolute reduction in these events with the
use of the hs assay (P = 0.018). CONCLUSION: Use of hs troponin testing of
patients hospitalised with possible ACS was associated with an increased rate of
non-invasive cardiac investigations and fewer inhospital adverse events.
PMID- 25588445
TI - Determinants of rural practice: positive interaction between rural background and
rural undergraduate training.
AB - OBJECTIVE: To determine the role of rural background and years of rural clinical
school training on subsequent rural clinical practice. DESIGN, SETTING AND
PARTICIPANTS: Retrospective cohort study of University of Queensland (UQ) medical
graduates who graduated during the period 2002-2011 (contacted via internet,
telephone and mail, using information obtained from UQ, the Australian Health
Practitioner Regulation Agency, and telephone directory and internet searches)
who completed an online or hard copy questionnaire during the period December
2012 to October 2013. MAIN OUTCOME MEASURE: Current clinical practice in a rural
location. RESULTS: Of 1572 graduates to whom the questionnaire was sent, 754
(48.0%) completed the questionnaire. Of the respondents, 236 (31.3%) had a rural
background and 276 (36.6%) had attended the University of Queensland Rural
Clinical School (UQRCS). Clinical practice location was rural for 18.8% (90/478)
of UQ metropolitan clinical school attendees and 41.7% (115/276) of UQRCS
attendees (P < 0.001). In the multivariate model with main effects, independent
predictors of rural practice were (OR [95% CI]): UQRCS attendance for 1 year
(1.84 [1.21-2.82]) or 2 years (2.71 [1.65-4.45]), rural background (2.30 [1.57
3.36]), partner with rural background (3.08 [1.96-4.84]), being single (1.98
[1.28-3.06]) and having a bonded scholarship (2.34 [1.37-3.98]). In the model
with interaction between UQRCS attendance and rural background, independent
predictors of rural practice were rural background and UQRCS attendance for 1
year (4.44 [2.38-8.29]) or 2 years (7.09 [3.57-14.10]), partner with rural
background (3.14 [1.99-4.96]), being single (2.02 [1.30-3.12]) and bonded
scholarship (2.27 [1.32-3.90]). The effects of rural background and UQRCS
attendance were duration dependent. CONCLUSIONS: This study strengthens evidence
that, after adjusting for multiple confounders, a number of exposures are
independent predictors of rural medical practice. The strong positive interaction
between rural background and rural clinical school exposure, and the duration
dependent relationships, could help inform policy changes aimed at enhancing the
efficacy of Australia's rural clinical school program.
PMID- 25588446
TI - Full medical program fees and medical student career intention.
AB - OBJECTIVE: To explore the future career preferences of Commonwealth-supported
place (CSP) and full-fee paying (FFP) medical students in Australia. DESIGN,
SETTING AND PARTICIPANTS: Data from the Medical Schools Outcomes Database and
Longitudinal Tracking (MSOD) Project exit questionnaire for CSP and FFP students
who graduated between 2008 and 2011 were analysed using logistic regression. The
influence of age, sex, marital status, rural background and fee-paying status on
future career preference were explored. MAIN OUTCOME MEASURE: Future career
preference (location and specialty) at graduation. RESULTS: Compared with CSP
students, domestic FFP students were more likely to nominate as their first
preference both urban locations (odds ratio [OR], 5.58; 95% CI, 2.04-15.26; P <
0.001) and higher-income specialties (OR, 1.37; 95% CI, 1.07-1.75; P < 0.05), and
less likely to nominate as their first preference in-need specialties (OR, 0.72;
95% CI, 0.52-1.00; P < 0.05), specifically general practice (OR, 0.71; 95% CI,
0.52-0.99; P < 0.05). There was a significant domestic FFP student by marital
status interaction effect, such that domestic FFP students who were married or
partnered on exit from medical school were more likely to prefer a rural location
(OR, 0.64; 95% CI, 0.44-0.95; P < 0.05). Also, students who were married or
partnered were less likely to select a one of the higher-income specialties as
their first preference (OR, 0.77; 95% CI, 0.64-0.92; P < 0.01). A rural
background increased preferences for rural location (OR, 0.18; 95% CI, 0.15-0.22;
P < 0.001) and in-need specialties (OR, 1.28; 95% CI, 1.04-1.57; P < 0.05), and
being older on entry to medical school also increased preferences for rural
location (OR, 0.96; 95% CI, 0.95-0.98; P < 0.001) and in-need specialties (OR,
1.03; 95% CI, 1.01-1.04; P < 0.01). International FFP students were more likely
to prefer urban practice (OR, 1.79; 95% CI, 1.19-2.72; P < 0.01). CONCLUSION:
Domestic FFP graduates are less likely to prefer careers in rural locations and
in lower-paid and in-need specialties, particularly general practice. Current
workforce implications might be minor, but if fees for CSP students increase or
more FFP places become available, potential impacts on workforce distribution
will need to be considered.
PMID- 25588447
TI - Toxic epidermal necrolysis - an investigation to dye for?
PMID- 25588448
TI - All about John.
PMID- 25588454
TI - Fatigue in chronic liver disease: exploring the role of the autonomic nervous
system.
PMID- 25588453
TI - Unemployment, government healthcare spending, and cerebrovascular mortality,
worldwide 1981-2009: an ecological study.
AB - BACKGROUND: The global economic downturn has been associated with unemployment
rises, reduced health spending, and worsened population health. This has raised
the question of how economic variations affect health outcomes. AIM: We sought to
determine the effect of changes in unemployment and government healthcare
expenditure on cerebrovascular mortality globally. METHODS: Data were obtained
from the World Bank and World Health Organization. Multivariate regression
analysis was used to assess the effect of changes in unemployment and government
healthcare expenditure on cerebrovascular mortality. Country-specific differences
in infrastructure and demographics were controlled for. One- to five-year lag
analyses and robustness checks were conducted. RESULTS: Across 99 countries
worldwide, between 1981 and 2009, every 1% increase in unemployment was
associated with a significant increase in cerebrovascular mortality (coefficient
187, CI: 86.6-288, P = 0.0003). Every 1% rise in government healthcare
expenditure, across both genders, was associated with significant decreases in
cerebrovascular deaths (coefficient 869, CI: 383-1354, P = 0.0005). The
association between unemployment and cerebrovascular mortality remained
statistically significant for at least five years subsequent to the 1%
unemployment rise, while the association between government healthcare
expenditure and cerebrovascular mortality remained significant for two years.
These relationships were both shown to be independent of changes in gross
domestic product per capita, inflation, interest rates, urbanization, nutrition,
education, and out-of-pocket spending. CONCLUSIONS: Rises in unemployment and
reductions in government healthcare expenditure are associated with significant
increases in cerebrovascular mortality globally. Clinicians may also need to
consider unemployment as a possible risk factor for cerebrovascular disease
mortality.
PMID- 25588455
TI - Loss of an ecological baseline through the eradication of oyster reefs from
coastal ecosystems and human memory.
AB - Oyster reefs form over extensive areas and the diversity and productivity of
sheltered coasts depend on them. Due to the relatively recent population growth
of coastal settlements in Australia, we were able to evaluate the collapse and
extirpation of native oyster reefs (Ostrea angasi) over the course of a
commercial fishery. We used historical records to quantify commercial catch of O.
angasi in southern Australia from early colonization, around 1836, to some of the
last recorded catches in 1944 and used our estimates of catch and effort to map
their past distribution and assess oyster abundance over 180 years. Significant
declines in catch and effort occurred from 1886 to 1946 and no native oyster
reefs occur today, but historically oyster reefs extended across more than 1,500
km of coastline. That oyster reefs were characteristic of much of the coastline
of South Australia from 1836 to 1910 appears not to be known because there is no
contemporary consideration of their ecological and economic value. Based on the
concept of a shifted baseline, we consider this contemporary state to reflect a
collective, intergenerational amnesia. Our model of generational amnesia accounts
for differences in intergenerational expectations of food, economic value, and
ecosystem services of nearshore areas. An ecological system that once surrounded
much of the coast and possibly the past presence of oyster reefs altogether may
be forgotten and could not only undermine progress towards their recovery, but
also reduce our expectations of these coastal ecosystems.
PMID- 25588456
TI - L-dopa does not add to the success of high-intensity language training in
aphasia.
AB - PURPOSE: L-dopa has been shown to improve outcome of moderate-intensity language
training after stroke in acute aphasia. Given the critical role of training
intensity we probed the effect of l-dopa in combination with high-intensity
language training in chronic post-stroke aphasia. METHODS: In this prospective,
randomized, placebo-controlled, double-blind study, aphasia patients (>1 year
post stroke) were administered 100/25 mg of l-dopa/carbidopa or placebo daily
prior to four hours of language training for two weeks. Conditions were crossed
over after a wash-out period of 4 weeks. RESULTS: An a-priori planned interim
analysis (n = 10) showed that naming performance and verbal communication
improved significantly and persistently for at least 6 months in every patient,
but l-dopa had no incremental effect to intensive training. CONCLUSION: High
intensity language training in chronic aphasia may take learning to a ceiling
that precludes additive benefits from l-dopa. Effects of l-dopa on post-stroke
recovery during less intense treatment in chronic aphasia remain to be evaluated.
PMID- 25588457
TI - Early hyaluronate injection improves quality of life but not neural recovery in
unilateral vocal fold paralysis: an open-label randomized controlled study.
AB - PURPOSE: To investigate the neurologic and functional effect of intracordal
hyaluronate injections in acute unilateral vocal fold paralysis (UVFP) in a
randomized controlled trial. METHODS: In this open-label, randomized controlled
study, 29 patients with UVFP were recruited within 6 months of their first
outpatient visit and were randomized to receive either single hyaluronate
injection (HI group) or conservative management (CM group). Quantitative
laryngeal electromyography, videolaryngostroboscopy, UVFP-related quality of life
(Voice Outcomes Survey, VOS), laboratory voice analysis, and health-related
quality of life (SF-36) were evaluated at baseline, and at 1, 3 and 6 months post
injection in the HI group, and at baseline and 6 months in the CM group. RESULTS:
Improvements in most quality of life domains and other assessments were
comparable between the HI and CM groups; however, the HI group had a greater
improvement in the mental health domain of quality of life at the end of follow
up. CONCLUSIONS: Early hyaluronate injection cannot improve nerve regeneration
but can result in long-lasting improvements in patients' psychosocial well-being,
thus highlighting the importance of early intervention for patients with UVFP.
PMID- 25588458
TI - Cortical inhibition and excitation by bilateral transcranial alternating current
stimulation.
AB - PURPOSE: Transcranial electric stimulations (tES) with amplitude-modulated
currents are promising tools to enhance neuromodulation effects. It is essential
to select the correct cortical targets and inhibitory/excitatory protocols to
reverse changes in specific networks. We aimed at assessing the dependence of
cortical excitability changes on the current amplitude of 20 Hz transcranial
alternating current stimulation (tACS) over the bilateral primary motor cortex.
METHODS: We chose two amplitude ranges of the stimulations, around 25 MUA/cm2 and
63 MUA/cm2 from peak to peak, with three values (at steps of about 2.5%) around
each, to generate, respectively, inhibitory and excitatory effects of the primary
motor cortex. We checked such changes online through transcranial magnetic
stimulation (TMS)-induced motor evoked potentials (MEPs). RESULTS: Cortical
excitability changes depended upon current density (p = 0.001). Low current
densities decreased MEP amplitudes (inhibition) while high current densities
increased them (excitation). CONCLUSIONS: tACS targeting bilateral homologous
cortical areas can induce online inhibition or excitation as a function of the
current density.
PMID- 25588459
TI - An ischemic stroke model of nonhuman primates for remote lesion studies: a
behavioral and neuroimaging investigation.
AB - PURPOSE: We aimed to develop a nonhuman primate (NHP) stroke model for studies of
secondary lesions in remote areas and to characterize its behavioral and
neuroimaging features. METHODS: Monkeys were either subjected to middle cerebral
artery occlusion (MCAO) distal to the M1 branch (n = 17) or sham operation (n =
7). Neurological assessment and magnetic resonance imaging (MRI) were performed
before and 1 week after operation. RESULTS: After MCAO, six monkeys showed
occlusion of the distal M1 segment and infarcts predominantly in the cortical and
subcortical regions, without hippocampal and thalamic involvement. They had
obvious neurological deficits. The other 11 monkeys showed blockage of the main
trunk of the MCA, with infarcts extending into the hippocampus and thalamus, but
no substantia nigra involvement. Their infarct volume were larger and
neurological deficits were more severe than those after distal M1 occlusion. All
sham-operated monkeys displayed normal behavior; however, MRI revealed small
infarcts in three animals. CONCLUSIONS: MCAO or even sham operations might cause
cerebral infarction in NHPs. Therefore, neurological assessment should be
combined with MRI for screening candidate stroke models. Our model is suitable
for studying secondary damage in remote regions, including the thalamus,
hippocampus, and substantia nigra, after stroke.
PMID- 25588460
TI - Treatment with amnion-derived cellular cytokine solution (ACCS) induces
persistent motor improvement and ameliorates neuroinflammation in a rat model of
penetrating ballistic-like brain injury.
AB - PURPOSE: The present work compared the behavioral outcomes of ACCS therapy
delivered either intravenously (i.v.) or intracerebroventricularly (i.c.v.) after
penetrating ballistic-like brain injury (PBBI). Histological markers for
neuroinflammation and neurodegeneration were employed to investigate the
potential therapeutic mechanism of ACCS. METHODS: Experiment-1, ACCS was
administered either i.v. or i.c.v. for 1 week post-PBBI. Outcome metrics included
behavioral (rotarod and Morris water maze) and gross morphological assessments.
Experiment-2, rats received ACCS i.c.v for either 1 or 2 weeks post-PBBI. The
inflammatory response was determined by immunohistochemistry for neutrophils and
microglia reactivity. Neurodegeneration was visualized using silver staining.
RESULTS: Both i.v. and i.c.v. delivery of ACCS improved motor outcome but failed
to improve cognitive outcome or tissue sparing. Importantly, only i.c.v. ACCS
treatment produced persistent motor improvements at a later endpoint. The i.c.v.
ACCS treatment significantly reduced PBBI-induced increase in myeloperoxidase
(MPO) and ionized calcium binding adaptor molecule 1 (Iba1) expression.
Concomitant reduction of both Iba1 and silver staining were detected in corpus
callosum with i.c.v. ACCS treatment. CONCLUSIONS: ACCS, as a treatment for TBI,
showed promise with regard to functional (motor) recovery and demonstrated strong
capability to modulate neuroinflammatory responses that may underline functional
recovery. However, the majority of beneficial effects appear restricted to the
i.c.v. route of ACCS delivery, which warrants future studies examining delivery
routes (e.g. intranasal delivery) which are more clinically viable for the
treatment of TBI.
PMID- 25588461
TI - Can transcranial direct current stimulation be useful in differentiating
unresponsive wakefulness syndrome from minimally conscious state patients?
AB - PURPOSE: Disorders of consciousness (DOC) diagnosis relies on the presence or
absence of purposeful motor responsiveness, which characterizes the minimally
conscious state (MCS) and the unresponsive wakefulness syndrome (UWS),
respectively. Functional neuroimaging studies have raised the question of
possible residual conscious awareness also in clinically-defined UWS patients.
The aim of our study was to identify electrophysiological parameters, by means of
a transcranial magnetic stimulation approach, which might potentially express the
presence of residual networks sustaining fragmentary behavioral patterns, even
when no conscious behavior can be observed. METHODS: We enrolled 25 severe DOC
patients, following post-anoxic or traumatic brain injury and 20 healthy
individuals (HC) as control group. Baseline electrophysiological evaluation
evidenced, in comparison to HC, a partial preservation of cortical effective
connectivity and excitability in clinically defined MCS, whereas these components
were absent in clinically defined UWS. Then, we applied an anodal transcranial
direct current stimulation (a-tDCS) protocol over the orbitofrontal cortex.
RESULT: a-tDCS was able to boost cortical connectivity and excitability in all
HC, MCS, and to unmask such excitability/connectivity in some UWS patients.
CONCLUSION: a-tDCS could be useful in identifying residual connectivity markers
in clinically-defined UWS, who may lack of purposeful behavior as a result of a
motor-output failure.
PMID- 25588462
TI - Caspase-3 inhibitor Z-DEVD-FMK enhances retinal ganglion cell survival and vision
restoration after rabbit traumatic optic nerve injury.
AB - PURPOSE: Vision loss after traumatic optic nerve injury is considered
irreversible because of the retrograde loss of retinal ganglion cells (RGCs)
which undergo apoptosis. Because the second messenger caspase-3 plays a major
role in apoptosis, we now evaluated the efficacy of the specific caspase-3
inhibitor, Z-DEVD-FMK, in a rabbit model of fluid percussion injury (FPI) which
mimics traumatic optic nerve injury in humans to enhance cell survival and
improve vision. METHODS: Survival of RGCs and recovery of vision were studied
using retinal morphological markers and visual evoked potentials (VEP),
respectively. The FPI traumatized animals were treated in their right eye with a
single intravitreal or peribulbar injection of Z-DEVD-FMK 30 min post-injury
compared to 2% DMSO control injections in their left eye. RESULTS: Intravitreal Z
DEVD-FMK, but not control injections, led to down-regulation of capase-3 and
reduced, in a dose-dependent manner, RGCs apoptosis from 7 to 21 days post
injury. These morphological improvements were accompanied by vision restoration
as documented by VEP. The neuroprotection after intravitreal injection of Z-DEVD
FMK was more effective than the peribulbar application. CONCLUSIONS: The caspase
3 inhibitor Z-DEVD-FMK is neuroprotective by inhibiting RGCs apoptosis when
injected 30 min after optic nerve damage and significantly promotes restoration
of vision. A controlled clinical trial is now needed to evaluate the efficacy and
safety of Z-DEVD-FMK in humans.
PMID- 25588463
TI - Quercetin ameliorates hypobaric hypoxia-induced memory impairment through
mitochondrial and neuron function adaptation via the PGC-1alpha pathway.
AB - PURPOSE: Acute hypobaric hypoxia (HH) causes persistent cognitive impairment,
affecting memory function specifically. Mitochondrial dysfunction and synaptic
morphological change were the prominent pathological features of HH exposure on
brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is
reported to prevent ischemia induced by neuronal injury. This study investigated
the efficacy of quercetin to ameliorate HH-induced memory deficit. METHODS: Rats
were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and
received quercetin daily (50, 75 or 100 mg/kg.bw) via gavage during the period of
exposure. Cognitive performance was assessed by the Morris water maze test. In
vitro, the effect of quercetin was tested in hippocampus tissue. RESULTS:
Quercetin, especially at 100 mg/kg.bw, significantly reduced HH-induced memory
decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions
were ameliorated by quercetin. Furthermore, quercetin regulated the expression of
sirtuin 1(Sirt1), PGC-1alpha, and the proteins related with mitochondrial
biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin
type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic
factor (BDNF), showing the PGC-1alpha/FNDC5/BNDF pathways might be involved in
neuronal adaptation. CONCLUSIONS: The results suggest quercetin has prophylactic
potential for amelioration of HH-induced memory impairment, which is associated
with the mitochondrial and neuronal adaptation in hippocampus.
PMID- 25588464
TI - Prefrontal cortex as a compensatory network in ataxic gait: a correlation study
between cortical activity and gait parameters.
AB - PURPOSE: To investigate whether prefrontal cortex (PFC) functioning during ataxic
gait is linked to compensatory mechanisms or to the typical intra-subject
variability of the ataxic gait. METHODS: Nineteen patients with chronic ataxia
and fifteen healthy subjects were evaluated. The subjects were requested to walk
along a straight distance of 10 meters while PFC oxygenation and gait parameters
were assessed. PFC activity was evaluated by NIRO-200 while gait analysis was
performed by the SMART-D500. To investigate the intra-subject variability of
gait, we calculated the coefficient of multiple correlation (CMC) of the hip,
knee and ankle kinematic waveforms furthermore, we evaluated the step width.
RESULTS: We observed a positive correlation between PFC bilateral oxygenation
changes and the step width (r = 0.54; p = 0.02 for the right PFC, and r = 0.50; p
= 0.03 for the left PFC). No correlation was found between PFC activity and CMC
of the hip, knee and ankle waveforms. CONCLUSIONS: Our results suggest that PFC
activity is linked to gait compensatory mechanisms more than to the variability
of the joint kinematic parameters caused by a defective cerebellar control.
PMID- 25588465
TI - Association between pneumoconiosis and pulmonary emboli. A Nationwide Population
Based Study in Taiwan.
AB - Studies on the association between pneumoconiosis and deep-vein thrombosis (DVT)
and pulmonary thromboembolism (PE) are few. This study was based on data obtained
from the Taiwan National Health Insurance Database from 2000 to 2006, with a
follow-up period extending to the end of 2011. We identified 3719 pneumoconiosis
patients and 14876 non-pneumoconiosis patients who were selected by frequency
matched based on sex, age, and the index year. We analysed the risks of DVT and
PE by using Cox proportional hazards regression models by including sex, age, and
CCI score. The risk of developing PE was 1.90-fold in the patients with
pneumoconiosis compared with the comparison cohort after adjustments for age,
sex, and CCI score. By contrast, we did not observe significant effect of
pneumoconiosis on DVT. However, the cumulative incidence curves for DVT were
similar in the pneumoconiosis patients and non-pneumoconiosis patients. The
multiplicative increased risks of PE were significant in patients with
pneumoconiosis and CCI score of one and more. In conclusion, physicians should
include pneumoconiosis in evaluating pulmonary embolism risk.
PMID- 25588466
TI - Molecular and phenotypic characteristics of maturity-onset diabetes of the young
compared with early onset type 2 diabetes in China.
AB - BACKGROUND: The aim of the present study was to investigate the contribution of
maturity-onset diabetes of the young (MODY) genes to the etiology of 14 Chinese
MODY families and to assess phenotypic differences between patients with MODY but
without a known genetic cause of diabetes (MODYX) and those with early onset type
2 diabetes (T2D). METHODS: The study included 14 MODY probands from unrelated
families and 59 patients (age of onset <=35 years) diagnosed as early onset T2D.
A standard meal test and metabolic studies were performed to characterize the
clinical features of all patients. All probands with MODY were analyzed for
nucleotide variations in promoters, exons, and exon-intron boundaries of 13 known
MODY genes by direct DNA sequencing. RESULTS: Mutations in 13 known MODY genes
were not present in the 14 Chinese families and they were classified as MODYX.
However, different polymorphisms were identified, with I27L (42.9%; 12/28) and
S487N (46.4%; 13/28) of hepatocyte nuclear factor 4alpha (HNF1alpha/MODY3) being
two most frequent polymorphisms. Two new polymorphisms, namely T412I and D504H,
were detected in carboxyl ester lipase (CEL/MODY8). Compared with patients with
early onset T2D, patients with MODYX were diagnosed with diabetes at a younger
age (28.3 +/- 6.5 vs 24.3 +/- 6.5 years; P < 0.05) and had a lower body mass
index (BMI; 28.3 +/- 6.1 vs 24.1 +/- 4.3 kg/m(2) ; P < 0.01) and homeostatic
model assessment of beta-cell function (47.6 [22.2-89.4] vs 18.5 [6.5-33.7]; P <
0.05). CONCLUSION: Herein we report on 14 Chinese families with MODYX and
describe its phenotype. Compared with early onset T2D, MODYX is characterized by
lower BMI and decreased insulin-secreting capacity.
PMID- 25588467
TI - Heterogeneity of tremor mechanisms assessed by tremor-related cortical potential
in mice.
AB - BACKGROUND: Identifying a neural circuit mechanism that is differentially
involved in tremor would aid in the diagnosis and cure of such cases. Here, we
demonstrate that tremor-related cortical potential (TRCP) is differentially
expressed in two different mouse models of tremor. RESULTS: Hybrid tremor
analysis of harmaline-induced and genetic tremor in mice revealed that two
authentic tremor frequencies for each type of tremor were conserved and showed an
opposite dependence on CaV3.1 T-type Ca(2+) channels. Electroencephalogram
recordings revealed that alpha1(-/-);alpha1G(-/-) mice double-null for the GABA
receptor alpha1 subunit (Gabra1) and CaV3.1 T-type Ca(2+) channels (Cacna1g), in
which the tremor caused by the absence of Gabra1 is potentiated by the absence of
Cacna1g, showed a coherent TRCP that exhibited an onset that preceded the
initiation of behavioral tremor by 3 ms. However, harmaline-induced tremor, which
is known to be abolished by alpha1G(-/-), showed no TRCP. CONCLUSIONS: Our
results demonstrate that the alpha1(-/-);alpha1G(-/-) double-knockout tremor
model is useful for studying cortical mechanisms of tremor.
PMID- 25588468
TI - Methods of a multi-faceted rapid knowledge synthesis project to inform the
implementation of a new health service model: Collaborative Emergency Centres.
AB - BACKGROUND: The aim of this rapid knowledge synthesis was to provide relevant
research evidence to inform the implementation of a new health service in Nova
Scotia, Canada: Collaborative Emergency Centres (CECs). CECs propose to deliver
both primary and urgent care to rural populations where traditional delivery is a
challenge. This paper reports on the methods used in a rapid knowledge synthesis
project to provide timely evidence to policy makers about this novel healthcare
delivery model. METHODS: We used a variety of methods, including a
jurisdictional/scoping review, modified systematic review methodologies, and
integrated knowledge translation. We scanned publicly available information about
similar centres across our country to identify important components of CECs and
CEC-type models to operationalize the definition of a CEC. We conducted
literature searches in PubMed, CINAHL, and EMBASE, and in the grey literature, to
identify evidence on the key structures and processes and effectiveness of CEC
type models of care delivery. Our searches were limited to published systematic
reviews. The research team facilitated two integrated knowledge translation
workshops during the project to engage stakeholders, to refine the research goals
and objectives, and to share interim and final results. Citations and included
articles were categorized by whether they addressed the CEC model or component
structures and processes. Data and key messages were extracted from these reviews
to inform implementation. RESULTS: CEC-type models have limited peer-reviewed
evidence available; no peer-reviewed studies on CECs as a standalone healthcare
model were found. As a result, our evidence search and synthesis was revised to
focus on core CEC-type structures and processes, prioritized through consensus
methods with the stakeholder group, and resulted in provision of a meaningful
evidence synthesis to help inform the development and implementation of CECs in
Nova Scotia. CONCLUSIONS: A variety of methods and partnership with decision
makers and stakeholders enabled the project to address the limitations in the
evidence regarding CECs and meet the challenge of identifying the best available
evidence in a transparent way to meet the needs of decision-makers in a short
timeframe.
PMID- 25588469
TI - Development, optimization, and single laboratory validation of an event-specific
real-time PCR method for the detection and quantification of Golden Rice 2 using
a novel taxon-specific assay.
AB - In this study, we developed, optimized, and in-house validated a real-time PCR
method for the event-specific detection and quantification of Golden Rice 2, a
genetically modified rice with provitamin A in the grain. We optimized and
evaluated the performance of the taxon (targeting rice Phospholipase D alpha2
gene)- and event (targeting the 3' insert-to-plant DNA junction)-specific assays
that compose the method as independent modules, using haploid genome equivalents
as unit of measurement. We verified the specificity of the two real-time PCR
assays and determined their dynamic range, limit of quantification, limit of
detection, and robustness. We also confirmed that the taxon-specific DNA sequence
is present in single copy in the rice genome and verified its stability of
amplification across 132 rice varieties. A relative quantification experiment
evidenced the correct performance of the two assays when used in combination.
PMID- 25588470
TI - Magnetic field switchable dry adhesives.
AB - A magnetic field controllable dry adhesive device is manufactured. The normal
adhesion force can be increased or decreased depending on the presence of an
applied magnetic field. If the magnetic field is present during the entire normal
adhesion test cycle which includes both applying a preloading force and measuring
the pulloff pressure, a decrease in adhesion is observed when compared to when
there is no applied magnetic field. Similarly, if the magnetic field is present
only during the preload portion of the normal adhesion test cycle, a decrease in
adhesion is observed because of an increased stiffness of the magnetically
controlled dry adhesive device. When the applied magnetic field is present during
only the pulloff portion of the normal adhesion test cycle, either an increase or
a decrease in normal adhesion is observed depending on the direction of the
applied magnetic field.
PMID- 25588471
TI - Beneficial effects of cannabinoid receptor type 2 (CB2R) in injured skeletal
muscle post-contusion.
AB - The aim of the current study was to investigate the effects of cannabinoid
receptor type 2 (CB2R) on the repair process of injured skeletal muscle, which
could potentially lay solid foundations as a novel target for curing muscular
fibrosis in future. A standardized rat model of skeletal muscle contusion was
established, where rats were treated with the CB2R agonist JWH-133 or antagonist
AM-630. The in vivo results revealed that CB2R activation with JWH-133
significantly diminished the fibrotic areas, down-regulated the mRNA levels of
collagen type I/III and augmented the number of multinucleated regenerating
myofibers in the injured zones. The reasons leading to the aforementioned results
were directly attributable to decreased mRNA levels of TGF-beta1, FN-EIIIA and
alpha-SMA, reduced accumulation of myofibroblasts, and concomitantly increased
mRNA levels of matrix metalloproteinase-1/2. However, we observed contrasting
changes in rats treated with the CB2R antagonist AM-630. These results revealed
multiple effects of CB2R in systematically inhibiting fibrotic formation and
improving muscle regeneration, alongside its potential for clinical application
in patients with skeletal muscle injuries and diseases.
PMID- 25588473
TI - [The state of the regenerative activity of the tympanic membrane tissues and the
results of myringoplasty at different time points of remission of experimental
otitis media].
AB - The objective of the present study was to estimate the regenerative potential of
the tympanic membrane tissues in the early period of remission after experimental
otitis media and evaluate the results of myringoplasty. The experiments were
carried out using 23 outbred dogs exhibiting no signs of "spontaneous otitis".
Experimental otitis media was induced in 20 animals using a Staphylococcus aureus
strain as the pathogenic organism. The treatment of the experimental animals was
started two weeks after the development of otitis and continued up to obtaining
the "dry ear" condition. The animals were allocated to 4 groups depending on the
time of myringoplasty. In the animals of group 1 myringoplasty was performed one
week after remission, those of groups 2, 3, and 4 underwent myringoplasty two,
three, and four weeks after the onset of remission respectively. The results of
the study indicate that the first two weeks after the inflammatory process in the
middle ear subsided are the optimal time for myringoplasty because the
proliferative activity during this period amounts to its maximum which promotes
the survival of the transplant and the closure of tympanic defects.
PMID- 25588472
TI - Modeling drug resistance in a conjoint normal-tumor setting.
AB - BACKGROUND: In this paper, we modify our previously developed conjoint tumor
normal cell model in order to make a distinction between tumor cells that are
responsive to chemotherapy and those that may show resistance. RESULTS: Using
this newly developed core model, the evolution of three cell types: normal,
tumor, and drug-resistant tumor cells, is studied through a series of numerical
simulations. In addition, we illustrate critical factors that cause different
dynamical patterns for normal and tumor cells. Among these factors are the co
dependency of the normal and tumor cells, the cells' response mechanism to a
single or multiple chemotherapeutic treatment, the drug administration sequence,
and the treatment starting time. CONCLUSION: The results provide us with a deeper
understanding of the possible evolution of normal, drug-responsive, and drug
resistant tumor cells during the cancer progression, which may contribute to
improving the therapeutic strategies.
PMID- 25588474
TI - [The emergency plastic reconstruction of the tympanic membrane defects of post
traumatic and iatrogenic etiology with the application of the nanostructured
bioplastic material].
AB - The objective of the present study was to estimate the effectiveness of the
application of the nanostructured bioplastic material for the plastic
reconstruction of tympanic defects of post-traumatic and iatrogenic etiology. The
authors report the results of the emergency plastic reconstruction of tympanic
defects of post-traumatic and iatrogenic nature with the application of the
nanostructured bioplastic material (giamatrix). The analysis of the results of
the study prfovidd definitive evidence of the effectiveness of plastic
reconstruction of tympanic defects with the application of the nanostructured
bioplastic material.
PMID- 25588475
TI - [The application of the nanostructured bioplastic material for the plastic
reconstruction of perforations in the nasal septum].
AB - The objective of the present work was to estimate the effectiveness of the
application of the nanostructured bioplastic material for the plastic
reconstruction of perforations in the nasal septum. A total of 80 patients were
recruited for the study. Half of them underwent plastic reconstruction of
perforations in the nasal septum with the application of the nanostructured
bioplastic material. Forty patients were treated using no biotransplants. The
functional state of nasal cavity mucosa was evaluated before and after surgery.
It is concluded that the nanostructured bioplastic material used in the present
study ensures efficacious reconstruction of nasal septum integrity after plastic
correction of septal perforations.
PMID- 25588476
TI - [Diagnostics of stylohyoid syndrome].
AB - This study was designed with the purpose of improving diagnostics of stylohyoid
syndrome. To this effect, 75 patients presenting with this condition were
examined with the use of clinical, roengenological, ultrasound, and
electrophysiological methods. A combination of the most frequent complaints and
objective symptoms underlain by the common mechanisms has been identified. It is
concluded that this combination may be used as a basis for diagnostics of the
pathology being considered.
PMID- 25588477
TI - [The gender- and age-specific differences in the structure of the styloid
processes of the temporal bone].
AB - The objective of the present study was to elucidate the significance of the
gender- and age-related alterations in the styloid processes of the temporal bone
and their gender specific structural changes in the subjects aged above 35 years
as the risk factors of the development of stylohyoid syndrome. A total of 72
styloid processes were harvested from the corpses during post-mortem autopsy.
Their fixed preparations were used to determine by means of digital
radiovisiography specific structural features of the bone tissue, the thickness
of the cortical layer, diameter of osteons and Haversian canals, the number of
osteons per unit area. The data obtained from the subjects below and above 35
years of age were compared. A distinctive morphological feature of styloid
processes taken from adult people was the presence of residual embryonic
cartilaginous tissue (in 40% of the observations) in which the processes of endo-
and perihondral oteogenesis continued (15% of the cases). The elder subjects were
characterized by the significantly decreased bone tissue density, reduced number
of osteons and osteocytes whereas the diameters of Haversian canals increased.
These changes were more pronounced in the women than in the men. It is concluded
that the continued growth of styloid processes and the development of bone tissue
osteopenia in the subjects older than 35 years may serve as the risk factors of
stylohyoid syndrome.
PMID- 25588478
TI - [The evaluation of nasal obstruction during pregnancy and its influence on the
quality of life of the women].
AB - The objective of the present study was to identify peculiar features of nasal
obstruction in the pregnant women and to evaluate parameters of the quality of
life in the patients suffering from rhinitis in comparison with those having
adequate nasal breathing. A total of 120 pregnant women were available for the
examination The estimated variables included the quality of life, ciliary
activity, results of rheoencehalography, and estradiol levels. The results of the
study indicate that the quality of life in the pregnant women presenting with
rhinitis and nasal obstruction depends on the estradiol level and changes in the
rheoencephalograms. The severity of clinical symptoms of nasal obstruction
increased in parallel to variations in the parameters of the mucociliary
transport.
PMID- 25588479
TI - [Hearing disorders in the children presenting with chronic pyelonephritis].
AB - The objective of the present study was to develop the criteria for early
diagnostics of hearing disorders in the children presenting with chronic
pyelonephritis. The study included 100 children of whom 37 (37%) suffered from
the sensorineural hearing loss. The early manifestations of this disorder and the
enhancement of the acoustic sensitivity threshold for the high frequencies in the
range from 6,000 to 8,000 Hz were documented. The study has demonstrated the
dependence of the severity of hearing loss on the duration and severity of
chronic pyelonephritis. The criteria for early diagnostics of hearing disorders
in the children presenting with chronic pyelonephritis were developed and
recommended for the inclusion in the standard examination of the patients with
pyelonephritis.
PMID- 25588480
TI - [Dynamic changes in the microbial contamination of the exudate and the mucous
membrane from the tympanic cavity in the course of experimental staphylococcal
otitis media].
AB - The objective of the present study was to determine the relationships between
characteristics of the microbial contamination of the pyogenic exudate and the
mucous membrane from the tympanic cavity in the course of experimental
suppurative otitis media caused by staphylococcal infection. The experiments were
carried out on 29 rabbits showing no signs of "spontaneous" otitis. Experimental
staphylococcal suppurative otitis was induced in 26 of these animals. The degree
of microbial contamination of the mucous membrane from the tympanic cavity was
expressed either in colony-forming units per swab (CFU/swab) or as the number of
microbial cells per 1 mg of the tissue. It was shown that microbial contamination
of the exudate and the mucous membrane from the tympanic cavity depended on the
extent of the inflammatory process in the middle ear in the course of
experimental staphylococcal otitis. The highest degree of contamination fell on
the acute phase of middle ear inflammation. Staphylococci disappeared from the
mucous membrane sooner than from the exudate. This difference can be attributed
to the different activity of the tssue immunity factors.
PMID- 25588481
TI - [The comparative characteristic of the microflora species composition in the
tympanic cavity, nasal mucous membrane and external ear mucosa in the course of
experimental suppurative staphylococcal otitis].
AB - The objective of the present work was to study the species composition of
microflora in the suppurative exudate from the tympanic cavity in the course of
development of experimental suppurative staphylococcal otitis and to identify the
initial sites of migration of secondary pathogens. The experiments were carried
out on 20 adult rabbits showing no signs of "spontaneous" otitis. Experimental
staphylococcal suppurative otitis was induced in 17 of these animals. The
microbiological study included isolation and identification of pure bacterial
cultures with the use of the classical method. The initial sites of migration of
secondary pathogens were detected from the results of comparison of the species
composition of microflora in tympanic exudate and the mucous membrane of the
nearest anatomical regions, such as the nasal cavity an external auditory canal.
The data obtained indicate that suppurative exudate from the tympanic cavity is
populated by polyflora containing secondary pathogens, besides the principal ones
(Staphylococci). The large amounts of secondary pathogens penetrate into the
tympanic cavity from the mucous membranes of the nasal cavity and nasopharynx. It
is concluded that the rhinotubal system is the major pathway through which
pathogenic microflora migrates into the middle ear.
PMID- 25588482
TI - [The role of neurobioregulation in the combined treatment of subjective
tympanophonia and dizziness].
AB - The objective of the present study was to evaluate the effectiveness of the
biological control technologies applied in the framework of the combined
treatment of the patients complaining of subjective tympanophonia and dizziness
with concomitant changes in the psychoemotional status. It was shown that the
disturbances in the psychoemotional sphere associated with complaints of
subjective tympanophonia and dizziness took place in 81.4% of the patients
included in the study although 17.2% of them had no signs of organic pathology in
the central and peripheral regions of the auditory and vestibular apparatuses. It
is concluded that the proposed therapeutic strategy can be recommended in the
case of poor effectiveness of the medicamnetal treatment in the patients
presenting with subjective tympanophonia and dizziness with concomitant changes
in the psychoemotional status because it permits to eliminate clinical
manifestations of the disease or reduce their severity.
PMID- 25588483
TI - [The biomechanical prerequisites for the preservation of stapedius muscle tendon
during stapedoplasty].
AB - The objective of the present biomechanical and clinical study was to evaluate the
consequences of the preservation of stapedius muscle tendon during stapedoplasty.
The biomechanical investigations included mathematical simulation with the
construction of the model based on the kinematic approach. The comparative
clinical study of the results of stapedoplasty carried out between 2001 and 2010
involved 340 patients (77 men and 263 women) at the mean age of 48.18 years.
Twenty patients underwent piston stapedoplasty by the method of Shi, 320 ones
were treated by stapedoplasty with the preservation of stapedius muscle tendon.
The state of speech hearing and the audiometric air-bone gap (ABG) were deduced
from the audiograms. The biomechanical study demonstrated a significant increase
in the range of the movements of the long crus of the incus, after the removal of
the stapedius tendon muscle and the preservation in part of the acoustic reflex
in case of tendon preservation. The preservation of the tendon partly dampened
excessive sound vibrations. The clinical study revealed the improvement of speech
hearing parameters throughout the three-year postoperative follow-up period; it
was especially pronounced within the first year after surgery with the
preservation of stapedius muscle tendon. The size of ABG at a the frequencies
falling in the 0.5-1 kHz and 6-8 kHz ranges after surgery with the preservation
of stapedius muscle tendon was smaller than after the removal of the tendon
during the three-year follow-up (p<0.005). The difference was especially well
apparent within the first year after stapedoplasty. The difference in this
parameter between the interventions with the preservation of stapedius muscle
tendon and with its removal was insignificant (p>0.05).
PMID- 25588484
TI - [The bacteriological aspects of post-implantation Highmore maxillary sinusitis].
AB - The present publication was designed to summarize the results of the studies on
etiopathogenesis of post-implantation Highmore maxillary sinusitis. The taxonomic
evaluation of the microbial "paysage" of the rhinosinonasal sphere following
maxillary intraosseous dental implantation is reported. The non-infectious
dystrophic nature of this pathological condition was demonstrated.
PMID- 25588486
TI - [The combined application of thermography and local thermometry for diagnostics,
prognostication, modeling, and evaluation of the effectiveness of the treatment
of acute sinusitis].
AB - The objective of the present work was to study the possibilities of the combined
application of thermography and local thermometry for diagnostics of acute
sinusitis, characteristic of dynamics of the clinical course of this pathology,
and evaluation of the effectiveness of its treatment. The study included 23
patients presenting with acute rhinosinusitis and 21 ones free from pathology of
paranasal sinuses. Contact thermometry was performed with the use of the
electronic thermometer applied to the anterior surface of the inferior turbinated
bone. An infrared thermovision camera was employed to carry out thermographic
measurements. The study demonstrated variations in endonasal and surface
temperature under effect of the treatment. Positive dynamics of the patients'
conditions was manifested as a drop of endonasal temperature and relatively
constant surface temperature. A rise in the surface temperature was associated
with the pathological process. In the patients showing slightly positive dynamics
of the disease, the surface temperature on the side of the pathological process
was lower than on the unaffected side. This difference was interpreted as an
indication of the reduced microcirculatory activity in this region. It was
hypothesized that dynamics of the inflammatory process is to a large extent
determined by the character of blood circulation in the affected region. The
authors conclude that the combined application of thermometry and thermography
not only improves the quality of diagnostics of acute rhinosinusitis but also
facilitates the evaluation of its dynamics and the effectiveness of the
treatment.
PMID- 25588485
TI - [The influence of local and combined acute suppurative Highmore maxillary
sinusitis on the serum lactoferrin and interleukin-8 levels in the children].
AB - The objective of the present study was to estimate the influence of isolated and
combined acute suppurative Highmore maxillary sinusitis on the serum lactoferrin
(LF) and interleukin-8 (IL-8) levels in the children. A total of 70 children at
the age varying from 4 to 15 years were available for the examination. Twenty of
them constituted the control group, 29 presented with acute suppurative Highmore
maxillary sinusitis, in 21 cildren this condition was combined with frontitis,
ethmoiditis, otitis, and adenoiditis. Serum lactoferrin and interleukin-8 levels
were measured by solid phase enzyme-linked immunoassay. It was shown that all the
aforementioned forms of rhinosinusitis were associated with a significant
increase of the serum LF level, an universal factor inactivating the propagation
of bacterial, viral, and fungal pathogens. The level of IL-8 known to activate
chemotaxis was increased only in the children presenting with combined forms of
suppurative Highmore maxillary sinusitis. It is concluded that this difference
can be used for the purpose of dufferential diagnostics of different forms of
suppurative maxillary sinusitis.
PMID- 25588487
TI - [A case of the late complication of stapedoplasty].
AB - The authors report a case of the late complication of stapedoplasty that
developed 1.5 years after the otherwise successful surgical intervention.
Computed tomography revealed the displacement of the stapedial prosthesis into
the internal ear. Upon revision, the prosthesis was replaced by a shorter one.
Intraoperatively, the vestibular manifestations underwent complete regression.
The substantial improvement of hearing was documented in the postoperative
period.
PMID- 25588488
TI - [Pharyngeal rhabdomyosarcoma].
PMID- 25588489
TI - [Pyocele of the posterior cells of the ethmoidal labyrinth and sphenoidal sinus
in the patient with the history of nasopharyngeal rhabdomyosarcoma].
PMID- 25588490
TI - [The experience with the use of neuromedin preparations for the treatment of
sensorineural impairment of hearing].
AB - The objective of the present study was to evaluate the effectiveness of the
application of neuromedin for the treatment of sensorineural loss of hearing of
different etiology. A total of 230 patients at the age varying from 20 to 60
years presenting with sensorineural impairment of hearing were available for the
observation. Neuromedin was administered intramuscularly at 15 mg/day (1.5%
solution at a dose of 1.0 ml) for 10 day; thereafter, the patients took 20 mg
neuromedin tablets thrice daily during one month. The majority of the patients
reported an improvement of hearing and speech intelligibility. Complete
restoration of hearing was documented in certain patients presenting with acute
sensorineural impairment of hearing.
PMID- 25588491
TI - [The role of tanakan in the improvement of the effectiveness of vestibular
rehabilitation].
AB - The objective of the present study was to estimate the influence of tanakan on
the duration of the period needed to achieve vestibular compensation in the
patients presenting with peripheral vestibular dizziness in the course of
vestibular rehabilitation with the use of the post-urographic system. 72 patients
at the age varying from 18 to 42 years (46 women and 26 men) suffering from
peripheral vestibular dizziness were treated on an individual basis for the
purpose of vestibular rehabilitation 3-5 times per week for a total period of 3-6
weeks. 42 of the 72 patients comprising group 1 were given Tanakan for 3 months
at a dose of 40 mg thrice daily, the remaining 30 patients (group 2) continued to
receive the vasoactive treatment as prescribed by attending physicians of other
medical and diagnostic centres (protocols of their treatment recommended at local
medical facilities did not include tanakan therapy). It is concluded that the use
of tanakan for the treatment of the patients presenting with peripheral
vestibular dizziness accelerates vestibular compensation and reduces the time
necessary to achieve vestibular rehabilitation. Moreover, the combined treatment
with the application of tanakan makes it possible to decrease the medicamental
loading.
PMID- 25588492
TI - [The comparative effectiveness of framycetin included in combined therapy of
adenoiditis in the children].
AB - The objective of the present study was to evaluate the effectiveness of
framycetin included in combined therapy of adenoiditis in the children. The study
involved 67 children at the mean age of 6.9+/-2.7 years. Group 1 was comprised of
35 children given framycetin as topical therapy, the patients of group 2 were
treated by the endonasal administration of a 2% silver proteinate solution. It
was shown that the use of framycetin as a component of combined therapy of
adenoiditis enhances the effectiveness of the treatment and compliance to therapy
in comparison with the same parameters in the case of the application of
traditional topical antibacterial preparations.
PMID- 25588493
TI - [The new approaches to the treatment of inflammatory pharyngeal pathology].
AB - The authors present a detailed characteristic of various topical medications
applied for the treatment of tonsillopharyngitis with special reference to non
steroidal anti-inflammatory drugs. These data give evidence of the advantages of
such preparations over other pharmaceutical products for the topical treatment.
It is concluded that the application of topical anti-inflammatory preparations
should be a major component of the treatment of inflammatory pharyngeal pathology
regardless of its etiology, either viral or bacterial.
PMID- 25588494
TI - [Ciliary epithelium and topical decongestants: how to minimize the undesirable
events?].
AB - The objective of the present study was to evaluate the influence of the
combination of 0.1% xylometazoline with seawater (Rinomaris, "Jadran", Croatia)
on the state and functional activity of the ciliary epithelium of the nasal
cavity. The results of the study confirm the safety of this treatment and the
possibility of its application in routine clinical practice.
PMID- 25588495
TI - QSIM: quantitative structured illumination microscopy image processing in ImageJ.
AB - BACKGROUND: Structured illumination microscopy has been extensively used in
biological imaging due to its low cost and easy implementation. However, the lack
of quantitative imaging capability limits its application in absolute irradiance
measurements. METHOD: We have developed a quantitative structured illumination
microscopy image processing algorithm (QSIM) as a plugin for the widely used
ImageJ software. QSIM can work with the raw images acquired by a traditional
structured illumination microscope and can quantitatively measure photon numbers,
with noise estimates for both wide-field images and sectioned images. RESULTS AND
CONCLUSION: We demonstrated the quantitative image processing capability of QSIM
by imaging a mouse kidney section in 3D. The results show that QSIM can transform
structured illumination microscopy from qualitative to quantitative, which is
essential for demanding fluorescence imaging applications.
PMID- 25588496
TI - An Anteroseptal Accessory Pathway in a Patient with Dextrocardia and Situs
Inversus.
PMID- 25588497
TI - Acute His-Bundle Injury Current during Permanent His-Bundle Pacing Predicts
Excellent Pacing Outcomes.
AB - INTRODUCTION: His-bundle (HB) pacing (P) is a physiological alternative to right
ventricular pacing (RVP), but is technically challenging and limited by higher
pacing thresholds. Myocardial injury current (IC) recorded during right
ventricular lead placement implies good tissue contact and is associated with low
pacing thresholds. IC at the HB has not been previously described. We
hypothesized that HBIC during permanent HBP may be associated with lower pacing
thresholds. METHODS: Permanent HBP was performed using Medtronic Select
Secure(tm) (Medtronic Inc., Minneapolis, MN, USA) delivered via a fixed-curve
(C315 His) sheath. HB electrogram (EGM) was recorded in a unipolar fashion from
the lead tip. Presence or absence of HBIC was documented. HBP threshold, sensing,
and impedances were recorded at implant, 2 weeks, 2 months, and 1 year. RESULTS:
Sixty patients (age 72 +/- 15 years; male 55%, sick sinus syndrome 40%,
atrioventricular block 60%, fluoroscopy duration 9.2 +/- 3.7 minutes) underwent
successful permanent HBP. HBIC was recorded in 22 (37%) patients (group I). HBEGM
without IC was recorded in the remaining 38 (63%) patients (group II). Pacing
threshold at implant, 2 weeks, 2 months, and 1 year were significantly lower in
group I (1.16 +/- 0.4 V; 1.18 +/- 0.5 V; 1.23 +/- 0.6 V; 1.3 +/- 0.6 V @ 0.5 ms)
compared to group II (1.75 +/- 0.7 V; 1.82 +/- 0.8 V; 1.93 +/- 0.8 V; 1.98 +/-
0.9 V @ 0.5 ms, P < 0.05), respectively. CONCLUSIONS: IC can be recorded at the
HB during permanent HBP in 37% of patients. HBIC is associated with significantly
lower pacing thresholds compared to patients in whom HBIC was not recorded. HBIC
may be a marker for superior short-term HBP thresholds.
PMID- 25588498
TI - Soluble epoxide hydrolase inhibitory activity of phenolic components from the
rhizomes and roots of Gentiana scabra.
AB - Two new (1 and 2) and seven known phenolic compounds were isolated from a
methanol extract of the rhizomes and roots of Gentiana scabra. Their structures
were identified by spectroscopic analysis and comparing with reported values. The
inhibitory effects of each compound on soluble epoxide hydrolase (sEH) were
evaluated. Among them, compounds 2, 6, and 9 potently inhibited sEH activity.
PMID- 25588500
TI - Dispersion in the presence of acetic acid or ammonia confers gliadin-like
characteristics to the glutenin in wheat gluten.
AB - Spray-dried gluten has unique properties and is commercially available in the
food industry worldwide. In this study, we examined the viscoelastic properties
of gluten powder prepared by dispersion in the presence of acetic acid or an
ammonia solvent and then followed by lyophilization instead of a spray drying.
Mixograph measurements showed that the acid- and ammonia-treated gluten powders
had marked decreases in the time to peak dough resistance when compared with the
control gluten powder. The integrals of the dough resistance and bandwidth for 3
min after peak dough resistance decreased in both treated gluten powders. Similar
phenomena were observed when gliadin was supplemented to gluten powders. Basic
and acidic conditions were applied to the acid- and ammonia-treated gluten
powders, respectively, and the viscoelastic behaviors were found to depend on the
pH in the gluten dispersion just before lyophilization. These behaviors suggest
that gluten may assume a reversible change in viscoelasticity by a fluctuation in
pH during gluten dispersion. SDS-PAGE showed that the extractable proteins
substantially increased in some polymeric glutenins including the low molecular
weight-glutenin subunit (LMW-GS) when the ammonia-treated gluten powder was
extracted with 70% ethanol. In contrast, the extractable proteins markedly
increased in many polymeric glutenins including the high molecular weight
glutenin subunit and/or the LMW-GS when the acid-treated gluten powder was
extracted with 70% ethanol. It thus follows that the extractability of polymeric
glutenin to ethanol increases similarly to gliadin when gluten is exposed to an
acidic or a basic pH condition; therefore, glutenin adopts gliadin-like
characteristics.
PMID- 25588503
TI - Predicting and setting conservation priorities for Bolivian mammals based on
biological correlates of the risk of decline.
AB - The recognition that growing proportions of species worldwide are endangered has
led to the development of comparative analyses to elucidate why some species are
more prone to extinction than others. Understanding factors and patterns of
species vulnerability might provide an opportunity to develop proactive
conservation strategies. Such comparative analyses are of special concern at
national scales because this is the scale at which most conservation initiatives
take place. We applied powerful ensemble learning models to test for biological
correlates of the risk of decline among the Bolivian mammals to understand
species vulnerability at a national scale and to predict the population trend for
poorly known species. Risk of decline was nonrandomly distributed: higher
proportions of large-sized taxa were under decline, whereas small-sized taxa were
less vulnerable. Body mass, mode of life (i.e., aquatic, terrestrial, volant),
geographic range size, litter size, home range, niche specialization, and
reproductive potential were strongly associated with species vulnerability.
Moreover, we found interacting and nonlinear effects of key traits on the risk of
decline of mammals at a national scale. Our model predicted 35 data-deficient
species in decline on the basis of their biological vulnerability, which should
receive more attention in order to prevent their decline. Our results highlight
the relevance of comparative analysis at relatively narrow geographical scales,
reveal previously unknown factors related to species vulnerability, and offer
species-by-species outcomes that can be used to identify targets for
conservation, especially for insufficiently known species.
PMID- 25588502
TI - The MAP kinase-interacting kinases regulate cell migration, vimentin expression
and eIF4E/CYFIP1 binding.
AB - The MAP kinase-interacting kinases (Mnk1 and Mnk2) are activated by ERK and are
best known for phosphorylating the translation initiation factor eIF4E. Genetic
knockout of the Mnks impaired the migration of embryonic fibroblasts both in two
dimensional wound-healing experiments and in three-dimensional migration assays.
Furthermore, a novel and selective Mnk inhibitor, Mnk-I1, which potently blocks
eIF4E phosphorylation, blocked the migration of fibroblasts and cancer cells,
without exerting 'off-target' effects on other signalling pathways such as Erk.
Mnk-I1 or genetic knockout of the Mnks decreased the expression of vimentin, a
marker of mesenchymal cells, without affecting vimentin mRNA levels. Vimentin
protein levels were much lower in Mnk1/2-knockout cells than in controls,
although mRNA levels were similar. Our data suggest that the Mnks regulate the
translation of the vimentin mRNA and the stability of the vimentin protein.
Inhibition or genetic knockout of the Mnks increased the binding of eIF4E to the
cytoplasmic FMRP-interacting protein 1 (CYFIP1), which binds the fragile-X mental
retardation protein, FMRP, a translational repressor. Since FMRP binds mRNAs for
proteins involved in metastasis, the Mnk-dependent release of CYFIP1 from eIF4E
is expected to release the repression of translation of FMRP-bound mRNAs,
potentially providing a molecular mechanism for the control of cell migration by
the Mnks. As Mnk1/2 are not essential for viability, inhibition of the Mnks may
be a useful approach to tackling cancer metastasis, a key process contributing to
mortality in cancer patients.
PMID- 25588501
TI - Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates
cardiac rhythmicity.
AB - Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac
function. To dissect the regulatory network of cardiac Ca(2+) handling, we
performed a chemical suppressor screen on zebrafish tremblor embryos, which
suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent
activity to restore coordinated contractions in tremblor. We show that efsevin
binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the
transfer of Ca(2+) from intracellular stores into mitochondria. In
cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+)
sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and
irregular contractions. We further show that overexpression of VDAC2
recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2
deficiency attenuates efsevin's rescue effect and that VDAC2 functions
synergistically with MCU to suppress cardiac fibrillation in tremblor. Together,
these findings demonstrate a critical modulatory role for VDAC2-dependent
mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity.
PMID- 25588504
TI - Day-by-day variation in affect, arousal and alcohol consumption in young adults.
AB - INTRODUCTION AND AIMS: Alcohol consumption has a well-established relationship
with mood, with higher positive and negative affect predicting alcohol use. More
recently, researchers have explored whether alcohol consumption occurs as a
response to affect variability as an attempt to self-medicate and stabilise
affect. Studies have revealed a positive association between alcohol use and
intra- and inter-individual affect variability in clinical and university student
samples; however not much is known of this relationship among the general
community. DESIGN AND METHODS: Ecological Momentary Assessment (EMA) methods were
used to investigate the relationship between affect and arousal variability and
alcohol use in 53 community volunteers. Participants self-reported affect and
arousal at three to five randomly timed moments throughout the day, as well as
every time they drank. RESULTS: On a day-to-day basis, higher positive affect was
associated with increased alcohol consumption. When analyses were restricted to
self-reported affect prior to alcohol consumption, only increased arousal and
decreased variability in arousal predicted the likelihood of alcohol consumption.
Mean level of arousal was associated with the extent of alcohol consumed.
DISCUSSION AND CONCLUSIONS: In this moderate drinking sample day-to-day affect
and arousal, and arousal variability, were associated with alcohol consumption.
Analyses restricted to pre-drinking observations provide further evidence that
self-medication accounts of alcohol consumption may explain drinking initiation
but that the relationship between affect factors and drinking behaviour may
change around the point of first drink.
PMID- 25588505
TI - Developing the eCPP: adapting an evidence-based parent training program for
digital delivery in primary care settings.
AB - BACKGROUND: Developing innovative delivery methods is needed to overcome time and
logistic barriers to in-person participation in evidence-based parent training
(PT) programs. PURPOSE: The purpose of this paper is to (a) describe the
systematic process for adapting an evidence-based group PT program (the Chicago
Parent Program) to a tablet-based delivery format, (b) present the adapted
program, and (c) discuss opportunities and challenges of adapting evidence-based
programs for alternative delivery methods. METHODS: To ensure consistency with
the original program and relevance to the intended program recipients, three
groups-parents (n = 10), CPP developers (n = 3), and digital delivery experts-
were engaged throughout the systematic steps of the delivery adaptation of the
Chicago Parent Program (eCPP). Group meetings were used to identify the program's
core components, develop the adaptation program model, assess potential
mismatches for the new delivery context, and adapt the original program model and
materials. RESULTS: The final eCPP is a six-module Internet-based intervention
that includes: interactive activities, video examples and explanations of
parenting strategies, reflection questions, assessment of parent knowledge with
feedback, and module practice assignments. LINKING EVIDENCE TO ACTION: Developing
innovative delivery approaches for evidenced-based interventions are promising to
increase intervention sustainability and participant access and engagement. It is
critical that these adaptations are systematic and developed with expert
consultation and community input.
PMID- 25588508
TI - The role of the lymphatic system in endometriosis: a comprehensive review of the
literature.
AB - Endometriosis is a benign gynecological disorder characterized by the presence of
tissue resembling the endometrium in locations outside the uterus. The
pathogenesis of endometriosis is still unknown; however, it is believed that the
lymphatic system plays major roles in the development and progression of the
disease. The lymphatic dissemination theory has been proposed to explain the
presence of endometrial and/or endometriotic tissue in lymphatic vessels, lymph
nodes, and rare sites, as well as high reoccurrence rates following treatment.
Despite the importance of the lymphatic system in many aspects of endometriosis,
there has been no previous thorough scientific update on its role in the disease.
A review of scientific literature on the lymphatic system, lymphangiogenesis, and
immunological changes associated with endometriosis was conducted.
Lymphangiogenic potential is disturbed and lymphatic vessel density increased in
the eutopic endometrium of women with endometriosis, likely promoting the entry
of endometrial tissues into the lymphatic circulation. Endometriotic lesions and
endometrial-like cells are present in uterine-draining nodes and various other
pelvic lymph nodes. Immune responses are impaired in uterine-draining nodes,
likely favoring the survival of endometrial cells and lesion establishment. In
addition, lymphangiogenesis in endometriotic lesions may contribute to lesion
growth and persistence, and promote the spread of endometrial cells to draining
lymph nodes. The evidence reviewed in this paper supports the theory of lymphatic
dissemination of endometriosis and highlights the roles of the lymphatic system
in the pathogenesis and persistence of endometriosis. Understanding these roles
is crucial for establishment of novel therapeutic approaches.
PMID- 25588509
TI - Roles of Toll-like receptors 2 and 4 in mediating experimental autoimmune
orchitis induction in mice.
AB - The mammalian testis is an immunoprivileged site where male germ cell antigens
are immunologically tolerated under physiological conditions. However, some
pathological conditions can disrupt the immunoprivileged status and induce
autoimmune orchitis, an etiological factor of male infertility. Mechanisms
underlying autoimmune orchitis induction are largely unknown. The present study
investigated the roles of Toll-like receptor 2 (TLR2) and TLR4 in mediating the
induction of experimental autoimmune orchitis (EAO) in mice after immunization
with male germ cell antigens emulsified with complete Freund adjuvant. Wild-type
mice developed severe EAO after three immunizations, which was characterized by
leukocyte infiltration, autoantibody production, and impaired spermatogenesis.
Tlr2 or Tlr4 deficient mice showed relatively low susceptibility to EAO induction
compared with wild-type mice. Notably, Tlr2 and Tlr4 double knockout mice were
almost completely protected from EAO induction. Moreover, we demonstrated that
TLR2 was crucial in mediating autoantibody production in response to
immunization. The results imply that TLR2 and TLR4 cooperatively mediate EAO
induction.
PMID- 25588511
TI - Stroke incidence and case-fatality among Indigenous and non-Indigenous
populations in the Northern Territory of Australia, 1999-2011.
AB - BACKGROUND: Stroke is a leading cause of death and disability in Australia. The
impact of stroke on the Australia Indigenous people is, however, unclear. AIM:
This study describes hospital-based stroke incidence and case fatality in the
Northern Territory population in Australia. METHODS: Retrospective study of
Northern Territory residents with a first-ever stroke episode and case fatality
among Northern Territory residents in 1999-2011. RESULTS: The rate ratio of age
adjusted stroke incidence between Indigenous and non-Indigenous populations was
2.8 for men and 2.7 for women, similar to those reported elsewhere in Australia.
The rate ratio increased to 3.8 (95% confidence interval: 3.4-4.3) after
adjusting for multiple risk factors. There was no change in annual incidence
between 1999 and 2011 for either non-Indigenous (incidence rate ratio per year
1.01, 95% confidence interval: 1.00-1.03) or Indigenous people (incidence rate
ratio: 1.00, 95% confidence interval: 0.98-1.02), although incidence did increase
for non-Indigenous people in the 15-39 year age group (incidence rate ratio:
1.09, 95% confidence interval: 1.02-1.17) and for Indigenous people in the 40-64
year age group (incidence rate ratio: 1.03, 95% confidence interva1.00-1.06). The
case fatality rate decreased from 22% in 1999 to 12% in 2011. In-hospital deaths
were more common among; older and Indigenous people, for those with other chronic
diseases, and from haemorrhagic stroke compared with ischemic stroke.
CONCLUSIONS: In the Northern Territory, as elsewhere in Australia, Indigenous
Australians are more likely than other Australians to suffer a stroke. Lack of
falling in incidence in the Northern Territory population highlights the
importance for ongoing comprehensive primary and acute care in reducing risk
factors and managing stroke patients.
PMID- 25588512
TI - Innovations in scholarly publishing. Evolving trends in research communication in
a digital age: examples from the BMJ.
AB - As technology and communication evolve rapidly in this digital age, scholarly
publishing is also undergoing a makeover to match the diverse needs of
researchers and clinicians. The BMJ has been at the forefront of innovating the
presentation of research to increase its readabillty and usefulness. This article
presents some of recent formats used for research communication at the BMJ.
PMID- 25588510
TI - Progesterone-based intrauterine device use is associated with a thinner apical
layer of the human ectocervical epithelium and a lower ZO-1 mRNA expression.
AB - Currently, whether hormonal contraceptives affect male to female human
immunodeficiency virus (HIV) transmission is being debated. In this study, we
investigated whether the use of progesterone-based intrauterine devices (pIUDs)
is associated with a thinning effect on the ectocervical squamous epithelium,
down-regulation of epithelial junction proteins, and/or alteration of HIV target
cell distribution in the human ectocervix. Ectocervical tissue biopsies from
healthy premenopausal volunteers using pIUDs were collected and compared to
biopsies obtained from two control groups, namely women using combined oral
contraceptives (COCs) or who do not use hormonal contraceptives. In situ staining
and image analysis were used to measure epithelial thickness and the presence of
HIV receptors in tissue biopsies. Messenger RNA levels of epithelial junction
markers were measured by quantitative PCR. The epithelial thickness displayed by
women in the pIUD group was similar to those in the COC group, but significantly
thinner as compared to women in the no hormonal contraceptive group. The thinner
epithelial layer of the pIUD group was specific to the apical layer of the
ectocervix. Furthermore, the pIUD group expressed significantly lower levels of
the tight junction marker ZO-1 within the epithelium as compared to the COC
group. Similar expression levels of HIV receptors and coreceptors CD4, CCR5, DC
SIGN, and Langerin were observed in the three study groups. Thus, women using
pIUD displayed a thinner apical layer of the ectocervical epithelium and reduced
ZO-1 expression as compared to control groups. These data suggest that pIUD use
may weaken the ectocervical epithelial barrier against invading pathogens,
including HIV.
PMID- 25588513
TI - Case report: Cavitation of mesenteric lymph nodes as the presenting feature of
coeliac disease.
AB - Cystic cavitation of the lymph nodes associated with hyposplenism is a rare and
under-recognised complication of coeliac disease. This report encompasses the
clinical, radiological and pathological features of this condition, while
demonstrating the pivotal role radiological imaging plays in achieving a clinical
diagnosis.
PMID- 25588514
TI - Scoring systems for heparin-induced thrombocytopenia (HIT): whither now?
PMID- 25588515
TI - Mechano-growth factor accelerates the proliferation and osteogenic
differentiation of rabbit mesenchymal stem cells through the PI3K/AKT pathway.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into chondroblasts,
adipocytes, or osteoblasts under appropriate stimulation. Mechano-growth factor
(MGF) reportedly displays a neuroprotective effect in cerebral regions that were
exposed to ischemia and is expressed in stromal cells of the eutopic endometrium
and in glandular cells of the ectopic endometrium. RESULTS: This study sought to
understand the potential involvement of phosphatidylinositol-3-kinase
(PI3K)/protein kinase B (AKT) in MGF-induced growth of rabbit MSCs (rMSCs). We
applied various concentrations of MGF to cultured rMSCs and observed the growth
rate of the cells, the changes in the phosphorylation state of AKT and mammalian
target of rapamycin (mTOR), and the expression levels of alkaline phosphatase and
osteocalcin. We found that the growth and osteogenic differentiation of MGF
induced rMSCs were promoted primarily by phosphorylated AKT, and that this
phosphorylation, as well mTOR phosphorylation, was mediated by the MGF receptor.
CONCLUSION: Our study suggests that MGF promotes the growth and osteogenic
differentiation of rMSCs primarily through the PI3K/AKT pathway.
PMID- 25588516
TI - An evaluation of methods used to teach quality improvement to undergraduate
healthcare students to inform curriculum development within preregistration nurse
education: a protocol for systematic review and narrative synthesis.
AB - BACKGROUND: Despite criticism, quality improvement (QI) continues to drive
political and educational priorities within health care. Until recently, QI
educational interventions have varied, targeting mainly postgraduates, middle
management and the medical profession. However, there is now consensus within the
UK, USA and beyond to integrate QI explicitly into nurse education, and faculties
may require redesign of their QI curriculum to achieve this. Whilst growth in QI
preregistration nurse education is emerging, little empirical evidence exists to
determine such effects. Furthermore, previous healthcare studies evaluating QI
educational interventions lend little in the way of support and have instead been
subject to criticism. They reveal methodological weakness such as no reporting of
theoretical underpinnings, insufficient intervention description, poor evaluation
methods, little clinical or patient impact and lack of sustainability. This study
aims therefore to identify, evaluate and synthesise teaching methods used within
the undergraduate population to aid development of QI curriculum within
preregistration nurse education. METHODS/DESIGN: A systematic review of the
literature will be conducted. Electronic databases, Cumulative Index to Nursing
and Allied Health Literature (CINAHL), Psychological Information (PsychINFO),
Education Resources Information Centre (ERIC), Medical Literature Analysis and
Retrieval System Online (MEDLINE) and Applied Social Sciences Index and Abstracts
(ASSIA), will be searched alongside reference list scanning and a grey literature
search. Peer-reviewed studies from 2000-2014 will be identified using key terms
quality improvement, education, curriculum, training, undergraduate, teaching
methods, students and evaluation. Studies describing a QI themed educational
intervention aimed at undergraduate healthcare students will be included and data
extracted using a modified version of the Reporting of Primary Studies in
Education (REPOSE) Guidelines. Studies will be judged for quality and relevance
using the Evidence for Policy and Practice Information and Co-ordinating Centre's
(EPPI) Weight of Evidence framework and a narrative synthesis of the findings
provided. DISCUSSION: This study aims to identify, evaluate and synthesise the
teaching methods used in quality improvement education for undergraduate
healthcare students where currently this is lacking. This will enable nursing
faculty to adopt the most effective methods when developing QI education within
their curriculum. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42014013847.
PMID- 25588517
TI - Acupuncture in the treatment of infantile colic.
AB - Regarding the recently published review "Looking for new treatments of Infantile
Colic" by Savino et al. we want to add that positive effects of acupuncture have
been demonstrated to release pain and agitation and that acupuncture seems to be
a safe treatment when performed by trained acupuncturists. Inconclusive results
in the few published articles on the subject can be due to different acupuncture
points, different insertion time, different needling methods, differences in the
outcome variables, in how the crying was measured and insufficient sample sizes.
Further research is needed on understanding the utility, safety, and
effectiveness of acupuncture in infants with colic.
PMID- 25588518
TI - Crystal-site engineering control for the reduction of Eu(3+) to Eu(2+) in
CaYAlO4: structure refinement and tunable emission properties.
AB - In this article, Eu-activated CaYAlO4 aluminate phosphors were synthesized by a
solid-state reaction. Under UV light excitation, characteristic red line emission
of Eu(3+) was detected in the range of 570-650 nm. In addition, we introduced
crystal-site engineering approach into the CaYAlO4 host through incorporation of
Si(4+)-Ca(2+) to replace Al(3+)-Y(3+), which would shrink the AlO6 octahedrons,
accompanied by the expansion of CaO9 polyhedron, and then enable the partial
reduction of Eu(3+) to Eu(2+). The crystal structure and underlying mechanism
have been clarified on the basis of the Rietveld refinement analysis. The PL
spectra of Ca0.99+xY1-xAl1-xSixO4:Eu0.01 (x = 0-0.30) exhibit both green emission
of Eu(2+) (4f(6)5d(1)-4f(7), broadband around 503 nm) and red-orange emission of
Eu(3+) ((5)D0-(7)F1,2, 593 and 624 nm) under UV light excitation with a quantum
yield of 38.5%. The CIE coordinates of Ca0.99+xY1-xAl1-xSixO4:Eu0.01 (x = 0-0.30)
phosphors are regularly shifted from (0.482, 0.341) to (0.223, 0.457) with
increasing x, which would expand the application of Eu. Furthermore, this
investigation reveals the correlations of structure and property of luminescent
materials, which would shed light on the development of novel phosphors suitable
for lighting and display applications.
PMID- 25588519
TI - 5HTT is associated with the phenotype psychological flexibility: results from a
randomized clinical trial.
AB - Adaption to changing environments is evolutionarily advantageous. Studies that
link genetic and phenotypic expression of flexible adjustment to one's context
are largely lacking. In this study, we tested the importance of psychological
flexibility, or goal-related context sensitivity, in an interaction between
psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic
polymorphism. Given the established role of the 5HTT-LPR polymorphism in
behavioral flexibility, we tested whether this polymorphism (short group vs. long
group) impacted therapy response as a function of various endophenotypes (i.e.,
psychological flexibility, panic, agoraphobic avoidance, and anxiety
sensitivity). Patients with PD/AG were recruited from a large multicenter
randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to
post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism
status differentiated pre- to post-treatment changes in the endophenotype
psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of
the specific symptom-related endophenotypes consistently for both the intent-to
treat sample (n = 228) and the treatment completers (n = 194). Based on the
consistency of these findings with existing theory on behavioral flexibility, the
specificity of the results across phenotypes, and the consistency of results
across analyses (i.e., completer and intent to treat), we conclude that 5HTT
polymorphism and the endophenotype psychological flexibility are important
variables for the treatment of PD/AG. The endophenotype psychological flexibility
may help bridge genetic and psychological literatures. Despite the limitation of
the post hoc nature of these analyses, further study is clearly warranted.
PMID- 25588520
TI - Circulating mitochondrial DNA content associated with the risk of liver
cirrhosis: a nested case-control study.
AB - BACKGROUND AND AIMS: Accumulating evidence has indicated that variations of
mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular
carcinoma (HCC). However, no study has been conducted to evaluate the association
of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of
HCC. METHODS: We conducted a nested case-control study including 136 cirrhotic
hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV
controls. We determined mtDNA content in serum DNA using quantitative real-time
PCR and analyzed its association with cirrhosis risk. RESULTS: We found that
cirrhotic HBV patients had significantly lower levels of mtDNA content than non
cirrhotic HBV controls (P = 0.0184). Compared to patients with high mtDNA
content, those with low mtDNA content had a 2.25-fold increased risk of cirrhosis
[odds ratio (OR) 2.25, 95 % confidence interval (CI) 1.26-4.02]. This association
exhibited a significant dose relationship as evidenced in both tertile and
quartile analyses (P for trend = 0.0018 and 0.0008, respectively). Stratified
analyses showed that the association was prominent in younger patients (P =
0.0122), males (P = 0.0069), never smokers (P = 0.0063), never drinkers (P =
0.0078), patients with a family history of HBV infection (P = 0.0062), and
patients with low values of aspartate aminotransferase to platelet ratio index
(APRI), a commonly used noninvasive marker for cirrhosis (P = 0.0109). Moreover,
a joint effect was observed between low mtDNA content and high APRI values on
cirrhosis risk (OR 24.07, 95 % CI 6.72-86.24). CONCLUSIONS: Low circulating mtDNA
content may confer an increased cirrhosis risk in HBV patients. Further
prospective studies are warranted to validate these findings and explore the
clinical significance.
PMID- 25588522
TI - Optofluidic ultrahigh-throughput detection of fluorescent drops.
AB - This paper describes an optofluidic droplet interrogation device capable of
counting fluorescent drops at a throughput of 254,000 drops per second. To our
knowledge, this rate is the highest interrogation rate published thus far. Our
device consists of 16 parallel microfluidic channels bonded directly to a filter
coated two-dimensional Complementary Metal-Oxide-Semiconductor (CMOS) sensor
array. Fluorescence signals emitted from the drops are collected by the sensor
that forms the bottom of the channel. The proximity of the drops to the sensor
facilitates efficient collection of fluorescence emission from the drops, and
overcomes the trade-off between light collection efficiency and field of view in
conventional microscopy. The interrogation rate of our device is currently
limited by the acquisition speed of CMOS sensor, and is expected to increase
further as high-speed sensors become increasingly available.
PMID- 25588521
TI - Incontinence and parent-reported oppositional defiant disorder symptoms in young
children--a population-based study.
AB - BACKGROUND: Oppositional defiant disorder (ODD) and incontinence are common
disorders of childhood. We have examined associations between ODD symptoms and
incontinence in a representative sample of young children. METHODS: A
questionnaire with seven questions referring to incontinence, eight DSM-IV items
of ODD, 15 items of the Home Situations Questionnaire and six items regarding
eating, drinking or toileting refusal was administered to the parents of 718
children at school-entry from a defined geographical area at school-entry.
RESULTS: Of the 718 6-year-old children included in the analysis, 8.2% had
nocturnal enuresis (NE), 1.5% had daytime urinary incontinence (DUI) and 1.1% had
faecal incontinence (FI). Significantly more boys than girls had NE (12 vs.
4.3%). Overall, 6.7% of children had ODD symptoms. Rates of ODD symptoms were
significantly higher in incontinent children (19.5%) than in continent children
(5.2%), with the highest rate of ODD symptoms in children with DUI (36.4%).
Children with incontinence (mean 6.1 episodes) or ODD symptoms (mean 8.4
episodes) showed non-compliant behaviours in more problem situations than
continent children (mean 4.5 episodes) or children without ODD symptoms (mean 4.5
episodes). CONCLUSIONS: Incontinence and ODD are common comorbid disorders at
school-entry age. Boys are more affected by both disorders. Children with DUI
have the highest rate of ODD symptoms. As ODD symptoms affect many daily family
situations, ODD needs to be diagnosed and treated in children with incontinence,
as it can negatively affect compliance.
PMID- 25588523
TI - Validity of the >=50% Response Threshold in Treatment With NASHA/Dx Injection
Therapy for Fecal Incontinence.
AB - OBJECTIVES: Many fecal incontinence (FI) studies define primary efficacy outcome
as a decrease from baseline of >=50% in the number of FI episodes; this threshold
has never been validated. We aimed to establish the validity and responsiveness
of >=50% reduction in FI episodes (responder50) as the threshold indicative of
clinically meaningful response. METHODS: Adults with a Cleveland Clinic Florida
fecal incontinence score >=10 were randomized to receive nonanimal stabilized
hyaluronic acid/dextranomer (NASHA/Dx) injection or sham treatment in a 6-month
trial. Validity and responsiveness of the primary end point were evaluated post
hoc. The data were compared using different thresholds for defining a responder
for a number of end points. RESULTS: Data from 206 patients (NASHA/Dx, n=136;
sham, n=70) were evaluated. Incremental patient response threshold increases
showed that although the percentage of patients who achieved response decreased
with increasing threshold, the difference between treatments remained significant
up to an 80% response threshold (NASHA/Dx, 23%; sham, 10%; P=0.02). Response
thresholds between 40% and 80% demonstrated evidence for convergent validity,
with the strongest correlation with the number of FI episodes, the number of FI
episodes when the patient was awake, and the number of FI-free days observed at
>=40% and >=50% thresholds. Further examination of the responder50 threshold
indicated that, regardless of treatment (NASHA/Dx or sham), responders performed
significantly better than nonresponders on nearly all secondary efficacy end
points. CONCLUSION: This study demonstrates the responsiveness, validity, and
clinical applicability of the >=50% response threshold in clinical studies of
patients with FI receiving treatment with NASHA/Dx.
PMID- 25588524
TI - Effect of exclusive enteral nutrition on the microbiota of children with newly
diagnosed Crohn's disease.
AB - OBJECTIVES: Exclusive enteral nutrition (EEN) is commonly used to treat pediatric
Crohn's disease (CD). Meta-analysis of pediatric studies that have compared the
effect of EEN with other treatments have shown that EEN induces remission in up
to 80-85% of patients. We aimed to gain a comprehensive understanding of the
effect of EEN on the microbiota of CD patients. METHODS: We used 16S rRNA gene
and whole-genome high throughout sequencing to determine changes in the fecal
microbiota of five CD children, before, during, and after EEN therapy and
compared this with five healthy controls. RESULTS: The microbial diversity
observed in CD patients tended to be lower than that in controls (CD: 2.25+/
0.24, controls: 2.75+/-0.14, P=0.11). In all CD patients, dysbiosis was observed
prior to therapy. EEN therapy had a positive effect in all patients, with 80%
going into remission. In some patients, the positive effect diminished following
the conclusion of EEN therapy. Significantly, the number of operational taxonomic
units (OTU) decreased dramatically upon starting EEN and this corresponded with
CD remission. Recurrence of CD corresponded with an increase in OTUs. Six
families within the Firmicutes were found to correlate with disease activity
during and following EEN therapy, a finding that was confirmed by whole-genome
high throughput sequencing. CONCLUSIONS: Our results demonstrate that EEN leads
to common and patient-specific alterations in the microbiota of CD patients, a
number of which correlate with disease activity.
PMID- 25588525
TI - Asparagopsis armata and Sphaerococcus coronopifolius as a natural source of
antimicrobial compounds.
AB - Methanol, n-hexane and dichloromethane extracts of twelve marine macro-algae
(Rhodophyta, Chlorophyta and Heterokontophyta divisions) from Peniche coast
(Portugal) were evaluated for their antibacterial and antifungal activity. The
antibacterial activity was evaluated by disc diffusion method against Bacillus
subtilis (gram positive bacteria) and Escherichia coli (gram negative bacteria).
Saccharomyces cerevisiae was used as a model for the antifungal activity by
evaluating the growth inhibitory activity of the extracts. The high antibacterial
activity was obtained by the Asparagopsis armata methanolic extract (10 mm-0.1
mg/disc), followed by the Sphaerococcus coronopifolius n-hexane extract (8 mm-0.1
mg/disc), and the Asparagopsis armata dichloromethane extract (12 mm-0.3 mg/disc)
against Bacillus subtilis. There were no positive results against Escherichia
coli. Sphaerococcus coronopifolius revealed high antifungal potential for n
hexane (IC50 = 40.2 ug/ml), dichloromethane (IC50 = 78.9 ug/ml) and methanolic
(IC50 = 55.18 ug/ml) extracts against Saccharomyces cerevisiae growth. The
antifungal potency of the Sphaerococcus coronopifolius extracts was similar with
the standard amphotericin B. Asparagopsis armata and Sphaerococcus coronopifolius
reveal to be interesting sources of natural compounds with antimicrobial
properties.
PMID- 25588527
TI - Continuous removal of nonylphenol by versatile peroxidase in a two-stage membrane
bioreactor.
AB - The ligninolytic enzymes versatile peroxidase (VP) and manganese peroxidase (MnP)
have been previously described as efficient oxidizers of the endocrine disrupting
chemical (EDC) nonylphenol at high concentrations of the pollutant. Envisaging
the application of an enzymatic technology as a tertiary treatment in wastewater
treatment plants, it is important to design a continuous reactor that performs
the efficient removal of nonylphenol under environmental conditions. In the
present research, a two-stage membrane bioreactor based on the production and use
of Mn(3+)-malonate (chemical oxidant) was applied. The bioreactor consisted of an
enzymatic reactor (R1) for the production of Mn(3+)-malonate by VP, coupled to an
oxidation reactor (R2), where the oxidation of nonylphenol by Mn(3+)-malonate
took place. The production of Mn(3+)-malonate in R1 was maintained constant: 500
700 MUM with minimal deactivation of the enzyme. The oxidation reactor attained
nearly complete removal of nonylphenol, even at a hydraulic retention time (HRT)
shorter than 20 min. The operation with real wastewater containing nonylphenol at
environmental concentrations (454 nM) was also successful, with a nonylphenol
removal of 99.5% at a rate of 0.73 MUM h(-1). Moreover, when the HRT of R2 was
sharply reduced to 6.8 and 3.6 min, the removal of nonylphenol was maintained
beyond 99%, which proves the feasibility of the system to remove the target
compound present in a real effluent, even at very short HRTs.
PMID- 25588528
TI - Effects of different biomass drying and lipid extraction methods on algal lipid
yield, fatty acid profile, and biodiesel quality.
AB - Three lipid extraction methods of hexane Soxhlet (Sox-Hex), Halim (HIP), and
Bligh and Dyer (BD) were applied on freeze-dried (FD) and oven-dried (OD)
Chlorella vulgaris biomass to evaluate their effects on lipid yield, fatty acid
profile, and algal biodiesel quality. Among these three methods, HIP was the
preferred one for C. vulgaris lipid recovery considering both extraction
efficiency and solvent toxicity. It had the highest lipid yields of 20.0 and
22.0% on FD and OD biomass, respectively, with corresponding neutral lipid yields
of 14.8 and 12.7%. The lipid profiling analysis showed that palmitic, oleic,
linoleic, and alpha-linolenic acids were the major fatty acids in the algal
lipids, and there were no significant differences on the amount of these acids
between different drying and extraction methods. Correlative models applied to
the fatty acid profiles concluded that high contents of palmitic and oleic acids
in algal lipids contributed to balancing the ratio of saturated and unsaturated
fatty acids and led to a high-quality algal biodiesel.
PMID- 25588529
TI - Isolation and molecular characterization of thermostable phytase from Bacillus
subtilis (BSPhyARRMK33).
AB - The thermostable phytase gene was isolated from Bacillus subtilis ARRMK33
(BsPhyARRMK33). The gene has an ORF of 1152 bp and that encodes a protein of 383
amino acids. Sequence analysis showed high homology with Bacillus sp. phytase
proteins, but no similarity was found with other phytases. SDS-PAGE analysis
exhibited a predicted molecular mass of 42 kDa. Homology modeling of BsPhyARRMK33
protein based on Bacillus amyloliquefaciens crystal structure disclosed its beta
propeller structure. BsPhyARRMK33 recombinant plasmid in pET-28a(+) was expressed
in Rosetta gami B DE3 cells and the maximum phytase activity 15.3 U mg(-1)
obtained. The enzyme exhibits high thermostability at various temperatures and
broad pH ranges. The recombinant protein retained 74% of its original activity
after incubation at 95 degrees C for 10 min. In the presence of Ca(2+), the
recombinant phytase activity was maximal where as it was inhibited by EDTA. The
optimal pH and temperature for the recombinant phytase activity is achieved at
7.0 and 55 degrees C, respectively. Thermostable nature and wide range of pH are
promising features of recombinant BsPhyARRMK33 protein that may be employed as an
efficient alternative to commercially known phytases and thereby alleviate
environmental eutrophication.
PMID- 25588530
TI - New erythromycin derivatives enhance beta-lactam antibiotics against methicillin
resistant Staphylococcus aureus.
AB - Newly synthesized erythromycin derivatives were screened for synergy with
oxacillin and other beta-lactam antibiotics against methicillin-resistant
Staphylococcus aureus (MRSA). MRSA ATCC43300 and some clinically isolated MRSA
were used. Several erythromycin derivatives were found to possess high synergism
with oxacillin against MRSA. The newly synthesized erythromycin derivatives were
also tested for their inhibitory effects against MRSA, either separately or in
combination with oxacillin, using serial broth dilution, disc diffusion, Etest
strips, growth curves and time-kill curves. A representative derivative, SIPI
8294, could potentiate almost all beta-lactam antibiotics tested against the
model strain MRSA ATCC43300 from 4 to 128 times and had synergism with oxacillin
against 12 of 16 clinical isolates of MRSA under one-fourth of the minimum
inhibitory concentration (MIC) of the compounds. This is the first report on the
synergistic activity of these new erythromycin derivatives. These findings
provide a new choice for the treatment of infection caused by MRSA and lead us to
further study the synergistic mechanism. SIGNIFICANCE AND IMPACT OF THE STUDY:
This study is the first report on the synergy of anti-MRSA between new
erythromycin derivatives and beta-lactam antibiotics in vitro. The results show
that although the erythromycin derivatives have poor anti-MRSA effects alone,
they possess high synergism with oxacillin against MRSA ATCC43300 and clinically
isolated MRSA. These novel compounds can significantly reduce the dosage of beta
lactam antibiotics against MRSA, while this synergistic effect is different from
the combination of beta-lactams and beta-lactamase inhibitors. The research may
provide a new choice for the treatment of infection caused by MRSA and be useful
to the research and development of new combination of medicines.
PMID- 25588531
TI - Relationship between electrocardiographic characteristics of left bundle branch
block and echocardiographic findings.
AB - BACKGROUND: Complete left bundle branch block (CLBBB) is an electrocardiographic
(ECG) dromotropic disorder seen in patients with various structural heart
diseases and sometimes is associated with poor prognosis. Its presence confounds
the application of standard ECG criteria for the diagnosis of left ventricular
hypertrophy (LVH), myocardial infarction (MI) in the chronic phase, and
pathologies that produce changes on ST-T segment. The aim of this investigation
was to establish the relationship between CLBBB and cardiac structural
abnormalities assessed by echocardiography. METHODS: This observational, cross
sectional study included ECG with CLBBB from 101 patients who also had
transthoracic echocardiogram (TTE) performed within 6 months. RESULTS: The
prevalence of structural heart disease on TTE was 90%. No ECG criterion was
useful to diagnose LVH since no relationship was observed between 9 different ECG
signs and increased left ventricular mass index. QRS duration (p = 0.16) and left
axis deviation (p = 0.09) were unrelated to reduced left ventricular ejection
fraction (LVEF). Eight ECG signs proposed for the diagnosis of the chronic phase
of MI demonstrated similar effectiveness, with high specificity and reduced
sensitivity. CONCLUSIONS: CLBBB is associated with elevated prevalence of cardiac
structural disease and hinders the application of common ECG criteria for the
diagnosis of LVH, reduced LVEF, or chronic phase of MI. No ECG finding
distinguished patients with structural heart disease from those with normal
hearts. Electrocardiographic criteria for the diagnosis of MI in the chronic
phase are useful when present, but when absent cannot rule it out.
PMID- 25588532
TI - Predictors of mortality in patients hospitalized for congestive heart failure
with left ventricular ejection fraction >= 40.
AB - BACKGROUND: There are limited data regarding the predictors of mortality in
patients with acute congestive heart failure (CHF) and left ventricular ejection
fraction (LVEF) >= 40%. METHODS: We evaluated clinical characteristics, mortality
and prognostic factors in a sample of consecutive patients hospitalized for CHF
with LVEF >= 40%. Multivariable Cox regression models were developed to predict
mortality using baseline clinical characteristics and echocardiographic
variables. RESULTS: The study population consisted of 191 patients, mean age 70
+/- 14.6 years (60% female) with average follow-up of 4.0 +/- 2.8 years.
Cumulative 5-year mortality was 58% in the entire population and it was 59% in
men and 57% in women (p = 0.411). In multivariable analyses, predictors of
mortality were the following: blood urea nitrogen (BUN) > 25 mg/dL (HR = 1.77; p
= 0.002); absence of hypertension (HR = 1.58; p = 0.032), left ventricular end
diastolic dimension (LVEDD) <= 4.1 cm (HR = 1.73; p = 0.011) and LVEF <= 45% (HR
= 1.69; p = 0.027). CONCLUSIONS: Patients hospitalized for heart failure with
LVEF >= 40% have very high mortality. Absence of hypertension, elevated BUN and
lower LVEF <= 45% indicate increased risk of short- and long-term mortality.
Lower LVEDD is an independent predictor of mortality in heart failure patients
with LVEF >= 40%.
PMID- 25588533
TI - Cardioversion differences among first detected episode, paroxysmal, and
persistent atrial fibrillation patients in the RHYTHM AF registry in Poland.
AB - BACKGROUND: The aim of the publication is to show differences among patients with
the first detected episode of atrial fibrillation (AF), paroxysmal, and
persistent AF patients, for whom cardioversion was planned in the hospital
setting in Poland. METHODS: We present an analysis of the Polish cohort of the
multicenter, multinational RHYTHM-AF registry. Consecutive patients in the
hospital setting, aged >= 18 years, with documented AF at the time of enrollment,
and for whom cardioversion of AF is one of the planned therapeutic options were
recruited. Follow-up data was collected 60 days after enrollment. RESULTS: Five
hundred-and-one patients were recruited, 483 with a defined AF type: 88 - first
detected, 191 paroxysmal, and 204 persistent AF. CHA2DS2VASc scores were not
significantly different between the groups, while treatment with vitamin K
antagonists (VKA) was significantly lower in paroxysmal AF group than in
persistent AF patients. Primary electrical cardioversion was most commonly
performed in patients with persistent AF (90.4%), while primary pharmacological
cardioversion - in the first detected AF (80.0%) and paroxysmal AF patients
(76.7%). During 2 months of follow-up, the rate of rehospitalization and
complications was comparable among the groups. CONCLUSIONS: Despite their
comparable CHA2DS2VASc scores, patients with persistent AF were more frequently
treated with VKA antagonists than other groups. Recurrence of AF within 2 months
after restoring sinus rhythm was present in about 25% of the patients, and the
rate of complications was not different among the three groups.
PMID- 25588534
TI - Perceived control as a predictor of cardiovascular disease mortality in Poland.
The HAPIEE study.
AB - BACKGROUND: Neither the development in methods of treatment of coronary heart
disease nor the changes in exposure to main cardiovascular disease (CVD) risk
factors do not fully explain the trends in CVD mortality in Poland. An influence
of psychosocial factors is considered. The aims of the study were: (1) to assess
the relationship between perceived control and the prevalence of classic CVD risk
factors; (2) to assess the relationship between perceived control and the risk of
death from all causes and from CVD. METHODS: A cohort study with 5-year follow-up
was conducted. Random sample of 10,728 permanent residents of Krakow aged 45-69
was examined. Perceived control was measured using a standard 11-item scale. The
studied group was divided into four subgroups of people with very high, high,
moderate, and low perceived control according to quartile values. Data on deaths
and causes were obtained from the local register, death certificates and
participants' families. An independent effect of perceived control on CVD
mortality was assessed using Cox proportional hazards models. RESULTS: Low
perceived control was strongly associated with a higher CVD mortality,
independently of age, education, marital status, history of CVD, hypertension,
hypercholesterolemia, smoking, body mass index, physical activity or diabetes in
both men and women (HR 2.68, 95% CI 1.36-5.31 and HR 5.18, 95% CI 1.17-22.96,
respectively). After adjustment for age, both in men and women, the highest risk
of death from all causes was observed in persons with low perceived control.
Further adjustment for covariates attenuated the relationship. CONCLUSIONS:
Perceived control is a strong independent predictor of CVD mortality and may be
considered a CVD risk factor in the Polish urban population.
PMID- 25588535
TI - Hybrid model of cardiac rehabilitation in men and women after myocardial
infarction.
AB - BACKGROUND: A relatively new alternative for post-myocardial infarction (MI)
patients' care is the hybrid cardiac rehabilitation (CR) consisting of ambulatory
and home-based parts. The aim of the study was to compare the influence of CR on
physical capacity, safety, adherence and return to work in post-MI male and
female patients with preserved left ventricular systolic function, and to assess
who benefited more from this model of trainings. METHODS: The study comprised 57
men aged 54.5 +/- 7.5 years and 30 women aged 52.2 +/- 6.7 years after MI. All
subjects underwent an 8-week training program consisting of 24 interval
trainings. The first 10 trainings were conducted in an out-patient clinic, then
both groups did their training at home with TeleECG monitoring. At the beginning
and after trainings all patients underwent a symptom-limited exercise stress
test. Assessment included results of exercise tests. Moreover, a comparative
analysis of adherence and returning to work in post MI female and male patients
was performed. RESULTS: We found that trainings led to a significant improvement
in physical capacity in all patients based on exercise test. When the training
effects were compared between men and women, no significant differences were
observed. The percentage of patients returning to work was higher in men than in
women (78.9% vs. 50%, p < 0.01). CONCLUSIONS: 1. Hybrid rehabilitation resulted
in a comparable improvement in physical capacity in post-MI low-risk male and
female patients. 2. Although hybrid rehabilitation facilitated patients'
adherence to the training program, their return to work was significantly greater
only in post-MI men.
PMID- 25588536
TI - Assessment of the relationship between a narrow fragmented QRS complex and
coronary slow flow.
AB - BACKGROUND: The coronary slow flow (CSF) phenomenon is a delayed antegrade
progression of contrast agent to the distal branch of a coronary artery in the
absence of obstructive coronary artery disease (CAD). A narrow fragmented QRS
(fQRS) has been reported as a significant predictor of sudden cardiac death in
patients with idiopathic dilated cardiomyopathy. The present study aimed to
investigate the relationship between a narrow fQRS on the admission
electrocardiogram (ECG) and CSF on coronary angiography. METHODS: This study
included 165 consecutive patients (112 CSF, 53 controls) who underwent first-time
diagnostic conventional coronary angiography for suspected CAD. Coronary flow was
quantified by thrombolysis in myocardial infarction (TIMI) frame count (TFC). The
patients were divided into two groups according to the presence or absence of a
narrow fQRS complex on the admission ECG. RESULTS: Forty four patients were in
the fQRS group (mean age, 52.97 +/- 3.13 years). There was no difference between
the two groups with respect to age, gender, body mass index, family history,
hyperlipidemia, hypertension, or diabetes mellitus. The extent of CSF was
significantly greater in the fQRS group compared to the non-fragmented group (p <
0.001). A significant correlation was also found between mean TFC values and fQRS
(p < 0.001). On multivariate analysis, only CSF (p = 0.03) was a significant
independent predictor for narrow fQRS, after adjustment for other parameters.
CONCLUSIONS: The narrow fQRS is a simple, inexpensive, and readily available
noninvasive ECG parameter that may be a new potential indicator of myocardial
damage in patients with CSF.
PMID- 25588537
TI - High-frequency QRS analysis compared to conventional ST-segment analysis in
patients with chest pain and normal ECG referred for exercise tolerance test.
AB - BACKGROUND: The novel analysis of high-frequency QRS components (HFQRS-analysis)
has been proposed in patients with chest pain (CP) and normal electrocardiography
(ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to
compare the diagnostic value of ex-ECG with ex-HFQRS-analysis. METHODS: Patients
with CP and normal ECG, troponin, and echocardiography were considered. All
patients underwent ex-ECG for conventional ST-segment-analysis and ex-HFQRS
analysis. A decrease >= 50% of the HFQRS signal intensity recorded in at least 2
contiguous leads was considered an index of ischemia, as ST-segment depression >=
2 mm or >= 1 mm and CP on ex-ECG. Exclusion criteria were: QRS duration >= 120 ms
and inability to exercise. End-point: The composite of coronary stenosis >= 70%
or acute coronary syndrome, revascularization, cardiovascular death at 3-month
follow-up. RESULTS: Three-hundred thirty-seven patients were enrolled (age 60 +/-
15 years). The percent-age of age-adjusted maximal predicted heart rate was 89 +/
10 beat per minute and the maximal systolic blood pressure was 169 +/- 23 mm Hg.
Nineteen patients achieved the end-point. In multivariate analysis, both ex-ECG
and ex-HFQRS were predictors of the end-point. The ex-HFQRS-analysis showed
higher sensitivity (63% vs. 26%; p < 0.05), lower specificity (68% vs. 95%; p <
0.001), and comparable negative predictive value (97% vs. 96%; p = 0.502) when
compared to ex-ECG-analysis. Receiver operator characteristics analysis showed
the incremental diagnostic value of HFQRS (area: 0.655, 95% CI 0.60-0.71) over
conventional ex-ECG (0.608, CI 0.55-0.66) and CP score (0.530, CI 0.48-0.59),
however without statistical significance in pairwise comparison by C-statistic.
CONCLUSIONS: In patients with CP submitted to ex-ECG, the novel ex-HFQRS-analysis
shows a valuable incremental diagnostic value over ST-segment-analysis.
PMID- 25588538
TI - [Clinicopathological correlations at the vitreoretinal interface].
AB - BACKGROUND: Clinicopathological studies of the vitreoretinal interface (VRI)
improve our understanding of the pathogenesis of vitreal maculopathy, facilitate
differential diagnoses and help to develop new treatment strategies. OBJECTIVE:
The aim of the study was to provide a comprehensive overview on
clinicopathological correlations of the VRI. METHODS: A semi-structured
literature search was performed in the Medline and Embase databases for relevant
original studies on clinicopathological correlations of vitreal maculopathy, in
addition to the latest books and review articles. RESULTS: Age-related vitreous
changes with persistent vitreomacular adhesions on the retinal surface promote
cellular migration and proliferation onto the vitreal side of the internal
limiting membrane (ILM), thereby cementing the vitreomacular adhesions and
strengthening the traction forces on retinal layers. Cellular or fibrocellular
proliferation at the vitreomacular interface can be seen in all vitreal
maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior
vitreous detachment causes the presence of vitreous cortex collagen fibrils on
the vitreal side of the ILM which is associated with epiretinal membrane
formation. Glial cells, hyalocytes and myofibroblasts represent the major cell
types in the epiretinal cell proliferation. Glial cells and hyalocytes are
capable of transdifferentiation into myofibroblasts which possess strong
contractive properties and are well known for the production of extracellular
matrix components. CONCLUSION: Removing vitreomacular adhesions and vitreous
cortex collagen fibrils from the retinal surface is most important for successful
treatment. In cases with epiretinal cell proliferation, however, removal of the
ILM during macular surgery is mandatory to avoid reproliferation and recurrence.
Improving the detection of epiretinal cell proliferation and cell distribution in
patient eyes by optical coherence tomography or by introduction of new
technologies should be addressed in the future.
PMID- 25588539
TI - Sex worker activism, feminist discourse and HIV in Bangladesh.
AB - This paper explores the relationship between sex worker activism and HIV-related
discourse in Bangladesh, relating recent developments in activism to the
influence of feminist thought. Following their eviction in 1991 from brothels
from red light areas, Bangladeshi sex workers started a social movement, at just
about the same time that programmes started to work with sex workers to reduce
the transmission of HIV. This paper argues that both sex worker activism and HIV
prevention initiatives find impetus in feminist pro-sex-work perspectives, which
place emphasis on individual and collective agency. However, by participating in
these programmes, sex workers failed to contest the imagery of themselves as
'vectors' of HIV. In this way, they were unwittingly complicit in reproducing
their identity as 'polluting others'. Moreover, by focusing on individual
behaviour and the agency of sex workers, HIV programmes ignored the fact that the
'choices' made by sex workers are influenced by a wide range of structural and
discursive factors, including gender norms and notions of bodily purity, which in
turn have implications for the construction of HIV-related risk.
PMID- 25588540
TI - Laser-induced fluorescence of free diamondoid molecules.
AB - We observe the fluorescence of pristine diamondoids in the gas phase, excited
using narrow band ultraviolet laser light. The emission spectra show well-defined
features, which can be attributed to transitions from the excited electronic
state into different vibrational modes of the electronic ground state. We assign
the normal modes responsible for the vibrational bands, and determine the
geometry of the excited states. Calculations indicate that for large diamondoids,
the spectral bands do not result from progressions of single modes, but rather
from combination bands composed of a large number of Deltav = 1 transitions. The
vibrational modes determining the spectral envelope can mainly be assigned to
wagging and twisting modes of the surface atoms. We conclude that our theoretical
approach accurately describes the photophysics in diamondoids and possibly other
hydrocarbons in general.
PMID- 25588541
TI - Central mucoepidermoid carcinoma of the anterior region of the mandible: report
of an unusual case and review of the literature.
AB - INTRODUCTION: Central mucoepidermoid carcinoma is a rare lesion, whose exact
pathogenesis is still not fully understood. Generally, it is more frequently
encountered in the mandible than in the maxilla and in the posterior than in the
anterior aspect of the jaws. Cases of central mucoepidermoid carcinomas are
rarely mentioned in the literature, and therefore, additional information
concerning this type of lesion is needed. CASE REPORT: In the present paper, we
report an extremely unusual case of a central mucoepidermoid carcinoma in the
anterior region of the mandible of a 37-year-old female patient. The diagnosis
and the surgical management of the tumor along with the reconstructive techniques
utilized to restore the mandible and a 6-year follow-up are discussed.
DISCUSSION: Central mucoepidermoid carcinoma is an unusual tumor of the jaws,
especially in the anterior region. It is only locally aggressive and has most
frequently a good prognosis if treated with wide surgical excision.
PMID- 25588543
TI - 'Social, innovative and smart cities are happy and resilient': insights from the
WHO EURO 2014 International Healthy Cities Conference.
AB - This paper provides a brief overview of, and elaborates on, some of the
presentations, discussions and conclusions from Day 4 of the 'WHO EURO 2014
International Healthy Cities Conference: Health and the City - Urban Living in
the 21st Century', held in Athens, Greece on 25 October 2014. The Internet of
Things (IoT) is made of sensors and other components that connect our version of
the world made of atoms, i.e., humans/our bodies, our devices, vehicles, roads,
buildings, plants, animals, etc., with a mirror digital version made of bits.
This enables cities and regions to be self-aware and dynamically reconfigurable
in real- or near-real-time, based on changes that are continuously monitored and
captured by sensors, similar to the way the internal biological systems of a
living being operate and respond to their environment (homeostasis). Data
collected by various IoT sensors and processed via appropriate analytics can also
help predict the immediate future with reasonable accuracy, which enables better
planned responses and mitigation actions. Cities and regions can thus become more
adaptable and resilient in face of adversity. Furthermore, IoT can link atoms
(humans) to other atoms (humans) (again via bits), resulting in the formation of
'smart(er) communities' that are socially connected in new ways and potentially
happier. Cities, but also less urbanised regions and the countryside, could all
benefit from, and harness the power of, IoT to improve the health, well-being and
overall quality of life of the local populations, actively engage citizens in a
smarter governance of their region, empower them to better care for one another,
promote stronger social inclusion, and ensure a greener, sustainable and more
enjoyable environment for all. Technology can also help reverse the 'brain drain'
from the countryside and smaller towns to larger metropolises by making the
former more attractive and connected, with better services akin to those found in
larger cities. The article also discusses some ways of measuring and benchmarking
the performance of smart cities and their impact on well-being. However, it
should be emphasised that technology is not a panacea and that other factors are
equally important in creating happier and healthier cities and regions.
PMID- 25588544
TI - Paradoxical his-atrial shortening: explain the mechanism.
PMID- 25588542
TI - Anaplastic thyroid cancer: outcome and the mutation/expression profiles of
potential targets.
AB - Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the
thyroid. No effective treatment modalities are currently available. Targeted
therapy against protein kinases showed promising results in preclinical studies.
Our goal was to assess the mutational status of potential therapeutic targets, as
well as the biomarker for immunotherapy in the clinical context. Using allele
specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we
assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1
in anaplastic thyroid cancer specimens. Results were compared to clinical
information and patient outcome to assess the utility of these biomarkers. There
were 13 patients in our study with a median overall survival of 19 weeks. Of the
13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found
in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1
expression was seen in 3 (23 %) patients, none of them were surgical candidates
due to unresectability and poor performance status. KRAS codon 12/13 and EGFR
exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase
inhibitors and immunotherapy may be useful adjuvant therapies for ATC.
PMID- 25588545
TI - Menopause--natural selection or modern disease?
PMID- 25588546
TI - Health knowledge, attitude, practice: the missing circle of breast cancer
screening programs in Iran.
PMID- 25588547
TI - Benzene partial hydrogenation: advances and perspectives.
AB - The partial hydrogenation of benzene to cyclohexene is an economically
interesting and technically challenging reaction. Over the last four decades, a
lot of work has been dedicated to the development of an exploitable process and
several approaches have been investigated. However, environmental constraints
often represent a limit to their industrial application, making further research
in this field necessary. The goal of this review is to highlight the main
findings of the different disciplines involved in understanding the governing
principles of this reaction from a sustainable chemistry standpoint. Special
emphasis is given to ruthenium-catalyzed liquid phase batch hydrogenation of
benzene.
PMID- 25588548
TI - Functional implications of the peptidoglycan recognition proteins in the immunity
of the yellow fever mosquito, Aedes aegypti.
AB - Peptidoglycan recognition proteins (PGRPs) play essential roles in the immune
systems of insects and higher animals against certain pathogens, including
bacteria. In insects, most studies on the functions of PGRPs have been performed
in Drosophila, with only limited studies in mosquitoes, which are important
disease vectors. In the present study, we analysed the PGRP sequences of the
yellow fever mosquito, Aedes aegypti, acquired from two genome databases, and
identified a total of seven PGRP genes; namely, PGRP-S1, -SC2, -LA, -LB, -LC, -LD
and -LE. Bacterial injection using the Gram-negative bacteria Escherichia coli
and the Gram-positive bacteria Micrococcus luteus showed that three PGRPs
responded directly to both bacterial stimuli. Subsequently, the transcriptional
expression of six of these PGRPs was knocked down using double-stranded RNA
injection-based RNA interference (RNAi). RNAi of the PGRPs resulted in different
impacts on the immune responses of Ae. aegypti to the two bacteria, as evidenced
by the changes in mosquito survival rates after bacterial challenges as well as
the differential regulation of several antimicrobial peptides and a number of
other genes involved in mosquito immune pathways. Our data suggest that PGRP-LC
is a significant factor in mediating immune responses to both E. coli and M.
luteus, and the other PGRPs play only minor roles against these two bacteria,
with PGRP-SC2 and -LB also serving as potential negative regulators for certain
immune pathway(s) in Ae. aegypti.
PMID- 25588549
TI - Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3)
C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.
AB - An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H
activation and the direct arylation of the C3-position of oxygen heterocycles,
such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient
stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives
(analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives
(analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3
position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the
corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds
with very high regio- and diastereoselectivities. The stereochemistry of the
products obtained in this work were unambiguously assigned on the basis of the X
ray structure analyses of representative compounds 3b, 3e, 4p, and 7.
PMID- 25588550
TI - Nanofabrication on unconventional substrates using transferred hard masks.
AB - A major challenge in nanofabrication is to pattern unconventional substrates that
cannot be processed for a variety of reasons, such as incompatibility with spin
coating, electron beam lithography, optical lithography, or wet chemical steps.
Here, we present a versatile nanofabrication method based on re-usable silicon
membrane hard masks, patterned using standard lithography and mature silicon
processing technology. These masks, transferred precisely onto targeted regions,
can be in the millimetre scale. They allow for fabrication on a wide range of
substrates, including rough, soft, and non-conductive materials, enabling feature
linewidths down to 10 nm. Plasma etching, lift-off, and ion implantation are
realized without the need for scanning electron/ion beam processing, UV exposure,
or wet etching on target substrates.
PMID- 25588551
TI - Expression and clinical significance of c-Met in advanced esophageal squamous
cell carcinoma.
AB - BACKGROUND: c-Met, one of current potential hot targets, has been suggested as a
potential tumor marker in the development of esophageal squamous cell carcinoma
(ESCC). Our aim was to investigate the expression of c-Met in advanced esophageal
squamous cell carcinoma in four phase II trials who had tumor tissues from
archival in our center and analyze the correlations between c-Met expression and
clinical features. METHODS: Ninety patients with advanced ESCC who were admitted
to the phase II clinical trials in the Department of Gastrointestinal Oncology,
Peking University Cancer Hospital and Institute from March 2007 to March 2014
were finally eligible for present study and the corresponding tissues and
clinical data were collected. The expression of c-Met in the tissue samples was
detected by immunohistochemistry (IHC). c-Met overexpression was defined as >=
the median value of H-score. Kaplan-Meier and Cox multivariate regression were
conducted to evaluate the relationship between c-Met expression and ESCC
survival. RESULTS: The overexpression of c-Met is 43.3% in advanced ESCC. There
was no statistical difference between c-Met expression and clinical features
except sex and tumor location. Survival analysis documented that the
overexpression of c-Met predicted a worse prognosis (OS: 253 d vs 422 d, P =
0.011). In the group treated with chemotherapy combined with anti-EGFR drugs,
patients with lowexpression of c-Met had a better OS than those with
overexpression of c-Met (OS: 577 d vs 232 d, P = 0.007). CONCLUSIONS: c-Met may
be an independent prognostic factor in advanced ESCC. The overexpression of c-Met
may predict a worse efficacy of anti-EGFR therapy.
PMID- 25588552
TI - Microbial quality of industrial liquid egg white: assumptions on spoiling issues
in egg-based chilled desserts.
AB - As a 1st step, this study aimed at investigating the microbial quality of liquid
egg white in a French egg processing company. Thirty raw and 33 pasteurized
liquid egg white samples were analyzed. Pasteurization was globally found
efficient on mesophilic contaminants (1.7 +/- 1.6 and 0.8 +/- 0.9 log CFU/mL in
raw and pasteurized samples, respectively), including for the control of
Salmonella. However, Gram-positive enterococci were still detected in the
pasteurized samples. As a 2nd step, a representative bacterial collection was
built for exploring the spoilage issue in egg-based chilled desserts. Custard
cream was chosen as growth medium since this food is widely used for the
production of French chilled desserts. All of the 166 isolates of the bacterial
collection were shown to be able to grow and to induce spoilage of the custard
cream at refrigeration temperature (10 degrees C). Several spoilage types were
highlighted in the custard cream, on the basis of changes regarding pH,
consistency, production of holes or gas. As a 3rd step, bacterial enzymatic
activities were explored on custard cream-based agar media. The bacterial
collection was reduced to 43 isolates, based on further selection regarding the
genera and the spoilage types previously highlighted. Albeit to different
degrees, all these isolates were able to produce proteases. A large part of these
isolates also expressed lipolytic and amylolytic activities. This study
emphasizes the need to control egg white contamination and especially with Gram
positive heat-resistant Enterococi, in order to guarantee the shelf life of egg
based chilled desserts.
PMID- 25588554
TI - Systems approaches to unravel innate immune cell diversity, environmental
plasticity and functional specialization.
AB - Innate immune cells are generated through central and peripheral differentiation
pathways, and receive multiple signals from tissue microenvironment. The complex
interplay between immune cell state and environmental signals is crucial for the
adaptation and efficient response to pathogenic threats. Here, we discuss how
systems biology approaches have brought global view and high resolution to the
characterization of (1) immune cell diversity, (2) phenotypic, transcriptional
and functional changes in response to environmental signals, (3) integration of
multiple stimuli. We will mostly focus on systems level studies in dendritic
cells and macrophages. Generalization of these approaches should elucidate innate
immune cell diversity and plasticity, and may be used in the human to generate
hypothesis on cell filiation and novel strategies for immunotherapy.
PMID- 25588553
TI - Carotid plaque inflammation assessed with (18)F-FDG PET/CT is higher in
symptomatic compared with asymptomatic patients.
AB - BACKGROUND: Carotid artery plaque inflammation is thought to be an important
marker of plaque vulnerability and increased stroke risk. AIM: The main aim of
this study was to assess the level of agreement between 2-deoxy-2-[(18)F] fluoro
D-glucose (18F-FDG) uptake on PET (positron emission tomography) scan in carotid
plaques, with cerebrovascular symptoms, carotid plaque ultrasound echogenicity
and histological assessments of plaque inflammation. METHODS: Thirty-six patients
with >=70% carotid stenosis scheduled for carotid endarterectomy underwent a
Colour Duplex ultrasound, (18)F-FDG PET/CT and blood tests less than 24 h prior
to surgery. Plaques were defined as symptomatic when associated with ipsilateral
cerebral ischemic symptoms within 30 days prior to inclusion. Plaques were
assessed histologically following endarterectomy. The level of agreement between
(18)F-FDG uptake (mean SUVmax and SUVmax ), and target-to-background ratio,
symptoms, plaque echolucency, and histological evidence of inflammation was
assessed. RESULTS: The amount of (18)F-FDG uptake in plaques and the amount of
inflammation on histological assessment were significantly correlated (r = 0.521,
P = 0.003). (18)F-FDG uptake was significantly higher in symptomatic plaques with
median SUVmax 1.75 (1.26-2.04) in symptomatic, and 1.43 (1.15-2.28) in
asymptomatic patients (P = 0.03). (18)F-FDG uptake was also positively correlated
with echolucency on Doppler ultrasound (P = 0.03). CONCLUSION: (18)F-FDG uptake
on PET/CT correlated with histological assessments of inflammation and was higher
in patients with symptomatic compared with asymptomatic carotid artery plaques.
These results support the use of (18)F-FDG PET/CT in the detection inflammation
in carotid atherosclerosis, which may be of help in the detection of vulnerable
plaques.
PMID- 25588555
TI - Improved 1,3-Propanediol Synthesis from Glycerol by the Robust Lactobacillus
reuteri Strain DSM 20016.
AB - Various Lactobacillus reuteri strains were screened for the ability to convert
glycerol to 1,3- propanediol (1,3-PDO) in a glycerol-glucose co-fermentation.
Only L. reuteri DSM 20016, a well-known probiotic, was able to efficiently carry
out this bioconversion. Several process strategies were employed to improve this
process. CO(2+) addition to the fermentation medium, led to a high product titer
(46 g/l) of 1,3-PDO and to improved biomass synthesis. L. reuteri DSM 20016
produced also ca. 3 MUg/g of cell dry weight of vitamin B12, conferring an
economic value to the biomass produced in the process. Incidentally, we found
that L. reuteri displays the highest resistance to CO(2+) ions ever reported for
a microorganism. Two waste materials (crude glycerol from biodiesel industry and
spruce hydrolysate from paper industry) alone or in combination were used as
feedstocks for the production of 1,3-PDO by L. reuteri DSM 20016. Crude glycerol
was efficiently converted into 1,3-PDO although with a lower titer than pure
glycerol (-18%). Compared with the fermentation carried out with pure substrates,
the 1,3- PDO produced was significantly lower (40.7 vs. 24.2 g/l) using
cellulosic hydrolysate and crude glycerol, but strong increases of the maximal
biomass produced (+27%) and of the glucose consumption rate (+46%) were found.
The results of this study lay the foundation for further investigations to
exploit the biotechnological potential of L. reuteri DSM 20016 to produce 1,3-PDO
and vitamin B12 using industry byproducts.
PMID- 25588556
TI - Gene Cloning, High-Level Expression, and Characterization of an Alkaline and
Thermostable Lipase from Trichosporon coremiiforme V3.
AB - The present study describes the gene cloning and high-level expression of an
alkaline and thermostable lipase gene from Trichosporon coremiiforme V3.
Nucleotide analysis revealed that this lipase gene has an open reading frame of
1,692 bp without any introns, encoding a protein of 563 amino acid residues. The
lipase gene without its signal sequence was cloned into plasmid pPICZalphaA and
overexpressed in Pichia pastoris X33. The maximum lipase activity of recombinant
lipase was 5,000 U/ml, which was obtained in fed-batch cultivation after 168 h
induction with methanol in a 50 L bioreactor. The purified lipase showed high
temperature tolerance, and being stable at 60 degrees C and kept 45% enzyme
activity after 1 h incubation at 70 degrees C. The stability, effects of metal
ions and other reagents were also determined. The chain length specificity of the
recombinant lipase showed high activity toward triolein (C18:1) and tripalmitin
(C16:0).
PMID- 25588557
TI - Kinetic and Energetic Parameters of Carob Wastes Fermentation by Saccharomyces
cerevisiae: Crabtree Effect, Ethanol Toxicity, and Invertase Repression.
AB - Carob waste is a useful raw material for the second-generation ethanol because
50% of its dry weight is sucrose, glucose, and fructose. To optimize the process,
we have studied the influence of the initial concentration of sugars on the
fermentation performance of Saccharomyces cerevisiae. With initial sugar
concentrations (S0) of 20 g/l, the yeasts were derepressed and the ethanol
produced during the exponential phase was consumed in a diauxic phase. The rate
of ethanol consumption decreased with increasing S0 and disappeared at 250 g/l
when the Crabtree effect was complete and almost all the sugar consumed was
transformed into ethanol with a yield factor of 0.42 g/g. Sucrose hydrolysis was
delayed at high S0 because of glucose repression of invertase synthesis, which
was triggered at concentrations above 40 g/l. At S0 higher than 250 g/l, even
when glucose had been exhausted, sucrose was hydrolyzed very slowly, probably due
to an inhibition at this low water activity. Although with lower metabolic rates
and longer times of fermentation, 250 g/l is considered the optimal initial
concentration because it avoids the diauxic consumption of ethanol and maintains
enough invertase activity to consume all the sucrose, and also avoids the
inhibitions due to lower water activities at higher S0.
PMID- 25588558
TI - Expression of Auxin Response Genes SlIAA1 and SlIAA9 in Solanum lycopersicum
During Interaction with Acinetobacter guillouiae SW5.
AB - Indole-3-acetic acid (IAA) production is a typical mechanism of plant growth
promotion by some rhizobacteria. However, a functional genomic study is necessary
to unravel the function and mechanism of IAA signaling during rhizobacteria-plant
interactions. In this study, the expression of SlIAA1 and SlIAA9 among the auxin
response genes in tomato was examined during the interaction between IAA
producing Acinetobacter guillouiae SW5 and tomato plants. When 3-day grown tomato
seedlings were treated for 30 min with 10~100 uM of IAA produced by bacteria from
tryptophan, the relative mRNA levels of SlIAA1 and SlIAA9 increased significantly
compared with those of the control, demonstrating that IAA produced by this
bacterium can induce the expressions of both genes. Inoculation of live A.
guillouiae SW5 to tomato seedlings also increased the expressions of SlIAA1 and
SlIAA9, with more mRNA produced at higher bacterial density. In contrast,
treatment of tomato seedlings with dead A. guillouiae SW5 did not significantly
affect the expression of SlIAA1and SlIAA9. When 3-day bacterial culture in tomato
root exudates was administered to tomato seedlings, the relative mRNA level of
SlIAA1 increased. This result indicated that the plant may take up IAA produced
by bacteria in plant root exudates, which may increase the expression of the
auxin response genes, with resulting promotion of plant growth.
PMID- 25588559
TI - Cloning, Expression, and Purification of Recombinant Uricase Enzyme from
Pseudomonas aeruginosa Ps43 Using Escherichia coli.
AB - Uricase is an important microbial enzyme that can be used in the clinical
treatment of gout, hyperuricemia, and tumor lysis syndrome. A total of 127
clinical isolates of Pseudomonas aeruginosa were tested for uricase production. A
Pseudomonas strain named Ps43 showed the highest level of native uricase enzyme
expression. The open reading frame of the uricase enzyme was amplified from Ps43
and cloned into the expression vector pRSET-B. Uricase was expressed using E.
coli BL21 (DE3). The ORF was sequenced and assigned GenBank Accession No.
KJ718888. The nucleotide sequence analysis was identical to the coding sequence
of uricase gene puuD of P. aeruginosa PAO1. We report the successful expression
of P. aeruginosa uricase in Escherichia coli. E. coli showed an induced protein
with a molecular mass of about 58 kDa that was confirmed by sodium dodecyl
sulfate-polyacrylamide gel electrophoresis and Western blotting. We also
established efficient protein purification using the Ni-Sepharose column with
activity of the purified enzyme of 2.16 IU and a 2-fold increase in the specific
activity of the pure enzyme compared with the crude enzyme.
PMID- 25588560
TI - Cloning, Overexpression, and Characterization of a Metagenome-Derived Phytase
with Optimal Activity at Low pH.
AB - A phytase gene was identified in a publicly available metagenome derived from
subsurface groundwater, which was deduced to encode for a protein of the
histidine acid phosphatase (HAP) family. The nucleotide sequence of the phytase
gene was chemically synthesized and cloned, in order to further overexpress the
phytase in Escherichia coli. Purified protein of the recombinant phytase
demonstrated an activity for phytic acid of 298 +/- 17 MUmol P/min/mg, at the pH
optimum of 2.0 with the temperature of 37 degrees C. Interestingly, the pH
optimum of this phytase is much lower in comparison with most HAP phytases known
to date. It suggests that the phytase could possess improved adaptability to the
low pH condition caused by the gastric acid in livestock and poultry stomachs.
PMID- 25588561
TI - Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer.
AB - Cationic liposomes have been actively used as gene delivery vehicles despite
their unsatisfactory efficiencies because of their relatively low toxicity. In
this study, we designed novel heterodimeric peptides as nonviral gene delivery
systems from TAT and NLS peptides using cysteine-to-cysteine disulfide bonds
between the two. Mixing these heterodimeric peptides with DNA before mixing with
lipofectamine resulted in higher transfection efficiencies in MCF-7 breast cancer
cells than mixing unmodified TAT, NLS, and a simple mixture of TAT and NLS with
DNA, but did not show an adverse effect on cell viability. In gel retardation
assays, the DNA binding affinities of heterodimeric peptides were stronger than
NLS but weaker than TAT. However, this enhancement was only observed when
heterodimeric peptides were premixed with DNA before being mixed with
lipofectamine. The described novel transfection-enhancing peptide system produced
by the heterodimerization of TAT and NLS peptides followed by simple mixing with
DNA, increased the gene transfer efficiency of cationic lipids without enhancing
cytotoxicity.
PMID- 25588562
TI - RETRACTION: The response differences of rubisco and cpcE-F genes to H2O2 in four
Spirulina platensis strains.
PMID- 25588563
TI - Active learning strategies to teach undergraduate nursing statistics: connecting
class and clinical to prepare students for evidence-based practice.
PMID- 25588564
TI - PCR-based specific techniques used for detecting the most important pathogens on
strawberry: a systematic review.
AB - BACKGROUND: Strawberry diseases are a major limiting factor that severely impact
plant agronomic performance. Regarding limitations of traditional techniques for
detection of pathogens, researchers have developed specific DNA-based tests as
sensitive and specific techniques. The aim of this review is to provide an
overview of polymerase chain reaction (PCR)-based methods used for detection or
quantification of the most widespread strawberry pathogens, such as Fusarium
oxysporum f.sp. fragariae, Phytophthora fragariae, Colletotrichum acutatum,
Verticillium dahliae, Botrytis cinerea, Macrophomina phaseolina, and Xanthomonas
fragariae. An updated and detailed list of published PCR protocols is presented
and discussed, aimed at facilitating access to information that could be
particularly useful for diagnostic laboratories in order to develop a rapid, cost
effective, and reliable monitoring technique. METHODS: The study design was a
systematic review of PCR-based techniques used for detection and quantification
of strawberry pathogens. Using appropriate subject headings, AGRICOLA, AGRIS,
BASE, Biological Abstracts, CAB Abstracts, Google Scholar, Scopus, Web of
Knowledge, and SpringerLink databases were searched from their inception up to
April 2014. Two assessors independently reviewed the titles, abstracts, and full
articles of all identified citations. Selected articles were included if one of
the mentioned strawberry pathogens was investigated based on PCR methods, and a
summary of pre-analytical requirements for PCR was provided. RESULTS: A total of
259 titles and abstracts were reviewed, of which 22 full texts met all the
inclusion criteria. Our systematic review identified ten different protocols for
X. fragariae, eight for P. fragariae, four for B. cinerea, six for C. acutatum,
three for V. dahlia, and only one for F. oxysporum. The accuracy and sensitivity
of PCR diagnostic methods is the focus of most studies included in this review.
However, a large proportion of errors in laboratories occur in the pre-analytical
phase of the testing process. Due to heterogeneity, results could not be meta
analyzed. CONCLUSIONS: From a systematic review of the currently available
published literature, effective detection assays to detect the major strawberry
pathogens have been developed. These assays can function as a basis for clinical
labs, regulatory personnel, and other diagnosticians to adapt or implement for
detection of these six important strawberry pathogens.
PMID- 25588565
TI - Deterministic entanglement distillation for secure double-server blind quantum
computation.
AB - Blind quantum computation (BQC) provides an efficient method for the client who
does not have enough sophisticated technology and knowledge to perform universal
quantum computation. The single-server BQC protocol requires the client to have
some minimum quantum ability, while the double-server BQC protocol makes the
client's device completely classical, resorting to the pure and clean Bell state
shared by two servers. Here, we provide a deterministic entanglement distillation
protocol in a practical noisy environment for the double-server BQC protocol.
This protocol can get the pure maximally entangled Bell state. The success
probability can reach 100% in principle. The distilled maximally entangled states
can be remaind to perform the BQC protocol subsequently. The parties who perform
the distillation protocol do not need to exchange the classical information and
they learn nothing from the client. It makes this protocol unconditionally secure
and suitable for the future BQC protocol.
PMID- 25588566
TI - Is modern external beam radiotherapy with androgen deprivation therapy still a
viable alternative for prostate cancer in an era of robotic surgery and
brachytherapy: a comparison of Australian series.
AB - INTRODUCTION: We compare the results of modern external-beam radiotherapy (EBRT),
using combined androgen deprivation and dose-escalated intensity-modulated
radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers
(DE-IG-IMRT), with recently published Australian series of brachytherapy and
surgery. METHODS: Five-year actuarial biochemical disease-free survival (bDFS),
metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were
calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation
therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A
search was conducted identifying Australian reports from 2005 onwards of IR and
HR patients treated with surgery or brachytherapy, reporting actuarial outcomes
at 3 years or later. RESULTS: With a median follow-up of 59 months, our 5-year
bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9%
overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR).
Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was
1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3
gastrointestinal toxicity. Eight reports of brachytherapy and surgery were
identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0%
and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR
patients. One LDR series reported 5-year bDFS of 85% for IR patients.
CONCLUSIONS: Modern EBRT is at least as effective as modern Australian surgical
and brachytherapy techniques. All patients considering treatment for localised
prostate cancer should be referred to a radiation oncologist to discuss EBRT as
an equivalent option.
PMID- 25588567
TI - Role of indigenous arsenate and iron(III) respiring microorganisms in controlling
the mobilization of arsenic in a contaminated soil sample.
AB - In this study two different treatment options were investigated for the release
of arsenic from a contaminated soil sample. The first option was based on the
"bioaugmentation" principle and involved addition of a pure Fe(III)-reducing
culture, i.e. Desulfuromonas palmitatis. The second option consisted in the
"biostimulation" of indigenous bacteria and involved simple addition of
nutrients. Due to the strong association of As with soil ferric oxides, the
reductive dissolution of soil oxides by D. palmitatis lead to 45 % arsenic
release in solution (2.15 mM). When only nutrients were supplied to the soil, the
same amounts of Fe and As were dissolved with slower rates and most aqueous As
was found to be in the trivalent state, indicating the presence of arsenate
reducing species. The arsenate reducing microorganisms were enriched with
successive cultures, using Na2HAsO4 as electron acceptor. The phylogenetic
analysis revealed that the enriched microbial consortium contained
Desulfosporosinus species, which are known arsenate reducers.
PMID- 25588568
TI - Preoperative intra-aortic balloon pump to reduce mortality in coronary artery
bypass graft: a meta-analysis of randomized controlled trials.
AB - INTRODUCTION: The intra-aortic balloon pump is routinely used in cardiac surgery;
however, its impact on outcome is still a matter of debate and several randomized
trials have been published recently. We perform an updated meta-analysis of
randomized controlled trials that investigated the use of preoperative intra
aortic balloon pump in adult patients undergoing coronary artery bypass grafting.
METHODS: Potentially eligible trials were identified by searching the Medline,
Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not
restricted by language or publication status and were updated in August 2014.
Randomized controlled trials on preoperative intra-aortic balloon pump in
patients undergoing coronary artery bypass grafting either with or without
cardiopulmonary bypass were identified. The primary end point was mortality at
the longest follow-up available and the secondary end point was 30-day mortality.
RESULTS: The eight included randomized clinical trials enrolled 625 patients (312
to the intra-aortic balloon pump group and 313 to control). The use of intra
aortic balloon pump was associated with a significant reduction in the risk of
mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to
0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight
studies included). The benefit on mortality reduction was confirmed restricting
the analysis to trials with low risk of bias, to those reporting 30-day follow-up
and to patients undergoing coronary artery bypass graft surgery with
cardiopulmonary bypass. CONCLUSIONS: Preoperative intra-aortic balloon pump
reduces perioperative and 30-day mortality in high-risk patients undergoing
elective coronary artery bypass grafting.
PMID- 25588569
TI - Characterization of a novel clade of Xanthomonas isolated from rice leaves in
Mali and proposal of Xanthomonas maliensis sp. nov.
AB - Four bacterial strains, designated M89, M92, M97(T), and M106, were isolated in a
previous study from surface-sterilized leaves of rice (Oryza sativa) or
murainagrass (Ischaemum rugosum) at three sites in Mali, Africa. Here they were
examined by a polyphasic taxonomic approach and analysis of a whole-genome
sequence. Phylogenetic analyses based on 16S rRNA sequence and multilocus
sequence analysis of seven genes showed that these four strains formed a distinct
lineage representing a novel species within the genus Xanthomonas. This was
supported by whole-genome average nucleotide identity values calculated from
comparisons of strain M97(T) with established Xanthomonas species. The strains
can be differentiated from the known Xanthomonas species on the basis of their
fatty acid and carbohydrate utilization profiles. Population growth studies on
rice confirmed that these bacteria multiply in rice leaves without causing
symptoms. Identification of this novel species can be accomplished by using
diagnostic primer sets or by gyrB gene sequence analysis. We propose to classify
these rice- and grass-associated bacteria as Xanthomonas maliensis sp. nov. with
strain M97(T) = CFBP7942(T) = LMG27592(T) as the type strain.
PMID- 25588571
TI - Burden of blood transmitted infections in substance users admitted for inpatient
treatment in Singapore and the associated factors.
AB - INTRODUCTION: There is paucity of local data on the prevalence of blood
transmitted infections (BTIs), such as hepatitis B, hepatitis C and human
immunodeficiency virus (HIV) infections, among illicit drug users. This study
aimed to examine the prevalence of BTIs among substance dependent inpatients and
identify the factors associated with BTIs. METHODS: We conducted a retrospective
analysis of clinical notes of 170 inpatients with a diagnosis of substance
dependence who were admitted at the National Addictions Management Service,
Singapore, between 1 June 2009 and 31 May 2010. RESULTS: Majority of the 170
inpatients were male (88.2%) and Chinese (58.2%). The mean age of the patients
was 43.1 years, and the main drug of abuse was opioids (86.5%). BTIs were found
in 70 (41.2%) inpatients; the prevalence of hepatitis B, hepatitis C and HIV
infections was 3.7%, 39.6% and 0%, respectively. Lifetime intravenous drug use,
but not needle-sharing, was more common among inpatients who were positive for
BTIs (p < 0.01). Logistic regression analysis showed that lifetime intravenous
drug use (OR 4.3, 95% CI 1.7- 10.8, p < 0.01) was the only significant predictor
of BTIs. CONCLUSION: A large proportion (41.2%) of the substance users seeking
help was positive for at least one BTI. Lifetime intravenous drug users were
found to be more than four times more likely to have a BTI. Early detection and
prevention is essential to improve prognosis.
PMID- 25588572
TI - Development of a peptidomimetic antagonist of neuropeptide FF receptors for the
prevention of opioid-induced hyperalgesia.
AB - Through the development of a new class of unnatural ornithine derivatives as
bioisosteres of arginine, we have designed an orally active peptidomimetic
antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration
of this compound to rats blocked opioid-induced hyperalgesia, without any
apparent side-effects. Interestingly, we also observed that this compound
potentiated opioid-induced analgesia. This unnatural ornithine derivative
provides a novel therapeutic approach for both improving analgesia and reducing
hyperalgesia induced by opioids in patients being treated for chronic pain.
PMID- 25588573
TI - Evaluation of right ventricular function using single-beat three-dimensional
echocardiography in neonate.
AB - Aim of our study was to evaluate right ventricular (RV) systolic function in
neonate using newly developed single-beat three-dimensional echocardiography
(sb3DE). We enrolled 15 healthy or premature neonates (0-53 days after birth). We
scanned one beat full volume using Siemens ACUSON SC2000 (Siemens AG)
echocardiography with 4Z1c full-volume transducer without ECG gating. RV end
diastolic volume (RVEDV) and RV end-systolic volume (RVESV) were computed with
special software dedicated to analysis for RV volume. RV ejection fraction (RVEF)
and RV stroke volume (3D-RVSV) were calculated. And RV stroke volume was also
determined from the recordings of ejection blood flow velocity and diameter at
the level of the pulmonary orifice in RV outflow tract (Doppler-RVSV). Tricuspid
annular plane systolic excursion (TAPSE) was also measured by 2D
echocardiography. RVEDV ranged from 5.1 to 10.7 ml (average 7.5 ml), RVESV ranged
from 2.3 to 5.8 ml (average 3.9 ml). There was a good correlation between 3D-RVSV
and Doppler-RVSV (r = 0.77). Bland-Altman plot revealed that 3D-RVSV became
underestimation of an average of 1.78 ml compared to Doppler-RVSV. And TAPSE
positively correlated with 3D-RVEF (r = 0.58, P = 0.038). Newly developed sb3DE
enables us to perform three-dimensional acquisition of RV volume without ECG
gating even in neonate. However, 3D-RVSV currently tends to be underestimated in
neonatal measurement.
PMID- 25588574
TI - Brazilian Group of Flow Cytometry (GBCFLUX) panels for acute leukemias--Response
to Matos.
PMID- 25588575
TI - Aiding a reassertion of self: a qualitative study of the views and experiences of
women with ovarian cancer receiving long-term nurse-led telephone follow-up.
AB - PURPOSE: This study explored the views and experiences of women following
treatment for ovarian cancer who had received long-term (at least 3 years) nurse
led telephone follow-up. Exploring the long-term experiences of follow-up for
women with ovarian cancer provides important information regarding the coping
processes of cancer survivors that can inform the development of innovative and
patient-centred approaches of cancer follow-up. METHODS: This is a qualitative
study approach using interpretative phenomenological analysis (IPA). Eleven women
were identified by a clinical nurse specialist as having received nurse-led
telephone follow-up for a period of at least 3 years. These women were
interviewed in person or over the telephone using a semi-structured interview
schedule; interviews were audio-recorded and transcriptions were analysed using
IPA. RESULTS: Nurse-led telephone follow-up was felt to support a reassertion of
self and a rejection of patient identity. Three core themes emerged regarding the
positive impact of nurse-led telephone follow-up: 'Somebody was looking out for
me' highlights the perception of increased psychosocial support; 'It's just
reassurance' includes both the deep trust in the expertise of the nurse and the
reassurance of the continued blood tests; and 'Time was never an issue' presents
the perception of relaxed follow-up appointments with time to talk and the
perceived practical benefits of this approach. CONCLUSIONS: Nurse-led telephone
follow-up was broadly recommended for women following treatment for ovarian
cancer, particularly for those later on in the survivorship trajectory when focus
may move from biomedical aspects of cure to holistic approaches to well-being.
Remote interventions which provide a perception of a consistent and constant
source of medical and psychosocial support may support adaption to cancer
survivorship by enabling a reassertion of self and a rejection of patient
identity.
PMID- 25588577
TI - Erratum to: heterosexual couples and prostate cancer support groups: a gender
relations analysis.
PMID- 25588576
TI - Communication dysfunction, body image, and symptom severity in postoperative head
and neck cancer patients: factors associated with the amount of speaking after
treatment.
AB - PURPOSE: The purpose of this study was to determine the relationships of
communication dysfunction, body image, and amount of speaking in patients who
were treated for head and neck cancers (HNCs). METHODS: This was a cross
sectional study of postoperative HNC patients at the otolaryngology outpatient
departments of two leading medical centers in northern Taiwan. Data were
collected using questionnaires to assess perceived communication dysfunction,
body image, symptom severity, and amount of speaking after treatment. RESULTS: A
total of 130 HNC patients were included in the analysis, and 70.8 % of patients
reported speaking less after surgery as compared to the period before having HNC
surgery. Overall, patients perceived a moderate level of communication
dysfunction. Those with higher distress over their body image, higher symptom
severity, and with hypopharyngeal and laryngeal cancer reported speaking less.
Patients with advanced stage cancer and a tumor in a facial area and those that
received reconstructive surgery were more likely to have a negative body image.
CONCLUSIONS: Dissatisfaction with body image, greater symptom severity, and
hypopharyngeal and laryngeal cancer are predictive of the amount HNC patients
speak, as compared with the amount they spoke before having HNC. Clinicians
should be aware of and systematically assess communication problems of HNC
patients to promote their social function. Further research on interventions that
facilitate the development of a positive body image and communication is strongly
suggested.
PMID- 25588578
TI - Coping with an altered mouth and perceived supportive care needs following head
and neck cancer treatment.
AB - PURPOSE: Oral health is essential to general health and well-being and is
severely impacted by head and neck cancer (HNC) and its treatment. This study
aimed to describe how people who have been treated for HNC cope with altered oral
health and function and to identify their supportive care needs. METHODS: A
qualitative, descriptive approach was used. Data was collected from individual
interviews with six participants 6 months after treatment. Data analysis was
performed by qualitative content analysis involving inductive and directed
approaches. Directed content analysis was guided by the Stress, Appraisal and
Coping Model. RESULTS: Three themes describing changed oral health were
identified from the data: dimensions of eating, maintaining oral health after
treatment and adapting to the chronic side effects of treatment. A strong use of
problem-focussed coping was described, in addition to the importance of peer
support in adapting to the psychosocial outcomes of treatment. Support needs
identified related to increased access to specialist dental oncology services
post treatment, information needs and a need for more psychological support.
CONCLUSION: The study findings describe the experience of a sample of people who
have received treatment for HNC. Due to a demographically homogenous sample and
the strong use of positive coping strategies, the results presented may not
describe the experience of the wider HNC population; however, these results
provide insight into factors that may influence positive coping.
PMID- 25588579
TI - The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics
technique.
AB - T-2 toxin is a common contaminant in grains and animal feedstuff, which becomes
an increasing threat to human and animal health due to its high toxicity.
Investigating the systemic effects of T-2 toxin is important to evaluate the
toxicity and facilitate the assessment of food safety. In our investigation, rats
were treated with a single dose of T-2 toxin at dosage levels of 0, 0.5, 2.0 and
4.0 mg kg(-1) body weight via gavage. The metabolic profiles of body fluids and
multiple organs were obtained by NMR spectroscopy and analyzed by multivariate
data analysis methods. The results showed that low and moderate doses of T-2
toxin only influenced the urinary metabonomes, while a high dose of T-2 toxin
induced metabolic alterations in urine and multiple organs. These changes
included alterations in the levels of membrane metabolites, TCA cycle
intermediates, a range of amino acids, nucleosides and nucleotides. T-2 toxin
exposure impaired spleen function, causing immunotoxicity, and inhibited protein
and DNA biosynthesis. In addition, T-2 toxin also caused oxidative stress and
disturbance in energy metabolism and gut microbiome. Our work provided a
comprehensive insight into T-2 toxicity and revealed the great potential of
metabonomics in assessing the impact of a toxic compound.
PMID- 25588580
TI - Reversing synapse loss in Alzheimer's disease: Rho-guanosine triphosphatases and
insights from other brain disorders.
AB - Alzheimer's disease (AD) is a monumental public health crisis with no effective
cure or treatment. To date, therapeutic strategies have focused almost
exclusively on upstream signaling events in the disease, namely on beta-amyloid
and amyloid precursor protein processing, and have, unfortunately, yielded few,
if any, promising results. An alternative approach may be to target signaling
events downstream of beta-amyloid and even tau. However, with so many pathways
already linked to the disease, understanding which ones are "drivers" versus
"passengers" in the pathogenesis of the disease remains a tremendous challenge.
Given the critical roles of Rho-guanosine triphosphatases (GTPases) in regulating
the actin cytoskeleton and spine dynamics, and the strong association between
spine abnormalities and cognition, it is not surprising that mutations in a
number of genes involved in Rho-GTPase signaling have been implicated in several
brain disorders, including schizophrenia and autism. And now, there is mounting
literature implicating Rho-GTPase signaling in AD pathogenesis as well. Here, I
review this evidence, with a particular emphasis on the regulators of Rho-GTPase
signaling, namely guanine nucleotide exchange factors and GTPase-activating
proteins. Several of these have been linked to various aspects of AD, and each
offers a novel potential therapeutic target for AD.
PMID- 25588581
TI - Diffusion Efficiency and Bioavailability of Resveratrol Administered to Rat Brain
by Different Routes: Therapeutic Implications.
AB - Resveratrol possesses anti-tumor activities against central nervous system (CNS)
tumors in vitro but has not yet been used clinically due to its low
bioavailability, particularly in the CNS. This study thus aimed to elucidate
brain bioavailability of trans-resveratrol by monitoring brain concentrations and
dwell times following administration of resveratrol through intragastric,
intraperitoneal, external carotid artery/ECA and intrathecal routes. In parallel,
we evaluated the biological responses of rat RG2 glioblastoma cells as well as
RG2-formed rat intracranial glioblastomas treated with resveratrol via
intrathecal administration. The results revealed that resveratrol was detected in
rat brains except when administered systemically. Intrathecal administration of
reseveratrol led to abundant apoptotic foci and increased staining of the
autophagy proteins, LC-3 and Beclin-1 and shrinkage of the intracranial tumors.
In conclusion, the BBB penetrability of resveratrol is remarkably increased by
intracthecal administration. Regular short-term resveratrol treatments suppress
growth and enhance autophagic and apoptotic activities of rat RG2 glioblastoma
cells in vitro and in vivo. Therefore, intrathecal administration of resveratrol
could be an optimal intervention approach in the adjuvant management of brain
malignancies.
PMID- 25588582
TI - Heterochromatin Protein 1 Alpha (HP1alpha: CBX5) is a Key Regulator in
Differentiation of Endothelial Progenitor Cells to Endothelial Cells.
AB - As the ability to control the differentiation of endothelial stem/progenitor
cells (EPCs) into vascular endothelial cell lineages could be useful for
promoting neovascularization, it is important to obtain a deeper understanding of
the epigenetic mechanisms that regulate EPC differentiation and
neovascularization. Heterochromatin protein 1alpha (HP1alpha) is known to be
involved in the epigenetic regulation of gene silencing. However, recent reports
demonstrate that HP1alpha can also activate gene expression during cell
differentiation. In this study, microarray analysis revealed that HP1alpha
expression was induced during EPC differentiation and is associated with the
expression of outgrowing endothelial cell (OEC)-specific protein markers. To
explore the role of HP1alpha in the differentiation of EPCs to OECs, its
expression was knocked-down or over-expressed in differentiating EPCs.
Overexpression of HP1alpha promoted the differentiation and angiogenic activity
of EPCs in vitro and in vivo, whereas knockdown of HP1alpha led to a defect in
OEC migration, tube formation, and angiogenic sprouting activity. Gene expression
profiling showed increased expression of angiogenic genes, including NOTCH1,
cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell
marker genes, including CD133, CXCR4, and C-KIT, in HP1alpha-overexpressing EPCs.
Also, increased HP1alpha at an early stage of EPC differentiation may regulate
angiogenic gene transcription by interacting with chromatin that modifies
epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring
finger 2, and DNA methyltransferases. Our findings demonstrate, for the first
time, that HP1alpha plays an important role in the differentiation and angiogenic
function of EPCs by regulating endothelial gene expression. Stem Cells
2015;33:1512-1522.
PMID- 25588583
TI - From exaggeration to silence in health related science news and academic press
releases: mindful bias?
PMID- 25588585
TI - Guidelines for skeletal survey in young children with fractures.
PMID- 25588584
TI - Dignified Palliative Long-Term Care: An Interpretive Systemic Framework of End-of
Life Integrated Care Pathway for Terminally Ill Chinese Older Adults.
AB - PURPOSE: To critically examine the system dynamics necessary for successfully
implementing a novel end-of-life integrated care pathway (EoL-ICP) program in
promoting dignity and quality of life among terminally-ill Chinese nursing home
residents. METHODS: Thirty stakeholders were recruited to participate in 4
interpretive-systemic focus groups. RESULTS: Framework analysis revealed 10
themes, organized into 3 categories, namely, (1) Regulatory Empowerment
(interdisciplinary teamwork, resource allocation, culture building, collaborative
policy making), (2) Family-Centered Care (continuity of care, family care
conference, partnership in care), and (3) Collective Compassion (devotion in
care, empathic understanding, compassionate actions). CONCLUSIONS: These findings
highlight the importance of organizational structure, social discourse, and
shared meaning in the provision of EoL-ICP in Chinese societies, underscoring the
significant triangulation between political, cultural, and spiritual contexts
embodied in the experience of dignity.
PMID- 25588586
TI - Accuracy of ultrasound-guided intra-articular injections in guinea pig knees.
AB - OBJECTIVE: Dunkin Hartley guinea pigs, a commonly used animal model of
osteoarthritis, were used to determine if high frequency ultrasound can ensure
intra-articular injections are accurately positioned in the knee joint. METHODS:
A high-resolution small animal ultrasound system with a 40 MHz transducer was
used for image-guided injections. A total of 36 guinea pigs were anaesthetised
with isoflurane and placed on a heated stage. Sterile needles were inserted
directly into the knee joint medially, while the transducer was placed on the
lateral surface, allowing the femur, tibia and fat pad to be visualised in the
images. B-mode cine loops were acquired during 100 ul. We assessed our ability to
visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical
changes due to the injection. RESULTS: From the ultrasound images, we were able
to visualise clearly the movement of anatomical landmarks in 75% of the
injections. The majority of these showed separation of the fat pad (67.1%),
suggesting the injections were correctly delivered in the joint space. We also
observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a
smaller subset of injections. CONCLUSION: The results demonstrate that this image
guided technique can be used to visualise the location of an intra-articular
injection in the joints of guinea pigs. Future studies using an ultrasound-guided
approach could help improve the injection accuracy in a variety of anatomical
locations and animal models, in the hope of developing anti-arthritic therapies.
Cite this article: Bone Joint Res 2015;4:1-5.
PMID- 25588587
TI - Intravenous iron isomaltoside 1000 administered by high single-dose infusions or
standard medical care for the treatment of fatigue in women after postpartum
haemorrhage: study protocol for a randomised controlled trial.
AB - BACKGROUND: Postpartum haemorrhage can lead to iron deficiency with and without
anaemia, the clinical consequences of which include physical fatigue. Although
oral iron is the standard treatment, it is often associated with gastrointestinal
side effects and poor compliance. To date, no published randomised controlled
studies have compared the clinical efficacy and safety of standard medical care
with intravenous administration of iron supplementation after postpartum
haemorrhage.The primary objective of this study is to compare the efficacy of an
intravenous high single-dose of iron isomaltoside 1000 with standard medical care
on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a
single centre, open-labelled, randomised trial, women with postpartum haemorrhage
exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron
isomaltoside 1000 or standard medical care. Healthy parturients with a singleton
pregnancy will be included within 48 hours after delivery.Participants will
complete structured questionnaires that focus on several dimensions of fatigue
and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal
Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up
visits after three days, one week, three weeks, eight weeks, and 12 weeks
postpartum. The primary endpoint is the aggregated change in physical fatigue
score within 12 weeks postpartum, as measured by a subscale of the
Multidimensional Fatigue Inventory. The primary objective will be considered to
have been met if an intravenous high single dose of iron isomaltoside 1000 is
shown to be superior to standard medical care in women after postpartum
haemorrhage regarding physical fatigue.For claiming superiority, we set the
minimal clinically relevant difference between the mean scores at 1.8, and the
assumed standard deviation at 4.2. Hence, 87 participants per treatment group are
needed in order to demonstrate superiority; to provide an extra margin for
missing data and dropouts, 200 women will be included. DISCUSSION: The study will
provide evidence on relevant clinical outcomes beyond biochemical parameters for
intravenous iron isomaltoside 1000 compared to standard medical care in women
after postpartum haemorrhage. TRIAL REGISTRATION: This trial is registered with
Clinicaltrials.gov (identifier: NCT01895218) on 26 June 2013.
PMID- 25588588
TI - An in vitro bone tissue regeneration strategy combining chondrogenic and vascular
priming enhances the mineralization potential of mesenchymal stem cells in vitro
while also allowing for vessel formation.
AB - Chondrogenic priming (CP) of mesenchymal stem cells (MSCs) and coculture of MSCs
with human umbilical vein endothelial stem cells (HUVECs) both have been shown to
significantly increase the potential for MSCs to undergo osteogenic
differentiation and mineralization in vitro and in vivo. Such strategies mimic
cartilage template formation or vascularization that occur during endochondral
ossification during early fetal development. However, although both
chondrogenesis and vascularization are crucial precursors for bone formation by
endochondral ossification, no in vitro bone tissue regeneration strategy has
sought to incorporate both events simultaneously. The objective of this study is
to develop an in vitro bone regeneration strategy that mimics critical aspects of
the endochondral ossification process, specifically (1) the formation of a
cartilage template and (2) subsequent vascularization of this template. We
initially prime the MSCs with chondrogenic growth factors, to ensure the
production of a cartilage template, and subsequently implement a coculture
strategy involving MSC and HUVECs. Three experimental groups were compared; (1)
CP for 21 days with no addition of cells; (2) CP for 21 days followed by
coculture of HUVECs (250,000 cells); (3) CP for 21 days followed by coculture of
HUVECs and MSCs (250,000 cells) at a ratio of 1:1. Each group was cultured for a
further 21 days in osteogenic media after the initial CP period. Biochemical
(DNA, Alkaline Phosphatase Activity, Calcium, and Vessel Endothelial Growth
Factor) and histological analyses (Alcian blue, alizarin red, CD31(+), and
collagen type X) were performed 1, 2, and 3 weeks after the media switch. The
results of this study show that CP provides a cartilage-like template that
provides a suitable platform for HUVEC and MSC cells to attach, proliferate, and
infiltrate for up to 3 weeks. More importantly we show that the use of the
coculture methodology, rudimentary vessels are formed within this cartilage
template and enhanced the mineralization potential of MSCs. Taken together these
results indicate for the first time that the application of both chondrogenic and
vascular priming of MSCs enhances the mineralization potential of MSCs in vitro
while also allowing the formation of immature vessels.
PMID- 25588589
TI - Pediatric cataract surgery in buphthalmos.
AB - PURPOSE: The pediatric eye offers many inherent surgical difficulties and when
associated with a large buphthalmic eyeball, acts as a challenging ground for
cataract surgeons. The purpose of our study is to describe the surgical outcome
of cataract surgery in 6 children with buphthalmos. METHODS: Eight eyes of 6
children with congenital glaucoma (buphthalmos) underwent phacoaspiration with or
without intraocular lens (IOL) implantation. Demographic data, history of
glaucoma surgery, intraocular pressure, biometry, surgical steps, and
intraoperative and surgical outcome were noted for all patients from medical
records. Postoperative outcome in terms of IOL stability, centration, visual
acuity, and intraocular pressure were evaluated. RESULTS: Pediatric cataract
surgery was performed in 8 eyes with buphthalmos. Implantation of IOL was
possible in 7/8 eyes. Primary posterior capsulorhexis (PPC) was done in 2/8 eyes.
The IOL was implanted in the bag in 3 eyes and captured in 4 eyes. Decentration
of IOL occurred in 100% of eyes where PPC was performed. Membranectomy for visual
axis obscuration was done in 3 eyes. CONCLUSIONS: Standard IOLs remain stable and
centered with endocapsular implantation or rhexis fixation of IOL after pediatric
cataract surgery in buphthalmos. However, PPC should not be attempted in the same
sitting, as it leads to decentration.
PMID- 25588591
TI - Consecutive laser in situ keratomileusis and accelerated corneal crosslinking in
highly myopic patients: preliminary results.
AB - PURPOSE: To report the preliminary results of an evaluation of the safety and
predictability of Lasik Xtra, a technique combining laser in situ keratomileusis
(LASIK) and accelerated corneal crosslinking, in highly myopic patients. METHODS:
In this consecutive comparative case series, 70 consecutive eyes undergoing LASIK
for correction of high myopia (-8.00 D to -19.00 D manifest refractive spherical
equivalent) were prospectively recruited and treated with Lasik Xtra and compared
with a retrospective consecutive control group of 64 eyes who had undergone LASIK
alone for correction of high myopia. The follow-up was 3 months. Outcome measures
included uncorrected distance visual acuity (UDVA), corrected distance visual
acuity (CDVA), and refraction. RESULTS: A total of 61% of LASIK only eyes
achieved UDVA of 20/25 or better, compared to 98% of Lasik Xtra eyes (p<0.001) at
3 months. A greater percentage of eyes were within +/-0.50 of the intended
correction in the Lasik Xtra group (88%) than in the LASIK only group (65%) at 3
months (p = 0.005). Linear regression of the scatterplot of attempted versus
achieved correction reveals a coefficient of determination of 0.83 in the LASIK
only group vs 0.99 in the Lasik Xtra group. A trend (p = 0.051) towards greater
refractive drift in the LASIK group (-0.13 D) vs the Lasik Xtra group (-0.04 D)
was observed. No adverse events were observed in either group. CONCLUSIONS: Lasik
Xtra did not reduce the refractive accuracy of the LASIK procedure. The addition
of crosslinking may induce early stabilization of the cornea after LASIK,
improving the predictability of refractive outcomes in highly myopic subjects.
PMID- 25588590
TI - Effect of continuous ultrasonic phacoemulsification with anterior chamber
maintainer on corneal endothelial damage in hard nuclear cataract.
AB - PURPOSE: To study the effects of continuous ultrasonic phacoemulsification
performed with and without an anterior chamber maintainer (ACM) on corneal
endothelial damage in patients with hard nuclear cataract. METHODS: Sixty eyes in
60 patients with hard nuclear cataract (grade IV), one lesion per eye, were
randomly allocated into 2 groups: continuous ultrasonic phacoemulsification with
(group A) or without (group B) ACM. The intraoperative accumulated energy complex
parameter (AECP), frequency of shallow anterior chamber, and postoperative
corneal incision edema, corneal endothelial cell counts, and visual recovery were
compared between the groups. RESULTS: The intraoperative AECP, postoperative
corneal incision edema, and postoperative visual recovery showed no significant
differences between the groups (p>0.05). At 1 month postoperatively, the corneal
endothelial cell loss rate and hexagonal cell percentage (postoperative compared
to preoperative) in groups A and B were 0.117 +/- 0.12 and 9.97 +/- 9.52% and
0.15 +/- 0.73 and 8.5 +/- 4.60%, respectively, with no significant difference
noted (p>0.05). The endothelial cell mutation rate was significantly lower in
group A than in group B at 6.41 +/- 6.78% and 28.27 +/- 27.95%, respectively
(p<0.05). The frequency of intraoperative shallow anterior chamber was
significantly lower in group A than in group B (2 vs 17 times, p<0.05).
CONCLUSIONS: Continuous ultrasonic phacoemulsification with ACM is a safe,
effective, simple, and easy method to treat hard nuclear cataract and causes
minimal damage to corneal endothelial cells. It is an ideal surgical option and
is worth popularizing.
PMID- 25588592
TI - Circulating dipeptidyl peptidase-4 activity is associated with diabetic
retinopathy in type 1 diabetic patients.
AB - PURPOSE: Diabetic retinopathy (DR) is the most frequent complication among
patients with type 1 diabetes mellitus (T1DM). Dipeptidyl peptidase-4 (DPP4) is a
protease with elevated activity in patients with T1DM. Several studies indicate
that DPP4 inhibitors might have beneficial effect on nonproliferative retinopathy
(NPR) development as well as on its progression to proliferative retinopathy
(PR). We aimed to explore the relationship between serum DPP4 activity and DR in
patients with T1DM. METHODS: This cross-sectional study recruited 44 patients
with T1DM. The DPP4 activity was measured by colorimetric assay in a microplate
reader. Photodocumented retinopathy status was made according to the EURODIAB
protocol. RESULTS: A total of 28 (63.6%) patients were men, mean age 45.36 years,
diabetes duration 23.71 years, glycated hemoglobin A1c (HbA1c) 7.4%. Patients
were stratified into 2 groups according to retinopathy prevalence. Group 1
comprised 14 (31.85%) patients with DR absence while the second group consisted
of 30 (68.15%) patients with both PR and NPR. Group 1 had lower fasting serum
DPP4 activity (25.85 vs 33.84 U/L, p<0.001) when compared to the second group. In
the binary logistic regression model adjusted for age, sex, diabetes duration,
and HbA1c level, DPP4 activity was associated with DR prevalence (odds ratio
1.887 [1.073-3.321]). CONCLUSIONS: Serum DPP4 activity may be independently
associated with both DR types in patients with T1DM. Further study is warranted
to elucidate whether there is an association between DPP4 activity and DR
severity and/or progression.
PMID- 25588593
TI - Macular buckling in optic disc pit maculopathy in association with the origin of
macular elevation: 13-year mean postoperative results.
AB - PURPOSE: To discuss the anatomical and functional results in cases of optic disc
pit maculopathy (ODP-M) with a follow-up of at least 11 years after scleral
buckling procedure (SBP). METHODS: We studied 12 eyes with ODP-M treated with
SBP, in a long-term follow-up of 12.8 +/- 1.5 years after surgery. All patients
underwent best-corrected visual acuity (BCVA) measurement, slit-lamp
biomicroscopy, fundus photography, fluorescein angiography, indocyanine green
angiography, B-scan ultrasonography, and optical coherence tomography at baseline
and 6-12 months, 2 years and at least 11 years postoperatively. RESULTS: Complete
macular reattachment was noticed between 6 and 12 months postoperatively. The
BCVA improved significantly at the first postoperative examination. Further
improvement was noticed at the second examination, while BCVA remained almost
stable at the last examination. Foveal restoration of ellipsoid layer (inner
segment/outer segment) was noted in 10 out of 12 cases. The existing vitreous
strands remained unchanged during the follow-up. Vitreous traction gradually
disappeared (4/5 eyes). Circulation in short/long posterior ciliary arteries was
unaffected, while neither recurrences nor complications were observed during the
follow-up period. Association of the scleral sponge to the scleral sheath of the
optic nerve remained unchanged during the follow-up. CONCLUSIONS: A total of 12.8
+/- 1.5 years after treatment, all the studied cases retained the successful
anatomical and functional results that they had 2 years postoperatively, without
inducing cataract during the follow-up period. The SBP seems to act equally well
as a barrier either obstructing the entrance of fluid from the vitreous cavity or
blocking the circulation of subarachnoid cerebrospinal fluid into the retina.
PMID- 25588594
TI - Retrobulbar dexmedetomidine decreases the MLAC of ropivacaine in vitreoretinal
surgery in children.
AB - PURPOSE: Dexmedetomidine can prolong the duration of local anesthetics, but the
effect of retrobulbar dexmedetomidine on the potency of ropivacaine for
retrobulbar block has not been investigated. Our study was designed to determine
the effect of retrobulbar dexmedetomidine on ropivacaine for retrobulbar block in
children. METHODS: A group of 90 children aged 10-16 years scheduled for
vitreoretinal surgery who received retrobulbar block were randomly assigned to 1
of 3 groups: group L (retrobulbar ropivacaine), group LD1 (ropivacaine plus 0.5
ug.kg-1 dexmedetomidine), or group LD2 (ropivacaine plus 1 ug.kg-1
dexmedetomidine). The minimum local anesthetic concentration (MLAC) was
determined according to a Dixon-Massey protocol. The primary endpoint of the
study was MLAC. Secondary outcomes were duration of postoperative analgesia,
postoperative pain scores, dexmedetomidine side effects, and time to hospital
discharge. RESULTS: The MLAC values of retrobulbar ropivacaine were 0.314%,
0.259%, and 0.246% in groups L, LD1, and LD2, respectively. The median
(interquartile range) durations of analgesia in the postoperative period were 66
(54-117), 89 (40-157), and 168 (120-194) minutes in groups L, LD1, and LD2,
respectively (L vs LD1 or LD2, p<0.05). Wake-up time was significantly increased
in groups LD1 and LD2. CONCLUSIONS: Retrobulbar dexmedetomidine reduces the MLAC
values of ropivacaine and improves postoperative analgesia in children without
any neurologic side effects.
PMID- 25588595
TI - Characterizing major bleeding in patients with nonvalvular atrial fibrillation: a
pharmacovigilance study of 27 467 patients taking rivaroxaban.
AB - BACKGROUND: In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to
prevent stroke and systemic embolism. OBJECTIVE: To evaluate major bleeding (MB)
in NVAF patients treated with rivaroxaban in a real-world clinical setting.
METHODS: From January 1, 2013, to March 31, 2014, US Department of Defense
electronic health care records were queried to describe MB rates and
demographics. Major bleeding was identified using a validated algorithm. RESULTS:
Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients,
an incidence of 2.86 per 100 person-years (95% confidence interval: 2.61-3.13).
The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years,
compared with non-MB patients. Patients with MB had higher rates of hypertension
(95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5%
vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking
20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients
took warfarin within the prior 30 days. Major bleeding was most commonly
gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients
received a transfusion, none had sufficient evidence of receiving any type of
clotting factor. Fourteen died during their MB hospitalization, yielding a fatal
bleeding incidence rate of 0.08 per 100 person-years (95% confidence interval:
0.05-0.14). Mean age at death was 82.4 years. CONCLUSIONS: In this large
observational study, the MB rate was generally consistent with the registration
trial results, and fatal bleeds were rare.
PMID- 25588596
TI - Association between blood erythrocyte lead concentrations and hemoglobin levels
in preschool children.
AB - Despite decades of intensive research, lead (Pb) toxicity still remains one of
the most frequently investigated subjects in environmental health. Whole blood
lead (BPb) is usually used to evaluate Pb exposure for both screening and
clinical diagnosis. However, it is generally recognized that BPb is not a
sensitive biomarker for Pb exposure in hematological studies. Considering
hematocrit (HCT) variation in different situations, HCT-adjusted BPb or
erythrocyte Pb (EPb) may be more relevant when evaluating the hematotoxicity of
blood Pb. Data collected from 855 preschool children, 3-7 years of age, allowed
us to examine the relationship between EPb and hemoglobin (Hb) levels.
Multivariate linear regression was performed to determine the significance of EPb
as predictor of Hb after covariate adjustment; then, mean differences of Hb
levels between quartiles of EPb and BPb (1st quartile as reference) were
determined using ANOVA followed by Student's t test. The dose-response curve
between EPb and HCT was plotted using locally weighted scatterplot smoothing
(LOWESS) method. A doubling of EPb was associated with a 2.44 g/L decrease in Hb
level. Compared to the 1st quartile group of EPb, the 3rd and 4th quartile groups
showed significant decreases in Hb levels (3.01 and 3.97 g/L, respectively).
Compared to the 1st quartile group of BPb, the 2nd quartile group showed a
decrease in Hb levels (0.63 g/L), while the 3rd and 4th quartile groups showed
increases in Hb levels (0.78 and 1.45 g/L, respectively). Increased EPb levels
are significantly associated with decreased Hb levels in preschool children. HCT
must be taken into consideration in investigating the hematological effects of
Pb. Compared to BPb, EPb or HCT-adjusted BPb appear as a more effective biomarker
to interpret the hematotoxicity of lead. Furthermore, blood erythrocytes are not
only a repository of Pb but also a primary target of its toxicity.
PMID- 25588598
TI - The photosensitized oxidation of mixture of parabens in aqueous solution.
AB - The work presents results of studies on the photosensitized oxidation of mixture
of five parabens (methyl-, ethyl-, propyl-, n-butyl-, and benzylparaben) in
aqueous solution. Aluminum phthalocyanine chloride tetrasulfonic acid and xenon
lamp simulating solar radiation were used as a photosensitizer and a light
source, respectively. The purpose was to investigate the influence of inhibitory
effect compounds present in the mixture on the reaction rate. The influence of
the addition of second photosensitizer on the parabens degradation rate was
investigated. The effect of additives: tert-butanol - hydroxyl radical scavenger
and sodium azide - singlet oxygen scavenger on reaction course was also
determined. The transformation products formed during the photosensitized
oxidation process were analyzed by UPLC-MS/MS. The efficiency of photosensitized
oxidation of parabens with natural sunlight irradiation in the central Poland was
checked.
PMID- 25588597
TI - Occurrence of polychlorinated diphenyl ethers in Nanjing section of the Yangtze
River: level and distribution pattern.
AB - Polychlorinated diphenyl ethers (PCDEs) are a group of halogenated aromatic
compounds and serious environmental pollutants. In the present study, sediment
and water samples from eight sites in Nanjing section of the Yangtze River were
characterized with 15 congeners of PCDEs. Concentrations and distributions of
these PCDEs in water phase and sediments were analyzed by GC/MS. Results
demonstrated that ?PCDE concentrations were higher in the low water period (1.15
1.80 MUg/L) than those in the high water period (0.73-1.30 MUg/L) in water phase.
Moreover, ?PCDE concentrations were higher in the low water period (1.58-3.98
MUg/kg) than those in the high water period (1.24-3.48 MUg/kg) in sediments. A
significant linear relationship existed between the ?PCDE concentrations and TOC
contents in sediments, but a poor linearity was found between ?PCDE
concentrations and DOC contents in water phase. Furthermore, the comparison of
the percentage compositions in sediments and in water phase showed that CDE-30
(2,4,6-tri-CDE) was the predominant congener in the studied sites, and higher
chlorinated congeners accounted for a larger proportion in sediments than those
in water phase. In conclusion, the present study demonstrated the prevalent
contamination by PCDEs in sediments and water from the Nanjing section of the
Yangtze River.
PMID- 25588599
TI - Uncertainty assessment of water quality modeling for a small-scale urban
catchment using the GLUE methodology: a case study in Shanghai, China.
AB - There is often great uncertainty in water quality modeling for urban drainage
systems because water quality variation in systems is complex and affected by
many factors. The stormwater management model (SWMM) was applied to a small-scale
urban catchment with a simple and well-maintained stormwater drainage system
without illicit connections. This was done to assess uncertainty in build-up and
wash-off modeling of pollutants within the generalized likelihood uncertainty
estimation (GLUE) methodology, based on a well-calibrated water quantity model.
The results indicated great uncertainty of water quality modeling within the GLUE
methodology. Comparison of uncertainties in various pollutant build-up and wash
off models that were available in SWMM indicated that those uncertainties varied
slightly. This may be a consequence of the specific characteristics of rainfall
events and experimental sites used in the study. The uncertainty analysis of
water quality parameters in SWMM is conducive to effectively evaluating model
reliability, and provides an experience base for similar research and
applications.
PMID- 25588600
TI - New abietane-type diterpene glycosides from the roots of Tripterygium wilfordii.
AB - Two new abietane diterpene glycosides, wilfordosides A (1) and B (2), were
isolated from the roots of Tripterygium wilfordii. The structures of compounds 1
and 2 were established using spectroscopic methods including extensive 1D and 2D
NMR analysis, in combination with chemical reactions.
PMID- 25588602
TI - Zoonotic origin of hepatitis E.
AB - The concept of zoonotic viral hepatitis E has emerged a few years ago following
the discovery of animal strains of hepatitis E virus (HEV), closely related to
human HEV, in countries where sporadic cases of hepatitis E were autochthonous.
Recent advances in the identification of animal reservoirs of HEV have confirmed
that strains circulating in domestic and wild pigs are genetically related to
strains identified in indigenous human cases. The demonstration of HEV
contamination in the food chain or pork products has indicated that HEV is
frequently a foodborne zoonotic pathogen. Direct contacts with infected animals,
consumption of contaminated animal meat or meat products are all potential means
of zoonotic HEV transmission. The recent identification of numerous other
genetically diverse HEV strains from various animal species poses additional
potential concerns for HEV zoonotic infection.
PMID- 25588604
TI - Information seeking in capuchins (Cebus apella): a rudimentary form of
metacognition?
AB - In previous research, great apes and rhesus macaques have demonstrated multiple
apparently metacognitive abilities, whereas capuchin monkeys have not. The
present experiment investigated whether at least a rudimentary form of
metacognition might be demonstrated in capuchins if a simplified metacognitive
task was used. Capuchins (Cebus apella) were required to locate a food reward
hidden beneath one of two inverted cups that sat on a Plexiglas tray. In some
conditions, the capuchins were shown where the food was hidden, in others they
could infer its location, and in yet others they were not given information about
the location of the food. On all trials, capuchins could optionally seek
information about the food's location by looking up through the Plexiglas beneath
the cups. In general, capuchins did this less often when they were shown the food
reward, but not when they could infer the reward's location. These data suggest
that capuchins-if metacognitive-only metacognitively control their information
seeking in some conditions, particularly those in which information is presented
in the visual domain. This may represent a rudimentary version of metacognitive
control, in comparison with that seen in great apes and humans.
PMID- 25588603
TI - Investigation of next-generation sequencing technologies as a diagnostic tool for
amyotrophic lateral sclerosis.
AB - The future of genetic diagnostics will see a move toward massively parallel next
generation sequencing of a patient's DNA. Amyotrophic lateral sclerosis (ALS) is
one of the diseases that would benefit from this prospect. Exploring this idea,
we designed a screening panel to sequence 25 ALS-linked genes and examined
samples from 95 patients with both familial and sporadic ALS. Forty-three rare
polymorphisms were detected in this cohort. A third of these have already been
reported with respect to ALS, leaving 28 novel variants all open for further
investigation. This study highlights the potential benefits of next-generation
sequencing as a reliable, cost and time efficient, diagnostic, and research tool
for ALS.
PMID- 25588605
TI - Z-estimation and stratified samples: application to survival models.
AB - The infinite dimensional Z-estimation theorem offers a systematic approach to
joint estimation of both Euclidean and non-Euclidean parameters in probability
models for data. It is easily adapted for stratified sampling designs. This is
important in applications to censored survival data because the inverse
probability weights that modify the standard estimating equations often depend on
the entire follow-up history. Since the weights are not predictable, they
complicate the usual theory based on martingales. This paper considers joint
estimation of regression coefficients and baseline hazard functions in the Cox
proportional and Lin-Ying additive hazards models. Weighted likelihood equations
are used for the former and weighted estimating equations for the latter.
Regression coefficients and baseline hazards may be combined to estimate
individual survival probabilities. Efficiency is improved by calibrating or
estimating the weights using information available for all subjects. Although
inefficient in comparison with likelihood inference for incomplete data, which is
often difficult to implement, the approach provides consistent estimates of
desired population parameters even under model misspecification.
PMID- 25588606
TI - Child impact on family functioning: a multivariate analysis in multiplex families
with children and mothers both affected by attention-deficit/hyperactivity
disorder (ADHD).
AB - ADHD seriously impacts family functioning, even the more in families with
simultaneous parental and child ADHD. The aim of the study was to examine
associations between family impact of child ADHD and child, mother and family
characteristics in multiplex families with children and mothers both affected by
ADHD. One hundred and forty-four mother-child pairs were assessed (children: mean
age 9.4 +/- 1.7 years, 73.6 % male). Family impact of child ADHD was rated by
mothers using the Family Impact Questionnaire (FIQ). Multiple linear regression
analyses were performed with child and maternal psychopathology and basic family
characteristics such as employment, partnership status and number of children as
predictors and FIQ subscores as criteria. Rates of variance explained by family
variables were 49 % for negative feelings towards the child, 37 % for impact on
partnership, 31 % for impact on social life and 27 % for impact on finances (p <
.001, respectively). Pearson correlations with family impact were especially
strong for child externalizing symptoms, maternal ADHD and co-morbid symptoms of
the mother. The strongest independent predictor was oppositional defiant child
behaviour. In ADHD multiplex families, mothers' perception of the impact of an
ADHD child on its family can be explained to a substantial degree by child
psychopathology, maternal psychopathology and basic family characteristics.
Although a cross-sectional design does not allow for causal interpretations, the
findings of this study offer important targets for the treatment of ADHD in a
family context pointing to the need for assessing and treating parental mental
health and co-morbid symptoms besides ADHD core symptoms.
PMID- 25588607
TI - pH dependence of cadmium-contaminated drinking water on the development of
cardiovascular injury in Wistar rats.
AB - The purpose of our study was to investigate the effect of water pH in the genesis
of cardiovascular injury caused by cadmium poisoning. For this study, 90 male
Wistar rats were used, divided into six groups: A, 15 rats that received 400 mg/l
cadmium chloride (CdCl2) in drinking water at a neutral pH of 7.0; B, 15 rats
that received CdCl2 (400 mg/l) in drinking water at an acidic pH of 5.0; C, 15
rats that received CdCl2 (400 mg/l) in drinking water at a basic pH of 8.0; D, 15
rats that received water at an acidic pH of 5.0; E, 15 rats that received water
at a basic pH of 8.0; and F, 15 rats that received water at a neutral pH of 7.0.
All animals were euthanized after 6 months. We collected the heart and aorta from
each rat for microscopic analysis. No microscopic changes were observed in the
hearts. In the aorta, fatty streaks appeared in a large proportion of animals in
groups A (50 %) and B (46 %), but fatty streaks appeared in a smaller minority of
animals in groups C (15.3 %), D (0 %), E (7 %), and F (13.3 %) (p < 0.05).
Cadmium exposure caused the development of fatty streaks in the aorta of animals
and the exposure to this metal in basic pH decreased the formation of these
lesions.
PMID- 25588608
TI - Luminescent cation sensors: from host-guest chemistry, supramolecular chemistry
to reaction-based mechanisms.
AB - Other than traditional cation detection strategies, which are solely based on the
ion-receptor complementarity, the extension of the concept of supramolecular
chemistry and the mechanisms of irreversible analyte-specific reactions have also
been integrated into the design of luminescent probes for the detection of cation
in view of the exploration of highly sensitive and selective sensors. In this
highlight, a versatile range of organic and organometallic architectures with
cation-sensing capabilities based on the above mechanisms will be discussed.
PMID- 25588609
TI - A fractal-like electrode based on double-wall nanotubes of anatase exhibiting
improved electrochemical behaviour in both lithium and sodium batteries.
AB - An anatase nanotube array has been prepared with a special morphology: two
concentric walls and a very small central cavity. The method used here to achieve
the double-wall structure is a single-step anodization process under a voltage
ramp. Thanks to this nanostructure, which is equivalent to a fractal electrode,
the electrochemical behaviour is improved, and the specific capacity is higher in
both lithium and sodium cells due to pseudocapacitance. The double-wall structure
of the nanotube enhances the surface of TiO2 being in contact with the
electrolyte solution, thus allowing an easy penetration of the alkali ions into
the electrode active material. The occurrence of sodium titanate in the electrode
material after electrochemical reaction with sodium is studied by using EPR,
HRTEM and NMR experiments.
PMID- 25588610
TI - Mental health and psychosocial functioning in adolescence: an investigation among
Indian students from Delhi.
AB - While developmental studies predominantly investigated adolescents' mental
illness and psychosocial maladjustment, the present research focused on positive
mental health of Indian adolescents within the Mental Health Continuum model.
Aims were to estimate their prevalence of mental health and to examine its
associations with mental distress and psychosocial functioning, taking into
account age and gender. A group of 539 students (age 13-18; 43.2% girls) in the
National Capital Territory of Delhi completed Mental Health Continuum Short Form,
Depression Anxiety and Stress Scales-21, Strengths and Difficulties
Questionnaire. Findings showed that 46.4% participants were flourishing, 51.2%
were moderately mentally healthy, and only 2.4% were languishing. A higher number
of girls and younger adolescents were flourishing compared to boys and older
adolescents. Moreover, flourishing youths reported lower prevalence of depression
and adjustment difficulties, and more prosocial behavior. Findings support the
need to expand current knowledge on positive mental health for well-being
promotion in adolescence.
PMID- 25588611
TI - A comparative study of patients' attitudes toward clinical research in the United
States and urban and rural China.
AB - As the number of clinical trials conducted in China increases, understanding
Chinese attitudes toward clinical research is critical for designing effective
and ethical studies. Two survey studies were conducted in 2012 and 2013 to
compare patient attitudes toward clinical research and factors affecting research
participation in the United States and urban and rural China. We surveyed 525
patients in 2012 (186 US, 186 urban, 153 rural China) and 690 patients in 2013
(412 US, 206 urban, 72 rural China). US patients were more likely to have no
concerns regarding research participation than Chinese patients. Most common
concerns of US patients were safety, privacy and confidentiality, and time
required. Safety was a top concern for many Chinese. Chinese patients,
particularly rural Chinese, were more concerned about the likelihood of self
benefit, and receiving free medical care and financial incentive had greater
influence on their participation. Being informed of the freedom to choose whether
to participate or to leave a study was less important to Chinese patients. Our
study provides important insights into Chinese patients' attitudes toward
clinical research and the need to educate them about their rights. These findings
help in designing cross-cultural clinical studies that maximize enrollment while
upholding Western ethical standards.
PMID- 25588612
TI - Testing for clustering at many ranges inflates family-wise error rate (FWE).
AB - BACKGROUND: Testing for clustering at multiple ranges within a single dataset is
a common practice in spatial epidemiology. It is not documented whether this
approach has an impact on the type 1 error rate. METHODS: We estimated the family
wise error rate (FWE) for the difference in Ripley's K functions test, when
testing at an increasing number of ranges at an alpha-level of 0.05. Case and
control locations were generated from a Cox process on a square area the size of
the continental US (~3,000,000 mi2). Two thousand Monte Carlo replicates were
used to estimate the FWE with 95% confidence intervals when testing for
clustering at one range, as well as 10, 50, and 100 equidistant ranges. RESULTS:
The estimated FWE and 95% confidence intervals when testing 10, 50, and 100
ranges were 0.22 (0.20 - 0.24), 0.34 (0.31 - 0.36), and 0.36 (0.34 - 0.38),
respectively. CONCLUSIONS: Testing for clustering at multiple ranges within a
single dataset inflated the FWE above the nominal level of 0.05. Investigators
should construct simultaneous critical envelopes (available in spatstat package
in R), or use a test statistic that integrates the test statistics from each
range, as suggested by the creators of the difference in Ripley's K functions
test.
PMID- 25588613
TI - The sleep loss epidemic: hunting ninjas in the dark.
PMID- 25588614
TI - The VPS-20 subunit of the endosomal sorting complex ESCRT-III exhibits an open
conformation in the absence of upstream activation.
AB - Members of the endosomal sorting complex required for transport (ESCRT) machinery
function in membrane remodelling processes during multivesicular endosome (MVE)
biogenesis, cytokinesis, retroviral budding and plasma membrane repair. During
luminal vesicle formation at endosomes, the ESCRT-II complex and the ESCRT-III
subunit vacuolar protein sorting (VPS)-20 play a specific role in regulating
assembly of ESCRT-III filaments, which promote vesicle scission. Previous work
suggests that Vps20 isoforms, like other ESCRT-III subunits, exhibits an auto
inhibited closed conformation in solution and its activation depends on an
association with ESCRT-II specifically at membranes [1]. However, we show in the
present study that Caenorhabditis elegans ESCRT-II and VPS-20 interact directly
in solution, both in cytosolic cell extracts and in using recombinant proteins in
vitro. Moreover, we demonstrate that purified VPS-20 exhibits an open extended
conformation, irrespective of ESCRT-II binding, in contrast with the closed auto
inhibited architecture of another ESCRT-III subunit, VPS-24. Our data argue that
individual ESCRT-III subunits adopt distinct conformations, which are tailored
for their specific functions during ESCRT-mediated membrane reorganization
events.
PMID- 25588615
TI - Effects of inoculation of commercial starter cultures on the quality and
histamine accumulation in fermented sausages.
AB - To meet the requirements of high-quality safe products, starter cultures are used
to produce fermented sausages. The effects of 3 commercial starter cultures,
namely SM-194, T-SPX, and SM-181, on histamine accumulation and quality
parameters including microbial quality, pH, water activity, and total volatile
base nitrogen, as well as the color and texture properties, were evaluated during
the fermentation and ripening of fermented sausages. Although initial counts of
Escherichia coli, Enterobacteriaceae, and Pseudomonas were similar in the 4
batches, the growth of these microorganisms was significantly inhibited (P <
0.05) in batches SM-194, T-SPX, and SM-181 throughout the fermentation and
ripening period. The counts of E. coli, Enterobacteriaceae, and Pseudomonas
increased to maximum levels of 3.89, 4.41, and 5.15 log10 colony forming units/g
in the control sausages, respectively. At the end of ripening, the levels of
histamine were 8.85, 0.32, 7.82, and 3.18 mg/kg for batches C, SM-194, T-SPX, and
SM-181, respectively. The results revealed that commercial starter cultures,
particularly starter cultures SM-194 and SM-181, made a great contribution to
histamine reduction. In addition, batches inoculated with starter cultures showed
a stronger acidification and lower level of total volatile base nitrogen than the
control sample during production (P < 0.05). In conclusion, it seems that the
inoculation of commercial starter cultures, particularly starter cultures SM-194
and SM-181, contributes to improving microbial quality, hygienic quality and food
safety of fermented sausages.
PMID- 25588617
TI - Threshold for NIH stroke scale in predicting vessel occlusion and functional
outcome after stroke thrombolysis.
AB - BACKGROUND: Data are limited on optimal threshold for baseline National
Institutes of Health Stroke Scale in predicting outcome after stroke thrombolysis
(intravenous thrombolysis). AIMS: Finding thresholds for baseline National
Institutes of Health Stroke Scale scores that predict functional outcome and
baseline vessel occlusion. METHODS: We analyzed 44 331 patients with available
modified Rankin Scale score at three-months and 11 632 patients with computed
tomography/magnetic resonance angiography documented vessel occlusion at baseline
in the SITS-International Stroke Thrombolysis Register. Main outcomes were
functional independency (modified Rankin Scale 0-2) at three-months and baseline
vessel occlusion. We obtained area under the curves by receiver operating
characteristic analysis and calculated multivariately adjusted odds ratio for the
outcomes of interest based on baseline National Institutes of Health Stroke Scale
scores. RESULTS: For functional independency, National Institutes of Health
Stroke Scale scores of 12 (area under the curve 0.775) and for baseline vessel
occlusion, scores of 11 (area under the curve 0.678) were optimal threshold
values. For functional independency, adjusted odds ratio decreased to 0.07 (95%
CI 0.05-0.11), and for presence of baseline occlusion, aOR increased to 3.28 (95%
CI 3.04-3.58) for National Institutes of Health Stroke Scale scores 12 and 11,
respectively, compared with National Institutes of Health Stroke Scale score 0.
National Institutes of Health Stroke Scale thresholds decreased with time from
stroke onset to imaging, with 2-3 points, respectively, if time to imaging
exceeded three-hours. CONCLUSIONS: Ideally, all acute stroke patients should have
immediate access to multimodal imaging. In reality these services are limited.
Baseline National Institutes of Health Stroke Scale scores of 11 and 12 were
identified as markers of baseline vessel occlusion and functional independency
after intravenous thrombolysis, respectively. These values are time dependent;
therefore, a threshold of National Institutes of Health Stroke Scale 9 or 10
points may be considered in the prehospital selection of patients for immediate
transfer to centers with multimodal imaging and availability of highly
specialized treatments.
PMID- 25588616
TI - Ligand-based 3D QSAR analysis of reactivation potency of mono- and bis-pyridinium
aldoximes toward VX-inhibited rat acetylcholinesterase.
AB - To predict unknown reactivation potencies of 12 mono- and bis-pyridinium
aldoximes for VX-inhibited rat acetylcholinesterase (rAChE), three-dimensional
quantitative structure-activity relationship (3D QSAR) analysis has been carried
out. Utilizing molecular interaction fields (MIFs) calculated by molecular
mechanical (MMFF94) and quantum chemical (B3LYP/6-31G*) methods, two satisfactory
ligand-based CoMFA models have been developed: 1. R(2)=0.9989, Q(LOO)(2)=0.9090,
Q(LTO)(2)=0.8921, Q(LMO(20%))(2)=0.8853, R(ext)(2)=0.9259, SDEP(ext)=6.8938; 2.
R(2)=0.9962, Q(LOO)(2)=0.9368, Q(LTO)(2)=0.9298, Q(LMO(20%))(2)=0.9248,
R(ext)(2)=0.8905, SDEP(ext)=6.6756. High statistical significance of the 3D QSAR
models has been achieved through the application of several data noise reduction
techniques (i.e. smart region definition SRD, fractional factor design FFD,
uninformative/iterative variable elimination UVE/IVE) on the original MIFs.
Besides the ligand-based CoMFA models, an alignment molecular set constructed by
flexible molecular docking has been also studied. The contour maps as well as the
predicted reactivation potencies resulting from 3D QSAR analyses help better
understand which structural features are associated with increased reactivation
potency of studied compounds.
PMID- 25588618
TI - Epigenetic modulation of metabolic decisions.
AB - In the recent years there has been a tremendous increase in our understanding of
chromatin, transcription and the importance of metabolites in their regulation.
This review highlights what is currently sparse information that suggest
existence of a refined system integrating metabolic and chromatin control. We
indicate possible regulatory modes, such as feed forward amplification, that may
help effect and stabilize long-lasting phenotypic decisions within and even
across generations using adipogenesis as the primary context.
PMID- 25588619
TI - Does practice make perfect? Resident experience with breast surgery influences
excision adequacy.
AB - BACKGROUND: The adequacy of breast-conserving surgery (BCS) for invasive or in
situ disease is largely determined by the final surgical margins. Although margin
status is associated with various clinicopathologic features, the influence of
resident involvement remains controversial. METHODS: Patients who underwent BCS
for malignancy from 2009 to 2012 were identified. The effects of various
clinicopathologic characteristics and resident involvement were evaluated.
RESULTS: Of the 502 cases performed, a resident assisted with most surgeries
(95%). The overall rate of positive margins was 30%, which was not associated
with resident involvement. Interns assisting from July to September had
significantly lower rates of positive margins. Margins were more likely to be
positive following any given resident's first 3 cases on their breast rotation
than throughout the remainder of their rotation. CONCLUSION: Although resident
level alone does not influence the adequacy of BCS, experience gained over time
does appear to be associated with lower rates of positive margins.
PMID- 25588620
TI - Doing well by doing good: linking access with quality.
AB - BACKGROUND: We hypothesize that medical centers that prioritize altruism can also
deliver superior quality care. METHODS: Data were obtained from California's
Office of Statewide Health Planning and Development, Medicare Hospital Compare,
and the Joint Commission US Census Bureau's American Community Survey. Outcomes
were measured using summary statistics, regression analysis, and quality indices.
Total discounted revenue/total revenue (TDR/TR) served as a proxy for altruistic
care. RESULTS: In nonprofit hospitals, TDR/TR positively correlated with 5
quality indices including pneumonia (P < .001), heart failure (P = .05), and
overall surgical process of care (P = .009). Hospital size predicted higher
quality surgical process (P = .06, 201 to 300 beds; P = .01, >301 beds), hospital
teaching status demonstrated positive correlation (beta = .048, P = .69), and
poverty was negatively correlated (beta = -.00072, P = .89). Positive TDR/TR did
not adversely affect mortality or readmission rates (P = .52). CONCLUSIONS:
TDR/TR predicts quality in nonprofit hospitals without increasing mortality and
readmission. Altruistic motivation may be associated with the delivery of higher
quality surgical care.
PMID- 25588621
TI - Appendectomy: a risk factor for colectomy in patients with Clostridium difficile.
AB - BACKGROUND: The appendix, considered an intestinal microbiota reservoir, may be
protective against the risk of fulminant Clostridium difficile infection.
METHODS: Retrospective analysis was performed in patients with C. difficile
infection at St. Francis Medical Center from 2007 to 2011. Outcome of infection
and history of appendectomy were compared. Statistical analysis was by chi-square
and multivariate logistic regression. RESULTS: In total, 507 patients were
hospitalized for C. difficile. Of 388 patients with intact appendix, 20 (5.2%)
developed fulminant infection and required colectomy, whereas of 119 patients
with previous appendectomy, 13 (10.9%) required colectomy. An increased severity
of disease, indicated by increased rate of colectomy, occurred for the group with
a history of appendectomy (P = .03). Age and sex were adjusted by multivariant
regression (P = .05). CONCLUSIONS: Appendectomy may be a risk factor for
increased severity of C. difficile infection. Although the mechanism is unknown,
further studies are warranted.
PMID- 25588623
TI - Uncovering the role of cathode buffer layer in organic solar cells.
AB - Organic solar cells (OSCs) as the third generation photovoltaic devices have
drawn intense research, for their ability to be easily deposited by low-cost
solution coating technologies. However the cathode in conventional OSCs, Ca, can
be only deposited by thermal evaporation and is highly unstable in ambient.
Therefore various solution processible cathode buffer layers (CBLs) are
synthesized as substitute of Ca and show excellent effect in optimizing
performance of OSCs. Yet, there is still no universal consensus on the mechanism
that how CBL works, which is evidently a critical scientific issue that should be
addressed. In this article detailed studies are targeted on the interfacial
physics at the interface between active layer and cathode (with and without
treatment of a polar CBL) by using ultraviolet photoelectron spectroscopy,
capacitance-voltage measurement, and impedance spectroscopy. The experimental
data demonstrate that CBL mainly takes effect in three ways: suppressing surface
states at the surface of active layer, protecting the active layer from being
damaged by thermally evaporated cathode, and changing the energy level alignment
by forming dipole moments with active layer and/or cathode. Our findings here
provide a comprehensive picture of interfacial physics in devices with and
without CBL.
PMID- 25588622
TI - Insulin-like growth factor-1 endues monocytes with immune suppressive ability to
inhibit inflammation in the intestine.
AB - The pathogenesis of some chronic inflammation such as inflammatory bowel disease
is unclear. Insulin-like growth factor-1 (IGF1) has active immune regulatory
capability. This study aims to investigate into the mechanism by which IGF1
modulates the monocyte (Mo) properties to inhibit immune inflammation in the
intestine. In this study, the production of IGF1 by intestinal epithelial cells
was evaluated by real time RT-PCR and Western blotting. Mos were analyzed by flow
cytometry. A mouse colitis model was created with trinitrobenzene sulfonic acid.
The results showed that mouse IECs produced IGF1, which could be up regulated by
exposure to CpG-ODN (CpG-oligodeoxynueleotides) in the culture. Culture the CpG
ODN-primed IEC cells and Mos or exposure of Mos to IGF1 in the culture induced
the Mos to express IL-10. The IGF1-primed Mos showed the immune suppressive
effect on inhibiting the immune inflammation in the mouse colon. In conclusion,
the IGF1-primed Mos are capable of suppressing immune inflammation in the
intestine.
PMID- 25588624
TI - Computational cancer biology: education is a natural key to many locks.
AB - BACKGROUND: Oncology is a field that profits tremendously from the genomic data
generated by high-throughput technologies, including next-generation sequencing.
However, in order to exploit, integrate, visualize and interpret such high
dimensional data efficiently, non-trivial computational and statistical analysis
methods are required that need to be developed in a problem-directed manner.
DISCUSSION: For this reason, computational cancer biology aims to fill this gap.
Unfortunately, computational cancer biology is not yet fully recognized as a
coequal field in oncology, leading to a delay in its maturation and, as an
immediate consequence, an under-exploration of high-throughput data for
translational research. Here we argue that this imbalance, favoring 'wet lab
based activities', will be naturally rectified over time, if the next generation
of scientists receives an academic education that provides a fair and competent
introduction to computational biology and its manifold capabilities. Furthermore,
we discuss a number of local educational provisions that can be implemented on
university level to help in facilitating the process of harmonization.
PMID- 25588625
TI - Implementation of evidence-based practice in relation to a clinical nursing
ladder system: a national survey in Taiwan.
AB - BACKGROUND: Although evidence-based practice (EBP) has been widely investigated,
few studies have investigated its correlation with a clinical nursing ladder
system. The current national study evaluates whether EBP implementation has been
incorporated into the clinical ladder system. METHODS: A cross-sectional
questionnaire survey was conducted nationwide of registered nurses among regional
hospitals of Taiwan in January to April 2011. Subjects were categorized into
beginning nurses (N1 and N2) and advanced nurses (N3 and N4) by the clinical
ladder system. Multivariate logistic regression model was used to adjust for
possible confounding demographic factors. RESULTS: Valid postal questionnaires
were collected from 4,206 nurses, including 2,028 N1, 1,595 N2, 412 N3, and 171
N4 nurses. Advanced nurses were more aware of EBP than beginning nurses (p <
0.001; 90.7% vs. 78.0%). In addition, advanced nurses were more likely to hold
positive beliefs about and attitudes toward EBP (p < 0.001) and possessed more
sufficient knowledge of and skills in EBP (p < 0.001). Furthermore, they more
often implemented EBP principles (p < 0.001) and accessed online evidence-based
retrieval databases (p < 0.001). The most common motivation for using online
databases was self-learning for advanced nurses and positional promotion for
beginning nurses. Multivariate logistic regression analyses showed advanced
nurses were more aware of EBP, had higher knowledge and skills of EBP, and more
often implemented EBP than beginning nurses. LINKING EVIDENCE TO ACTION: The
awareness of, beliefs in, attitudes toward, knowledge of, skills in, and
behaviors of EBP among advanced nurses were better than those among beginning
nurses. The data indicate that a clinical ladder system can serve as a useful
means to enhance EBP implementation.
PMID- 25588626
TI - Postpancreatoduodenectomy Hemorrhage Treated by Combined Transcatheter Arterial
Embolization and Superior Mesenteric Artery to Iliac Artery Bypass: Report of a
Case.
AB - Postpancreatectomy hemorrhage is a potentially life-threatening complication. We
report herein our experience with a 65-year-old man with locally advanced
pancreatic adenocarcinoma who underwent pancreatoduodenectomy with
lymphadenectomy following neoadjuvant chemoradiotherapy. On postoperative day 45,
he developed massive hematemesis. Angiography revealed active bleeding from the
common hepatic artery, and transcatheter coil embolization of that vessel was
successfully performed. On postoperative day 64, he again developed massive
hematemesis. Angiography revealed active bleeding from the proximal superior
mesenteric artery. Immediately after coil embolization of that vessel, bypass
grafting between the superior mesenteric artery and the right common iliac artery
was performed, using a greater saphenous vein graft. The combination of
embolization and bypass grafting is an option for treatment of bleeding from the
superior mesenteric artery in an emergent situation.
PMID- 25588627
TI - Diabolical points in multi-scatterer optomechanical systems.
AB - Diabolical points, which originate from parameter-dependent accidental
degeneracies of a system's energy levels, have played a fundamental role in the
discovery of the Berry phase as well as in photonics (conical refraction), in
chemical dynamics, and more recently in novel materials such as graphene, whose
electronic band structure possess Dirac points. Here we discuss diabolical points
in an optomechanical system formed by multiple scatterers in an optical cavity
with periodic boundary conditions. Such configuration is close to experimental
setups using micro-toroidal rings with indentations or near-field scatterers. We
find that the optomechanical coupling is no longer an analytic function near the
diabolical point and demonstrate the topological phase arising through the
mechanical motion. Similar to a Fabry-Perot resonator, the optomechanical
coupling can grow with the number of scatterers. We also introduce a minimal
quantum model of a diabolical point, which establishes a connection to the motion
of an arbitrary-spin particle in a 2D parabolic quantum dot with spin-orbit
coupling.
PMID- 25588628
TI - DNA barcoding largely supports 250 years of classical taxonomy: identifications
for Central European bees (Hymenoptera, Apoidea partim).
AB - This study presents DNA barcode records for 4118 specimens representing 561
species of bees belonging to the six families of Apoidea (Andrenidae, Apidae,
Colletidae, Halictidae, Megachilidae and Melittidae) found in Central Europe.
These records provide fully compliant barcode sequences for 503 of the 571 bee
species in the German fauna and partial sequences for 43 more. The barcode
results are largely congruent with traditional taxonomy as only five closely
allied pairs of species could not be discriminated by barcodes. As well, 90% of
the species possessed sufficiently deep sequence divergence to be assigned to a
different Barcode Index Number (BIN). In fact, 56 species (11%) were assigned to
two or more BINs reflecting the high levels of intraspecific divergence among
their component specimens. Fifty other species (9.7%) shared the same Barcode
Index Number with one or more species, but most of these species belonged to a
distinct barcode cluster within a particular BIN. The barcode data contributed to
clarifying the status of nearly half the examined taxonomically problematic
species of bees in the German fauna. Based on these results, the role of DNA
barcoding as a tool for current and future taxonomic work is discussed.
PMID- 25588629
TI - Hybrid granular cell tumor/perineurioma.
PMID- 25588630
TI - Myoepithelial carcinoma of soft tissue: a case report and review of the
literature.
PMID- 25588631
TI - Combined squamous cell carcinoma and follicular carcinoma of the thyroid.
PMID- 25588632
TI - Primary leiomyosarcoma of adrenal gland with tissue eosinophilic infiltration.
PMID- 25588633
TI - A Case of Type II Enteropathy-Associated T-Cell Lymphoma with Epstein-Barr Virus
Positivity.
PMID- 25588634
TI - Indolent CD56-Positive Clonal T-Cell Lymphoproliferative Disease of the Stomach
Mimicking Lymphomatoid Gastropathy.
PMID- 25588635
TI - A case of epithelioid blue nevus.
PMID- 25588636
TI - Digital papillary carcinoma.
PMID- 25588637
TI - Periductal stromal tumor of breast: a case report and a review of literature.
PMID- 25588638
TI - A case of mixed adenoneuroendocrine carcinoma of the common bile duct: initially
diagnosed as cholangiocarcinoma.
PMID- 25588639
TI - Peritoneal Carcinosarcoma and Ovarian Papillary Serous Carcinoma Are the Same
Origin: Analysis of TP53 Mutation and Microsatellite Suggests a Monoclonal
Origin.
PMID- 25588640
TI - Malignant perivascular epithelioid cell tumor of the uterus with lung metastasis.
PMID- 25588641
TI - Lymphoepithelioma-like Carcinoma of the Renal Pelvis: A Case Report and Review of
the Literature.
PMID- 25588642
TI - Supratentorial hemangioblastoma with unusual features.
PMID- 25588643
TI - A rare case of mesothelioma showing micropapillary and small cell differentiation
with aggressive behavior.
PMID- 25588644
TI - Going places: Does the two-minute walk test predict the six-minute walk test in
lower extremity amputees?
AB - OBJECTIVE: Assessing a patient's ability to walk the distance required for
community ambulation (at least 300 m) is important in amputee rehabilitation.
During the 2-min walk test, most amputees cannot walk 300 m. Thus, the 6-min walk
test may be preferred, but it has not been fully validated in this population.
This study examined the convergent and discriminative validity of the 6-min walk
test and assessed whether the 2-min test could predict the results of the 6-min
test. METHODS: A total of 86 patients with unilateral or bilateral amputations at
the Syme, transtibial, knee disarticulation or transfemoral level completed the 6
min walk test, 2-min walk test, Timed Up and Go test, Locomotor Capabilities
Index version 5, Houghton Scale of Prosthetic Use, and Activity-Specific Balance
Confidence scale. RESULTS: The 6-min walk test correlated with the other tests (R
= 0.57-0.95), demonstrating convergent validity. It demonstrated discriminative
validity with respect to age, aetiology of amputation, and K-level (p < 0.0001).
The 2-min walk test was highly predictive of the 6-min walk test distance (R2 =
0.91). CONCLUSION: The 6-min walk test is a valid measure of amputee ambulation.
However, the results suggest that it may not be necessary, since the 2-min walk
test strongly predicts the 6-min walk test. Clinicians could therefore save time
by using the shorter test.
PMID- 25588645
TI - Editorial.
PMID- 25588646
TI - Medicare per capita spending by age and service: new data highlights oldest
beneficiaries.
PMID- 25588647
TI - Mesoporous alumina from colloidal biotemplating of Al clusters.
AB - A simple and green synthesis route was disclosed for the achievement of
mesoporous alumina microparticles employing polysaccharide nanoparticles (alpha
chitin nanorods) as templates. Pore textures can be tuned by the cationic alumina
precursor. Compared to small cations, the use of Al13 and Al30 oxo-hydroxo
clusters leads to better defined and elongated mesopores. Electron microscopy and
spectroscopic ((13) C, (27) Al NMR, XPS) measurements demonstrated that this is
related to the effective coating of alpha-chitin nanorods by these pre-condensed
colloids.
PMID- 25588648
TI - Identification of mutations in the HVR1 and PKR-BD regions in HCV-infected
patients resistant to PEG-IFNalpha/RBV therapy.
AB - The identification of mutations in the HVR1 region of hepatitis type C virus
(HCV) is time-consuming and expensive, and there is a need for a rapid,
inexpensive method of screening for these mutations to predict the
ineffectiveness of pegylated interferon alpha combined with ribavirin (PEG
IFNalpha/RBV) therapy. The project was designed to evaluate the usefulness of the
high resolution melting (HRM) technique to screen for mutation in the cDNAs
encoding the HVR1 and protein kinase R-binding domain (PKR-BD) regions in a group
of 36 patients infected with HCV and resistant to 12 months of combined therapy
with PEG-IFNalpha/RBV. Viral RNA was isolated, reverse transcribed, and the
fragments encoding the HVR1 and PKR-BD regions were polymerase chain reaction
(PCR)-amplified, cloned, sequenced, and the melting profiles and the melting
temperature (Tm) were determined by the HRM technique. After the treatment, the
melting profiles of HVR1 cDNAs revealed a dominant peak corresponding to the Tm
of about 85 degrees C (HCVs85) in almost all patients. One or more minor peaks
were also observed, indicating the existence of cDNA(s) of different Tm. The HMR
analysis suggested four typical forms of response to treatment. These
suppositions were supported by sequencing. The HRM analysis revealed no changes
in the melting profiles of PKR-BD cDNAs in the same patient before and after the
therapy, suggesting that, within 12 months of treatment, new mutations were not
introduced in PKR-BD. These findings were substantiated by sequencing. The HRM
technique can be applied for the rapid screening for mutations in the cDNAs
encoding the HVR and PKR-BD regions of HCV. We suggest that the detection of
HCVs85 peak before the IFNalpha/RBV therapy might predict the ineffectiveness of
treatment.
PMID- 25588649
TI - Genome-wide association study of antibody level response to NDV and IBV in
Jinghai yellow chicken based on SLAF-seq technology.
AB - Newcastle disease (ND) and avian infectious bronchitis (IB) are contagious
diseases of chickens. To identify genes associated with antibody levels against
ND and IB, a genome-wide association study was performed using specific-locus
amplified fragment sequencing (SLAF-seq) technology in Jinghai yellow chickens.
This determined six single-nucleotide polymorphisms (SNPs) that were associated
with antibody levels against Newcastle disease virus (NDV): rsZ2494661,
rsZ2494710, rs1211307701, rs1211307711, rs1218289310 and rs420701988. Of these,
rsZ2494661 and rsZ2494710 reached the 5 % Bonferroni genome-wide significance
level (5.5E-07) and they were both 134.7 kb downstream of the SETBP1 gene. The
remaining four SNPs had 'suggestive' genome-wide significance levels (1.1E-05)
and they were within or near the Plexin B1, LRRN1 and PDGFC genes. IB had two
SNPs associated with antibody levels: rs149988433 and rs16170823; both reached
chromosome-wide significance levels and they were near the USP7 and TRIM27 genes,
respectively. Bioinformatics, GO annotation and pathway analysis indicated that
five of these genes (Plexin B1, TRIM27, PDGFC, SETBP1 and USP7) may be important
for the generation of protective antibodies against NDV and infectious bronchitis
virus (IBV). This paves the way for further research on host immune responses
against NDV.
PMID- 25588650
TI - Contribution of the BacT/Alert MB Mycobacterium bottle to bloodstream infection
surveillance in Thailand: added yield for Burkholderia pseudomallei.
AB - Community-acquired bloodstream infections cause substantial morbidity and
mortality worldwide, but microbiology capacity and surveillance limitations have
challenged good descriptions of pathogen distribution in many regions, including
Southeast Asia. Active surveillance for bloodstream infections has been conducted
in two rural Thailand provinces for >7 years. Blood specimens were divided into
two culture bottles, one optimized for aerobic growth (F bottle) and a second for
enhanced growth of mycobacteria (MB bottle), and processed with the BactT/Alert
3D system. Because the routine use of MB culture bottles is resource intensive
(expensive and requires prolonged incubation), we assessed the added yield of MB
bottles by comparing the proportion of pathogens detected by MB versus that by F
bottles from 2005 to 2012. Of 63,066 blood cultures, 7,296 (12%) were positive
for at least one pathogen; the most common pathogens were Escherichia coli (28%),
Burkholderia pseudomallei (11%), Klebsiella pneumoniae (9%), and Staphylococcus
aureus (6%). Two bottles improved the yield overall, but the added yield
attributable to the MB bottles was limited to a few pathogens. In addition to the
detection of mycobacteria and some fungi, MB bottles improved the detection of B.
pseudomallei (27% [MB] versus 8% [F]; P < 0.0001), with added benefit if therapy
was initiated prior to the blood culture. The targeted use of MB bottles is
warranted for patients at risk for mycobacterial and fungal infections and for
infection with B. pseudomallei, a common cause of septicemia in Thailand.
PMID- 25588651
TI - Evaluation of antigen-specific immunoglobulin g responses in pulmonary
tuberculosis patients and contacts.
AB - This study aimed to evaluate the serodiagnostic potential of immunoglobulin G
(IgG) responses to Mycobacterium tuberculosis antigens in pulmonary tuberculosis
(TB) patients, recent TB contacts with latent TB infection (LTBI), and healthy
subjects. Infections were assessed using tuberculin skin tests, QuantiFERON-TB
Gold In-Tube tests, drug susceptibility testing, and molecular genotyping of
clinical isolates. Serum IgG responses to selective M. tuberculosis antigens,
including the 38-kDa and 16-kDa antigens, lipoarabinomannan (LAM), and
recombinant early secreted antigen target 6 kDa (ESAT-6) and culture filtrate
protein 10 kDa (CFP-10), were determined. We found that the serum IgG responses
to all antigens might differentiate between active TB and LTBI, with LAM having
the highest diagnostic value (area under the curve [AUC] of 0.7756, P < 0.001).
Recurrent TB cases showed significantly higher IgG responses to 38 kDa, CFP-10 (P
< 0.01), and LAM (P < 0.05) than new cases, and male patients had higher levels
of antigen-specific IgG than females (P < 0.05). Conversely, drug resistance and
patient body mass index did not affect IgG responses (P > 0.05). LAM-specific IgG
responses differentiated between acid-fast bacillus (AFB) smear-positive and
negative patients (P < 0.01), whereas antigen-specific IgG responses did not vary
with the M. tuberculosis genotype (P > 0.05). Significantly higher IgG responses
to 38 kDa and 16 kDa were observed in AFB smear-negative patients than in
controls. These results suggest that assessment of serum IgG responses to
selective purified M. tuberculosis antigens may help improve the diagnosis of
active TB, particularly for sputum smear-negative patients or recurrent cases,
and these may also help to differentiate between active TB and LTBI.
PMID- 25588654
TI - Development of a real-time PCR Assay for identification of Coccidioides immitis
by use of the BD Max system.
AB - Rapid real-time PCR (RT-PCR) can be performed in a community hospital setting to
identify Coccidioides species using the new Becton Dickinson molecular instrument
BD Max. Following sample preparation, DNA extraction and PCR were performed on
the BD Max using the BD Max extraction kit ExK-DNA-1 test strip and a master mix
prepared by BioGX (Birmingham, AL). Sample preparation took 2 h, and testing on
the BD Max took an additional 2 h. Method sensitivity and specificity were
evaluated along with the limits of detection to confirm that this convenient
method would provide medically useful information. Using serial dilutions, the
lower limit of detection was determined to be 1 CFU/MUl. Testing with this method
was validated using samples from various body sites, including bronchial alveolar
lavage (BAL) fluid; sputum and lung tissue samples; and pleural and spinal
fluids. Safety protocols were established, and specimen preparation processes
were developed for the various types of specimens. The range for the cycle
threshold (CT) indicating adequate fluorescent signal to signify a positive
result was established along with the acceptable range for the internal standard.
Positive controls run with each batch were prepared by spiking a pooled BAL fluid
specimen with a known dilution of Coccidioides immitis organism. Our experience
with testing >330 patient samples shows that clinically relevant information can
be available within 4 h using an RT-PCR method on the BD Max to identify
Coccidioides spp., with sensitivity equivalent to culture.
PMID- 25588652
TI - Multicenter evaluation of the BioFire FilmArray gastrointestinal panel for
etiologic diagnosis of infectious gastroenteritis.
AB - The appropriate treatment and control of infectious gastroenteritis depend on the
ability to rapidly detect the wide range of etiologic agents associated with the
disease. Clinical laboratories currently utilize an array of different
methodologies to test for bacterial, parasitic, and viral causes of
gastroenteritis, a strategy that suffers from poor sensitivity, potentially long
turnaround times, and complicated ordering practices and workflows. Additionally,
there are limited or no testing methods routinely available for most
diarrheagenic Escherichia coli strains, astroviruses, and sapoviruses. This study
assessed the performance of the FilmArray Gastrointestinal (GI) Panel for the
simultaneous detection of 22 different enteric pathogens directly from stool
specimens: Campylobacter spp., Clostridium difficile (toxin A/B), Plesiomonas
shigelloides, Salmonella spp., Vibrio spp., Vibrio cholerae, Yersinia
enterocolitica, enteroaggregative E. coli, enteropathogenic E. coli,
enterotoxigenic E. coli, Shiga-like toxin-producing E. coli (stx1 and stx2)
(including specific detection of E. coli O157), Shigella spp./enteroinvasive E.
coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica,
Giardia lamblia, adenovirus F 40/41, astrovirus, norovirus GI/GII, rotavirus A,
and sapovirus. Prospectively collected stool specimens (n = 1,556) were evaluated
using the BioFire FilmArray GI Panel and tested with conventional stool culture
and molecular methods for comparison. The FilmArray GI Panel sensitivity was 100%
for 12/22 targets and >=94.5% for an additional 7/22 targets. For the remaining
three targets, sensitivity could not be calculated due to the low prevalences in
this study. The FilmArray GI Panel specificity was >=97.1% for all panel targets.
The FilmArray GI Panel provides a comprehensive, rapid, and streamlined
alternative to conventional methods for the etiologic diagnosis of infectious
gastroenteritis in the laboratory setting. The potential advantages include
improved performance parameters, a more extensive menu of pathogens, and a
turnaround time of as short as 1 h.
PMID- 25588653
TI - Development and validation of a quantitative PCR assay using multiplexed
hydrolysis probes for detection and quantification of Theileria orientalis
isolates and differentiation of clinically relevant subtypes.
AB - Theileria orientalis is an emerging pathogen of cattle in Asia, Australia, and
New Zealand. This organism is a vector-borne hemoprotozoan that causes clinical
disease characterized by anemia, abortion, and death, as well as persistent
subclinical infections. Molecular methods of diagnosis are preferred due to their
sensitivity and utility in differentiating between pathogenic and apathogenic
genotypes. Conventional PCR (cPCR) assays for T. orientalis detection and typing
are laborious and do not provide an estimate of parasite load. Current real-time
PCR assays cannot differentiate between clinically relevant and benign genotypes
or are only semiquantitative without a defined clinical threshold. Here, we
developed and validated a hydrolysis probe quantitative PCR (qPCR) assay which
universally detects and quantifies T. orientalis and identifies the clinically
associated Ikeda and Chitose genotypes (UIC assay). Comparison of the UIC assay
results with previously validated universal and genotype-specific cPCR results
demonstrated that qPCR detects and differentiates T. orientalis with high
sensitivity and specificiy. Comparison of quantitative results based on percent
parasitemia, determined via blood film analysis and packed cell volume (PCV)
revealed significant positive and negative correlations, respectively. One-way
analysis of variance (ANOVA) indicated that blood samples from animals with
clinical signs of disease contained statistically higher concentrations of T.
orientalis DNA than animals with subclinical infections. We propose clinical
thresholds to assist in classifying high-, moderate-, and low-level infections
and describe how parasite load and the presence of the Ikeda and Chitose
genotypes relate to disease.
PMID- 25588655
TI - Defining the phylogenomics of Shigella species: a pathway to diagnostics.
AB - Shigellae cause significant diarrheal disease and mortality in humans, as there
are approximately 163 million episodes of shigellosis and 1.1 million deaths
annually. While significant strides have been made in the understanding of the
pathogenesis, few studies on the genomic content of the Shigella species have
been completed. The goal of this study was to characterize the genomic diversity
of Shigella species through sequencing of 55 isolates representing members of
each of the four Shigella species: S. flexneri, S. sonnei, S. boydii, and S.
dysenteriae. Phylogeny inferred from 336 available Shigella and Escherichia coli
genomes defined exclusive clades of Shigella; conserved genomic markers that can
identify each clade were then identified. PCR assays were developed for each
clade-specific marker, which was combined with an amplicon for the conserved
Shigella invasion antigen, IpaH3, into a multiplex PCR assay. This assay
demonstrated high specificity, correctly identifying 218 of 221 presumptive
Shigella isolates, and sensitivity, by not identifying any of 151 diverse E. coli
isolates incorrectly as Shigella. This new phylogenomics-based PCR assay
represents a valuable tool for rapid typing of uncharacterized Shigella isolates
and provides a framework that can be utilized for the identification of novel
genomic markers from genomic data.
PMID- 25588656
TI - Evaluation of enzyme immunoassays and real-time PCR for detecting Shiga toxin
producing Escherichia coli in Southern Alberta, Canada.
AB - Two immunoassays (Shiga Toxin Chek and Shiga Toxin Quik Chek) and real-time PCR
were used to detect Shiga toxin-producing Escherichia coli. For enriched culture,
the sensitivity and specificity of the three methods ranged from 80.0% to 98.2%
and 98.0% to 100.0%, respectively. STEC isolates were identified in 2.6% of the
784 samples.
PMID- 25588657
TI - Characterization of enterovirus activity, including that of enterovirus D68, in
pediatric patients in Alberta, Canada, in 2014.
PMID- 25588658
TI - Detection of a transient R292K mutation in influenza A/H3N2 viruses shed for
several weeks by an immunocompromised patient.
AB - We describe the case of an immunocompromised patient, positive for influenza A
virus (H3N2), in whom the neuraminidase R292K mutation was transiently detected
during oseltamivir treatment. The R292K mutation was identified by direct testing
in 3 of 11 respiratory specimens collected throughout the patient's illness but
in none of the cultures from those specimens.
PMID- 25588660
TI - Detection of mycobacteria, Mycobacterium avium subspecies, and Mycobacterium
tuberculosis complex by a novel tetraplex real-time PCR assay.
AB - Mycobacterium tuberculosis complex, Mycobacterium avium, and many other
nontuberculous mycobacteria are worldwide distributed microorganisms of major
medical and veterinary importance. Considering the growing epidemiologic
significance of wildlife-livestock-human interrelation, developing rapid
detection tools of high specificity and sensitivity is vital to assess their
presence and accelerate the process of diagnosing mycobacteriosis. Here we
describe the development and evaluation of a novel tetraplex real-time PCR for
simultaneous detection of Mycobacterium genus, M. avium subspecies, and M.
tuberculosis complex in an internally monitored single assay. The method was
evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28)
strains, tissues spiked with different CFU amounts of three mycobacterial species
(n = 57), archival clinical samples (n = 233), and strains isolated from various
hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M.
bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked
samples were analyzed, the method consistently detected as few as 100 to 1,000
mycobacterial CFU per gram. The sensitivity and specificity values for the panel
of clinical samples were 97.5 and 100% using a verified culture-based method as
the reference method. The assays performed on clinical isolates confirmed these
results. This PCR was able to identify M. avium and M. tuberculosis complex in
the same sample in one reaction. In conclusion, the tetraplex real-time PCR we
designed represents a highly specific and sensitive tool for the detection and
identification of mycobacteria in routine laboratory diagnosis with potential
additional uses.
PMID- 25588662
TI - Do turtles follow the rules? Latitudinal gradients in species richness, body
size, and geographic range area of the world's turtles.
AB - Understanding how and why biodiversity is structured across the globe has been
central to ecology, evolution, and biogeography even before those disciplines
took their modern forms. Three global-scale patterns in particular have been the
focus of research and debate for decades: latitudinal gradients in species
richness (richness decreases with increasing latitude), body size (body size
increases with increasing latitude in endotherms; Bergmann's rule), and
geographic range size (range size increases with increasing latitude; Rapoport's
rule). Despite decades of study, the generality and robustness of these trends
have been debated, as have their underlying causes. Here we investigate
latitudinal gradients in species richness, body size, and range size in the
world's turtles (Testudines), and add more evidence that these rules do not seem
to apply across all taxa. We show that turtle diversity actually peaks at 25
degrees north, a highly unusual global pattern. Turtles also fail to follow
Bergmann's Rule, and may show the converse (larger at lower latitudes), though
trends are weak. Turtles also show a complex relationship between latitude and
range size that does not directly follow Rapoport's rule. Body size and
geographic range size are significantly correlated, and multiple abiotic and
biotic variables help explain the relationships between latitude and species
diversity, body size, and range size. Although we show that turtles do not
strictly follow some classic biogeographical rules, we also call for further in
depth research to investigate potential causal mechanisms for these atypical
patterns.
PMID- 25588661
TI - Twist1 and Snail link Hedgehog signaling to tumor-initiating cell-like properties
and acquired chemoresistance independently of ABC transporters.
AB - The Hedgehog (Hh) signaling pathway has been implicated in acquired
chemoresistance. However, it remains unclear whether and how the Hh pathway may
maintain the chemoresistant phenotype by controlling the tumor-initiating cell
like properties of acquired chemoresistant cancer cells. In this study, using
well-established acquired chemoresistant cancer cells and chemosensitive KB
cancer cells with artificially elevated Hh pathway activity, we found that Hh
pathway activity may transcriptionally control the expression of twist1 and
snail, thereby maintaining the tumor-initiating cell-like properties and
consequently the chemoresistant phenotype. Meanwhile, we obtained direct evidence
that twist1, which may amplify Hh signaling activity and plays an essential role
in limb development, is a direct transcriptional target of Gli, similar to snail.
We further observed that the expression of ATP-binding cassette (ABC)
transporters was dispensable for the chemoresistance mediated by twist1 and
snail. Collectively, these findings demonstrate that twist1, together with snail,
links the Hh pathway to the tumor-initiating cell-like properties of
chemoresistant cells. This consequently promotes chemoresistance independently of
ABC transporters, thereby contributing to future development of strategies for
combating chemoresistance through Hh pathway interference. Furthermore, our
finding that twist1 is a direct target of the transcription factor Gli improves
the interpretation of the association between twist1 and the Hh pathway and the
nature of the signaling transduction of the Hh pathway.
PMID- 25588659
TI - Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent
assays and two rapid diagnostic tests for diagnosing dengue fever.
AB - We evaluated four dengue diagnostic devices from Alere, including the SD Bioline
Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette
(IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG
capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled,
multicenter study in Peru, Venezuela, Cambodia, and the United States, using
samples from 1,021 febrile individuals. Archived, well-characterized samples from
an additional 135 febrile individuals from Thailand were also used. Reference
testing was performed on all samples using an algorithm involving virus
isolation, in-house IgM and IgG capture ELISAs, and plaque reduction
neutralization tests (PRNT) to determine the infection status of the individual.
The primary endpoints were the clinical sensitivities and specificities of these
devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95%
confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9
to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue
Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity
of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA
had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to
92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a
sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%)
during days 4 to 14 p.s.o. for identification of secondary dengue infections.
This multicountry prospective study resulted in reliable real-world performance
data that will facilitate data-driven laboratory test choices for managing
patient care during dengue outbreaks.
PMID- 25588663
TI - Modified dorsal percutaneous screw fixation through a transtrapezial approach for
scaphoid fractures.
PMID- 25588664
TI - Arm versus forearm tourniquet for carpal tunnel decompression - Which is better?
A randomized controlled trial.
AB - Tourniquet pain is a common source of complaint for patients undergoing carpal
tunnel decompression and practice varies as to the tourniquet position used.
There is little evidence to suggest benefit of one position over another. Our aim
was to compare patient and surgeon experience of forearm and arm tourniquets.
Following a power calculation, 100 patients undergoing open carpal tunnel
decompression under local anaesthetic were randomized to either an arm or a
forearm tourniquet. Measurements of blood pressure, heart rate and pain were
taken at 2.5 min intervals. The operating surgeon also provided a visual analogue
scale rating for the extent of bloodless field achieved and for any obstruction
caused by the tourniquet. There was no statistically significant inter-group
difference in patient pain or physiological response, tourniquet time, bloodless
field or length of procedure. The degree of obstruction caused by the tourniquet
was significantly higher in the forearm group. LEVEL OF EVIDENCE: I. Prospective
Randomized Controlled Trial.
PMID- 25588665
TI - Subperiosteal ganglion cyst in distal end radius in an adolescent.
PMID- 25588666
TI - Surgical adhesive BioGlueTM does not benefit tendon repair strength: an ex vivo
study.
AB - Surgical adhesives are useful supplements in surgery, but their benefit in tendon
repair is uncertain. The purpose of this study was to evaluate the effect of
BioGlueTM on strength of flexor tendon repair. A total of 60 porcine flexor
tendons were divided into three groups. In group one, a conventional core and
peripheral suture repair was used. In group two, a core suture and BioGlueTM were
used. In group three, a conventional core and peripheral suture repair and
BioGlueTM were used. We performed static and cyclic axial load testing and
measured diameter of the repair site. We found that BioGlueTM did not improve the
tensile strength when added to a core and peripheral suture and that there was an
increase in bulk at the repair site. We conclude that BioGlueTM application
cannot replace a peripheral suture as tensile strength significantly decreases
without a peripheral suture, and it does not benefit a tendon already repaired
with a core and peripheral suture. LEVEL OF EVIDENCE: n/a.
PMID- 25588667
TI - Crowdfunding: from startup businesses to startup science.
PMID- 25588668
TI - Osteometric sorting of skeletal elements from a sample of modern Colombians: a
pilot study.
AB - The Colombian armed conflict has been catalogued not only as the longest civil
war in the western hemisphere, but also as having one of the highest indexes of
missing persons. Among the several challenges faced by forensic practitioners in
Colombia, the commingling of human remains has been recognised as one of the most
difficult to approach. The method of osteometric sorting described by Byrd and
Adams and Byrd (2008) has proven relevant as a powerful tool to aid in the
reassociation process of skeletal structures. The aim of this research was to
evaluate the three osteometric sorting models developed by Byrd (2008) (paired
elements, articulating bone portions and other bone portions) in a sample of
modern Colombian individuals. A set of 39 linear measurements was recorded from a
sample of 100 individuals (47 females and 53 males aged between 20 and 74 and 18
and 77 years, respectively), which was used to create a reference sample
database. A different subset of eight individuals (five females aged between 23
and 48 years, and three males aged between 27 and 43 years) was employed to
randomly create six small-scale commingled assemblages for the purposes of
testing the osteometric sorting models. Results demonstrate that this method has
significant potential for use in the Colombian forensic context.
PMID- 25588669
TI - Comment on "major source of error when calculating bone mechanical properties".
PMID- 25588670
TI - A poroviscohyperelastic model for numerical analysis of mechanical behavior of
single chondrocyte.
AB - The aim of this paper is to use a poroviscohyperelastic (PVHE) model, which is
developed based on the porohyperelastic (PHE) model to explore the mechanical
deformation properties of single chondrocytes. Both creep and relaxation
responses are investigated by using finite element analysis models of
micropipette aspiration and atomic force microscopy experiments, respectively.
The newly developed PVHE model is compared thoroughly with the standard neo
Hookean solid and PHE models. It has been found that the PVHE can accurately
capture both creep and stress relaxation behaviors of chondrocytes better than
other two models. Hence, the PVHE is a promising model to investigate mechanical
properties of single chondrocytes.
PMID- 25588673
TI - The toxicity of carbofuran to the freshwater rotifer, Philodina roseola.
AB - In this study, the effects of exposing the rotifer Philodina roseola to the
pesticide carbofuran were investigated. Its range of sensitivity to potassium
dichromate, the acute toxicity of active ingredient carbofuran and of carbofuran
dosed as its commercial form, Furadan((r)) 350 SC were determined. Chronic
toxicity of carbofuran dosed as Furadan((r)) 350 SC on P. roseola survival and
fecundity were also studied. The sensitivity of P. roseola to K2Cr2O7 ranged from
29.52 to 64.67 mg L(-1), averaging 47.10 mg L(-1). The 48-h EC50 were 13.36 +/-
2.63 mg L(-1) for carbofuran and 89.32 +/- 6.52 mg L(-1) for commercial form.
Chronic toxicity tests showed that the survival of this rotifer was not affected
by the carbofuran dosed as Furadan((r)) 350 SC at the concentrations tested and
that at 1.56 and 3.12 mg L(-1) their fecundity was higher than in the absence of
this commercial product, characterizing the hormesis phenomenon. The sensitivity
profile of several species to carbofuran indicated that P. roseola is more
susceptible to this pesticide than the fish Clarias batrachus, the bacterium
Vibrio fischeri, the protozoan Paramecium caudatum and the rotifer Brachionus
calyciflorus, although the acute toxicity of carbofuran dosed as Furadan((r)) 350
SC to P. roseola is much lower than that of active ingredient carbofuran. The
results also imply that the exacerbated use of pesticides and the constant,
accelerated expansion of agricultural activity will make aquatic non-target
species even more vulnerable. Furthermore, the relevant role of benthic organisms
in aquatic environments justifies the inclusion of P. roseola and other benthic
species in toxicity screening for risk assessment, regarding this environmental
compartment.
PMID- 25588675
TI - Yellowing of desflurane in the vaporizer.
PMID- 25588674
TI - Effects of tetracycline on developmental toxicity and molecular responses in
zebrafish (Danio rerio) embryos.
AB - The extensive use of pharmaceuticals has resulted in the intensive contamination
of water bodies. Tetracycline is a type of antibiotic and its potential toxicity
is causing environmental concern. The effects of developmental toxicity and the
mechanisms of tetracycline on fish embryos are not well understood. Zebrafish
embryos are used in this study to investigate the developmental toxicity of this
compound. Four hour post-fertilization (hpf) zebrafish embryos are exposed to
different concentrations of tetracycline until 96 hpf. The larvae display
developmental delay phenotypes, including hatching delay, shorter body length,
increased yolk sac area and uninflated swim bladder upon exposure to
tetracycline. Delayed yolk sac absorption and swim bladder deficiency at 96 hpf
are observed in the zebrafish larvae upon exposure to 20 MUg/L of tetracycline.
To test whether tetracycline causes oxidative damage and the resulting oxidative
stress-induced apoptosis, the generation of reactive oxygen species (ROS),
Acridine Orange staining and real time polymerase chain reaction have been
performed in this study. The results indicate that tetracycline exposure results
in significant increases in ROS production and cell apoptosis, mainly in the tail
areas at 96 hpf. The gene expression pattern demonstrates that tetracycline
induces ROS which causes apoptosis in the zebrafish larvae, and the results also
indicate that caspase-dependent apoptotic pathways may greatly contribute to
tetracycline-induced apoptosis in the early-life stages of the zebrafish. In
addition, we have investigated the effects of tetracycline on marker genes
related to resistance mechanisms and gene regulating drug biotransformation. The
results of these gene expression studies indicate that tetracycline could induce
zebrafish to resist pharmaceuticals and Cytochrome P450s that are involved in the
biotransformation of tetracycline in zebrafish larvae. The overall results
indicate that tetracycline can produce oxidative stress and induce apoptosis,
which brings about significant developmental delay in zebrafish embryos.
PMID- 25588676
TI - Differential regulation of hsp70 genes in the freshwater key species Gammarus
pulex (Crustacea, Amphipoda) exposed to thermal stress: effects of latitude and
ontogeny.
AB - Temperature is one of the main abiotic factors influencing the distribution and
abundance of organisms. In the Rhone River Valley, populations of the crustacean
Gammarus pulex are distributed along a 5 degrees C thermal gradient from the
North to the South of the valley. In this present work, we investigated the heat
shock response of G. pulex according to latitudinal distribution (northern vs.
southern populations) and ontogeny (adults vs. embryos from early stages). We
isolated two isoforms (one constitutive hsc70 and one inducible hsp70) of heat
shock proteins 70 (HSP70) and quantitatively compared their amounts of mRNA after
heat shocks, using real-time PCR. Whereas the hsc70 (constitutive) gene did not
vary between the two populations, a significant effect of the population was
observed on the expression of the hsp70 (inducible) gene in adult specimens. The
northern population of amphipods showed a greater magnitude of induction and a 2
degrees C lower onset temperature when compared to the southern population,
suggesting that the northern population is more affected by elevated temperature
than the southern one. We demonstrated that the expression of hsp70 may play a
crucial role in the persistence of biogeographical patterns of G. pulex, since it
reflects the natural distribution of this species along the latitudinal thermal
gradient. A differential regulation of hsc70 gene was also observed according to
the ontogenetic stage, with a switch from heat inducible in early life stages to
constitutively and highly expressed in adults. These findings demonstrate the
importance of considering the entire life cycle to better understand the adaptive
response to thermal stress.
PMID- 25588678
TI - The future of MCH nutrition services: a commentary on the importance of
supporting leadership training to strengthen the nutrition workforce.
PMID- 25588677
TI - Platelet transfusions in platelet consumptive disorders are associated with
arterial thrombosis and in-hospital mortality.
AB - While platelets are primary mediators of hemostasis, there is emerging evidence
to show that they may also mediate pathologic thrombogenesis. Little data are
available on risks and benefits associated with platelet transfusions in
thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT)
and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide
Inpatient Sample to evaluate the current in-hospital platelet transfusion
practices and their association with arterial/venous thrombosis, acute myocardial
infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age
and gender-adjusted odds ratios (adjOR) associated with platelet transfusions
were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and
79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and
25.8% ITP admissions. Platelet transfusions in TTP were associated with higher
odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0,
95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous
thrombosis. Platelet transfusions in HIT were associated with higher odds of
arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2,
95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships
remained significant after adjusting for clinical severity and acuity. No
associations were significant for ITP. Platelet transfusions are associated with
higher odds of arterial thrombosis and mortality among TTP and HIT patients.
PMID- 25588679
TI - Mixed transcortical aphasia: a case report.
PMID- 25588680
TI - Neural correlates of consciousness: what we know and what we have to learn!
AB - Consciousness is a multifaceted concept with two major components: awareness of
environment and of self (i.e., the content of consciousness) and wakefulness
(i.e., the level of consciousness). Medically speaking, consciousness is the
state of the patient's awareness of self and environment and his responsiveness
to external stimulation and inner need. A basic understanding of consciousness
and its neural correlates is of major importance for all clinicians, especially
those involved with patients suffering from altered states of consciousness. To
this end, in this review it is shown that consciousness is dependent on the
brainstem and thalamus for arousal; that basic cognition is supported by
recurrent electrical activity between the cortex and the thalamus at gamma band
frequencies; and that some kind of working memory must, at least fleetingly, be
present for awareness to occur. New advances in neuroimaging studies are also
presented in order to better understand and demonstrate the neurophysiological
basis of consciousness. In particular, recent functional magnetic resonance
imaging studies have offered the possibility to measure directly and non
invasively normal and severely brain damaged subjects' brain activity, whilst
diffusion tensor imaging studies have allowed evaluating white matter integrity
in normal subjects and patients with disorder of consciousness.
PMID- 25588682
TI - A novel experimental study on the fabrication and biological characteristics of
canine bone marrow mesenchymal stem cells sheet using vitamin C.
AB - The aim of this study was to fabricate canine bone marrow mesenchymal stem cell
sheet through the use of vitamin C, to identify the biological characteristics of
the resulting cell sheets, and to reveal the potential mechanism of cell-sheet
promotion by vitamin C. This study used vitamin C to induce bone marrow
mesenchymal stem cells to proliferate. The resulting cells secreted large amounts
of collagen, thereby shortening the construction time of the cell-sheet layer. In
addition to these aims, we identified biological microcharacteristics of the cell
sheet through histological observation, transmission electron microscopy, real
time PCR detection, immunohistochemical detection, and osteogenesis-induction
experiments on the cell sheet. We were able to stably and rapidly construct bone
marrow mesenchymal stem cell sheet, effectively harvest it, and transfer the seed
cells for tissue engineering. This study indicates that the use of vitamin C for
harvesting mesenchymal stem cell sheets from bone marrow may provide an easy and
practical approach for bone tissue regeneration.
PMID- 25588681
TI - A case of type B lactic acidosis as a complication of chronic myelomonocytic
leukaemia: a case report and review of the literature.
AB - INTRODUCTION: Type B lactic acidosis represents a rare and often lethal
complication of haematological malignancy. Here, we present a patient who
developed a type B lactic acidosis presumably due to a concurrent chronic
myelomonocytic leukaemia. Upon swift initiation of cytoreductive chemotherapy
(doxorubicin), the lactic acidosis was rapidly brought under control. This case
adds to the literature reporting other haematological malignancies that can cause
a type B lactic acidosis and its successful treatment. CASE PRESENTATION: We
report the case of a 77-year-old Caucasian man brought to our Accident and
Emergency department following an unwitnessed collapse; he was found surrounded
by coffee-ground vomit. Although haemodynamically stable on admission, he rapidly
deteriorated as his lactic acid rose. An initial arterial blood gas revealed a pH
of 7.27 and lactate of 18mmol/L (peaking at 21mmol/L). CONCLUSIONS: A high degree
of clinical suspicion for haematological malignancy should be held when presented
with a patient with lactic acidosis in clinical practice, even without evidence
of poor oxygenation or another cause. Treatment with emergency chemotherapy, in
lieu of a definitive diagnosis, was rapidly successful at lowering lactate levels
within 8 hours. This may suggest a causal and perhaps direct relationship between
lactic acid production and the presence of leukemic cells. Veno-venous
haemofiltration had no apparent effect on reducing the lactic acidosis and
therefore its benefit is questioned in this setting, especially at the cost of
delaying chemotherapy. In the face of a life-threatening lactic acidosis,
pragmatic clinical judgement alone may justify the rapid initiation of
chemotherapy.
PMID- 25588683
TI - Tissue engineering and regenerative medicine in applied research: a year in
review of 2014.
AB - Tissue engineering and regenerative medicine (TERM) remains to be one of the
fastest growing fields, which covers a wide scope of topics of both basic and
applied biological researches. This overview article summarized the advancements
in applied researches of TERM area, including stem cell-mediated tissue
regeneration, material science, and TERM clinical trial. These achievements
demonstrated the great potential of clinical regenerative therapy of tissue/organ
disease or defect through stem cells and tissue engineering approaches.
PMID- 25588685
TI - A novel marker to predict early recurrence after atrial fibrillation ablation:
the ablation effectiveness quotient.
AB - INTRODUCTION: Inability to predict clinical outcome despite acutely successful
pulmonary vein isolation (PVI) remains the Achilles' heel of atrial fibrillation
ablation (AFA). Arrhythmia recurrence is frequently due to recovery of
radiofrequency (RF) ablation lesions believed to be complete at the original
procedure. OBJECTIVES: We hypothesized that a high ratio between post-AFA levels
of serum high sensitivity cardiac troponin T (HScTnT), a highly specific marker
of acute myocardial injury, and duration of RF application (the ablation
effectiveness quotient, AEQ) would indicate effective ablation and correlate with
early clinical success. METHODS: We prospectively measured HScTnT levels in 60
patients (42 [70%] male, 22 [37%] with paroxysmal AF [PAF], mean age 62.5 +/-
10.6 years) 12-18 hours after AFA and calculated the AEQ for each. Patients were
followed-up with ECGs and Holter monitors for recurrence of atrial
tachyarrhythmia (AT). RESULTS: Early recurrence of AT within 6 months occurred in
22 (37%). AT recurrence was not significantly related to left atrial size or
comorbidities, nor to RF time or HScTnT level. Mean AEQ was significantly lower
in those with recurrence than those without (0.35 +/- 0.14 ng/L/s vs. 0.45 +/-
0.18 ng/L/s), P = 0.02. Subgroup analysis showed this finding was due to patients
with PAF in whom early significance was maintained to one year, with an AEQ >0.4
ng/L/s having 75% sensitivity and 90% specificity in predicting freedom from AT.
CONCLUSION: A high AEQ correlates well with freedom from AT in patients with PAF
in both the short and medium term. If confirmed in further studies, AEQ may
become a useful marker of risk of AT post-AFA.
PMID- 25588686
TI - Toxic Epidermal Necrolysis During Dronedarone Treatment: First Report of a Severe
Serious Adverse Event Of A New Antiarrhythmic Drug.
AB - A 77-year-old female patient with symptomatic atrial fibrillation with fast
ventricular rate despite conventional antiarrhythmic therapy was treated with
dronedarone. Five days later, she developed a maculopapulous exanthema and small
flaccid blisters, which spread over the common integument predominantly located
on the dorsal trunk. Over few days, the patient showed a severe epidermal
necrolysis of approximately 30 % of the body area and ultimately died in
multiorgan failure. Here, we report a rare case of toxic epidermal necrolysis
during treatment with dronedarone leading to patient death.
PMID- 25588688
TI - Health literacy, vulnerable patients, and health information technology use:
where do we go from here?
PMID- 25588687
TI - The Natural Antimicrobial Subtilosin A Synergizes with Lauramide Arginine Ethyl
Ester (LAE), epsilon-Poly-L-lysine (Polylysine), Clindamycin Phosphate and
Metronidazole, Against the Vaginal Pathogen Gardnerella vaginalis.
AB - Bacterial vaginosis (BV) is a common, recurrent vaginal infection linked to
increased chances of preterm delivery, incidence of sexually transmitted
infections and fertility problems. BV is caused by a shift of the vaginal
ecosystem from predominately Lactobacillus to a multispecies Actinomyces biofilm
with the most common representatives identified as Gardnerella vaginalis and
Prevotella spp. Current treatments have been associated with increased resistance
as well as negative effects on healthy microbiota. The objective of this study
was to evaluate the synergistic potential of ten two-antimicrobial combinations
against G. vaginalis and four representative lactobacilli. The four tested
antimicrobials were lauramide arginine ethyl ester, epsilon-poly-L-lysine,
clindamycin phosphate, metronidazole and the bacteriocin subtilosin A. The use of
bacteriocins as either synergist or alternative treatment positions bacteriocins
as an excellent alternative to current antibiotics. The microdilution method was
used to determine the minimum inhibitory concentration (MIC) of each of the
antimicrobials individually, and the checkerboard assay was used to evaluate
these MICs in combination. Clindamycin and subtilosin (CS), and metronidazole and
subtilosin were synergistic against G. vaginalis in terms of fractional
inhibitory concentration index (FICI). All tested combinations were found to have
Bliss synergy. The combination of clindamycin and polylysine (CP) was identified
as antagonistic against L. acidophilus in terms of both FICI and Bliss synergy.
The combination of clindamycin and metronidazole (CM) was antagonistic against L.
vaginalis for both FICI and Bliss synergy. The combinations of CP, clindamycin
and LAE, CS, and LAE and polylysine were identified as Bliss antagonistic against
L. vaginalis but did not indicate FICI antagonism.
PMID- 25588689
TI - Control of selectivity in allylic alcohol oxidation on gold surfaces: the role of
oxygen adatoms and hydroxyl species.
AB - Gold catalysts display high activity and good selectivity for partial oxidation
of a number of alcohol species. In this work, we discuss the effects of oxygen
adatoms and surface hydroxyls on the selectivity for oxidation of allylic
alcohols (allyl alcohol and crotyl alcohol) on gold surfaces. Utilizing
temperature programmed desorption (TPD), reactive molecular beam scattering
(RMBS), and density functional theory (DFT) techniques, we provide evidence to
suggest that the selectivity displayed towards partial oxidation versus
combustion pathways is dependent on the type of oxidant species present on the
gold surface. TPD and RMBS results suggest that surface hydroxyls promote partial
oxidation of allylic alcohols to their corresponding aldehydes with very high
selectivity, while oxygen adatoms promote both partial oxidation and combustion
pathways. DFT calculations indicate that oxygen adatoms can react with acrolein
to promote the formation of a bidentate surface intermediate, similar to
structures that have been shown to decompose to generate combustion products over
other transition metal surfaces. Surface hydroxyls do not readily promote such a
process. Our results help explain phenomena observed in previous studies and may
prove useful in the design of future catalysts for partial oxidation of alcohols.
PMID- 25588690
TI - Right anterior mini-thoracotomy direct aortic self-expanding trans-catheter
aortic valve implantation: A single center experience.
AB - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has been designed to
treat elderly patients with severe aortic stenosis at high risk for surgery.
These patients are also often affected by severe iliac-femoral arteriopathy,
rendering the trans-femoral approach unusable. We report our experience with the
direct-aortic approach to treat these patients. METHODS: From May 2008 to
November 2013 two hundred and thirty-two patients (131 female, 56%) with severe
symptomatic aortic stenosis and no reasonable surgical option due to excessive
risk were evaluated for TAVI at our department. Of these patients, 202 were
deemed eligible for TAVI. Of this group, 50 underwent CoreValve implantation by
the direct aortic approach through a right anterior mini-thoracotmy (28 female,
56%), mean age 81.2+/-6.9. A combined team of cardiologists, cardiac surgeons
with expertise in hybrid procedures, and anesthetists performed all the
procedures. RESULTS: Twenty-eight (56%) patients were female and 11 (22%) were
redo at TAVI. We used a 23-mm CoreValve Evolute in 3 patients (6%), and the most
used valve size was the 29mm in 46% of patients. Mean hemodynamic trans-aortic
gradient was less than 5mmHg. The paravalvular regurgitation was <= grade 1 in 46
patients as assessed by peri-procedural transesophageal echocardiography (TEE).
Seven patients (7/43, 16%) required a permanent pacemaker implantation; 30-day
mortality was 6% (3 patients). Seven patients (14.8%) died during follow-up.
Actuarial survival at 2years is 84.7+/-5.3%. CONCLUSIONS: Transcatheter aortic
valve implantation with the direct aortic approach is safe and feasible, offering
a new attractive option to treat selected high-risk patients with severe aortic
stenosis and peripheral vasculopathy, including those requiring a re-do
procedure.
PMID- 25588691
TI - Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try"
Legislation?
AB - PURPOSE: The Food and Drug Administration Expanded Access (EA) program and "Right
to-Try" legislation aim to provide seriously ill patients who have no other
comparable treatment options to gain access to investigational drugs and
biological agents. Physicians and institutions need to understand these programs
to respond to questions and requests for access. METHODS: FDA EA programs and
state and federal legislative efforts to provide investigational products to
patients by circumventing FDA regulations were summarized and compared. RESULTS:
The FDA EA program includes Single Patient-Investigational New Drug (SP-IND),
Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval
rates for all categories exceed 99%. Approval requires FDA and Institutional
Review Board (IRB) approval, and cooperation of the pharmaceutical partner is
essential. "Right-to-Try" legislation bypasses some of these steps, but provides
no regulatory or safety oversight. CONCLUSION: The FDA EA program is a reasonable
option for patients for whom all other therapeutic interventions have failed. The
SP-IND not only provides patient access to new drugs, but also maintains a
balance between immediacy and necessary patient protection. Rather than
circumventing existing FDA regulations through proposed legislation, it seems
more judicious to provide the knowledge and means to meet the EA requirements.
PMID- 25588692
TI - Irisin: a new molecular marker and target in metabolic disorder.
AB - Irisin is a newly discovered exercise-mediated myokine which regulates energy
metabolism and has been the subject of much recent research. Irisin plays an
important role in metabolic diseases making it a potential new target to combat
obesity and its associated disorders, such as T2DM. However, the results of
several recent studies investigating the effects of irisin have been
controversial. The present review will introduce the discovery of irisin, the
role of irisin in metabolic disorders, possible mechanisms, and unanswered
questions for future research.
PMID- 25588693
TI - Differential competence of redox-regulatory mechanism under extremes of
temperature determines growth performances and cross tolerance in two indica rice
cultivars.
AB - The present study investigated the relationship between reactive oxygen species
(ROS) accumulation (total and individual), antioxidant and radical scavenging
capacity (total and individual), transcript abundance of some antioxidative genes
and oxidative damages to membrane protein and lipid in germinating tissues of a
salt resistant (SR26B) and salt sensitive (Ratna) rice cultivars under extremes
of temperature to elucidate redox-regulatory mechanism governing differential
oxidative stress tolerance associated with better growth and yield potential and
identification of cross tolerance, if any. Imbibitional heat and chilling stress
caused disruption of redox-homeostasis and oxidative damage to a newly assembled
membrane system by increasing pro-oxidant/antioxidant ratio and by aggravating
membrane lipid peroxidation and protein oxidation [measured in terms of
accumulation of thiobarbituric acid reactive substances (TBARS), free carbonyl
content (CO groups), and membrane protein thiol level (MPTL)]. A concomitant
increase in accumulation of individual ROS (superoxide and hydrogen peroxide) and
significant reduction of radical scavenging activity (assessed in terms of ABTS,
FRAP and DPPH methods), non-enzymatic and enzymatic anti-oxidative defense
[assessed in terms of total thiol content and activities of superoxide dismutase
(EC 1.15.1.1), catalase (EC 1.11.1.6), ascorbate peroxidase (EC 1.11.1.11), and
glutathione reductase (EC 1.6.4.2)] are also noticed in both the salt sensitive
(Ratna) and resistant (SR26B) germinating tissues of rice cultivars. When
compared, salt resistant cultivar SR26B was found to suffer significantly less
redox-imbalance and related oxidative damages to membrane protein and lipid as
compared to salt sensitive cultivar Ratna. The salt tolerant cultivar SR26B
resisted imbibitional chilling and heat stress due to its early preparedness to
combat oxidative stress by up-regulation of gene expression of anti-oxidative
enzymes and better capacity of redox-regulation and mitigation of oxidative
damage to membrane protein and lipid as compared to salt sensitive cultivar
Ratna, under the same magnitude of imbibitional heat and chilling stress. A model
for redox-homeostasis in which the ROS-antioxidant interaction acts as a
metabolic interface for up-regulation of gene expression necessary for cross
tolerance is also proposed.
PMID- 25588694
TI - Differential accumulation of glycinebetaine and choline monooxygenase in bladder
hairs and lamina leaves of Atriplex gmelini under high salinity.
AB - Atriplex gmelini is a halophyte and possesses bladder hairs on the leaf surface.
It is also known to accumulate the osmoprotectant glycinebetaine (GB). However,
it remains unclear whether GB and its biosynthetic enzyme choline monooxygenase
(CMO) accumulate in the bladder hairs. Microscopic observation of young leaves
showed many bladder hairs on their surfaces, but their total number decreased
along with leaf maturity. Sodium Green fluorescent approach revealed Na(+)
accumulation in bladder cells of young leaves when A. gmelini was grown at high
salinity (250 mM NaCl). Due to fewer bladder hairs in mature leaves, Na(+)
accumulation was mostly found in mesophyll cells of mature leaves under high
salinity. GB accumulation was found at significant level in both bladder- and
laminae-cells without any addition of NaCl and its content increased at high
salinity. CMO was not found in bladder hairs or young leaf laminae. Instead, the
CMO protein expression was observed in mature leaves and that showed increased
accumulation with increasing concentration of NaCl. Furthermore, in situ
hybridization experiments revealed the expression of a transporter gene for GB,
AgBetT, in the bladder hairs. Based on these results, the synthesis and
translocation of GB in A. gmelini were discussed.
PMID- 25588695
TI - Carbon utilization by fruit limits shoot growth in alternate-bearing citrus
trees.
AB - Fruit load in alternate-bearing citrus trees is reported to alter shoot number
and growth during spring, summer, and autumn flushes, and the source-sink
balance, which affects the storage and mobilization of reserve nutrients. The aim
of this work was to assess the extent of shoot growth inhibition resulting from
the presence of fruits in 'Moncada' mandarin trees loaded with fruit (ON) or with
very light fruit load (OFF), and to identify the role of carbohydrates and
nitrogenous compounds in the competition between fruits and shoots. Growth of
reproductive and vegetative organs was measured on a monthly basis. (13)C- and
(15)N-labeled compounds were supplied to trace the allocation of reserve
nutrients and subsequent translocation from source to sink. At the end of the
year, OFF trees produced more abundant flushes (2.4- and 4.9-fold higher in
number and biomass, respectively) than ON trees. Fruits from ON trees accumulated
higher C amounts at the expense of developing flushes, whereas OFF trees
exhibited the opposite pattern. An inverse relationship was identified between
the amount of C utilized by fruits and vegetative flush growth. (13)C-labeling
revealed an important role for mature leaves of fruit-bearing branches in
supporting shoot/fruit growth, and the elevated sink strength of growing fruits
on shoots. N availability for vegetative shoots was not affected by the presence
or absence of fruits, which accumulated important amounts of (15)N. In
conclusion, our results show that shoot growth is resource-limited as a
consequence of fruit development, and vegetative-growth inhibition is caused by
photoassimilate limitation. The competence for N is not a decisive factor in
limiting vegetative growth under the experimental conditions of this study.
PMID- 25588696
TI - Alcohol consumption in adolescent homicide victims in the city of Johannesburg,
South Africa.
AB - AIMS: To describe the blood alcohol concentration (BAC) of adolescent homicide
victims in Johannesburg, South Africa and to identify the victim and event
characteristics associated with a positive BAC at the time of death. DESIGN:
Logistic regression of mortality data collected by the National Injury Mortality
Surveillance System (NIMSS). SETTING: Johannesburg, South Africa. PARTICIPANTS: A
total of 323 adolescent (15-19 years) homicide victims for the period 2001-9 who
had been tested for the presence of alcohol. MEASUREMENTS: Data on the victims'
BAC level, demographics, weapon or method used, scene, day and time of death were
drawn from NIMSS. FINDINGS: Alcohol was present in 39.3% of the homicide victims.
Of these, 88.2% had a BAC level equivalent to or in excess of the South African
limit of 0.05 g/100 ml for intoxication. Multivariate logistic analysis showed
that a positive BAC in homicide victims was associated significantly with the
victim's sex [male: odds ratio (OR) = 2.127; 95% confidence interval (CI) = 1.012
4.471], victim's age (18-19 years: OR = 2.364; CI = 1.343-4.163); weapon used
(sharp instruments: OR = 2.972; CI = 1.708-5.171); and time of death (weekend: OR
= 3.149; CI = 1.842-5.383; night-time: OR = 2.175; CI = 1.243-3.804).
CONCLUSIONS: Excessive alcohol consumption is associated with a substantial
proportion of adolescent homicides in Johannesburg, South Africa, and is more
prevalent among male and older adolescent victims and in victims killed with
sharp instruments over the weekends and during the evenings.
PMID- 25588697
TI - Direct and simultaneous quantification of tannin mean degree of polymerization
and percentage of galloylation in grape seeds using diffuse reflectance fourier
transform-infrared spectroscopy.
AB - The direct and simultaneous quantitative determination of the mean degree of
polymerization (mDP) and the degree of galloylation (%G) in grape seeds were
quantified using diffuse reflectance infrared Fourier transform spectroscopy and
partial least squares (PLS). The results were compared with those obtained using
the conventional analysis employing phloroglucinolysis as pretreatment followed
by high performance liquid chromatography-UV and mass spectrometry detection.
Infrared spectra were recorded in solid state samples after freeze drying. The
2nd derivative of the 1832 to 1416 and 918 to 739 cm(-1) spectral regions for the
quantification of mDP, the 2nd derivative of the 1813 to 607 cm(-1) spectral
region for the degree of %G determination and PLS regression were used. The
determination coefficients (R(2) ) of mDP and %G were 0.99 and 0.98,
respectively. The corresponding values of the root-mean-square error of
calibration were found 0.506 and 0.692, the root-mean-square error of cross
validation 0.811 and 0.921, and the root-mean-square error of prediction 0.612
and 0.801. The proposed method in comparison with the conventional method is
simpler, less time consuming, more economical, and requires reduced quantities of
chemical reagents and fewer sample pretreatment steps. It could be a starting
point for the design of more specific models according to the requirements of the
wineries.
PMID- 25588698
TI - Alteration of structure and function of ATP synthase and cytochrome c oxidase by
lack of Fo-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation.
AB - Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial
disorders. Typically, these are missense mutations, but another type is
represented by the 9205delTA microdeletion, which removes the stop codon of the
MT-ATP6 gene and affects the cleavage site in the MT-ATP8/MT-ATP6/MT-CO3
polycistronic transcript. This interferes with the processing of mRNAs for the
Atp6 (Fo-a) subunit of ATP synthase and the Cox3 subunit of cytochrome c oxidase
(COX). Two cases described so far presented with strikingly different clinical
phenotypes-mild transient lactic acidosis or fatal encephalopathy. To gain more
insight into the pathogenic mechanism, we prepared 9205delTA cybrids with
mutation load ranging between 52 and 99% and investigated changes in the
structure and function of ATP synthase and the COX. We found that 9205delTA
mutation strongly reduces the levels of both Fo-a and Cox3 proteins. Lack of Fo-a
alters the structure but not the content of ATP synthase, which assembles into a
labile, ~60 kDa smaller, complex retaining ATP hydrolytic activity but which is
unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of
COX but does not alter the structure of the enzyme. Consequently, the diminished
mitochondrial content of COX and non-functional ATP synthase prevent most
mitochondrial ATP production. The biochemical effects caused by the 9205delTA
microdeletion displayed a pronounced threshold effect above ~90% mutation
heteroplasmy. We observed a linear relationship between the decrease in subunit
Fo-a or Cox3 content and the functional presentation of the defect. Therefore we
conclude that the threshold effect originated from a gene-protein level.
PMID- 25588699
TI - Is Pulse Pressure an Independent Risk Factor for Incident Stroke, REasons for
Geographic And Racial Differences in Stroke.
AB - BACKGROUND: Pulse pressure (PP) is a potential risk factor of stroke. The
relationship of incident stroke with systolic blood pressure (SBP), diastolic
blood pressure (DBP), mean arterial pressure (MAP), and PP was examined. METHODS:
Data were from the REasons for Geographic And Racial Differences in Stroke
national cohort study of 30,239 black and white participants aged >=45 years,
enrolled between 2003 and 2007. PP (SBP-DBP) and MAP (MAP = DBP + 1/3*PP) were
calculated. Telephone follow-up occurred every six months for self or proxy
reported suspected stroke events, confirmed using expert adjudication. Cox
proportional hazards models examined the association of incident stroke for the
different BP measurements with multivariable adjustment for sociodemographic and
clinical risk factors including gender and race. RESULTS: Men and women without
prevalent stroke at baseline were analyzed (n = 25,462). During follow-up (mean
6.3+/-2.3 years, maximum 10 years), 916 strokes occurred. Unadjusted PP (hazard
ratio [HR] = 1.30; 95% confidence interval [CI] 1.24-1.35), SBP (HR = 1.22; 95%
CI 1.18-1.32), MAP (HR = 1.24; 95% CI 1.16-1.32), and DBP (HR = 1.09; 95% CI 1.01
1.17) were associated with stroke risk; however, after adjustment for SBP and
other risk factors, the association with PP was attenuated (HR = 0.98; 95% CI
0.90-1.07), whereas SBP persisted as a predictor (HR = 1.14; 95% CI 1.06-1.23).
These associations were consistent across age (younger vs. older >70 years) and
race (black vs. white). CONCLUSIONS: PP is positively associated with incident
stroke, but not independently from SBP; and, there were no significant gender,
racial, or regional differences in that association.
PMID- 25588700
TI - R Wave in aVL Lead is a Robust Index of Left Ventricular Hypertrophy: A Cardiac
MRI Study.
AB - BACKGROUND: In patients free from overt cardiac disease, R wave in aVL lead
(RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by
transthoracic echocardiography. The aim of the present study was to extend this
finding to other settings (cardiomyopathy or conduction disorders), by comparing
ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR). METHODS:
In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR
LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women. RESULTS: RaVL was
independently correlated with LVMI in patients with or without myocardial
infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently
correlated with LVMI and LV enlargement only in patients without MI. In the whole
cohort, RaVL had area under receiver-operating characteristic curve of 0.729
(specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance
of RaVL was remarkable in women, in Caucasians, and in the presence of right
bundle branch block. It decreased in case of MI. Overall, it is proposed that
below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH.
Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be
used. Using this algorithm allowed classifying appropriately 85% of the patients.
CONCLUSIONS: Our results showed that RaVL is a good index of LVH with a univocal
threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL
in some conditions, namely LV enlargement to increase its performance.
PMID- 25588702
TI - Portable oxidative stress sensor: dynamic and non-invasive measurements of
extracellular H2O2 released by algae.
AB - Reactive oxygen species (ROS) generated by aerobic organisms are essential for
physiological processes such as cell signaling, apoptosis, immune defense and
oxidative stress mechanisms. Unbalanced oxidant/antioxidant budgets are involved
in many diseases and, therefore, the sensitive measurement of ROS is of great
interest. Here, we present a new device for the real-time monitoring of oxidative
stress by measuring one of the most stable ROS, namely hydrogen peroxide (H2O2).
This portable oxidative stress sensor contains the heme protein cytochrome c (cyt
c) as sensing element whose spectral response enables the detection of H2O2 down
to a detection limit of 40 nM. This low detection limit is achieved by
introducing cyt c in a random medium, enabling multiscattering that enhances the
optical trajectory through the cyt c spot. A contact microspotting technique is
used to produce reproducible and reusable cyt c spots which are stable for
several days. Experiments in static and microfluidic regimes, as well as
numerical simulations demonstrate the suitability of the cyt c/H2O2 reaction
system for the real-time sensing of the kinetics of biological processes without
H2O2 depletion in the measurement chamber. As an example, we detect the release
of H2O2 from the green alga Chlamydomonas reinhardtii exposed to either 180 nM
functionalized CdSe/ZnS core shell quantum dots, or to 10 mg/l TiO2
nanoparticles. The continuous measurement of extracellular H2O2 by this optical
sensor with high sensitivity is a promising new means for real-time cytotoxicity
tests, the investigation of oxidative stress and other physiological cell
processes.
PMID- 25588701
TI - Salivary alpha amylase diurnal pattern and stress response are associated with
body mass index in low-income preschool-aged children.
AB - Physiological stress responses are proposed as a pathway through which stress can
"get under the skin" and lead to health problems, specifically obesity. We tested
associations of salivary alpha amylase (sAA) diurnal patterns and stress
responses with body mass index (BMI) in young, low-income children (51% male; 54%
non-Hispanic white). Diurnal saliva samples were collected three times per day
across three days for 269 children (M age 50.8 months, SD 6.3). Individual sAA
intercept and slope values were calculated using random effect models to
represent morning sAA levels and rate of sAA change across the day. A subset of
children (n=195; M age 56.6 months, SD 6.9) participated in a lab-based
behavioral stress protocol. Area under the curve increase (AUCI) across four
timepoints was calculated to represent increase in sAA output during stress
elicitation. Children were weighed and height measured and BMI z-score was
calculated. Linear regression was used to evaluate associations of sAA intercept,
sAA slope, and sAA AUCI with BMI z-score, controlling for child age, sex, and
race/ethnicity; maternal weight status; and family income-to-needs ratio. Diurnal
and stress-response sAA patterns were related to child adiposity: for each 1
standard deviation unit (SDU) decrease in morning sAA level, the child's BMI z
score increased by 0.11 (SE 0.05) SDU's (p<.04); for each 1-SDU increase in sAA
slope across the day, the child's BMI z-score increased by 0.12 (SE 0.05) SDU's
(p<.03); and for each 1-SDU decrease in sAA AUCI during the stress elicitation,
the child's BMI z-score increased by 0.14 (SE 0.06) SDU's (p<.03). Blunted stress
responses and atypical diurnal patterns of sAA have been found following exposure
to chronic life stressors such as poverty. Findings suggest that associations of
stress, sAA, and elevated body mass index may develop very early in the lifespan.
PMID- 25588703
TI - A facile fluorescence method for versatile biomolecular detection based on
pristine alpha-Fe2O3 nanoparticle-induced fluorescence quenching.
AB - This work investigated the interactions of alpha-Fe2O3 nanoparticles (NPs) with
different structural nucleic acids and their fluorescence quenching ability
towards fluorophore-labelled nucleic acid probes. Different from bulk alpha-Fe2O3
samples, nanoscale alpha-Fe2O3 particles exhibit the unique properties of strong
adsorption and fluorescence quenching to fluorophore-labelled single-stranded DNA
(ssDNA) probes. Based on these findings, a facile fluorescence method was
developed for versatile quantification of nucleic acids. The size scale of NPs
makes a significant impact on this sensing platform. Better selectivity was given
by bigger NP (50-100 nm)-based nucleic acid-sensing platform compared with
smaller NP (30 nm)-based one. In the 50-100 nm alpha-Fe2O3 NP-based sensing
platform, single nucleotide mismatch or single base-pair mismatch can even be
effectively discriminated. The targets of micro-RNA (miRNA), ssDNA and double
stranded DNA (dsDNA) are sensitively detected with detection limits of 0.8 nM,
1.1 nM and 0.64 nM (S/N=3), respectively. Significantly, alpha-Fe2O3 NPs possess
different affinities towards ssDNA probes with different lengths, and can be used
as a universal quencher for ssDNA probes labelled with different fluorescent
dyes. On the basis of these properties, the pristine alpha-Fe2O3 NPs hold the
potential to be widely utilized in the development of novel biosensors with
signal amplification or simultaneous multiple target detection strategies.
PMID- 25588704
TI - Kidney transplant recipients carrying the CYP3A4*22 allelic variant have reduced
tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations.
AB - CYP3A4*22 is an allelic variant of the cytochrome P450 3A4 associated with a
decreased activity. Carriers of this polymorphism may require reduced tacrolimus
(Tac) doses to reach the target residual concentrations (Co). We tested this
hypothesis in a population of kidney transplant recipients extracted from a
multicenter, prospective and randomized study. Among the 186 kidney transplant
recipients included, 9.3% (18 patients) were heterozygous for the CYP3A4*22
genotype and none were homozygous (allele frequency of 4.8%). Ten days after
transplantation (3 days after starting treatment with Tac), 11% of the CYP3A4*22
carriers were within the target range of Tac Co (10-15 ng/mL), whereas among the
CYP3A4*1/*1 carriers, 40% were within the target range (p = 0.02, OR = 0.19
[0.03; 0.69]). The mean Tac Co at day 10 in the CYP3A4*1/*22 group was 23.5 ng/mL
(16.6-30.9) compared with 15.1 ng/mL (14-16.3) in the CYP3A4*1/*1 group, p <
0.001. The Tac Co/dose significantly depended on the CYP3A4 genotype during the
follow-up (random effects model, p < 0.001) with the corresponding equivalent
dose for patients heterozygous for CYP3A4*22 being 0.67 [0.54; 0.84] times the
dose for CYP3A4*1/*1 carriers. In conclusion, the CYP3A4*22 allelic variant is
associated with a significantly altered Tac metabolism and carriers of this
polymorphism often reach supratherapeutic concentrations.
PMID- 25588706
TI - The electrical network of maize root apex is gravity dependent.
AB - Investigations carried out on maize roots under microgravity and hypergravity
revealed that gravity conditions have strong effects on the network of plant
electrical activity. Both the duration of action potentials (APs) and their
propagation velocities were significantly affected by gravity. Similarly to what
was reported for animals, increased gravity forces speed-up APs and enhance
synchronized electrical events also in plants. The root apex transition zone
emerges as the most active, as well as the most sensitive, root region in this
respect.
PMID- 25588705
TI - Liposome encapsulated zoledronate favours M1-like behaviour in murine macrophages
cultured with soluble factors from breast cancer cells.
AB - BACKGROUND: Tumour stromal macrophages differentiate to tumour-associated
macrophages (TAMs) with characteristics of immunosuppressive M2-type macrophages,
having a central role in promoting tumour vascularisation, cancer cell
dissemination and in suppressing anti-cancer immune responses. Bisphosphonates
(BPs) are a group of drugs commonly used as anti-resorptive agents. Further,
nitrogen containing BPs like Zoledronate (ZOL), are known to cause unspecific
inflammatory reactions hence the hypothesis that its use could modulate TAMs
polarization toward a more inflammatory phenotype. METHODS: We studied the in
vitro polarization of J774 murine macrophages upon culture in 4T1 breast cancer
cell-conditioned medium (4T1CM) and stimulation with LPS and free and liposome
encapsulated bisphosphonates. RESULTS: In this system, breast cancer soluble
factors reduced the pro-inflammatory activation of macrophages but increased the
secretion of matrix metalloproteinases (MMPs). In the presence of 4T1CM, a non
cytotoxic dose of liposome-encapsulated ZOL (ZOL-LIP) enhanced the expression of
iNOS and TNF-alpha, markers of M1 activation, but did not diminish the expression
of M2-type markers. In contrast, clodronate treatment either as a free drug (CLO)
or liposome-encapsulated (CLO-LIP) decreased the expression of the M1-type
markers and was highly cytotoxic to the macrophages. CONCLUSIONS: Breast cancer
cells soluble factors modulate macrophages toward M2 activation state.
Bisphosphonates may be applied to counteract this modulation. We propose that ZOL
LIP may be suitable for favouring cytotoxic immune responses by TAMs in breast
cancer, whereas CLO-LIP may be appropriate for TAM depletion.
PMID- 25588707
TI - Anatomical and Scanning Electron Microscopic Study of the Tongue in the Meerkat
(Suricata suricatta, Schreber, 1776).
AB - This research presents the first anatomical description of the tongue and lingual
papillae of the meerkat and compares the different information on the morphology
of the other carnivore species. For this purpose, three tongues were used as
material. The tongue was elongated with an oval or rounded apex. On the dorsal
and ventrolateral surfaces of the tongue, filiform papillae had extent variations
in morphology. Papillary body of each filiform papilla on the ventrolateral
surface of the lingual body was ramified into 2-5 glovelike projections, and all
pointed tips of these projections were directed caudally. On the dorsal lingual
surface, each filiform papilla leaned on another without any space and both
lateral borders of each filiform papilla included 4-6 small secondary projections
or spines. A few rounded fungiform papillae were randomly distributed and
embedded among the filiform papillae. On the caudal one-third of the body, there
were two elongated circumvallate papillae. Some superficial fissures and taste
pores were detected on the flat surfaces of each circumvallate papilla which was
surrounded by a prominent and continuous gustatory groove. On the radix of the
tongue, numerous dome-shaped protuberances of lingual salivary glands beneath the
epithelium and one centrally located orificium was very invincible on the convex
surface of each protuberance. Anatomical distribution of lingual papillae
differed from those of other carnivores and represented morphological adaptation
to the food type and feeding habits.
PMID- 25588708
TI - Biological interaction of living cells with COSAN-based synthetic vesicles.
AB - Cobaltabisdicarbollide (COSAN) [3,3'-Co(1,2-C2B9H11)2](-), is a complex boron
based anion that has the unusual property of self-assembly into membranes and
vesicles. These membranes have similar dimensions to biological membranes found
in cells, and previously COSAN has been shown to pass through synthetic lipid
membranes and those of living cells without causing breakdown of membrane barrier
properties. Here, we investigate the interaction of this inorganic membrane
system with living cells. We show that COSAN has no immediate effect on cell
viability, and cells fully recover when COSAN is removed following exposure for
hours to days. COSAN elicits a range of cell biological effects, including
altered cell morphology, inhibition of cell growth and, in some cases, apoptosis.
These observations reveal a new biology at the interface between inorganic,
synthetic COSAN membranes and naturally occurring biological membranes.
PMID- 25588709
TI - Prevalence of Gender Nonconformity in Flanders, Belgium.
AB - Gender nonconformity refers to the extent to which a person's gender identity,
gender role and/or gender expression differs from the cultural norms prescribed
for people of a particular sex, within a certain society and era. Most data on
gender nonconformity focus on the prevalence of gender dysphoria (which also
includes a distress factor) or on the number of legal sex changes. However, not
every gender nonconforming individual experiences distress or applies for
treatment. Population-based research on the broad spectrum of gender
nonconformity is scarce and more information on the variance outside the gender
binary is needed. This study aimed to examine the prevalence of gender
incongruence (identifying stronger with the other sex than with the sex assigned
at birth) and gender ambivalence (identifying equally with the other sex as with
the sex assigned at birth) based on two population-based surveys, one of 1,832
Flemish persons and one of 2,472 sexual minority individuals in Flanders. In the
general population, gender ambivalence was present in 2.2 % of male and 1.9 % of
female participants, whereas gender incongruence was found in 0.7 % of men and
0.6 % of women. In sexual minority individuals, the prevalence of gender
ambivalence and gender incongruence was 1.8 and 0.9 % in men and 4.1 and 2.1 % in
women, respectively. With a current Flemish population of about 6 million, our
results indicate a total of between 17,150 and 17,665 gender incongruent men and
between 14,473 and 15,221 gender incongruent women in Flanders.
PMID- 25588710
TI - Development of a high affinity, non-covalent biologic to add functionality to
Fabs.
AB - Functionalization of monoclonal antibodies (mAbs) requires chemical
derivatization and/or genetic manipulation. Inherent in these methods are
challenges with protein heterogeneity, stability and solubility. Such
perturbations could potentially be avoided by using a high affinity, non-covalent
intermediate to bridge the desired functionality to a stable mAb. Recently, we
engineered a binding site for a peptide named "meditope" within the Fab of
trastuzumab. Proximity of the meditope site to that of protein L suggested an
opportunity to enhance the meditope's moderate affinity. Joined by a peptide
linker, the meditope-protein L construct has a KD ~ 180 pM - a 7000-fold increase
in affinity. The construct is highly specific to the engineered trastuzumab, as
demonstrated by flow cytometry. Moreover, the fusion of a bulky GFP to this
construct did not affect the association with cell surface antigens.
Collectively, these data indicate this specific, high affinity construct can be
developed to rapidly add new functionality to mAbs.
PMID- 25588712
TI - Increased risk of depressive disorder following a diagnosis of neovascular age
related macular degeneration.
PMID- 25588711
TI - [The PLIF and TLIF techniques. Indication, technique, advantages, and
disadvantages].
AB - BACKGROUND: Posterior fusion procedures (posterior lumbar interbody fusion, PLIF;
transforaminal lumbar interbody fusion, TLIF) are long-established surgical
techniques for lumbar interbody fusion. They differ from anterior lumbar
interbody fusion (ALIF) and extreme lateral interbody fusion (XLIF) procedures by
approach and associated complications. OBJECTIVES: The posterior fusion
procedures PLIF and TLIF are presented and compared with other fusion methods,
including advantages and disadvantages. Furthermore, the surgical technique and
their complications are described. Based on the current literature, it is
discussed which surgical techniques can be used in various cases. MATERIALS AND
METHODS: A PubMed search of "posterior spinal fusion treatments" and the clinical
experience of the authors are summarized in this review article. RESULTS: PLIF
and TLIF procedures reduced back and leg pain, restored the sagittal profile of
the lumbar spine, and achieved good fusion rates and long-term stability.
Advantages of the TLIF procedure include shorter operative times, less blood
loss, less intraoperative risk of injury to neural structures, and shorter
convalescence. Compared with the interposition of a cage in the ALIF technique, a
further step with the risk of vascular injury is eliminated. CONCLUSIONS: The
PLIF and TLIF procedures are almost equivalent posterior fusion procedures with
high fusion rates, good long-term clinical outcomes, and low risk of
complications. The TLIF procedure is slightly advantageous: lower nerve
irritation rates, shorter operative times, and less extensive operation. Thus,
the TLIF procedure is available for cases with single-sided pathologies and the
PLIF procedure is available for bilateral compressions.
PMID- 25588714
TI - Adult choledochal cysts: current update on classification, pathogenesis, and
cross-sectional imaging findings.
AB - Approximately 20% of choledochal cysts (CC) present in adult patients and they
are commonly associated with a high risk of complications, including malignancy.
Additionally, children who underwent internal drainage procedures for CCs can
develop complications during adulthood despite treatment. Concepts regarding
classification and pathogenesis of the CCs have been evolving. While new subtypes
are being added to the widely accepted Todani classification system, simplified
classification schemes have also been proposed to guide appropriate management.
The exact etiology of CCs is currently unknown. The two leading theories involve
either the presence of an anomalous pancreatico-biliary junction with associated
reflux of pancreatic juice into the biliary system or, more recently, some form
of antenatal biliary obstruction with resulting proximal bile duct dilation.
Imaging studies play an important role in the initial diagnosis, surgical
planning, and long-term surveillance of CCs.
PMID- 25588713
TI - Sustained virological response to antiviral therapy in a randomized trial of
cyclosporine versus tacrolimus in liver transplant patients with recurrent
hepatitis C infection.
AB - BACKGROUND: Choice of calcineurin inhibitor may influence response to antiviral
therapy in liver transplant patients with hepatitis C virus (HCV) infection.
MATERIAL AND METHODS: In a randomized, multicenter, 80-week trial, liver
transplant recipients (>6 months and L10 years post-transplant) with recurrent
HCV infection received cyclosporine (n=50) or tacrolimus (n=42) with a 48-week
course of pegylated interferon (peg-IFNalpha2a) and ribavirin. Twenty-three
patients in each group completed the trial on study medication. The primary
endpoint was sustained virological response (SVR) 24 weeks after the end of
antiviral therapy, for which 43 patients were eligible for analysis. RESULTS: The
rate of SVR was 60.0% (12/20) with cyclosporine and 43.5% (10/23) with tacrolimus
(adjusted odds ratio 1.85; 95% CI 0.53-6.43; p=0.331). There were no significant
intergroup differences for rapid or early virological response, relapse, HCV RNA
viral load, or fibrosis progression. One cyclosporine-treated patient experienced
acute rejection. One patient died in each group. Adverse events, treatment
related adverse events, and serious adverse events were similar between groups.
CONCLUSIONS: Since fewer patients were recruited than planned (92 versus 355),
the study was underpowered and robust conclusions cannot be drawn regarding the
effect of cyclosporine and tacrolimus on virological responses to antiviral
treatment for recurrent HCV after liver transplantation. However, as reported in
other trials, SVR was higher in cyclosporine-treated patients.
PMID- 25588715
TI - Contrast-enhanced ultrasound (CEUS) of cystic and solid renal lesions: a review.
AB - Incidentally detected renal lesions have traditionally undergone imaging
characterization by contrast-enhanced computer tomography (CECT) or magnetic
resonance imaging. Contrast-enhanced ultrasound (CEUS) of renal lesions is a
relatively novel, but increasingly utilized, diagnostic modality. CEUS has
advantages over CECT and MRI including unmatched temporal resolution due to
continuous real-time imaging, lack of nephrotoxicity, and potential cost savings.
CEUS has been most thoroughly evaluated in workup of complex cystic renal
lesions, where it has been proposed as a replacement for CECT. Using CEUS to
differentiate benign from malignant solid renal lesions has also been studied,
but has proven difficult due to overlapping imaging features. Monitoring
minimally invasive treatments of renal masses is an emerging application of CEUS.
An additional promising area is quantitative analysis of renal masses using CEUS.
This review discusses the scientific literature on renal CEUS, with an emphasis
on imaging features differentiating various cystic and solid renal lesions.
PMID- 25588717
TI - Utility of endoscopy for diagnosis of barrett in a non-Western society:
endoscopic and histopathologic correlation.
AB - Barrett esophagus is metaplastic transformation of esophageal squamous epithelium
to columnar cells. A total of 1370 patients who had undergone upper endoscopy
because of dyspeptic complaints were enrolled in the study. Age, sex, alcohol and
smoking habits, body mass index, type and duration of symptoms (heartburn,
epigastric pain, nausea, vomiting), and use of proton pump inhibitors were
evaluated in all patients and recorded on standardized forms. Patients were
grouped as normal esophagogastric junction, long-segment Barrett esophagus, and
short-segment Barrett. Biopsies were taken from at least 6 points and examined
histopathologically. Of the 1370 patients involved in the study, 748 (54.6%) were
female and 622 (45.4%) were male. Mean age was 47.2 +/- 15.30 years. Short
segment Barrett esophagus was detected in 16 patients, and long-segment Barrett
was detected in 11 patients. Although Barrett esophagus was detected in 11 cases
that were suspected to have Barrett during endoscopy, histopathology was negative
in all cases that were not suspected to have Barrett. Barrett esophagus
prevalence was significantly higher in people who used alcohol and tobacco and
who had hiatal hernia. Although Barrett esophagus was detected in 40% of cases
that were suspected to have Barrett during endoscopy, histopathology was negative
in all cases that were not suspected to have Barrett. Barrett was detected in
40.7% of cases that were suspected to have Barrett during endoscopy;
histopathology was negative in all cases that were not suspected to have Barrett.
Senstivity of endoscopy is questionable in detection of short-segment Barrett.
PMID- 25588719
TI - lncRNA-MFDL: identification of human long non-coding RNAs by fusing multiple
features and using deep learning.
AB - Long noncoding RNAs (lncRNAs) are emerging as a novel class of noncoding RNAs and
potent gene regulators, which play an important and varied role in cellular
functions. lncRNAs are closely related with the occurrence and development of
some diseases. High-throughput RNA-sequencing techniques combined with de novo
assembly have identified a large number of novel transcripts. The discovery of
large and 'hidden' transcriptomes urgently requires the development of effective
computational methods that can rapidly distinguish between coding and long
noncoding RNAs. In this study, we developed a powerful predictor (named as lncRNA
MFDL) to identify lncRNAs by fusing multiple features of the open reading frame,
k-mer, the secondary structure and the most-like coding domain sequence and using
deep learning classification algorithms. Using the same human training dataset
and a 10-fold cross validation test, lncRNA-MFDL can achieve 97.1% prediction
accuracy which is 5.7, 3.7, and 3.4% higher than that of CPC, CNCI and lncRNA
FMFSVM predictors, respectively. Compared with CPC and CNCI predictors in other
species (e.g., anole lizard, zebrafish, chicken, gorilla, macaque, mouse,
lamprey, orangutan, xenopus and C. elegans) testing datasets, the new lncRNA-MFDL
predictor is also much more effective and robust. These results show that lncRNA
MFDL is a powerful tool for identifying lncRNAs. The lncRNA-MFDL software package
is freely available at for academic users.
PMID- 25588718
TI - Controlling two-step multimode switching of dihydroazulene photoswitches.
AB - We present the synthesis and switching studies of systems with two photochromic
dihydroazulene (DHA) units connected by a phenylene bridge at either para or meta
positions, which correspond to a linear or cross-conjugated pathway between the
photochromes. According to UV/Vis absorption and NMR spectroscopic measurements,
the meta-phenylene-bridged DHA-DHA exhibited sequential light-induced ring
openings of the two DHA units to their corresponding vinylheptafulvenes (VHFs).
Initially, the VHF-DHA species was generated, and, ultimately, after continued
irradiation, the VHF-VHF species. Studies in different solvents and quantum
chemical calculations indicate that the excitation of DHA-VHF is no longer a
local DHA excitation but a charge-transfer transition that involves the
neighboring VHF unit. For the linearly conjugated para-phenylene-bridged dimer,
electronic communication between the two units is so efficient that the
photoactivity is reduced for both the DHA-DHA and DHA-VHF species, and DHA-DHA,
DHA-VHF, and VHF-VHF were all present during irradiation. In all, by changing the
bridging unit, we can control the degree of stepwise photoswitching.
PMID- 25588720
TI - Unmanned aerial mass spectrometer systems for in-situ volcanic plume analysis.
AB - Technology advances in the field of small, unmanned aerial vehicles and their
integration with a variety of sensor packages and instruments, such as miniature
mass spectrometers, have enhanced the possibilities and applications of what are
now called unmanned aerial systems (UAS). With such technology, in situ and
proximal remote sensing measurements of volcanic plumes are now possible without
risking the lives of scientists and personnel in charge of close monitoring of
volcanic activity. These methods provide unprecedented, and otherwise
unobtainable, data very close in space and time to eruptions, to better
understand the role of gas volatiles in magma and subsequent eruption products.
Small mass spectrometers, together with the world's smallest turbo molecular
pump, have being integrated into NASA and University of Costa Rica UAS platforms
to be field-tested for in situ volcanic plume analysis, and in support of the
calibration and validation of satellite-based remote sensing data. These new UAS
MS systems are combined with existing UAS flight-tested payloads and assets, such
as temperature, pressure, relative humidity, SO2, H2S, CO2, GPS sensors, on-board
data storage, and telemetry. Such payloads are capable of generating real time 3D
concentration maps of the Turrialba volcano active plume in Costa Rica, while
remote sensing data are simultaneously collected from the ASTER and OMI space
borne instruments for comparison. The primary goal is to improve the
understanding of the chemical and physical properties of emissions for mitigation
of local volcanic hazards, for the validation of species detection and abundance
of retrievals based on remote sensing, and to validate transport models.
PMID- 25588716
TI - Targeting interferon response genes sensitizes aromatase inhibitor resistant
breast cancer cells to estrogen-induced cell death.
AB - INTRODUCTION: Estrogen deprivation using aromatase inhibitors (AIs) is currently
the standard of care for postmenopausal women with hormone receptor-positive
breast cancer. Unfortunately, the majority of patients treated with AIs
eventually develop resistance, inevitably resulting in patient relapse and,
ultimately, death. The mechanism by which resistance occurs is still not
completely known, however, recent studies suggest that impaired/defective
interferon signaling might play a role. In the present study, we assessed the
functional role of IFITM1 and PLSCR1; two well-known interferon response genes in
AI resistance. METHODS: Real-time PCR and Western blot analyses were used to
assess mRNA and protein levels of IFITM1, PLSCR1, STAT1, STAT2, and IRF-7 in AI
resistant MCF-7:5C breast cancer cells and AI-sensitive MCF-7 and T47D cells.
Immunohistochemistry (IHC) staining was performed on tissue microarrays
consisting of normal breast tissues, primary breast tumors, and AI-resistant
recurrence tumors. Enzyme-linked immunosorbent assay was used to quantitate
intracellular IFNalpha level. Neutralizing antibody was used to block type 1
interferon receptor IFNAR1 signaling. Small interference RNA (siRNA) was used to
knockdown IFITM1, PLSCR1, STAT1, STAT2, IRF-7, and IFNalpha expression. RESULTS:
We found that IFITM1 and PLSCR1 were constitutively overexpressed in AI-resistant
MCF-7:5C breast cancer cells and AI-resistant tumors and that siRNA knockdown of
IFITM1 significantly inhibited the ability of the resistant cells to proliferate,
migrate, and invade. Interestingly, suppression of IFITM1 significantly enhanced
estradiol-induced cell death in AI-resistant MCF-7:5C cells and markedly
increased expression of p21, Bax, and Noxa in these cells. Significantly elevated
level of IFNalpha was detected in AI-resistant MCF-7:5C cells compared to
parental MCF-7 cells and suppression of IFNalpha dramatically reduced IFITM1,
PLSCR1, p-STAT1, and p-STAT2 expression in the resistant cells. Lastly,
neutralizing antibody against IFNAR1/2 and knockdown of STAT1/STAT2 completely
suppressed IFITM1, PLSCR1, p-STAT1, and p-STAT2 expression in the resistant
cells, thus confirming the involvement of the canonical IFNalpha signaling
pathway in driving the overexpression of IFITM1 and other interferon-stimulated
genes (ISGs) in the resistant cells. CONCLUSION: Overall, these results
demonstrate that constitutive overexpression of ISGs enhances the progression of
AI-resistant breast cancer and that suppression of IFITM1 and other ISGs
sensitizes AI-resistant cells to estrogen-induced cell death.
PMID- 25588722
TI - Maximizing ion transmission from atmospheric pressure into the vacuum of mass
spectrometers with a novel electrospray interface.
AB - We have discovered that an electrode containing a conical channel with a small
angular divergence can transmit into the vacuum almost 100% of an electrospray
ion current produced at atmospheric pressure. Our first implementation of such a
conical duct, which we term "ConDuct," uses a conductive plastic pipette tip
containing an approximately 1.6 degrees divergent channel at its entrance. We
observed that the beam formed by the ConDuct electrode has a very low divergence
(less than 1 degrees ) and persists for long distances in vacuum. Intrigued by
these properties, we incorporated this electrode into a novel atmosphere-to
vacuum ion transmission interface, and devised a technique for evaluating its
performance relative to the commercial reference interfaces that contain heated
metal capillaries. We determined that our new interface transmits at least 400
times more ions than the commercial Thermo LCQ DECA XP atmosphere-to-vacuum
interface and 2 to 3 times more than the commercial interface in the Thermo Velos
Orbitrap and the Q Exactive mass spectrometers. We conclude that it might be
possible to optimize the properties of the transmitted ions further by
manufacturing ConDuct inlet electrodes from metal rather than conductive plastic
and by determining the optimum angle of channel divergence and channel length.
PMID- 25588723
TI - Concise review: bullseye: targeting cancer stem cells to improve the treatment of
gliomas by repurposing disulfiram.
AB - Cancer stem cells (CSCs) are thought to be at the root of cancer recurrence
because they resist conventional therapies and subsequently reinitiate tumor cell
growth. Thus, targeting CSCs could be the bullseye to successful cancer
therapeutics in the future. Brain tumors are some of the most challenging types
of cancer to treat and the median survival following the initial diagnosis is 12
18 months. Among the different types of brain tumors, glioblastoma (GBM) is
considered the most aggressive and remains extremely difficult to treat. Despite
surgery, radiation, and chemotherapy, most patients develop refractory disease.
Temozolomide (TMZ) is a chemotherapy used to treat GBM however resistance
develops in most patients. The underlying mechanisms for TMZ resistance (TMZ
resistant) involve the expression of DNA repair gene O(6)-methylguanine-DNA
methyltransferase. CSC genes such as Sox-2, BMI-1, and more recently Y-box
binding protein-1 also play a role in resistance. In order to develop novel
therapies for GBM, libraries of small interfering RNAs and off-patent drugs have
been screened. Over the past few years, several independent laboratories
identified disulfiram (DSF) as an off-patent drug that kills GBM CSCs. Reportedly
DSF has several modes of action including its ability to inhibit aldehyde
dehydrogenases, E3 ligase, polo-like kinase 1, and NFkB. Due to the fact that GBM
is a disease of heterogeneity, chemotherapy with multitargeting properties may be
the way of the future. In broader terms, DSF kills CSCs from a range of different
cancer types further supporting the idea of repurposing it for "target practice."
PMID- 25588725
TI - Signal transduction.
PMID- 25588721
TI - Sample multiplexing with cysteine-selective approaches: cysDML and cPILOT.
AB - Cysteine-selective proteomics approaches simplify complex protein mixtures and
improve the chance of detecting low abundant proteins. It is possible that
cysteinyl-peptide/protein enrichment methods could be coupled to isotopic
labeling and isobaric tagging methods for quantitative proteomics analyses in as
few as two or up to 10 samples, respectively. Here we present two novel cysteine
selective proteomics approaches: cysteine-selective dimethyl labeling (cysDML)
and cysteine-selective combined precursor isotopic labeling and isobaric tagging
(cPILOT). CysDML is a duplex precursor quantification technique that couples
cysteinyl-peptide enrichment with on-resin stable-isotope dimethyl labeling.
Cysteine-selective cPILOT is a novel 12-plex workflow based on cysteinyl-peptide
enrichment, on-resin stable-isotope dimethyl labeling, and iodoTMT tagging on
cysteine residues. To demonstrate the broad applicability of the approaches, we
applied cysDML and cPILOT methods to liver tissues from an Alzheimer's disease
(AD) mouse model and wild-type (WT) controls. From the cysDML experiments, an
average of 850 proteins were identified and 594 were quantified, whereas from the
cPILOT experiment, 330 and 151 proteins were identified and quantified,
respectively. Overall, 2259 unique total proteins were detected from both cysDML
and cPILOT experiments. There is tremendous overlap in the proteins identified
and quantified between both experiments, and many proteins have AD/WT fold-change
values that are within ~20% error. A total of 65 statistically significant
proteins are differentially expressed in the liver proteome of AD mice relative
to WT. The performance of cysDML and cPILOT are demonstrated and advantages and
limitations of using multiple duplex experiments versus a single 12-plex
experiment are highlighted.
PMID- 25588729
TI - Long-term outcome of 424 childhood-onset myasthenia gravis patients.
AB - The objective of this study was to describe the clinical characteristics, outcome
and factors that may affect the outcome of childhood-onset myasthenia gravis
(CMG) patients in China. We have followed up 424 patients with CMG for at least 5
years at Tongji Hospital. At the end of follow-up, the outcome of all the
patients was measured according to MGFA Post-intervention Status. In this study,
the patients have been followed up for 9.8 +/- 5.4 years. The mean onset age was
5.4 +/- 3.6 years. Ocular myasthenia gravis (OMG) was the major type of CMG
within 2 years after onset (95%). Thymic hyperplasia was found in 116 patients,
and thymoma was confirmed in 6 patients. Acetylcholine receptor antibodies were
elevated in 69.5% of the patients. All the patients were routinely treated.
Thymectomy was performed in 34 patients (8.0%). At the end of follow-up, seventy
one patients (16.7%) were significantly improved, 66 patients (15.6%) remained
unchanged, 53 patients (12.5%) were worsened, and 234 patients (55.2%) were
exacerbated. Importantly, fifty OMG patients (12.4%) had transformed into
generalized myasthenia gravis (GMG) over 2 years after onset. Thymectomy did not
effectively reduce the transformation from OMG to GMG. However, GMG cases
significantly benefited from the surgery. This study indicated that the cases
with autoimmune CMG account for over 50% in Chinese MG population. The long-term
follow-up discloses that CMG patients have a low percentage of improvement, and a
high percentage of worsening and exacerbation. The treatment should not be
withdrawn too early after the patients obtain complete stable remission. More
studies are needed to gain better control of CMG symptoms.
PMID- 25588730
TI - MuSK myasthenia gravis as a manifestation of immune restoration disease in an HIV
positive patient.
PMID- 25588732
TI - Palpitations and dizziness in a 64-year-old man: reassure and send him home.
PMID- 25588733
TI - Cytotoxic, antitumour-promoting and inhibition of protein denaturation effects of
flavonoids, isolated from Potentilla evestita Th. Wolf.
AB - This study was designed to evaluate the isolated flavonoids (chrysin 1, and
umbelliferone 2) from Potentilla evestita for cytotoxic, antitumour-promoting and
inhibition of protein denaturation activities. The results showed marked
cytotoxic effect of compounds 1 and 2 in brine shrimp cytotoxic assay at various
concentrations with LD50 of 34.5 and 31.8 mg/mL, respectively. In Epstein-Barr
virus early antigen activation assay, both compounds 1 and 2 illustrated
significant antitumour-promoting effect with IC50 values of 462 and 308 mol
ratio/32 pmol TPA, respectively. The cytotoxic and antitumour-promoting effects
of compounds were strongly supported by inhibition of protein denaturation
activity with IC50 of 119 and 112 MUg/mL, respectively. In conclusion, both
compounds possess strong cytotoxic, antitumour-promoting and inhibition of
protein denaturation activities.
PMID- 25588731
TI - Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.
AB - Increased fracture risk is commonly reported in cancer patients receiving
radiotherapy, particularly at sites within the field of treatment. The direct and
systemic effects of ionizing radiation on bone at a therapeutic dose are not well
characterized in clinically relevant animal models. Using 20-week-old male
C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and
microarchitecture were evaluated prospectively by microcomputed tomography and
histomorphometry and compared to contralateral-shielded bone (left hindlimb) and
non-irradiated control bone. One week postirradiation, trabecular bone volume
declined in irradiated tibias (-22%; p < 0.0001) and femurs (-14%; p = 0.0586)
and microarchitectural parameters were compromised. Trabecular bone volume
declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at
the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity
were increased in irradiated bone relative to contralateral and non-irradiated
bone, whereas osteoblast number was unchanged. Despite no change in osteoblast
number 1 week postirradiation, dynamic bone formation indices revealed a
reduction in mineralized bone surface and a concomitant increase in unmineralized
osteoid surface area in irradiated bone relative to contralateral and non
irradiated control bone. Further, dose-dependent and time-dependent calvarial
culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast
like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and
osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours
postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy)
stimulated murine macrophage RAW264.7 cell differentiation, and coculture of
irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this
effect. These studies highlight the multifaceted nature of radiation-induced bone
loss by demonstrating direct and systemic effects on bone and its many cell types
using clinically relevant doses; they have important implications for bone health
in patients treated with radiation therapy.
PMID- 25588734
TI - Phloem as capacitor: radial transfer of water into xylem of tree stems occurs via
symplastic transport in ray parenchyma.
AB - The transfer of water from phloem into xylem is thought to mitigate increasing
hydraulic tension in the vascular system of trees during the diel cycle of
transpiration. Although a putative plant function, to date there is no direct
evidence of such water transfer or the contributing pathways. Here, we trace the
radial flow of water from the phloem into the xylem and investigate its diel
variation. Introducing a fluorescent dye (0.1% [w/w] fluorescein) into the phloem
water of the tree species Eucalyptus saligna allowed localization of the dye in
phloem and xylem tissues using confocal laser scanning microscopy. Our results
show that the majority of water transferred between the two tissues is
facilitated via the symplast of horizontal ray parenchyma cells. The method also
permitted assessment of the radial transfer of water during the diel cycle, where
changes in water potential gradients between phloem and xylem determine the
extent and direction of radial transfer. When injected during the morning, when
xylem water potential rapidly declined, fluorescein was translocated, on average,
farther into mature xylem (447 +/- 188 um) compared with nighttime, when xylem
water potential was close to zero (155 +/- 42 um). These findings provide
empirical evidence to support theoretical predictions of the role of phloem-xylem
water transfer in the hydraulic functioning of plants. This method enables
investigation of the role of phloem tissue as a dynamic capacitor for water
storage and transfer and its contribution toward the maintenance of the
functional integrity of xylem in trees.
PMID- 25588735
TI - Phosphoenolpyruvate Carboxylase in Arabidopsis Leaves Plays a Crucial Role in
Carbon and Nitrogen Metabolism.
AB - Phosphoenolpyruvate carboxylase (PEPC) is a crucial enzyme that catalyzes an
irreversible primary metabolic reaction in plants.Previous studies have used
transgenic plants expressing ectopic PEPC forms with diminished feedback
inhibition to examine the role of PEPC in carbon and nitrogen metabolism. To
date, the in vivo role of PEPC in carbon and nitrogen metabolism has not been
analyzed in plants. In this study, we examined the role of PEPC in plants,
demonstrating that PPC1 and PPC2 were highly expressed genes encoding PEPC in
Arabidopsis (Arabidopsis thaliana) leaves and that PPC1 and PPC2 accounted for
approximately 93% of total PEPC activity in the leaves. A double mutant,
ppc1/ppc2, was constructed that exhibited a severe growth-arrest phenotype. The
ppc1/ppc2 mutant accumulated more starch and sucrose than wild-type plants when
seedlings were grown under normal conditions. Physiological and metabolic
analysis revealed that decreased PEPC activity in the ppc1/ppc2 mutant greatly
reduced the synthesis of malate and citrate and severely suppressed ammonium
assimilation. Furthermore, nitrate levels in the ppc1/ppc2 mutant were
significantly lower than those in wild-type plants due to the suppression of
ammonium assimilation. Interestingly, starch and sucrose accumulation could be
prevented and nitrate levels could be maintained by supplying the ppc1/ppc2
mutant with exogenous malate and glutamate, suggesting that low nitrogen status
resulted in the alteration of carbon metabolism and prompted the accumulation of
starch and sucrose in the ppc1/ppc2 mutant. Our results demonstrate that PEPC in
leaves plays a crucial role in modulating the balance of carbon and nitrogen
metabolism in Arabidopsis.
PMID- 25588736
TI - Membrane-localized extra-large G proteins and Gbg of the heterotrimeric G
proteins form functional complexes engaged in plant immunity in Arabidopsis.
AB - In animals, heterotrimeric G proteins, comprising Ga, Gb, and Gg subunits, are
molecular switches whose function tightly depends on Ga and Gbg interaction.
Intriguingly, in Arabidopsis (Arabidopsis thaliana), multiple defense responses
involve Gbg, but not Ga. We report here that the Gbg dimer directly partners with
extra-large G proteins (XLGs) to mediate plant immunity. Arabidopsis mutants
deficient in XLGs, Gb, and Gg are similarly compromised in several pathogen
defense responses, including disease development and production of reactive
oxygen species. Genetic analysis of double, triple, and quadruple mutants
confirmed that XLGs and Gbg functionally interact in the same defense signaling
pathways. In addition, mutations in XLG2 suppressed the seedling lethal and cell
death phenotypes of BRASSINOSTEROID INSENSITIVE1-associated receptor kinase1
interacting receptor-like kinase1 mutants in an identical way as reported for
Arabidopsis Gb-deficient mutants. Yeast (Saccharomyces cerevisiae) three-hybrid
and bimolecular fluorescent complementation assays revealed that XLG2 physically
interacts with all three possible Gbg dimers at the plasma membrane. Phylogenetic
analysis indicated a close relationship between XLGs and plant Ga subunits,
placing the divergence point at the dawn of land plant evolution. Based on these
findings, we conclude that XLGs form functional complexes with Gbg dimers,
although the mechanism of action of these complexes, including
activation/deactivation, must be radically different form the one used by the
canonical Ga subunit and are not likely to share the same receptors. Accordingly,
XLGs expand the repertoire of heterotrimeric G proteins in plants and reveal a
higher level of diversity in heterotrimeric G protein signaling.
PMID- 25588737
TI - Characterization of chloroplast protein import without Tic56, a component of the
1-megadalton translocon at the inner envelope membrane of chloroplasts.
AB - We report on the characterization of Tic56, a unique component of the recently
identified 1-MD translocon at the inner envelope membrane of chloroplasts (TIC)
in Arabidopsis (Arabidopsis thaliana) comprising Tic20, Tic100, and Tic214. We
isolated Tic56 by copurification with Tandem Affinity Purification-tagged Toc159
in the absence of precursor protein, indicating spontaneous and translocation
independent formation of the translocon at the outer envelope membrane of
chloroplasts (TOC) and TIC supercomplexes. Tic56 mutant plants have an albino
phenotype and are unable to grow without an external carbon source. Using
specific enrichment of protein amino termini, we analyzed the tic56-1 and plastid
protein import2 (toc159) mutants to assess the in vivo import capacity of
plastids in mutants of an outer and inner envelope component of the anticipated
TOC-TIC supercomplex. Inboth mutants, we observed processing of several import
substrates belonging to various pathways. Our results suggest that despite the
severe developmental defects, protein import into Tic56-deficient plastids is
functional to a considerable degree, indicating the existence of alternative
translocases at the inner envelope membrane.
PMID- 25588738
TI - Comparison of mercury bioaccumulation between wild and mariculture food chains
from a subtropical bay of Southern China.
AB - Bioaccumulation and trophic transfer of mercury (Hg) both in the natural marine
ecosystem and the mariculture ecosystem were studied at Daya Bay, a subtropical
bay in Southern China. Averaged Hg concentrations in sediment, phytoplankton,
macrophyte, shrimp, crab, shellfish, planktivorous fish, carnivorous fish, farmed
pompano, farmed snapper, compound feed and trash fish were 0.074, 0.054, 0.044,
0.098, 0.116, 0.171, 0.088, 0.121, 0.210, 0.125, 0.038 and 0.106 MUg g(-1) dw,
respectively. These Hg levels were at the low-middle ends of the global range.
Positive correlation between Hg concentrations in farmed fish and fish
weights/sizes was observed, whereas no clear correlation between Hg
concentrations and lipid contents was found. Hg concentrations followed
macrophyte < phytoplankton < sediment < planktivorous fish < shrimp < crab <
carnivorous fish < shellfish, and commercial feed < trash fish < farmed fish. Hg
was biomagnified along the marine food chain in the ecosystem of Daya Bay. Hg
levels in the farmed fish were higher than those in the wild fish primarily
because of the higher Hg level in fish feed and the smaller size of marine wild
fish.
PMID- 25588739
TI - Evaluation of in vivo antitumor effects of ANT2 shRNA delivered using PEI and
ultrasound with microbubbles.
AB - Gene therapy using RNA interference can be directed against tumors through
various strategies, but has been hindered owing to the inefficiency of non-viral
delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2
(ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the
polyethylenimine (PEI) and an ultrasound gene delivery method, human breast
carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL
2Rgamma(null)) mice. The results showed greater tumor regression (*P<0.05) as
well as an increased survival rate in the group receiving ANT2 shRNA+two types of
enhancer relative to the groups receiving ANT2 shRNA without enhancer. These
findings demonstrate that the introduction of PEI and ultrasound with SonoVue
exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI
and ultrasound provided the best results with respect to tumor regression, the
antitumor effects from the individual enhancers were approximately equivalent. In
addition, we confirmed that there was no toxicity on aspartate aminotransferase
and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen
or creatine kinase levels in the kidney following the various gene delivery
methods.
PMID- 25588740
TI - Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in
adult and neonate rats.
AB - Intracerebral administration of recombinant adeno-associated vector (AAV) has
been performed in several clinical trials. However, delivery into the brain
requires multiple injections and is not efficient to target the spinal cord, thus
limiting its applications. To assess widespread and less invasive strategies, we
tested intravenous (IV) or intrathecal (that is, in the cerebrospinal fluid
(CSF)) delivery of a rAAVrh10-egfp vector in adult and neonate rats and studied
the effect of the age at injection on neurotropism. IV delivery is more efficient
in neonates and targets predominantly Purkinje cells of the cerebellum and
sensory neurons of the spinal cord and dorsal root ganglia. A single intra-CSF
administration of AAVrh10, single strand or oversized self-complementary, is
efficient for the targeting of neurons in the cerebral hemispheres, cerebellum,
brainstem and spinal cord. Green fluorescent protein (GFP) expression is more
widespread in neonates when compared with adults. More than 50% of motor neurons
express GFP in the three segments of the spinal cord in neonates and in the
cervical and thoracic regions in adults. Neurons are almost exclusively
transduced in neonates, whereas neurons, astrocytes and rare oligodendrocytes are
targeted in adults. These results expand the possible routes of delivery of
AAVrh10, a serotype that has shown efficacy and safety in clinical trials
concerning neurodegenerative diseases.
PMID- 25588742
TI - Preferable sites and orientations of transgene inserted in the adenovirus vector
genome: The E3 site may be unfavorable for transgene position.
AB - The adenovirus vector (AdV) can carry two transgenes in its genome, the
therapeutic gene and a reporter gene, for example. The E3 insertion site has
often been used for the expression of the second transgene. A transgene can be
inserted at six different sites/orientations: E1, E3 and E4 sites, and right and
left orientations. However, the best combination of the insertion sites and
orientations as for the titers and the expression levels has not sufficiently
been studied. We attempted to construct 18 AdVs producing GFP or LacZ gene driven
by the EF1alpha promoter and Cre gene driven by the alpha-fetoprotein promoter.
The AdV containing GFP gene at E3 in the rightward orientation (GFP-E3R) was not
available. The LacZ-E3R AdV showed 20-fold lower titer and 50-fold lower level of
fiber mRNA than the control E1L AdV. Notably, we found four aberrantly spliced
mRNAs in the LacZ-E3L/R AdVs, probably explaining their very low titers. Although
the transgene expression levels in the E4R AdVs were about threefold lower than
those in the E1L AdVs, their titers are comparable with that of E1L AdVs. We
concluded that E1L and E4R sites/orientations are preferable for expressing the
main target gene and a second gene, respectively.
PMID- 25588741
TI - Potent antitumor activity of Oct4 and hypoxia dual-regulated oncolytic adenovirus
against bladder cancer.
AB - Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and
expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor
selective replication of oncolytic adenoviruses may be hindered by oxygen
deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus,
retaining its antitumor activity even in a hypoxic environment. We have
previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven
by nine copies of the Oct4 response element (ORE) for specifically killing Oct4
overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual
regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response
element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2alpha and
Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF
2alpha was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited
higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells,
while sparing normal cells. AdLCY exerted potent antitumor effects in mice
bearing human bladder tumor xenografts and syngeneic bladder tumors. It could
target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may
have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4
is expressed in various cancers, AdLCY may be further explored as a broad
spectrum anticancer agent.
PMID- 25588743
TI - Replicating reoviruses with a transgene replacing the codons for the head domain
of the viral spike.
AB - The capacity to modify the reovirus genome facilitates generation of new
therapeutic reoviruses. We describe a method for generating replication-competent
reoviruses carrying a heterologous transgene. The strategy is based on the
expanded-tropism reovirus mutant jin-3, which can infect cells independent of the
reovirus receptor junction-adhesion molecule A (JAM-A). Jin-3 harbors a mutation
in the S1 segment, resulting in a G196R substitution in the tail of the spike
protein sigma1. The use of the jin-3 tail-encoding S1 segment allows replacing
the codons for the JAM-A-binding head domain by up to 522 nucleotides of foreign
sequences, without exceeding the size of the wild-type S1 segment. We inserted
the codons for the porcine teschovirus-1 2A element fused with those encoding the
fluorescent protein iLOV. Replicating rS1His-2A-iLOV reoviruses were generated by
co-transfection of expression plasmids for all reovirus segments. These
reoviruses contain the S1His-2A-iLOV segment in the absence of the wild-type S1
segment. Density-gradient centrifugation confirmed the association of the sigma1
tail fragment with the capsid. Both JAM-A-positive and -negative cells exposed to
the rS1His-2A-iLOV reoviruses exhibited iLOV fluorescence, confirming the jin-3
derived expanded-tropism phenotype. These data demonstrated the feasibility of
generating decapitated replication-competent T3D reoviruses carrying a
heterologous transgene.
PMID- 25588744
TI - Sendai virus-mediated gene transfer of the c-myc suppressor far-upstream element
binding protein-interacting repressor suppresses head and neck cancer.
AB - Far-upstream element-binding protein-interacting repressor (FIR) is a
transcription factor that inhibits c-Myc expression and has been shown to have
antitumor effects in some malignancies. Here, we evaluated the antitumor effects
of FIR using fusion gene-deleted Sendai virus (SeV/DeltaF) as a nontransmissible
vector against head and neck squamous cell carcinoma (HNSCC). Using in vitro and
in vivo xenograft mouse models, we observed efficient expression of green
fluorescent protein (GFP) following transduction with the SeV/DeltaF vector
encoding GFP (GFP-SeV/DeltaF) into HNSCC cells. In vitro and in vivo studies
revealed that administration of the FIR-encoded SeV/DeltaF (FIR-SeV/DeltaF)
vector exerted significant antitumor effects, suppressed c-Myc expression and
induced apoptosis in HNSCC. Additionally, the antitumor effects of FIR or the
expression of GFP following administration of the FIR- or GFP-SeV/DeltaF vector,
respectively, were dependent on the multiplicity of infection or titer.
Furthermore, the SeV/DeltaF vector itself had no cytotoxic effects. Therefore,
the SeV/DeltaF vector may be safe and useful for the treatment of HNSCC, allowing
for high-titer SeV/DeltaF vector administration for anticancer gene therapy. In
addition, SeV/DeltaF vector-mediated FIR gene therapy demonstrated effective
tumor suppression in HNSCC, suggesting that this therapy may have the potential
for clinical use as a novel strategy for HNSCC treatment.
PMID- 25588747
TI - Spontaneous fractures in custom-made porous hydroxyapatite cranioplasty implants:
is fragility the only culprit?
AB - BACKGROUND: Although the porous hydroxyapatite (PHA) used in custom-made
cranioplasty implants is a material appreciated for its biomimetic properties,
before osteointegration it is initially very fragile. Nevertheless, we wondered
whether this primary fragility is entirely due to brittleness or whether the
surgeon's actions may influence the behavior of the material. METHODS: To study
the influence of the surgeon's behavior, we made a virtual model of a custom-made
PHA cranioplasty implant and submitted it to three implant procedural variables
using finite element methods. In the first test, a scenario in which the
surgeon's design, validation, and positioning techniques are impeccable, the
edges of the implant adhered well to the craniectomy margins. In the second test,
a discrepancy between a portion of the perimeter of the craniectomy and the
profile of the prosthesis was modeled, and in the third test, several gaps were
simulated between the implant and the craniectomy margins. RESULTS: Our
mathematical model showed that when local and general discontinuities were
included in the test scenarios, there was an increase in the load coming to bear
on the cranioplasty implant, which amounted to 80 and 50 %, respectively.
CONCLUSIONS: The fragility of custom-made PHA cranioplasty implants increases if
the surgeon fails to achieve a precise design and validation, and/or an accurate
surgical procedure. Nevertheless, careful attention during these phases helps to
maintain the strength of the implant, given the more favorable mechanical
conditions, without interfering with its biomimetic capacity.
PMID- 25588745
TI - Functional characterization and developmental expression profiling of gibberellin
signalling components in Vitis vinifera.
AB - Gibberellins (GAs) regulate numerous developmental processes in grapevine (Vitis
vinifera) such as rachis elongation, fruit set, and fruitlet abscission. The
ability of GA to promote berry enlargement has led to its indispensable use in
the sternospermocarpic ('seedless') table grape industry worldwide. However,
apart from VvGAI1 (VvDELLA1), which regulates internode elongation and
fruitfulness, but not berry size of seeded cultivars, little was known about GA
signalling in grapevine. We have identified and characterized two additional
DELLAs (VvDELLA2 and VvDELLA3), two GA receptors (VvGID1a and VvGID1b), and two
GA-specific F-box proteins (VvSLY1a and VvSLY1b), in cv. Thompson seedless. With
the exception of VvDELLA3-VvGID1b, all VvDELLAs interacted with the VvGID1s in a
GA-dependent manner in yeast two-hybrid assays. Additionally, expression of these
grape genes in corresponding Arabidopsis mutants confirmed their functions in
planta. Spatiotemporal analysis of VvDELLAs showed that both VvDELLA1 and
VvDELLA2 are abundant in most tissues, except in developing fruit where VvDELLA2
is uniquely expressed at high levels, suggesting a key role in fruit development.
Our results further suggest that differential organ responses to exogenous GA
depend on the levels of VvDELLA proteins and endogenous bioactive GAs.
Understanding this interaction will allow better manipulation of GA signalling in
grapevine.
PMID- 25588748
TI - Peroneal intraneural ganglion cysts at the fibular neck: the layered "U" surgical
approach to the articular branch and superior tibiofibular joint.
AB - BACKGROUND: Intraneural ganglia most commonly occur within the peroneal nerve
near the fibular neck. Disconnection of the articular branch is required in their
treatment. Surgical intervention can be challenging because of unfamiliarity with
the region or scarring from previous surgery. METHOD: We present the layered "U"
technique for peroneal intraneural ganglia with clinical examples. Dissection is
carried down in parallel to the U-shaped course of the articular branch to
provide optimal visualization and avoid injury to major branches of the nerve.
CONCLUSION: This pathoanatomic approach provides direct and safe exposure of the
articular branch of the common peroneal nerve.
PMID- 25588746
TI - The role of minimally invasive surgery in pediatric solid tumors.
AB - During recent years, minimally invasive surgery (MIS) has become the standard
approach for various operations in infants and children. MIS in pediatric
thoracic and abdominal tumors is a controversial approach in the surgical
management of childhood cancer. Meanwhile, more and more oncological biopsies and
resections are being performed laparoscopically or thoracoscopically. Despite its
increasing role in pediatric tumor surgery, the different national and
international multicenter trial groups have not yet implemented MIS within
guidelines and recommendations in most of the current treatment protocols. An
increasing number of retrospective reports describes a potential role of MIS in
the management of different pediatric oncological entities. Over the time, there
has been a diverse development of this approach with regard to the different
neoplasms. Nevertheless, there is a lack of prospective randomized trails
assessing MIS. This still represents a requirement for evidence-based medicine
and judging the advantages and disadvantages of this approach. The purpose of
this state-of-the-art article is to review the current literature to describe the
application of MIS in pediatric solid tumors.
PMID- 25588749
TI - Complications of cranioplasty using a bone flap sterilised by autoclaving
following decompressive craniectomy.
AB - BACKGROUND: Increasing use of decompressive craniectomies has led to a
corresponding number of cranioplasties performed to replace the subsequent bone
defect created. We aimed to evaluate the morbidity associated with cranioplasty
using an autologous bone flap sterilised in an autoclave. METHODS: We
retrospectively analysed data from 149 patients who underwent cranioplasty
following decompressive craniectomy during the time period January 1998 to
December 2012. Autologous bone flaps were sterilised in an autoclave and stored
in a refrigerator at a temperature of 8 degrees above zero until cranioplasty was
performed. Complications were registered and patient data were analysed in order
to identify risk factors for surgical site infection and bone flap resorption
after cranioplasty. Only the patients with a follow-up period of >24 months were
included in the analysis of bone flap resorption (110 patients). RESULTS:
Surgical side infection occurred in only five patients (3.3%), whereas bone flap
resorption developed in 22 patients (20%). The multivariate analysis of the
presented data identified the operating time of >120 min (p = 0.0277; OR, 16.877;
95% CI, 1.364-208.906) and the presence of diabetes mellitus (p = 0.0016; OR,
54.261; 95% CI, 4.529-650.083) as independent risk factors of development of
infection and the presence of ventriculo-peritoneal (VP) shunt (p < 0.0001; OR,
35.564; 95% CI, 9.962-126.960) as independent risk factor of development of the
bone flap resorption. CONCLUSIONS: Reimplantation of the autoclaved autologous
bone flap following decompressive craniectomy is a simple and cheep alternative
to other techniques and is available to any institution that provides autoclaving
sterilisation services. This method is associated with a low rate of surgical
site infection, but with a significant rate of the bone flap resorption.
PMID- 25588750
TI - Authors' reply to letter to the editor regarding "coincident pituitary adenoma
and sellar meningioma".
PMID- 25588751
TI - Spinal cord injury induced neuropathic pain: Molecular targets and therapeutic
approaches.
AB - Neuropathic pain, especially that resulting from spinal cord injury, is a
tremendous clinical challenge. A myriad of biological changes have been
implicated in producing these pain states including cellular interactions,
extracellular proteins, ion channel expression, and epigenetic influences.
Physiological consequences of these changes are varied and include functional
deficits and pain responses. Developing therapies that effectively address the
cause of these symptoms require a deeper knowledge of alterations in the
molecular pathways. Matrix metalloproteinases and tissue inhibitors of
metalloproteinases are two promising therapeutic targets. Matrix
metalloproteinases interact with and influence many of the studied pain pathways.
Gene expression of ion channels and inflammatory mediators clearly contributes to
neuropathic pain. Localized and time dependent targeting of these proteins could
alleviate and even prevent neuropathic pain from developing. Current therapeutic
options for neuropathic pain are limited primarily to analgesics targeting the
opioid pathway. Therapies directed at molecular targets are highly desirable and
in early stages of development. These include transplantation of exogenously
engineered cell populations and targeted gene manipulation. This review describes
specific molecular targets amenable to therapeutic intervention using currently
available delivery systems.
PMID- 25588752
TI - Predicting the survival probability of gastric cancer patients developing
metastatic epidural spinal cord compression (MESCC).
AB - To create a tool for estimating the survival of gastric cancer patients
developing MESCC, clinical factors were evaluated in 29 patients. Factors were
age, gender, performance status, affected vertebrae, ambulatory status, further
bone metastases, visceral metastases, time from gastric cancer diagnosis until
MESCC and rapidity of developing weakness of legs. On multivariate analyses,
visceral metastases (risk ratio: 6.80; p = 0.003) and rapidity of weakening of
legs (risk ratio: 2.73; p = 0.023) had a significant effect on survival and were
included in the tool. Scoring points for each of the two factors were either 0 or
1, depending on the 6-month survival rates. According to the sum of the points,
three groups were built: 0 points (n = 12), 1 point (n = 10) and 2 points (n =
7). Six-month survival rates were 0, 20 and 100 % (p < 0.001). This tool for
patients with MESCC from gastric cancer estimates survival probabilities, which
is important for tailoring treatment to patients' needs.
PMID- 25588754
TI - The vulnerability of rules in complex work environments: dynamism and uncertainty
pose problems for cognition.
AB - Many complex work environments rely heavily on cognitive operators using rules.
Operators sometimes fail to implement rules, with catastrophic human, social and
economic costs. Rule-based error is widely reported, yet the mechanisms of rule
vulnerability have received less attention. This paper examines rule
vulnerability in the complex setting of airline transport operations. We examined
'the stable approach criteria rule', which acts as a system defence during the
approach to land. The study experimentally tested whether system state complexity
influenced rule failure. The results showed increased uncertainty and dynamism
led to increased likelihood of rule failure. There was also an interaction
effect, indicating complexity from different sources can combine to further
constrain rule-based response. We discuss the results in relation to recent
aircraft accidents and suggest that 'rule-based error' could be progressed to
embrace rule vulnerability, fragility and failure. This better reflects the
influence that system behaviour and cognitive variety have on rule-based
response. Practitioner Summary: In this study, we examined mechanisms of rule
vulnerability in the complex setting of airline transport operations. The results
suggest work scenarios featuring high uncertainty and dynamism constrain rule
based response, leading to rules becoming vulnerable, fragile or failing
completely. This has significant implications for rule-intensive, safety critical
work environments.
PMID- 25588753
TI - Translational horizons in the tumor microenvironment: harnessing breakthroughs
and targeting cures.
AB - Chemotherapy and targeted therapy have opened new avenues in clinical oncology.
However, there is a lack of response in a substantial percentage of cancer
patients and diseases frequently relapse in those who even initially respond.
Resistance is, at present, the major barrier to conquering cancer, the most
lethal age-related pathology. Identification of mechanisms underlying resistance
and development of effective strategies to circumvent treatment pitfalls thereby
improving clinical outcomes remain overarching tasks for scientists and
clinicians. Growing bodies of data indicate that stromal cells within the
genetically stable but metabolically dynamic tumor microenvironment confer
acquired resistance against anticancer therapies. Further, treatment itself
activates the microenvironment by damaging a large population of benign cells,
which can drastically exacerbate disease conditions in a cell nonautonomous
manner, and such off-target effects should be well taken into account when
establishing future therapeutic rationale. In this review, we highlight relevant
biological mechanisms through which the tumor microenvironment drives development
of resistance. We discuss some unsolved issues related to the preclinical and
clinical trial paradigms that need to be carefully devised, and provide
implications for personalized medicine. In the long run, an insightful and
accurate understanding of the intricate signaling networks of the tumor
microenvironment in pathological settings will guide the design of new clinical
interventions particularly combinatorial therapies, and it might help overcome,
or at least prevent, the onset of acquired resistance.
PMID- 25588755
TI - Oxidative stress: a concept in redox biology and medicine.
AB - "Oxidative stress" as a concept in redox biology and medicine has been formulated
in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this
term. This concept has its merits and its pitfalls. Among the merits is the
notion, elicited by the combined two terms of (i) aerobic metabolism as a steady
state redox balance and (ii) the associated potential strains in the balance as
denoted by the term, stress, evoking biological stress responses. Current
research on molecular redox switches governing oxidative stress responses is in
full bloom. The fundamental importance of linking redox shifts to
phosphorylation/dephosphorylation signaling is being more fully appreciated,
thanks to major advances in methodology. Among the pitfalls is the fact that the
underlying molecular details are to be worked out in each particular case, which
is bvious for a global concept, but which is sometimes overlooked. This can lead
to indiscriminate use of the term, oxidative stress, without clear relation to
redox chemistry. The major role in antioxidant defense is fulfilled by
antioxidant enzymes, not by small-molecule antioxidant compounds. The field of
oxidative stress research embraces chemistry, biochemistry, cell biology,
physiology and pathophysiology, all the way to medicine and health and disease
research.
PMID- 25588756
TI - Understanding the basics of posterior tibial tendon dysfunction and the
associated flatfoot: conservative and surgical thoughts.
PMID- 25588758
TI - How much is too much breast screening?
PMID- 25588757
TI - Pulmonary vein isolation for atrial fibrillation in the postpneumonectomy
population: a feasibility, safety, and outcomes study.
AB - BACKGROUND: Pulmonary vein isolation (PVI) of the remnant pulmonary vein (PV)
stumps in pneumonectomy patients has not been well characterized. METHODS: This
is a multicenter observational study of patients with a remnant PV stump after
pneumonectomy. Consecutive patients with a history of pneumonectomy and who had
undergone RF ablation for drug refractory AF were identified from the AF database
at the participating institutions. RESULTS: There were 15 patients in whom
pneumonectomy was performed, for resection of tumors in 10, infection in 4, and
bullae in 1 patient and who underwent RF ablation for AF. The mean age was 63 +/-
7 years. The stumps were from the right lower PV in 5, left upper PV in 5, left
lower PV in 3, and right upper PV in 2 patients. All the PV stumps were
electrically active with PV potentials and 9 (60%) of them had triggered
activity. PVI was performed in 14 and focal isolation in 1 patient. At 1-year
follow-up, 80% were free of AF, off of antiarrhythmic medications. CONCLUSION: PV
stumps in AF patients with previous pneumonectomy are electrically active and are
frequently the sites of active firing. Isolation of these PV stumps can be
accomplished safely and effectively using catheter ablation with no practical
concern for PV stenosis or compromising PV stump integrity.
PMID- 25588759
TI - Concluding remarks: summary of some of our recent studies in the field of
conjugating plasmonic gold nanoparticles to single cancer cells and their
molecular and cellular dynamics.
AB - This Faraday meeting was indeed very educational and important. We should all
thank the organizing committee, and especially our Chair, Professor Nguyen TK
Thanh, for a job well done. The Faraday Discussion format is certainly very
creative and effective. Getting each presenter of one of the excellent posters to
summarize the topic of their poster in five minutes was very important in
encouraging the delegates to spend their time in the poster sessions with the
speakers working on research that overlapped with his or her own.
PMID- 25588762
TI - Recirculation during veno-venous extra-corporeal membrane oxygenation--a
simulation study.
AB - PURPOSE: Veno-venous ECMO is indicated in reversible life-threatening respiratory
failure without life-threatening circulatory failure. Recirculation of oxygenated
blood in the ECMO circuit decreases efficiency of patient oxygen delivery but is
difficult to measure. We seek to identify and quantify some of the factors
responsible for recirculation in a simulation model and compare with clinical
data. METHODS: A closed-loop real-time simulation model of the cardiovascular
system has been developed. ECMO is simulated with a fixed flow pump 0 to 5 l/min
with various cannulation sites - 1) right atrium to inferior vena cava, 2)
inferior vena cava to right atrium, and 3) superior+inferior vena cava to right
atrium. Simulations are compared to data from a retrospective cohort of 11
consecutive adult veno-venous ECMO patients in our department. RESULTS:
Recirculation increases with increasing ECMO-flow, decreases with increasing
cardiac output, and is highly dependent on choice of cannulation sites. A more
peripheral drainage site decreases recirculation substantially. CONCLUSIONS:
Simulations suggest that recirculation is a significant clinical problem in veno
venous ECMO in agreement with clinical data. Due to the difficulties in measuring
recirculation and interpretation of the venous oxygen saturation in the ECMO
drainage blood, flow settings and cannula positioning should rather be optimized
with help of arterial oxygenation parameters. Simulation may be useful in
quantification and understanding of recirculation in VV-ECMO.
PMID- 25588761
TI - Current roles of endoscopy in the management of intraductal papillary mucinous
neoplasm of the pancreas.
AB - Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized
by intraductal papillary proliferation of mucin-producing epithelial cells that
exhibit various degrees of dysplasia. IPMN is classified into four histological
subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) according to its
histomorphological and immunohistochemical characteristics. Endoscopic retrograde
cholangiopancreatography plays a crucial role in the evaluation of these features
of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than
computed tomography or magnetic resonance imaging for early detection of
malignancy. The present review addresses the current roles of endoscopy and
related techniques in the management of IPMN. The particular focus is on
diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer
concomitant with IPMN, differentiating the epithelial subtypes of IPMN,
determining the optimal strategy for the management of branch duct IPMN, and
discussing innovative endoscopic technology related to IPMN. The disadvantages of
endoscopic examinations of IPMN and different attitudes toward EUS-guided fine
needle aspiration for IPMN between Japan (negative) and other countries (active)
are also discussed.
PMID- 25588763
TI - Pre-clinical evaluation of an adult extracorporeal carbon dioxide removal system
with active mixing for pediatric respiratory support.
AB - The objective of this work was to conduct pre-clinical feasibility studies to
determine if a highly efficient, active-mixing, adult extracorporeal carbon
dioxide removal (ECCO2R) system can safely be translated to the pediatric
population. The Hemolung Respiratory Assist System (RAS) was tested in vitro and
in vivo to evaluate its performance for pediatric veno-venous applications. The
Hemolung RAS operates at blood flows of 350-550 ml/min and utilizes an integrated
pump-gas exchange cartridge with a membrane surface area of 0.59 m2 as the only
component of the extracorporeal circuit. Both acute and seven-day chronic in vivo
tests were conducted in healthy juvenile sheep using a veno-venous cannulation
strategy adapted to the in vivo model. The Hemolung RAS was found to have gas
exchange and pumping capabilities relevant to patients weighing 3-25 kg. Seven
day animal studies in juvenile sheep demonstrated that veno-venous extracorporeal
support could be used safely and effectively with no significant adverse
reactions related to device operation.
PMID- 25588764
TI - On the roughness measurement on knee prostheses.
AB - The majority of total knee replacements currently implanted present an
articulation composed of two metal parts, femoral and tibial components, between
which there is a polyethylene insert serving as a bearing surface. The finishing
surface of the metal components is a very important factor in minimizing the
polyethylene wear rate and, later, the gradual production of metal and plastic
debris. Considering the role of surface roughness on volumetric wear rates, the
purpose of this study is to develop a protocol for the roughness characterization
of total knee prosthesis (TKP) metal components, taking into consideration a
limited number of points on each surface. Six mobile TKP of different sizes
(three size 2 and three size 6) were tested on a knee joint simulator to compare
the wear behavior of each group. After 2 million cycles the weight loss by the
polyethylene inserts was measured with gravimetric method and the surface
roughness of the metallic components was assessed in terms of average surface
roughness, Ra, skewness, Rsk, and total roughness, Rt. Roughness measurement
involved 29 points on each femoral condyle and 26 points on each metal tibial
plate. The data collected has shown an increased roughness upon wear testing for
both the investigated TKP sizes. No statistical differences were observed between
the two groups for both the parameters Ra, Rsk, and Rt. The surface of all
metallic components became more negatively skewed, indicating diminishing peaks.
The various parameters were correlated to the volumetric loss using a linear
regression analysis.
PMID- 25588765
TI - Low-flow veno-venous extracorporeal CO2 removal: first clinical experience in
lung transplant recipients.
AB - BACKGROUND: Low-flow extracorporeal CO2 removal devices are easy to setup and
manage and may provide valuable ventilation support. METHODS: We employed a new
device (ProLUNG) recently introduced into the clinical arsenal that exploits a
simple hemoperfusion technique sustained by blood flows lower than 500 ml/min to
remove CO2 from the venous blood. It was used as an adjunctive support to
mechanical ventilation during and after four lung transplantations in our center.
RESULTS: Two patients with cystic fibrosis, one with pulmonary fibrosis, and one
with emphysema were included. They underwent lung transplantation and presented
hypercapnia and respiratory acidosis before, during, or after the surgical
procedure. After 1 h of treatment with the ProLUNG circuit, all patients showed
reduced CO2 levels and increased pH; these variables remained stable until the
end of treatment. CONCLUSIONS: Our data suggest that this new device is effective
in removing CO2 and stabilizing the pH.
PMID- 25588766
TI - Feasibility of a priori numerical assessment of plaque scaffolding after carotid
artery stenting in clinical routine: proof of concept.
AB - PURPOSE: Carotid artery stenting (CAS) is an alternative procedure for the
treatment of severely stenosed carotid artery lesions in high-risk patients.
Appropriate patient selection and stent design are paramount to achieve a low
stroke and death rate in these complex high-risk procedures. This study
introduces and evaluates a novel virtual, patient-specific, pre-operative
environment to quantify scaffolding parameters based on routine imaging
techniques. METHODS: Two patients who underwent CAS with two different sizes of
the Acculink stent (Abbott Vascular, Santa Clara, CA, USA) were studied. Pre
operative data were used to build the numerical models for the virtual procedure.
Numerical results were validated with post-operative angiography. Using novel
virtual geometrical tools, incomplete stent apposition, free cell area and
largest fitting sphere in the stent cell were evaluated in situ as quantitative
measures of successful stent placement and to assess potential risk factors for
CAS complications. RESULTS: A quantitative validation of the numerical outcome
with post-operative images noted differences in lumen diameter of 5.31 +/- 8.05%
and 4.12 +/- 9.84%, demonstrating the reliability of the proposed methodology.
The quantitative measurements of the scaffolding parameters on the virtually
deployed stent geometry highlight the variability of the device behavior in
relation to the target lesion. The free cell area depends on the target diameter
and oversizing, while the largest fitting spheres and apposition values are
influenced by the local concavity and convexity of the vessel. CONCLUSIONS: The
proposed virtual environment may be an additional tool for endovascular
specialists especially in complex anatomical cases where stent design and
positioning may have a higher impact on procedural success and outcome.
PMID- 25588767
TI - Preliminary evidence of the effects of high-frequency repetitive transcranial
magnetic stimulation (rTMS) on swallowing functions in post-stroke individuals
with chronic dysphagia.
AB - BACKGROUND: There is growing evidence of potential benefits of repetitive
transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia.
However, the site and frequency of stimulation for optimal effects are not clear.
AIMS: The aim of this pilot study is to investigate the short-term effects of
high-frequency 5 Hz rTMS applied to the tongue region of the motor cortex on
swallowing functions and the quality of life of post-stroke individuals with
dysphagia. METHODS & PROCEDURES: Two male and two female participants were
assigned randomly to active and sham groups. The participants in the active group
received 10 sessions of active rTMS for 2 weeks, whereas the sham participants
received 10 sessions of sham rTMS for 2 weeks. Each participant received a total
of 3000 pulses of 5 Hz active or sham rTMS per day for 10 days. Outcome measures
were taken at baseline, 1 week and 1 month post-rTMS. OUTCOMES & RESULTS:
Participants who received active rTMS had improved swallowing functions and
swallowing-related quality of life at 1 week and 1 month post-stimulation.
CONCLUSIONS & IMPLICATIONS: The study showed that excitatory rTMS applied over
the tongue motor cortex is a feasible approach in individuals with chronic post
stroke dysphagia. Further investigation with larger sample population is
warranted to support the benefit of this stimulation protocol.
PMID- 25588769
TI - NHS England pulls funding from 25 cancer treatments.
PMID- 25588768
TI - The combined effects of alcohol consumption and body mass index on hepatic
steatosis in a general population sample of European men and women.
AB - BACKGROUND: Research on the association between alcohol consumption and hepatic
steatosis revealed conflictive results. AIM: To investigate the associations
between average daily alcohol consumption and binge drinking with hepatic
steatosis, and to analyse combined effects of average daily alcohol consumption
and binge drinking with body mass index (BMI) on hepatic steatosis. METHODS: Data
from the population-based Study of Health in Pomerania (SHIP) conducted in north
east Germany comprising 4009 adults were used. Alcohol consumption was assessed
by self-report. Serum carbohydrate-deficient transferrin (CDT) was analysed as
biomarker for alcohol consumption. Hepatic steatosis was diagnosed by
ultrasonography. RESULTS: Analyses revealed a dose-response relationship between
average daily alcohol consumption and hepatic steatosis in men starting with a
consumption of 20 g of alcohol per day [adjusted odds ratio (OR) compared to
abstainers 1.53; 95% confidence interval (CI) 1.15-2.05]. Using CDT as
alternative exposure variable confirmed these results. Binge drinking was
associated with hepatic steatosis in men (adjusted OR of binge drinkers compared
to nonbinge drinkers 1.36, 95% CI 1.06-1.74). The likelihood of having hepatic
steatosis increased in men and women with increasing levels of average daily
alcohol consumption in combination with overweight or obesity. Similarly, binge
drinking in combination with overweight or obesity enhanced the likelihood of
having hepatic steatosis. CONCLUSIONS: Overweight or obesity substantially
enhanced the effect of high levels of average daily alcohol consumption and binge
drinking on hepatic steatosis in the present study population. This finding
underlines the necessity to screen for multiple risk factors in the prevention of
hepatic steatosis.
PMID- 25588770
TI - Anterior chamber depth measurement using ultrasound to assess elevated
intraocular pressure.
PMID- 25588771
TI - Circulating microRNA predicts insensitivity to glucocorticoid therapy in Graves'
ophthalmopathy.
AB - Glucocorticoid (GC) insensitivity occurs commonly in Graves' ophthalmopathy (GO),
and GC therapy is associated with major adverse effects. A reliable and easily
accessible biomarker is required to predict the outcome of GC therapy. This study
aimed to evaluate the performance of circulating microRNA (miRNA) to predict GC
insensitivity in GO patients. A total of 35 consecutive patients were included in
this study. A cumulative dose of 4.5 g of methylprednisolone (MP) was
administered intravenously for 12 weeks. Pretreatment serum miRNAs from the best-
(N = 5) and worst- (N = 4) responding patients were profiled using miScript PCR
arrays and validated by quantitative PCR in all patients. We calculated the
predictive value of pretreatment assays of serum miRNAs with regard to GC
insensitivity. We further investigated the roles of target miRNAs in modulating
NF-kappaB activity and restoring transrepression of an NF-kappaB reporter by
dexamethasone. Nine miRNAs displayed significant differences between responsive
and resistant patients by miScript PCR arrays. Validation of the top two miRNAs
in all 35 patients confirmed a significantly lower serum level of miR-224-5p (p =
0.0048) in resistant patients. A multivariate logistic regression model
identified a composite biomarker combining baseline serum miR-224-5p and TRAb was
independently associated with GC response (OR: 2.565, 95 % CI 1.011-6.505, p =
0.047). Receiver operating characteristic (ROC) curves analysis revealed the
composite marker combining miR-224-5p and TRAb led to a 91.67 % positive
prediction value (PPV) and a 69.56 % negative prediction value (NPV) with regard
to GC resistance. Overexpression of miR-224-5p restored transrepression of the NF
kappaB reporter by dexamethasone under induced resistance, which may be via
targeting GSK-3beta to increase GR protein level. Our study demonstrated baseline
serum miR-224-5p was associated with GC sensitivity in GO and in vitro
overexpression of miR-224-5p restored GC sensitivity in a resistant cell model. A
parameter combined serum miR-224-5p and TRAb could effectively predict GC
sensitivity in GO patients.
PMID- 25588773
TI - Systematic evaluation of bundled SPC water for biomolecular simulations.
AB - In bundled SPC water models, the relative motion of groups of four water
molecules is restrained by distance-dependent potentials. Bundled SPC models have
been used in hybrid all-atom/coarse-grained (AA/CG) multiscale simulations, since
they enable to couple atomistic SPC water with supra-molecular CG water models
that effectively represent more than a single water molecule. In the present
work, we systematically validated and critically tested bundled SPC water models
as solvent for biomolecular simulations. To that aim, we investigated both
thermodynamic and structural properties of various biomolecular systems through
molecular dynamics (MD) simulations. Potentials of mean force of dimerization of
pairs of amino acid side chains as well as hydration free energies of single side
chains obtained with bundled SPC and standard (unrestrained) SPC water agree
closely with each other and with experimental data. Decomposition of the
hydration free energies into enthalpic and entropic contributions reveals that in
bundled SPC, this favorable agreement of the free energies is due to a larger
degree of error compensation between hydration enthalpy and entropy. The
Ramachandran maps of Ala3, Ala5, and Ala7 peptides are similar in bundled and
unrestrained SPC, whereas for the (GS)2 peptide, bundled water leads to a slight
overpopulation of extended conformations. Analysis of the end-to-end distance
autocorrelation times of the Ala5 and (GS)2 peptides shows that sampling in more
viscous bundled SPC water is about two times slower. Pronounced differences
between the water models were found for the structure of a coiled-coil dimer,
which is instable in bundled SPC but not in standard SPC. In addition, the
hydration of the active site of the serine protease alpha-chymotrypsin depends on
the water model. Bundled SPC leads to an increased hydration of the active site
region, more hydrogen bonds between water and catalytic triad residues, and a
significantly slower exchange of water molecules between the active site and the
bulk. Our results form a basis for assessing the accuracy that can be expected
from bundled SPC water models. At the same time, this study also highlights the
importance of evaluating beforehand the effects of water bundling on the
biomolecular system of interest for a particular multiscale simulation
application.
PMID- 25588772
TI - The fat body mass increase after adjuvant androgen deprivation therapy is
predictive of prostate cancer outcome.
AB - Androgen deprivation therapy (ADT) leads to important changes in body
composition. No data are currently available about the relationship between these
treatment-related changes and patient outcome. Using dual-energy X-ray
absorptiometry, bone mineral density (BMD), fat body mass (FBM), and lean body
mass (LBM) were determined at baseline, and after 1 and 2 years in 53 non
metastatic prostate cancer (PC) patients with high-risk disease treated with
adjuvant ADT. Changes in these parameters were correlated with patient outcome in
terms of adverse skeletal events, disease recurrence, and overall survival. ADT
led to a significant decrease in BMD (p < 0.03) and LBM (p < 0.03), and an
increase in FBM, (p < 0.0001). Changes in BMD failed to show any relationship
with time to skeletal-related events (SRE), disease recurrence, and death. FBM
increase was a significant predictor of higher risk of SRE [hazard ratio (HR)
3.024, 95 % CI 1.004-10.353, p < 0.02], higher risk of death (HR 2.373, 95 % CI
1.012-5.567, p = 0.04), and a non-significant higher risk of disease recurrence
(HR 2.219, 95 % CI 0.956-5.150, p = 0.13). LBM decrease did not correlate with
either time to SRE or survival, while a non-significant association with disease
recurrence (HR 1.550, 95 % CI 0.670-3.605, p = 0.06) was observed. The early
increase in FBM may provide predictive information of poor outcome in PC patients
given ADT. These data suggest that the adoption of early preventive measures
aiming to reduce fat increase can potentially reduce the morbidity and mortality
risk.
PMID- 25588774
TI - Homolytic H2 cleavage by a mercury-bridged Ni(I) pincer complex [{(PNP)Ni}2{MU
Hg}].
AB - Reduction of the pincer nickel(ii) complex [(PNP)NiBr] with sodium amalgam
(Na/Hg) forms the mercury-bridged dimer [{(PNP)Ni}2{MU-Hg}], which homolytically
cleaves dihydrogen to form [(PNP)NiH]. Reversible CO2 insertion into the Ni-H
bond is observed for [(PNP)NiH], forming the monodentate kappa(1)O-formate
complex [(PNP)NiOC(O)H].
PMID- 25588775
TI - Perioperative catabolism.
AB - PURPOSE: This article reviews the pathophysiology, clinical relevance, and
therapy of the catabolic response to surgical stress. PRINCIPLE FINDINGS: The key
clinical features of perioperative catabolism are hyperglycemia and loss of body
protein, both metabolic consequences of impaired insulin function. Muscle
weakness and (even moderate) increases in perioperative blood glucose are
associated with morbidity after major surgery. Although the optimal glucose
concentration for improving clinical outcomes is unknown, most medical
associations recommend treatment of random blood glucose > 10 mmol.L(-1).
Neuraxial anesthesia blunts the neuroendocrine stress response and enhances the
anabolic effects of nutrition. There is evidence to suggest that the avoidance of
preoperative fasting prevents insulin resistance and accelerates recovery after
major abdominal surgery. CONCLUSIONS: Current anticatabolic therapeutic
strategies include glycemic control and perioperative nutrition in combination
with optimal pain control and the avoidance of preoperative starvation. All these
elements are part of Enhanced Recovery After Surgery (ERAS) programs.
PMID- 25588778
TI - Spectroscopic and theoretical studies of acid-base behaviors of N-confused
porphyrins: effects of meso-aryl substituents.
AB - The acid-base properties of a series of meso-aryl-substituted N-confused
porphyrins (NCPs) were examined in aqueous sodium dodecyl sulfate (SDS) micellar
solutions by both spectrophotometric methods and theoretical calculations.
Reflecting the unsymmetrical structure of NCP having an outward-pointing pyrrolic
nitrogen atom, the first and second protonations were distinguishable in the
absorption and (1)H NMR spectra, unlike for porphyrins, and the pK3 and pK4
values were determined discretely. The individual basicities of the NCPs were
directly related to the inductive effect of para substituents on the meso-phenyl
groups: A linear relationship between the pK3 (pK4) and Hammett sigmapara
parameters was revealed. In the case of deprotonation, the structure of
monoanionic NCP species was similarly characterized by the absorption and (1)H
NMR spectra. For the second deprotonation, the pK1 value was determined to be
11.39 for the NCP derivative with pentafluorophenyl groups. DFT calculations
support the changes in electronic structures and aromaticity of the cationic and
anionic species. It is demonstrated that NCPs are easily protonated and
deprotonated compared to the corresponding regular congeners.
PMID- 25588776
TI - Serum-free isolation and culture system to enhance the proliferation and bone
regeneration of adipose tissue-derived mesenchymal stem cells.
AB - Cell therapy using human mesenchymal stem cells (MSCs) is an attractive approach
for many refractory diseases. Adipose tissue-derived mesenchymal stem cells (AT
MSCs) are considered as a favorable tool due to its abundance in the body, easy
proliferation, and high cytokine production potency. In order to avoid the risks
associated with the use of fetal bovine serum (FBS) in culture that includes
batch variations and contamination with pathogens, development of serum-free
culture system has been initiated. We have formulated a completely serum-free
culture medium (SFM) that could be used not only for the expansion of AT-MSCs but
also for initial isolation. We demonstrate that the AT-MSCs isolated and cultured
in serum-free medium (AT-MSCs/SFM) possess high proliferation capacity and
differentiation potency to osteoblast, adipocyte, and chondrocyte lineages in
vitro. In in vivo bone fraction model analysis, AT-MSCs/SFM showed higher bone
repair potency and quality of the regenerated bone than the cells cultured in
serum-containing medium (AT-MSCs/SCM). This was attributed to the (i) presence of
translated cells in the bone, as evidenced by in vivo imaging of the illuminated
translated cells and (ii) high level of expression and induction capacity of AT
MSCs/SFM for cytokine BMP2, CCL2, and CCL5. Taken together, we report a new serum
free culture system for AT-MSCs that is suitable for cell therapy.
PMID- 25588777
TI - Development of a sensitive in vitro assay to quantify the biological activity of
pro-inflammatory phorbol esters in Jatropha oil.
AB - New health safety concerns may arise from the increasing production and use of
Jatropha oil, a biodiesel feedstock that also contains toxic, pro-inflammatory,
and co-carcinogenic phorbol esters. Based on the exceptional sensitivity of Madin
Darby canine kidney (MDCK) cells to the model phorbol ester 12-O
tetradecanoylphorbol-13-acetate (TPA), a robust bioassay was developed to
quantify the biological activity of Jatropha phorbol esters directly in oil,
without sample extraction. We first verified that the characteristic response of
MDCK cells to TPA was also observed following direct exposure to phorbol esters
in Jatropha oil. We further confirmed that similarly to TPA, Jatropha oil's
phorbol esters can activate protein kinase C (PKC). We then assessed the
transcriptional response of MDCK cells to Jatropha oil exposure by measuring the
expression of cyclooxygenase-2 (COX-2), a gene involved in inflammatory processes
which is strongly upregulated following PKC activation. Based on the
parameterization of a TPA dose-response curve, the transcriptional response of
MDCK cells to Jatropha oil exposure was expressed in term of TPA toxic equivalent
(TEQ), a convenient metric to report the inflammatory potential of complex
mixtures. The sensitive bioassay described in this manuscript may prove useful
for risk assessment, as it provides a quantitative method and a convenient metric
to report the inflammatory potential of phorbol esters in Jatropha oil. This
bioassay may also be adapted for the detection of bioactive phorbol esters in
other matrices.
PMID- 25588779
TI - Lipidomic profiling of sinus mucosa from patients with chronic rhinosinusitis.
AB - Sinusitis is a cause of significant morbidity, substantial healthcare costs, and
negative effects on quality of life. The primary objective of this study is to
characterize the previously unknown lipid profile of sinonasal mucosa from
patients with chronic rhinosinusitis (CRS) and from controls. Sinus mucosa
samples were analyzed from 9 CRS patients with concomitant nasal polyps, 11 CRS
patients without polyps, and 12 controls. Ten lone polyp samples were also
analyzed. Samples were subjected to a modified Bligh/Dyer lipid extraction, then
high performance thin layer chromatography (HPTLC), combined gas
chromatography/electron impact-mass spectrometry (GC/EI-MS), and flow
injection/electrospray ionization-tandem mass spectrometry (FI/ESI-MS/MS). Data
was analyzed for identification and profiling of major components. HPTLC revealed
an array of species reflecting the lipid complexity of the samples. GC/EI-MS
revealed cholesterol and several fatty acids. FI/ESI-MSMS revealed numerous lipid
species, namely a host of phosphatidylcholines, phosphatidylethanolamines,
ceramides and cholesteryl esters, but no detectable amounts of
phosphatidyinositols or sulfated lipids. These results are a first step to
uncover unique molecular biomarkers in CRS.
PMID- 25588780
TI - Patterns of relapse in extrapulmonary small cell carcinoma: retrospective
analysis of outcomes from two cancer centres.
AB - OBJECTIVES: We conducted a retrospective review of patients with extrapulmonary
small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns
of relapse and outcomes by primary site. SETTING: We have reviewed the outcomes
of one of the largest data sets of consecutive patients with EPSCC identified
from two major cancer centres. PARTICIPANTS: Consecutive patients with a
histopathological diagnosis of EPSCC from the two institutions were
retrospectively identified. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were
evaluated including stage at presentation, treatments given, sites of relapse,
time to distant relapse, progression-free survival and overall survival (OS).
RESULTS: From a total 159 patients, 114 received first-line chemotherapy, 80.5%
being platinum-based. Response rate was 48%. Commonest primary sites were
genitourinary and gynaecological. 44% of patients presented with metastatic
disease. 55.9% relapsed with liver the commonest site, whereas only 2.5%
developed brain metastases. Median OS was 13.4 months for all patients, 7.6
months and 19.5 months for those with metastatic and non-metastatic disease,
respectively. Gynaecological and head and neck patients had significantly better
OS compared to gastrointestinal patients. CONCLUSIONS: EPSCCs demonstrate high
response rates to chemotherapy and high rates of distant metastases. Primary
sites may influence prognosis, and survival is optimal with a radical strategy.
Brain metastases are rare and we therefore do not recommend prophylactic cranial
irradiation.
PMID- 25588781
TI - Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using
the Japanese national claims database.
AB - OBJECTIVE: The primary objective was to estimate the national prevalence of
psoriasis and palmoplantar pustulosis (PPP) in Japan. Secondary objectives were
to determine (1) whether psoriasis and PPP disease activity varies by season, and
(2) whether disease severity is associated with concurrent diabetes mellitus,
hyperlipidaemia and hypertension. SETTINGS: Patients with a psoriasis or PPP
diagnosis code between April 2010 and March 2011 were identified using a Japanese
national database. PARTICIPANTS: 565 903 patients with psoriasis or PPP were
identified. No patient was excluded. PRIMARY AND SECONDARY OUTCOME MEASURES:
National prevalence was calculated using census data. We estimated the difference
in the proportion of patients who used healthcare services, as a proxy for
disease activity, between the hot and cold seasons and the difference in the
standardised prevalence of comorbidities between severe and mild disease. The
measures were estimated separately for the two broad disease categories of
psoriasis and PPP but not in all patients as planned because the two disease
categories had major differences. RESULTS: The national prevalence of psoriasis
and PPP was 0.34% (95% CI 0.34% to 0.34%) and 0.12% (0.12% to 0.12%),
respectively. The difference in the proportion of patients who used healthcare
services in the hot compared to the cold season was -0.3% (-0.5% to -0.1%) for
psoriasis and 10.0% (9.8% to 10.3%) for PPP. The difference in the standardised
prevalence between severe and mild psoriasis was 3.1% (2.7% to 3.4%), 3.2% (2.8%
to 3.6%) and 5.1% (4.7% to 5.6%) for concurrent diabetes mellitus,
hyperlipidaemia and hypertension, respectively. No significant difference in the
prevalence of comorbidity was observed for PPP. CONCLUSIONS: The national
prevalence, seasonal variation in disease activity and prevalence of
comorbidities in Japanese patients with psoriasis and PPP estimated in this
descriptive study may be used as basic information for future studies.
PMID- 25588782
TI - Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double
blind, randomised, placebo-controlled study.
AB - OBJECTIVE: To estimate the efficacy of a probiotic yogurt compared to a
pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in
children. DESIGN AND SETTING: This was a multisite, randomised, double-blind,
placebo-controlled clinical trial conducted between September 2009 and 2012. The
study was conducted through general practices and pharmacies in Launceston,
Tasmania, Australia. PARTICIPANTS AND INTERVENTIONS: Children (aged 1-12 years)
prescribed antibiotics, were randomised to receive 200 g/day of either yogurt
(probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis
(Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo)
for the same duration as their antibiotic treatment. OUTCOMES: Stool frequency
and consistency were recorded for the duration of treatment plus 1 week. Primary
outcome was stool frequency and consistency, classified at different levels of
diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons
between groups were made using Fisher's exact analysis. RESULTS: 72 children
commenced and 70 children (36 placebo and 34 probiotic) completed the trial.
There were no incidents of severe diarrhoea (stool consistency >=6, >=3
stools/day for >=2 consecutive days) in the probiotic group and six in the
placebo group (Fisher's exact p=0.025). There was also only one episode of minor
diarrhoea (stool consistency >=5, >=2 stools/day for >=2 days in the probiotic
group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic
group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had
headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite
and 1 had nausea). CONCLUSIONS: A yogurt combination of LGG, La-5 and Bb-12 is an
effective method for reducing the incidence of antibiotic-associated diarrhoea in
children. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials
Registry ACTRN12609000281291.
PMID- 25588783
TI - The African, Caribbean and European (ACE) Pathways to Care study: a qualitative
exploration of similarities and differences between African-origin, Caribbean
origin and European-origin groups in pathways to care for psychosis.
AB - OBJECTIVES: This paper reports on a qualitative exploration of the reasons for
differences in pathways to care and duration of untreated psychosis (DUP) in the
African, Caribbean and European (ACE) Pathways to Care study from the perspective
of respondents to the study and their families. SETTING: Ontario, Canada.
PARTICIPANTS: Thirty-four participants in total. Twenty-five young people who had
experienced a first episode of psychosis and nine family members. Participants
were part of the ACE Pathways to Care study. DESIGN: We implemented six focus
groups. Furthermore, we implemented four in-depth interviews with two African
origin young women, one Caribbean-origin woman, and one European-origin woman
with lived experience of psychosis. RESULTS: Factors that influenced help-seeking
delays across the three groups were: personal awareness of symptoms, family
members' knowledge of psychotic symptoms and knowledge of mental health services.
Youth and their family members described how stigma played a key role in pathways
to care by stopping them from asking for help. The way in which stigma operated
on the three groups' members, from feeling ashamed to feeling guilty for their
mental illnesses, helped to explain differences in DUP between the groups. Guilt
feelings emerged as a prominent theme among members from the African and
Caribbean groups and it was not discussed in the European focus group. Delay in
entering into first-episode psychosis programmes was also influenced by the
stigma perceived by young people in healthcare settings. This had an impact on
the therapeutic relationships, disclosure of symptoms and overall trust in the
healthcare system. CONCLUSIONS: The findings of this paper suggest that stigma,
especially internalised stigma, may operate in different ways in European-origin,
African-origin and Caribbean-origin groups. These findings could inform the
development of more equitable services for people in early stages of psychosis.
PMID- 25588784
TI - Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding:
protocol for response-adaptive randomised placebo-controlled dose-finding
parallel group trial (DexFEM).
AB - INTRODUCTION: Heavy menstrual bleeding (HMB) diminishes individual quality-of
life and poses substantial societal burden. In HMB endometrium, inactivation of
cortisol (by enzyme 11beta hydroxysteroid dehydrogenase type 2 (11betaHSD2)), may
cause local endometrial glucocorticoid deficiency and hence increased
angiogenesis and impaired vasoconstriction. We propose that 'rescue' of luteal
phase endometrial glucocorticoid deficiency could reduce menstrual bleeding.
METHODS AND ANALYSIS: DexFEM is a double-blind response-adaptive parallel-group
placebo-controlled trial in women with HMB (108 to be randomised), with active
treatment the potent oral synthetic glucocorticoid dexamethasone, which is
relatively resistant to 11betaHSD2 inactivation. Participants will be aged over
18 years, with mean measured menstrual blood loss (MBL) for two screening cycles
>=50 mL. The primary outcome is reduction in MBL from screening. Secondary end
points are questionnaire assessments of treatment effect and acceptability.
Treatment will be for 5 days in the mid-luteal phases of three treatment
menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg
twice daily) will be compared with placebo, to ascertain optimal dose, and
whether this has advantage over placebo. Statistical efficiency is maximised by
allowing randomisation probabilities to 'adapt' at five points during enrolment
phase, based on the response data available so far, to favour doses expected to
provide greatest additional information on the dose-response. Bayesian Normal
Dynamic Linear Modelling, with baseline MBL included as covariate, will determine
optimal dose (re reduction in MBL). Secondary end points will be analysed using
generalised dynamic linear models. For each dose for all end points, a 95%
credible interval will be calculated for effect versus placebo. ETHICS AND
DISSEMINATION: Dexamethasone is widely used and hence well-characterised safety
wise. Ethical approval has been obtained from Scotland A Research Ethics
Committee (12/SS/0147). Trial findings will be disseminated via open-access peer
reviewed publications, conferences, clinical networks, public lectures, and our
websites. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01769820; EudractCT
2012-003405-98.
PMID- 25588786
TI - Elevated matrix metalloproteinase-7 expression promotes metastasis in human lung
carcinoma.
AB - BACKGROUND: Matrix metalloproteinase 7 (MMP-7) promotes tumor invasion and
metastasis in several cancers. However, its role in lung cancer progression is
understudied. In this study, we investigated the correlation between MMP-7
expression and lung cancer pathology. METHODS: We searched the databases PubMed,
Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, China BioMedicine (CBM)
and China National Knowledge Infrastructure (CNKI) for scientific literature
relevant to MMP-7 and lung cancer. Carefully selected studies were pooled and ORs
with 95% CI were calculated. Subgroup analyses and publication bias were analyzed
to understand the retrieved data in greater detail. Version 12.0 STATA software
was used for statistical analysis. RESULTS: We retrieved a total of 121 studies
through database searches. Finally, 14 cohort studies satisfied our
inclusion/exclusion criteria, and these 14 studies, published between 2004 and
2012, were selected for meta-analysis to understand the influence of MMP-7
expression in lung cancer progression. Our results showed consistent differences
in MMP-7 expression when comparisons were made between TNM I-II versus III-IV (OR
= 1.82, 95% CI: 1.19 to 2.78, P = 0.006); histologic grade 1 to 2 versus 3 to 4
(OR = 1.67, 95% CI: 1.14 to 2.42, P = 0.008); and lymph node-negative versus
lymph node-positive samples (OR = 2.81, 95% CI: 1.73 to 4.58, P <0.001), with
significantly higher MMP-7 expression levels found in the more advanced stages.
Subgroup analysis showed that age was not the factor influencing the associations
between histologic grade, LN metastasis and MMP-7 expression in lung cancer
patients, as both under 60 and over 60 age groups showed strong correlations (all
P <0.05). However, when TNM staging was analyzed for its association with MMP-7
expression, only patients under age 60 showed a statistically significant
correlation. CONCLUSIONS: Our meta-analysis results revealed that MMP-7
overexpression is associated with advanced TNM and histological grades, and is
linked to aggressive LN metastasis in lung cancer patients; thus MMP-7 is a
useful biomarker to assess the disease status in lung cancers.
PMID- 25588785
TI - Efficacy of metformin in pregnant obese women: a randomised controlled trial.
AB - INTRODUCTION: Increasing evidence suggests obesity has its origins prior to
birth. There is clear correlation between maternal obesity, high birthweight and
offspring risk of obesity in later life. It is also clear that women who are
obese during pregnancy are at greater risk of adverse outcomes, including
gestational diabetes and stillbirth. The mechanism(s) by which obesity causes
these problems is unknown, although hyperglycaemia and insulin resistance are
strongly implicated. We present a protocol for a study to test the hypothesis
that metformin will improve insulin sensitivity in obese pregnant women, thereby
reducing the incidence of high birthweight babies and other pregnancy
complications. METHODS AND ANALYSIS: The Efficacy of Metformin in Pregnant Obese
Women, a Randomised controlled (EMPOWaR) trial is a double-masked randomised
placebo-controlled trial to determine whether metformin given to obese (body mass
index >30 kg/m(2)) pregnant women from 16 weeks' gestation until delivery reduces
the incidence of high birthweight babies. A secondary aim is to test the
mechanism(s) of any effect. Obese women with a singleton pregnancy and normal
glucose tolerance will be recruited prior to 16 weeks' gestation and prescribed
study medication, metformin or placebo, to be taken until delivery. Further study
visits will occur at 28 and 36 weeks' gestation for glucose tolerance testing and
to record anthropometric measurements. Birth weight and other measurements will
be recorded at time of delivery. Anthropometry of mother and baby will be
performed at 3 months postdelivery. As of January 2014, 449 women had been
randomised across the UK. ETHICS AND DISSEMINATION: The study will be conducted
in accordance with the principles of Good Clinical Practice. A favourable ethical
opinion was obtained from Scotland A Research Ethics Committee, reference number
10/MRE00/12. Results will be disseminated at conferences and published in peer
reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN51279843.
PMID- 25588787
TI - Chromatin looping and eRNA transcription precede the transcriptional activation
of gene in the beta-globin locus.
AB - Enhancers are closely positioned with actively transcribed target genes by
chromatin looping. Non-coding RNAs are often transcribed on active enhancers,
referred to as eRNAs (enhancer RNAs). To explore the kinetics of enhancer
promoter looping and eRNA transcription during transcriptional activation, we
induced the beta-globin locus by chemical treatment and analysed cross-linking
frequency between the beta-globin gene and locus control region (LCR) and the
amount of eRNAs transcribed on the LCR in a time course manner. The cross-linking
frequency was increased after chemical induction but before the transcriptional
activation of gene in the beta-globin locus. Transcription of eRNAs was increased
in concomitant with the increase in cross-linking frequency. These results show
that chromatin looping and eRNA transcription precedes the transcriptional
activation of gene. Concomitant occurrence of the two events suggests functional
relationship between them.
PMID- 25588788
TI - Association between neighborhood walkability and GPS-measured walking, bicycling
and vehicle time in adolescents.
AB - OBJECTIVES: To investigate relations of walking, bicycling and vehicle time to
neighborhood walkability and total physical activity in youth. METHODS:
Participants (N=690) were from 380 census block groups of high/low walkability
and income in two US regions. Home neighborhood residential density, intersection
density, retail density, entertainment density and walkability were derived using
GIS. Minutes/day of walking, bicycling and vehicle time were derived from
processing algorithms applied to GPS. Accelerometers estimated total daily
moderate-to-vigorous physical activity (MVPA). Models were adjusted for nesting
of days (N=2987) within participants within block groups. RESULTS: Walking
occurred on 33%, active travel on 43%, and vehicle time on 91% of the days
observed. Intersection density and neighborhood walkability were positively
related to walking and bicycling and negatively related to vehicle time.
Residential density was positively related to walking. CONCLUSIONS: Increasing
walking in youth could be effective in increasing total physical activity. Built
environment findings suggest potential for increasing walking in youth through
improving neighborhood walkability.
PMID- 25588790
TI - Immunogenic peptide discovery in cancer genomes.
AB - As immunotherapies to treat malignancy continue to diversify along with the tumor
types amenable to treatment, it will become very important to predict which
treatment is most likely to benefit a given patient. Tumor neoantigens, novel
peptides resulting from somatic tumor mutations and recognized by the immune
system as foreign, are likely to contribute significantly to the efficacy of
immunotherapy. Multiple in silico methods have been developed to predict whether
peptides, including tumor neoantigens, will be presented by the major
histocompatibility complex (MHC) Class I or Class II, and interact with the T
cell receptor (TCR). The methods for neoantigen prediction will be reviewed here,
along with the most important examples of their use in the field of oncology.
PMID- 25588791
TI - Non-operative advances: what has happened in the last 50 years in paediatric
surgery?
AB - Paediatric surgeons remain paediatric clinicians who have the unique skill set to
treat children with surgical problems that may require operative intervention.
Many of the advances in paediatric surgical care have occurred outside the
operating theatre and have involved significant input from medical, nursing and
allied health colleagues. The establishment of neonatal intensive care units,
especially those focusing on the care of surgical infants, has greatly enhanced
the survival rates and long-term outcomes of those infants with major congenital
anomalies requiring surgical repair. Educational initiatives such as the advanced
trauma life support and emergency management of severe burns courses have
facilitated improved understanding and clinical care. Paediatric surgeons have
led with the non-operative management of solid organ injury following blunt
abdominal trauma. Nano-crystalline burn wound dressings have enabled a reduced
frequency of painful dressing changes in addition to effective antimicrobial
efficacy and enhanced burn wound healing. Burns care has evolved so that many
children may now be treated almost exclusively in an ambulatory care setting or
as day case-only patients, with novel technologies allowing accurate prediction
of burn would outcome and planning of elective operative intervention to achieve
burn wound closure.
PMID- 25588789
TI - The long-term dynamics of Campylobacter colonizing a free-range broiler breeder
flock: an observational study.
AB - A free-range broiler breeder flock was studied in order to determine the natural
patterns of Campylobacter colonization over a period of 63 weeks. Campylobacter
sequence types (STs) were not mutually exclusive and on average colonized only
17.7% of the birds tested at any time. Campylobacter STs typically reached a peak
in prevalence upon initial detection in the flock before tailing off, although
the ST and antigenic flaA short variable region in combination were stable over a
number of months. There was evidence that, with a couple of exceptions, the
ecology of C. jejuni and C. coli differed, with the latter forming a more stable
population. Despite being free range, no newly colonizing STs were detected over
a 6-week period in autumn and a 10-week period in winter, towards the end of the
study. There was limited evidence that those STs identified among broiler chicken
flocks on the same farm site were likely to colonize the breeder flock earlier
(R(2) 0.16, P 0.01). These results suggest that there is natural control of
Campylobacter dynamics within a flock which could potentially be exploited in
designing new intervention strategies, and that the two different species should
perhaps be considered separately.
PMID- 25588792
TI - Quantitative motor unit action potential analysis of supraspinatus,
infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport
horses.
AB - REASONS FOR PERFORMING STUDY: Reference values for quantitative electromyography
(QEMG) in shoulder and hindlimb muscles of horses are limited. OBJECTIVES: To
determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus
(IS), deltoideus (DT) and biceps femoris (BF) muscles. STUDY DESIGN: Experimental
observational study and retrospective case series. METHODS: Seven adult healthy
Royal Dutch sport horses underwent quantitative motor unit action potential
analysis of each muscle using commercial electromyography equipment. Measurements
were made according to published methods. One-way ANOVA was used to compare
quantitative motor unit action potential variables between muscles, with post hoc
testing according to Bonferroni, with significance set at P<0.05. The QEMG and
clinical information from horses with lower motor neuron disorders (n = 7) or
myopathy (n = 4) were summarised retrospectively. RESULTS: The 95% confidence
intervals of duration, amplitude, phases, turns, area and size index of
quantitative motor unit action potential were 8.7-10.4 ms, 651-867 MUV, 3.2-3.7,
3.7-4.7, 1054-1457 MUV.ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 MUV, 3.3-3.7,
3.8-4.7, 1349-2204 MUV.ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 MUV, 2.9-3.7,
2.8-4.5, 380-1374 MUV.ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 MUV, 2.7-3.2,
2.6-3.1, 296-484 MUV.ms and 0.2-0.5 for BF, respectively. Mean duration,
amplitude, number of phases and turns, area and size index were significantly
(P<0.01) higher in SS and IS than in DT and BF muscles. In addition, 4 of 7
normal horses had >15% polyphasic motor unit action potentials in SS and IS
muscles. CONCLUSIONS: Differences between muscles should be taken into account
when performing QEMG in order to be able to distinguish normal horses from horses
with suspected neurogenic or myogenic disorders. These normal data provide the
basis for objective QEMG assessment of shoulder and hindlimb muscles.
Quantitative electromyography appears to be helpful in diagnosing neuropathies
and discriminating these from myopathies.
PMID- 25588794
TI - Stress exposure and the risk for the onset of alcohol use disorders and nicotine
dependence in deployed military personnel: the role of prior internalizing
disorders.
AB - OBJECTIVE: This prospective study aimed to investigate whether prior
internalizing disorders (PIDs) moderate the relationship between stress exposure
(SE) and the onset of alcohol use disorders (AUDs) and nicotine dependence (ND)
in deployed military personnel. METHODS: 358 male soldiers were examined directly
before and 12months after return from deployment using standardized interviews.
Combat experiences, concerns about family disruptions, and difficult living and
working environment were assessed as different aspects of SE. PID diagnoses (mood
disorders (PMDs), anxiety disorders (PADs)) and substance use disorders were
defined according to the DSM-IV-TR. RESULTS: PMDs were related to a stronger
association between concerns about family disruptions and the risk of AUD onset
(OR=7.7, 95% CI 1.8-32.8, p=0.006). The number of PID diagnoses (OR per
diagnosis: 1.7, 95% CI 1.0-2.8, p=0.036) and PADs (OR: 2.6, 95% CI 1.1-6.3,
p=0.038) were further related to a stronger association between difficult living
and working environment and the risk of AUD onset. With regard to ND, PMDs were
related to a weaker association between difficult living and working environment
and the risk of ND onset (OR=0.4, 95% CI 0.2-0.8, p=0.013). CONCLUSIONS: PIDs
might be related to an increased risk for the onset of AUDs but not ND following
SE. This effect is probably restricted to specific constellations of PADs, PMDs,
comorbid PIDs and specific aspects of SE. These critical constellations of PIDs
and SE might be a promising target for future research and could contribute to
the development of preventive measures to reduce the risk of AUDs following SE.
PMID- 25588793
TI - Associations between childhood trauma and non-fatal overdose among people who
inject drugs.
AB - INTRODUCTION: Although people who inject drugs (IDU) remain at a high risk of
accidental overdose, interventions that address overdose remain limited.
Accordingly there is a continuing need to identify psychological and social
factors that shape overdose risk. Despite being reported frequently among IDU,
childhood trauma has received little attention as a potential risk factor for
overdose. This study aims to evaluate relationships between non-fatal overdose
and five forms of childhood maltreatment among a cohort of IDU in Vancouver,
Canada. METHODS: Data was obtained from two prospective cohorts of IDU between
December 2005 and May 2013. Multivariate generalized estimating equations (GEEs)
were used to explore relationships between five forms of childhood trauma and non
fatal overdose, adjusting for potential confounders. RESULTS: During the study
period, 1697 IDU, including 552 (32.5%) women, were followed up. At baseline,
1136 (67.0%) participants reported at least one form of childhood trauma, while 4
9% reported a non-fatal overdose at each semi-annual follow-up. In multivariate
analyses, physical [adjusted odds ratio (AOR): 1.36, 95% confidence interval
(CI): 1.08-1.71], sexual (AOR: 1.48, CI: 1.17-1.87), and emotional abuse (AOR:
1.54, CI: 1.22-1.93) and physical neglect (AOR: 1.28, CI: 1.01-1.62) were
independently associated with non-fatal overdose (all p<0.05). CONCLUSIONS:
Childhood trauma was common among participants, and reporting an experience of
trauma was positively associated with non-fatal overdose. These findings
highlight the need to provide intensive overdose prevention to trauma survivors
and to incorporate screening for childhood trauma into health and social programs
tailored to IDU.
PMID- 25588795
TI - Arterial-left ventricular-left atrial coupling late after repair of aortic
coarctation and interruption.
AB - AIMS: This study aimed to explore the arterial-left ventricular (LV)-left atrial
(LA) interaction in adolescents and young adults late after intervention for
coarctation of the aorta (CoA) and interrupted aortic arch (IAA). METHODS AND
RESULTS: Thirty-one (16 males) patients aged 23.4 +/- 6.3, at 20.6 +/- 5.2 years
after intervention, and 31 controls were studied. Carotid arterial stiffness and
intima-media thickness (IMT) and brachial-ankle pulse wave velocity were
determined by radiofrequency-based echocardiography and oscillometry,
respectively. Tissue Doppler and speckle tracking echocardiography (STE) were
performed to assess, respectively, LV myocardial tissue velocities and linear and
torsional deformation. Left atrial positive, negative, and total strain and
strain rate at ventricular systole (aSRs), early diastole (aSRed), and atrial
contraction (aSRac) were also determined using STE. Patients had significantly
greater arterial stiffness and IMT than controls (all P < 0.05). Mitral annular
systolic and diastolic velocities, LV longitudinal and radial strain and early
diastolic strain rates, peak torsion and untwisting velocity, and LA peak
positive and total strain, aSRs, aSRed, and aSRac were significantly lower in
patients than in controls (all P < 0.05). Arterial stiffness correlated inversely
with LV longitudinal strain and systolic and early diastolic strain rate (all P <
0.05), while LA total strain and aSRed were associated positively with LV
diastolic annular velocity, longitudinal SRe, and peak untwisting velocity (all P
< 0.05). Multiple linear regression further revealed arterial stiffness as an
independent determinant of LA total strain (beta = -1.3, P = 0.034). CONCLUSION:
Our findings suggest impairment of arterial function and LV and LA mechanics in
patients after CoA and IAA repair and implicate an abnormal arterial-LV-LA
interaction.
PMID- 25588796
TI - Utility of cardiac FDG-PET imaging coupled to magnetic resonance for the
management of an acute myocarditis with non-informative endomyocardial biopsy.
PMID- 25588797
TI - Association between pulmonary vein orientation and atrial fibrillation-free
survival in patients undergoing endoscopic laser balloon ablation.
AB - AIMS: Obtaining optimal pulmonary vein (PV) occlusion with the endoscopic laser
balloon ablation system (EAS) can be difficult, hypothetically influenced by PV
geometry. The aim of this study was to determine the impact of PV orientation on
atrial fibrillation (AF)-free survival after PV isolation (PVI) using the EAS.
METHODS AND RESULTS: Forty-three patients undergoing a single EAS PVI were
included. Left atrial electrocardiogram -triggered computed tomography was
performed in all patients prior to PVI. Of all four PVs, the orientation at the
insertion in the left atrium was measured in both the transverse and frontal
plane and assigned to one of the four orientation groups: ventral-caudal, dorsal
caudal, ventral-cranial, and dorsal-cranial. Mean age was 56 years; 86% had
paroxysmal AF. Overall, AF-free survival after a median follow-up of 18.2 months
was 51.2%. AF-free survival varied between 21 and 88% depending on left upper PV
orientation (P = 0.045). Furthermore, AF-free survival varied between 21 and 86%
depending on left lower PV orientation (P = 0.010) and AF-free survival varied
between 29 and 88% depending on right lower PV orientation (P = 0.053). No
association was found between right upper PV orientation and AF-free survival
after EAS PVI (P = 0.794). In multivariate analysis, only left lower PV
orientation was associated with AF-free survival [hazards ratio (HR) 10.4, P =
0.019]. CONCLUSION: PV orientation is associated with AF-free survival after EAS
PVI. PV orientation assessment may be useful for selecting the most suitable
patients for EAS PVI.
PMID- 25588798
TI - Video-assisted transmitral resection of primary cardiac lipoma originated from
the left ventricular apex.
PMID- 25588799
TI - Evaluation of ischaemia in patients with atrial fibrillation: impact of stress
protocol on myocardial perfusion imaging accuracy.
AB - BACKGROUND: To evaluate the accuracy of myocardial perfusion imaging (MPI) on a
novel cadmium-zinc-thelluride camera in detecting significant coronary artery
disease (CAD) in patients with atrial fibrillation (AF). METHODS AND RESULTS:
Seventy-four subjects with AF submitted to stress-rest MPI and coronary
angiography were consecutively enrolled. One hundred and forty-eight patients in
sinus rhythm, matched for age, sex, and type of stress-test protocol and with
known coronary anatomy served as controls. The summed difference score, as
measure of reversible myocardial ischaemia, was calculated. A coronary stenosis
>=70% was considered significant. The prevalence of significant CAD did not
differ between AF patients and controls. At receiving operating characteristic
analysis MPI showed relevant accuracy in unmasking the presence of significant
CAD both in AF and in control patients (areas under the curve 0.71 vs. 0.80, P
for difference: 0.212). However, after stratifying patients according to the
stress protocol, a significant interaction between the presence of AF and MPI
diagnostic power was evident. While in the case of a vasodilator stress-test MPI
diagnostic accuracy remained high in both groups of patients (P for difference:
0.664), in those submitted to an exercise stress-test the diagnostic power of MPI
was significantly lower in the presence of AF (P for difference: 0.039), because
of a lower specificity. Interestingly, at multivariate analysis, a lower exercise
duration (P = 0.017) was the major predictor of reduced MPI specificity.
CONCLUSION: The presence of AF impairs MPI accuracy on the detection significant
CAD. This effect was only apparent in the case of an exercise stress-test, while
disappeared in patients submitted to vasodilator stress.
PMID- 25588800
TI - (Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the
evolution of chronic aortic dissections.
AB - AIMS: Despite adequate medical management, dissection of the descending aorta
(type B) may develop complications, including aneurysmal progression and
eventually rupture. Partial false lumen thrombosis has been identified as a
marker of adverse evolution in chronic dissection. The aim of this study was to
test the ability of complementary information, provided by (18)F
fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography
(PET/CT) and peripheral biomarkers, to add pathophysiological significance and a
prognostic value to morphological data. METHODS AND RESULTS: We explored serial
aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23
patients with type B dissection to predict complications from initial data and to
investigate potential associations with aneurysmal expansion during follow-up.
Complications occurred in 17 patients. Acute initial characteristics associated
with complications were male gender (P = 0.021), arterial hypertension (P =
0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false
channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During
follow-up (mean 16.7 +/- 8.0 months), aneurysmal expansion was associated with
false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029),
elevated plasma concentrations of biomarkers of platelets (P-selectin, P =
0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis
(PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation
and fibrinolysis were related to false channel morphology, suggesting that
thrombus biological dynamics may drive progressive expansion of type B
dissections. CONCLUSION: Enhanced FDG uptake may be considered as a complementary
imaging marker associated with secondary complications in type B dissections.
During follow-up, aneurysmal progression is related to PET/CT and biomarkers of
thrombus renewal and lysis.
PMID- 25588801
TI - Prognostic value of Doppler echocardiographic-derived coronary flow velocity
reserve of left anterior descending artery in octogenarians with stress
echocardiography negative for wall motion criteria.
AB - AIMS: Doppler-derived coronary flow velocity reserve (CFVR) of left anterior
descending (LAD) artery is an effective tool to predict overall mortality. The
aim was to investigate the capability of CFVR to predict outcome in an unselected
cohort of patients older than 80 years having stress echo negative by wall motion
criteria. METHODS AND RESULTS: The study group refers to 369 patients aged > 80
years (156 men; mean age 83 +/- 2 years) who had undergone dipyridamole stress
echocardiography with CFVR assessment of LAD artery of known (n = 144) or
suspected (n = 225) coronary artery disease. Stress echocardiography was negative
for wall motion criteria in all cases. Mean CFVR was 2.07 +/- 0.53. During a
median follow-up of 21 months, there were 62 major adverse cardiac events (MACEs;
45 deaths and 17 non-fatal myocardial infarctions). With a receiver operating
characteristic analysis, a CFVR of <= 1.93 was the best cut-off for predicting
mortality and MACE. At individual patient analysis, 152 (41%) subjects had a CFVR
of < 1.93. Annual mortality was 9.8% in patients with CFVR <1.93 and 3.7% in
those with CFVR > 1.93 (P = 0.001); an annual MACE rate was 14.8% in the former
and 4.5% in the latter (P < 0.0001). Of 15 clinical and echocardiographic
parameters analysed, CFVR <= 1.93 [hazard ratio (HR) = 2.17, 95% CI 1.14-4.10]
and resting wall motion abnormality (RWMA; HR = 2.60; 95% CI 1.35-5.00) were
multivariable indicators of mortality. Moreover, CFVR <= 1.93 (HR = 2.69, 95% CI
1.56-4.67), and RWMA (HR = 2.38; 95% CI 1.31-4.33) were also strong independent
predictors of MACEs. At incremental analysis, CFR <= 1.93 added prognostic
information over clinical evaluation and RWMA when both mortality and MACE were
taken as clinical end points. CONCLUSIONS: A reduced CFVR of LAD artery is a
strong and independent indicator of both mortality and MACE, adding prognostic
information over clinical evaluation and RWMA. Conversely, a preserved CFVR
predicts a favourable outcome particularly in subjects with no RWMA.
PMID- 25588802
TI - Identification and quantification of macrophage presence in coronary
atherosclerotic plaques by optical coherence tomography.
AB - AIMS: Vulnerable plaques are characterized by a high macrophage content. We
investigated the optical coherence tomography (OCT) capability of identifying
coronary plaque macrophage presence using tissue property indexes. METHODS AND
RESULTS: Fifteen epicardial coronary arteries were imaged by OCT and subsequently
analysed by histology. Correlating OCT-histological sections were identified and
regions of interest (ROIs) were selected on both atherosclerotic plaques and
normal appearing vessel tracts. OCT-derived tissue property indexes named
normalized standard deviation (NSD), signal attenuation, and granulometry index
were applied on ROIs to identify inflamed ROIs defined as a macrophage percentage
>10 by histology. Forty-three paired samples (OCT frame and histology section)
were considered suitable as ROIs for analysis. Eleven out of 43 ROIs were
considered inflamed and the remaining 32 ROIs were non-inflamed on the basis of
histological count of macrophage percentage. All OCT-derived tissue property
indexes were positively correlated with macrophage percentage (P = 0.0001 for
all). Receiver operating characteristic curve analysis showed that NSD,
granulometry index, and signal attenuation had a significant area under the curve
(area = 0.906, 0.804, and 0.793, respectively). A two-step algorithm requiring to
first apply NSD with a cut-off value of 0.0570 followed by granulometry index was
able to identify an inflamed ROI with a sensitivity of 100% and a specificity of
96.8%. CONCLUSION: OCT was able to identify and quantify macrophage presence in
coronary artery specimens using tissue property indexes. NSD and granulometry
index showed the highest accuracy in identifying a significant plaque
inflammation, especially if used together in a two-step algorithm.
PMID- 25588803
TI - Management of gallbladder dyskinesia: patient outcomes following positive
99mtechnetium (Tc)-labelled hepatic iminodiacetic acid (HIDA) scintigraphy with
cholecystokinin (CCK) provocation and laparoscopic cholecystectomy.
AB - AIMS: To evaluate clinical outcomes in patients with typical biliary pain, normal
ultrasonic findings, and a positive (99m)technetium (Tc)-labelled hepatic
iminodiacetic acid analogue (HIDA) scintigraphy with cholecystokinin (CCK)
provocation indicating gallbladder dyskinesia, as per Rome III criteria,
undergoing laparoscopic cholecystectomy (LC). METHODS AND MATERIALS: Consecutive
patients undergoing LC for gallbladder dyskinesia were identified
retrospectively. They were followed up by telephone interview and review of the
electronic case records to assess symptom resolution. RESULTS: One hundred
consecutive patients (median age 44; 80% female) with abnormal gallbladder
ejection fraction (GB-EF <35%) were followed up for a median of 12 months (range
2-80 months). Following LC, 84% reported symptomatic improvement and 52% had no
residual pain. Twelve percent had persisting preoperative-type pain of either
unchanged or worsening severity. Neither pathological features of chronic
cholecystitis (87% of 92 incidences when histology available) nor reproduction of
pain on CCK injection were significantly predictive of symptom outcome or pain
relief post-LC. CONCLUSION: In one of the largest outcome series of gallbladder
dyskinesia patients in the UK with a positive provocation HIDA scintigraphy
examination and LC, the present study shows that the test is a useful functional
diagnostic tool in the management of patients with typical biliary pain and
normal ultrasound, with favourable outcomes following surgery.
PMID- 25588804
TI - Nurse-administered intravitreal injections: a systematic review.
PMID- 25588805
TI - DFT study of the molybdenum-catalyzed deoxydehydration of vicinal diols.
AB - The mechanism of the molybdenum-catalyzed deoxydehydration (DODH) of vicinal
diols has been investigated using density functional theory. The proposed
catalytic cycle involves condensation of the diol with an Mo(VI) oxo complex,
oxidative cleavage of the diol resulting in an Mo(IV) complex, and extrusion of
the alkene. We have compared the proposed pathway with several alternatives, and
the results have been corroborated by comparison with the molybdenum-catalyzed
sulfoxide reduction recently published by Sanz et al. and with experimental
observations for the DODH itself. Improved understanding of the mechanism should
expedite future optimization of molybdenum-catalyzed biomass transformations.
PMID- 25588806
TI - Arabidopsis PED2 positively modulates plant drought stress resistance.
AB - Abscisic acid (ABA) is an important phytohormone that functions in seed
germination, plant development, and multiple stress responses. Arabidopsis
Peroxisome defective 2 (AtPED2) (also known as AtPEXOXIN14, AtPEX14), is involved
in the intracellular transport of thiolase from the cytosol to glyoxysomes, and
perosisomal matrix protein import in plants. In this study, we assigned a new
role for AtPED2 in drought stress resistance. The transcript level of AtPED2 was
downregulated by ABA and abiotic stress treatments. AtPED2 knockout mutants were
insensitive to ABA-mediated seed germination, primary root elongation, and
stomatal response, while AtPED2 over-expressing plants were sensitive to ABA in
comparison to wide type (WT). AtPED2 also positively regulated drought stress
resistance, as evidenced by the changes of water loss rate, electrolyte leakage,
and survival rate. Notably, AtPED2 positively modulated expression of several
stress-responsive genes (RAB18, RD22, RD29A, and RD29B), positively affected
underlying antioxidant enzyme activities and negatively regulated reactive oxygen
species (ROS) level under drought stress conditions. Moreover, multiple carbon
metabolites including amino acids, organic acids, sugars, sugar alcohols, and
aromatic amines were also positively regulated by AtPED2. Taken together, these
results indicated a positive role for AtPED2 in drought resistance, through
modulation of stress-responsive genes expression, ROS metabolism, and metabolic
homeostasis, at least partially.
PMID- 25588807
TI - Vietnam's forest transition in retrospect: demonstrating weaknesses in business
as-usual scenarios for REDD.
AB - One of the prerequisites of the REDD+ mechanism is to effectively predict
business-as-usual (BAU) scenarios for change in forest cover. This would enable
estimation of how much carbon emission a project could potentially prevent and
thus how much carbon credit should be rewarded. However, different factors like
forest degradation and the lack of linearity in forest cover transitions
challenge the accuracy of such scenarios. Here we predict and validate such BAU
scenarios retrospectively based on forest cover changes at village and district
level in North Central Vietnam. With the government's efforts to increase the
forest cover, land use policies led to gradual abandonment of shifting
cultivation since the 1990s. We analyzed Landsat images from 1973, 1989, 1998,
2000, and 2011 and found that the policies in the areas studied did lead to
increased forest cover after a long period of decline, but that this increase
could mainly be attributed to an increase in open forest and shrub areas. We
compared Landsat classifications with participatory maps of land cover/use in
1998 and 2012 that indicated more forest degradation than was captured by the
Landsat analysis. The BAU scenarios were heavily dependent on which years were
chosen for the reference period. This suggests that hypothetical REDD+ activities
in the past, when based on the remote sensing data available at that time, would
have been unable to correctly estimate changes in carbon stocks and thus produce
relevant BAU scenarios.
PMID- 25588808
TI - Modeling future land use scenarios in South Korea: applying the IPCC special
report on emissions scenarios and the SLEUTH model on a local scale.
AB - This study developed three scenarios of future land use/land cover on a local
level for the Kyung-An River Basin and its vicinity in South Korea at a 30-m
resolution based on the two scenario families of the Intergovernmental Panel on
Climate Change (IPCC) Special Report Emissions Scenarios (SRES): A2 and B1, as
well as a business-as-usual scenario. The IPCC SRES A2 and B1 were used to define
future local development patterns and associated land use change. We quantified
the population-driven demand for urban land use for each qualitative storyline
and allocated the urban demand in geographic space using the SLEUTH model. The
model results demonstrate the possible land use/land cover change scenarios for
the years from 2000 to 2070 by examining the broad narrative of each SRES within
the context of a local setting, such as the Kyoungan River Basin, constructing
narratives of local development shifts and modeling a set of 'best guess'
approximations of the future land use conditions in the study area. This study
found substantial differences in demands and patterns of land use changes among
the scenarios, indicating compact development patterns under the SRES B1 compared
to the rapid and dispersed development under the SRES A2.
PMID- 25588810
TI - Polyamino acid display on cell surfaces enhances salt and alcohol tolerance of
Escherichia coli.
AB - Microbes employ cell membranes for reducing exogenous stresses. Polyamino acid
display on microbial cell surfaces and their effects on microbial chemical stress
tolerance were examined. Growth analysis revealed that displays of polyarginine,
polyaspartate and polytryptophan substantially enhanced tolerance of Escherichia
coli to NaCl. A titration assay indicated that polyarginine and polyaspartate
altered cell surface charges, implying tolerance enhancement via ion atmosphere
and/or ionic bond network formations for electrostatic ion repulsion. The
enhancement by polytryptophan may have arisen from surface hydrophobicity
increase for hydrophobic ion exclusion, because of a strong correlation between
hydrophobic characters of amino acids and their effects on tolerance enhancement.
The display also enhanced tolerance to other salts and/or alcohols in E. coli and
to NaCl in Saccharomyces cerevisiae. Thus polyamino acid display has the
potential as an approach for conferring chemical stress tolerance on various
microbes.
PMID- 25588809
TI - Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2
(Nrf2) expression in gastric cancer.
AB - BACKGROUND: The transcription factor nuclear factor (erythroid-2)-related factor
2 (Nrf2) was originally identified as a critical regulator of intracellular anti
oxidants and of phase II detoxification enzymes through its transcriptional up
regulation of many anti-oxidant response element (ARE)-containing genes. Nrf2
protects not only normal cells but also cancer cells from cellular stress, and
enhances cancer cell survival. Some studies have shown that Nrf2 expression in
cancer patients has clinical significance. However, there has been no
comprehensive analysis of the nuclear expression level of Nrf2 in
gastrointestinal cancer cells. In this study we aimed to immunohistochemically
evaluate the expression of Nrf2, and to assess its clinical significance in
gastric cancer. METHODS: A total of 175 gastric cancer patients who received R0
gastrectomy with standard lymph node dissection were enrolled. We
immunohistochemically evaluated Nrf2 expression in the paraffin-embedded
surgically resected specimens of these 175 patients. Group differences were
analyzed using the chi (2) test, Fisher's exact test, and the Mann-Whitney U
test. Associations between Nrf2 expression and clinicopathological features,
including clinical outcome, were assessed using univariate and multivariate
analyses, and Kaplan-Meier curves with the log-rank test, respectively. RESULTS:
Nrf2 immunoreactivity was predominantly identified in the nucleus of gastric
cancer cells. Nrf2 positivity was closely associated with tumor size, tumor
depth, lymph node metastases, lymphovascular invasion, histology and stage (p <
0.05 for all). A log-rank test indicated that the overall survival of the Nrf2
positive group was significantly poorer than that of the Nrf2-negative group (p <
0.01). And, positive Nrf2 expression was significantly associated with resistance
to 5FU-based adjuvant chemotherapy (p = 0.024). CONCLUSIONS: Nrf2 expression was
positively associated with aggressive tumor behavior in gastric cancer. This
result suggests that Nrf2 expression in gastric cancer is a potential indicator
of worse prognosis.
PMID- 25588811
TI - Enhanced charge separation in ternary P3HT/PCBM/CuInS2 nanocrystals hybrid solar
cells.
AB - Geminate recombination of bound polaron pairs at the donor/acceptor interface is
one of the major loss mechanisms in organic bulk heterojunction solar cells. One
way to overcome Coulomb attraction between opposite charge carriers and to
achieve their full dissociation is the introduction of high dielectric
permittivity materials such as nanoparticles of narrow band gap semiconductors.
We selected CuInS2 nanocrystals of 7.4 nm size, which present intermediate energy
levels with respect to poly(3-hexylthiophene) (P3HT) and Phenyl-C61-butyric acid
methyl ester (PCBM). Efficient charge transfer from P3HT to nanocrystals takes
place as evidenced by light-induced electron spin resonance. Charge transfer
between nanocrystals and PCBM only occurs after replacing bulky dodecanethiol
(DDT) surface ligands with shorter 1,2-ethylhexanethiol (EHT) ligands. Solar
cells containing in the active layer a ternary blend of P3HT:PCBM:CuInS2-EHT
nanocrystals in 1:1:0.5 mass ratio show strongly improved short circuit current
density and a higher fill factor with respect to the P3HT:PCBM reference device.
Complementary measurements of the absorption properties, external quantum
efficiency and charge carrier mobility indicate that enhanced charge separation
in the ternary blend is at the origin of the observed behavior. The same trend is
observed for blends using the glassy polymer poly(triarylamine) (PTAA).
PMID- 25588812
TI - Glial beta-oxidation regulates Drosophila energy metabolism.
AB - The brain's impotence to utilize long-chain fatty acids as fuel, one of the
dogmas in neuroscience, is surprising, since the nervous system is the tissue
most energy consuming and most vulnerable to a lack of energy. Challenging this
view, we here show in vivo that loss of the Drosophila carnitine
palmitoyltransferase 2 (CPT2), an enzyme required for mitochondrial beta
oxidation of long-chain fatty acids as substrates for energy production, results
in the accumulation of triacylglyceride-filled lipid droplets in adult Drosophila
brain but not in obesity. CPT2 rescue in glial cells alone is sufficient to
restore triacylglyceride homeostasis, and we suggest that this is mediated by the
release of ketone bodies from the rescued glial cells. These results demonstrate
that the adult brain is able to catabolize fatty acids for cellular energy
production.
PMID- 25588813
TI - Evaluating the association between CACNA1C rs1006737 and schizophrenia risk: A
meta-analysis.
AB - INTRODUCTION: Genetic analyses including genome-wide association studies have
reported an intronic single nucleotide polymorphism (SNP) rs1006737 in CACNA1C
gene (encoded calcium channel, voltage-dependent, L type, alpha 1C subunit) as a
risk factor for schizophrenia in European populations. The replications in other
ethnic populations such as East Asians have also been conducted, but the results
were inconsistent, either likely due to the limited sample size of single study
or genetic heterogeneity between continental populations on this locus. METHODS:
We performed a comprehensive meta-analysis of all available samples from existing
studies of East Asian populations, including a total of 9,432 cases and 10,661
controls, to further confirm whether CACNA1C rs1006737 is an authentic risk SNP
for schizophrenia in East Asian populations. RESULTS: Our results revealed a
significant association between rs1006737 and schizophrenia (allelic model, P =
4.39 * 10(-6) , pooled odds ratio [OR] = 1.20), and the results were much
strengthened when the European and East Asian samples were combined together (P =
2.40 * 10(-17) , pooled OR = 1.12). There is no significant heterogeneity or
publication bias between individual studies, and removal of any single study
still remained significant associations between rs1006737 and schizophrenia.
DISCUSSION: Our results further confirmed that rs1006737 should be categorized as
an authentic risk SNP for schizophrenia in the general populations.
PMID- 25588814
TI - Longitudinal associations between cyber-bullying perpetration and victimization
and problem behavior and mental health problems in young Australians.
AB - OBJECTIVES: To investigate associations between Grade 9 and 10 cyber-bullying
perpetration and victimization and Grade 11 problem behavior and mental health
problems after controlling for risk factors for these outcomes in the analyses.
METHODS: The sample comprised 927 students from Victoria, Australia who completed
a modified version of the self-report Communities That Care Youth Survey in
Grades 9-11 to report on risk factors, traditional and cyber-bullying
perpetration and victimization, problem behavior, and mental health. Complete
data on over 650 participants were analyzed. RESULTS: Five per cent of Grade 9
and 10 students reported cyber-bullying perpetration only, 6-8% reported
victimization only, and 8-9% both cyber-bullied others and were cyber-bullied.
Results showed that cyber-bullying others in Grade 10 was associated with theft
in Grade 11, cyber-victimization in Grade 10 was linked with Grade 11 depressive
symptoms, and Grade 10 cyber-bullying perpetration and victimization combined
predicted Grade 11 school suspension and binge drinking. CONCLUSIONS: Prevention
approaches that target traditional and cyber-bullying, and established risk
factors are necessary. Such multi-faceted programs may also reduce problem
behavior and mental health problems.
PMID- 25588816
TI - Image Integration of Coronary Cine-Angiography with 3D Electroanatomic Mapping
Using CartoUnivu for Left Coronary Cusp Ventricular Tachycardia.
PMID- 25588815
TI - Stillbirth in an Anglophone minority of Canada.
AB - OBJECTIVES: We assessed trends in stillbirth over time for Francophones and
Anglophones of Quebec, a large Canadian province with publically funded health
care and an English-speaking minority. METHODS: We calculated stillbirth rates
for Francophones and Anglophones, and estimated hazard ratios (HR) by decade from
1981 to 2010, adjusting for maternal characteristics. We analyzed temporal trends
by gestational interval and cause of fetal death. RESULTS: Stillbirth rates
decreased in Quebec during the three decades, due to improved rates in
Francophones. Rates decreased for Anglophones in 1991-2000, but increased in 2001
2010 at term, during the second trimester, and for most causes of fetal death. In
the 2000s, the hazard of stillbirth for Anglophones was nearly the same as the
hazard for Francophones in the 1980s (HR 0.93, 95 % confidence interval 0.82,
1.05). CONCLUSIONS: Stillbirth rates declined in both Francophones and
Anglophones before the turn of the century, but increased thereafter for
Anglophones, suggesting that linguistic inequalities in stillbirth may be
emerging in Quebec. Linguistic status may be a useful marker for surveillance of
inequalities in stillbirth.
PMID- 25588817
TI - Human 3-hydroxyanthranilate 3,4-dioxygenase () dynamics and reaction, a
multilevel computational study.
AB - 3-Hydroxyanthranilate 3,4-dioxygenase () is a non-heme iron dependent enzyme. It
catalyses the cleavage of the benzene ring of 3-hydroxyanthranilic acid (3-Ohaa),
an intermediate in the kynurenine pathway, and therefore represents a potential
target in treating numerous disorders related to the concentration of quinolinic
acid (QUIN), the kynurenine pathway product, in tissues. The stability and
behaviour of the enzyme in nearly physiological conditions, studied by the
empirical molecular modelling methods enabled us to determine the influence of
several, for the enzyme activity relevant, point mutations (Arg43Ala, Arg95Ala
and Glu105Ala) on the protein structure, particularly on the active site
architecture and the metal ion environment, as well as on the substrate, 3-Ohaa,
binding. Besides, the water population of the active site, and the protein
flexibility as well as the amino acid residues interaction networks relevant for
the enzyme activity were determined for the 3-Ohaa complexes with the native and
mutated enzyme variants. Finally, using the hybrid quantum-mechanics/molecular
mechanics (QM/MM) calculations the catalysed 3-Ohaa oxidation into 2-amino-3
carboxymuconic acid semialdehyde was elucidated.
PMID- 25588818
TI - Open your eyes for prediction errors.
AB - Previous studies have demonstrated that autonomic arousal is increased following
correct task performance on a difficult, relative to an easy, task. Here, we
hypothesized that this arousal response reflects the (relative) surprise of
correct performance following a difficult versus an easy task. Following this
line of reasoning, we would expect to find a reversed pattern following erroneous
responses, because errors are less expected during an easy than during a
difficult task. To test this, participants performed a flanker task while pupil
size was measured online. As predicted, the results demonstrated that pupil size
was larger following difficult (incongruent) correct trials than following easy
(congruent) correct trials, but smaller following difficult than following easy
incorrect trials. Moreover, participants with larger congruency effects, and
hence a larger difference in outcome expectancies between the two trial types,
showed larger differences in pupil size after both correct and incorrect
responses, further corroborating the idea that pupil size increased as a measure
of performance prediction errors.
PMID- 25588819
TI - Validity of the Acti4 method for detection of physical activity types in free
living settings: comparison with video analysis.
AB - This study examined the ability of the Acti4 software for identifying physical
activity types from accelerometers during free-living with different levels of
movement complexity compared with video observations. Nineteen aircraft cabin
cleaners with ActiGraph GT3X+ accelerometer at the thigh and hip performed one
semi-standardised and two non-standardised sessions (outside and inside aircraft)
with different levels of movement complexity during working hours. The
sensitivity for identifying different activity types was 75.4-99.4% for the semi
standardised session, 54.6-98.5% outside the aircraft and 49.9-90.2% inside the
aircraft. The specificity was above 90% for all activities, except 'moving'
inside the aircraft. These findings indicate that Acti4 provides good estimates
of time spent in different activity types during semi-standardised conditions,
and for sitting, standing and walking during non-standardised conditions with
normal level of movement complexity. The Acti4 software may be a useful tool for
researchers and practitioners in the field of ergonomics, occupational and public
health. Practitioner Summary: Being inexpensive, small, water-resistant and
without wires, the ActiGraph GT3X+ by applying the Acti4 software may be a useful
tool for long-term field measurements of physical activity types for researchers
and practitioners in the field of ergonomics, occupational and public health.
PMID- 25588821
TI - Characterization of monoclonal antibodies against duck Tembusu virus E protein:
an antigen-capture ELISA for the detection of Tembusu virus infection.
AB - The E protein of flaviviruses is the primary antigen that induces protective
immunity, but a monoclonal antibody (mAb) against the E protein of duck Tembusu
virus (DTMUV) has never been characterized. Six hybridoma cell lines secreting
DTMUV anti-E mAbs were prepared and designated 2A5, 1F3, 1G2, 1B11, 3B6, and 4F9,
respectively. An immunofluorescence assay indicated that the mAbs could
specifically bind to duck embryo fibroblast (DEF) cells infected with DTMUV and
that the E protein was distributed in the cytoplasm of the infected cells.
Immunoglobulin isotyping differentiated the mAbs as IgG1 (1G2, 1B11, 4F9, 1F3,
and 2A5) and IgG2b (3B6). The mAbs were used to identify three epitopes, A (2A5,
1F3, and 1G2), B (1B11 and 4F9), and C (3B6) on the E protein on the basis of a
competitive binding assay. By using mAbs 1F3 and 3B6, we developed an antigen
capture enzyme-linked immunosorbent assay (AC-ELISA) to detect E antigen from
clinical samples. The AC-ELISA did not react with other known pathogens,
indicating that the mAbs are specific for DTMUV. Compared to RT-PCR, the
specificity and sensitivity of the AC-ELISA was 94.1 % and 98.0 %, respectively.
This AC-ELISA thus represents a sensitive and rapid method for detecting DTMUV
infection in birds.
PMID- 25588820
TI - Enrichment of human hematopoietic stem/progenitor cells facilitates transduction
for stem cell gene therapy.
AB - Autologous hematopoietic stem cell (HSC) gene therapy for sickle cell disease has
the potential to treat this illness without the major immunological complications
associated with allogeneic transplantation. However, transduction efficiency by
beta-globin lentiviral vectors using CD34-enriched cell populations is suboptimal
and large vector production batches may be needed for clinical trials.
Transducing a cell population more enriched for HSC could greatly reduce vector
needs and, potentially, increase transduction efficiency. CD34(+) /CD38(-) cells,
comprising ~1%-3% of all CD34(+) cells, were isolated from healthy cord blood
CD34(+) cells by fluorescence-activated cell sorting and transduced with a
lentiviral vector expressing an antisickling form of beta-globin (CCL-beta(AS3)
FB). Isolated CD34(+) /CD38(-) cells were able to generate progeny over an
extended period of long-term culture (LTC) compared to the CD34(+) cells and
required up to 40-fold less vector for transduction compared to bulk CD34(+)
preparations containing an equivalent number of CD34(+) /CD38(-) cells.
Transduction of isolated CD34(+) /CD38(-) cells was comparable to CD34(+) cells
measured by quantitative PCR at day 14 with reduced vector needs, and average
vector copy/cell remained higher over time for LTC initiated from CD34(+) /38(-)
cells. Following in vitro erythroid differentiation, HBBAS3 mRNA expression was
similar in cultures derived from CD34(+) /CD38(-) cells or unfractionated CD34(+)
cells. In vivo studies showed equivalent engraftment of transduced CD34(+) /CD38(
) cells when transplanted in competition with 100-fold more CD34(+) /CD38(+)
cells. This work provides initial evidence for the beneficial effects from
isolating human CD34(+) /CD38(-) cells to use significantly less vector and
potentially improve transduction for HSC gene therapy.
PMID- 25588822
TI - To Forgive and Discredit: Bipolar Identities and Medicated Selves Among Female
Youth in Residential Treatment.
AB - Based on 11 months of ethnographic fieldwork at a residential treatment center in
the United States, this article explores the varied meanings that female youth
attribute to behavior and the strategic (mis)use of knowledge about psychiatric
diagnosis and medication at a time when the scope of behaviors pathologized in
young people continues to expand. Drawing upon psychological and critically
applied medical anthropology, as well as contributions from philosophy on how
classifications of people come into being and circulate, attention is paid to the
multiple contradictions at work in diagnosing young people with mental disorders.
A detailed examination of an exchange that occurred during one particular group
therapy session is presented to demonstrate how psychiatric selves emerge in this
environment when conventional labeling practices no longer suffice as an
explanation of behavior. This turn to psychiatry reveals both the salience of and
confusion around mental health treatment and diagnosis among adolescents, opens
up the distinctions young people make between "real selves" and "medicated
selves," and invokes the possibility of psychiatric disorder as a means to both
forgive and discredit.
PMID- 25588823
TI - Sports-related eye injuries: the current picture.
AB - PURPOSE: This study aims to represent the epidemiologies, findings, treatments,
use of resources, outcomes and protective-eyewear-use recommendations in sports
related eye injuries by sport type. METHODS: The study population is comprised of
all new eye injury patients in 1 year in Helsinki University Eye Hospital. Data
were collected from patient questionnaires and hospital records. The follow-up
period was 3 months. RESULTS: 149/1151 (12.9%) of eye injuries were sports
related. Thirty two percent were related to floorball (type of hockey played on a
mat with a stick and a ball); football, tennis and ice hockey were the next most
common eye-injury-causing sports. Relatively, the most dangerous sports were rink
bandy, (bandy played on ice hockey rink with a stick and a ball) (0.50 injuries
in 12 months/1000 participants, CI 0.10-1.46), floorball (0.47, CI 0.34-0.62) and
tennis (0.47, CI 0.26-0.77). Contusion was the primary diagnosis in 77% of cases;
41% of contusion patients had severe, mainly retinal findings. The number of
outpatient visits was 459; inpatient days 25 and major surgeries 31. One hundred
and eight patients were estimated to need life-long follow-up. Seventeen patients
had a permanent functional impairment, 4 in ice hockey, 3 in floorball, 2 each in
tennis and badminton. CONCLUSION: Compared to a previous study, ice hockey eye
injuries are increasing and relatively severe, and a third of these injuries
occurred despite visor use. Floorball eye injury incidence has significantly
declined, mainly due to recently enforced mandatory protective eyewear for
younger age groups. Based on these findings, we recommend, in floorball, that
protective eyewear should be mandatory in all age groups. Universally in ice
hockey, the proper use of a visor should be emphasised.
PMID- 25588824
TI - Unlocking the sost gene.
PMID- 25588825
TI - An orthodontic bracket embedded in the medial pterygoid surface: a case report.
AB - There is a potential risk that orthodontic brackets can become dislodged into the
aerodigestive tract. This case illustrates the management of an orthodontic
bracket, which became embedded in the deep tissues of the oropharynx. We aim to
highlight the potential risk misplaced dental instruments and materials pose,
including that they may become embedded in the soft tissues of the throat and
suggest that that this possibility should be considered when they cannot be
localized.
PMID- 25588826
TI - Applicability of the Tanaka-Johnston and Moyers mixed dentition analyses in
Northeast Han Chinese.
AB - OBJECTIVES: To assess applicability of the Tanaka-Johnston and Moyers prediction
methods in a Han ethnic group from Northeast China and to develop prediction
equations for this same population. DESIGN: Cross-sectional study. SETTING:
Department of Orthodontics, School of Stomatology, Jiamusi University,
Heilongjiang, China. PARTICIPANTS: A total of 130 subjects (65 male and 65
female) aged 16-21 years from a Han ethnic group of Northeast China were
recruited from dental students and patients seeking orthodontic treatment.
Ethnicity was verified by questionnaire. MATERIAL AND METHODS: Mesio-distal tooth
width was measured using Digital Vernier calipers. Predicted values were obtained
from the Tanaka-Johnston and Moyers methods in both arches were compared with the
actual measured widths. Based on regression analysis, prediction equations were
developed. RESULTS: Tanaka-Johnston equations were not precise, except for the
upper arch in males. However, the Moyers 85th percentile in the upper arch and
75th percentile in the lower arch predicted the sum precisely in males. For
females, the Moyers 75th percentile predicted the sum precisely for the upper
arch, but none of the Moyers percentiles predicted in the lower arch.
CONCLUSIONS: Both the Tanaka-Johnston and Moyers method may not be applied
universally without question. Hence, it may be safer to develop regression
equations for specific populations. Validating studies must be conducted to
confirm the precision of these newly developed regression equations.
PMID- 25588827
TI - Actual versus theoretical torsional play in conventional and self-ligating
bracket systems.
AB - OBJECTIVE: The aim of this study was to assess the amount of torsional play in 32
commercially available self-ligating and conventional 0.018-inch and 0.022-inch
bracket systems in relation to 0.017*0.022-inch and 0.019*0.025-inch stainless
steel wires, respectively, and compare the results with the theoretical amount of
play for the given bracket/wire combinations. METHODS: Torque moments were
measured in a mechanical force testing system by twisting straight pieces of
stainless steel wire seated in the bracket slot in increments of 0.5 degrees
until a full torsional expression was registered. Five upper central incisor
brackets from each of the 32 different bracket systems were selected for the
study. RESULTS: The result from the laboratory testing clearly showed that
wire/slot play was larger than anticipated from the nominal values, especially
regarding the 0.022-inch brackets and particularly in relation to the passive
self-ligating brackets. The play ranged from 19.8 to 36.1 degrees of play for
the most imprecise bracket system. CONCLUSIONS: The result does not favour the
use of self-ligating brackets when focussing on torque control. The actual play
is larger due to oversized slots and the inability of self-ligation brackets to
press the archwire into the bottom of the slot. In conventional brackets, the
initial torque moment is generated by the steel ligatures pressing the arch wire
against the bottom of the slot. The oversize of the slot is thus less critical in
relation to the conventional than in relation to the passive self-ligation
bracket.
PMID- 25588828
TI - How patient and carer expectations of orthodontic treatment vary with ethnicity.
AB - OBJECTIVE: To investigate if the orthodontic treatment expectations of Black
British children and their primary carers vary compared with White British
children and their primary carers. SETTING: A hospital orthodontic department
(Queen Mary's Hospital, Sidcup, London, UK). PARTICIPANTS: Patients and their
accompanying primary carers who had not received fixed orthodontic appliance
treatment and were aged between 12 and 14 years old. METHOD: Informed consent was
obtained from 100 patients and their primary carers, who completed a
psychometrically validated questionnaire, to measure their expectations before a
new patient orthodontic consultation. This cohort consisted of 50 Black British
patients and their primary carers and 50 White British patients and their primary
carers. RESULTS: Mean responses from patients and their primary carers for each
ethnic group were compared using the independent groups t-test. Significant
statistical differences were found between the two ethnic groups. The greatest
statistical differences occurred between Black British patients and their primary
carer and Black British primary carers and White British primary carers. Patients
tended to have similar orthodontic expectations. There were no statistical
significant differences in expectations between White British children and their
primary carers. CONCLUSION: Differences in expectations of orthodontic treatment
were more common between Black British and White British primary carers, than
their children. White British primary carers had higher expectations at their
child's initial appointment and expected dental extractions to be part of the
orthodontic treatment plan. These differences have some implications for the
provision of orthodontic care. A clinicians understanding of patients and their
primary carer's expectations at the start of treatment can help in the quality
and delivery of orthodontic care provided.
PMID- 25588830
TI - SEPT12 orchestrates the formation of mammalian sperm annulus by organizing core
octameric complexes with other SEPT proteins.
AB - Male infertility has become a worldwide health problem, but the etiologies of
most cases are still unknown. SEPT12, a GTP-binding protein, is involved in male
fertility. Two SEPT12 mutations (SEPT12(T89M) and SEPT12(D197N)) have been
identified in infertile men who have a defective sperm annulus with a bent tail.
The function of SEPT12 in the sperm annulus is still unclear. Here, we found that
SEPT12 formed a filamentous structure with SEPT7, SEPT 6, SEPT2 and SEPT4 at the
sperm annulus. The SEPT12-based septin core complex was assembled as octameric
filaments comprising the SEPT proteins 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12. In
addition, the GTP-binding domain of SEPT12 was crucial for its interaction with
SEPT7, and the N- and C-termini of SEPT12 were required for the interaction of
SEPT12 with itself to polymerize octamers into filaments. Mutant mice carrying
the SEPT12(D197N) mutation, which disrupts SEPT12 filament formation, showed a
disorganized sperm annulus, bent tail, reduced motility and loss of the SEPT ring
structure at the sperm annulus. These phenotypes were also observed in an
infertile man carrying SEPT12(D197N). Taken together, our results demonstrate the
molecular architecture of SEPT12 filaments at the sperm annulus, their mechanical
support of sperm motility, and their correlation with male infertility.
PMID- 25588829
TI - Acetylation of the RhoA GEF Net1A controls its subcellular localization and
activity.
AB - Net1 isoform A (Net1A) is a RhoA GEF that is required for cell motility and
invasion in multiple cancers. Nuclear localization of Net1A negatively regulates
its activity, and we have recently shown that Rac1 stimulates Net1A
relocalization to the plasma membrane to promote RhoA activation and cytoskeletal
reorganization. However, mechanisms controlling the subcellular localization of
Net1A are not well understood. Here, we show that Net1A contains two nuclear
localization signal (NLS) sequences within its N-terminus and that residues
surrounding the second NLS sequence are acetylated. Treatment of cells with
deacetylase inhibitors or expression of active Rac1 promotes Net1A acetylation.
Deacetylase inhibition is sufficient for Net1A relocalization outside the
nucleus, and replacement of the N-terminal acetylation sites with arginine
residues prevents cytoplasmic accumulation of Net1A caused by deacetylase
inhibition or EGF stimulation. By contrast, replacement of these sites with
glutamine residues is sufficient for Net1A relocalization, RhoA activation and
downstream signaling. Moreover, the N-terminal acetylation sites are required for
rescue of F-actin accumulation and focal adhesion maturation in Net1 knockout
MEFs. These data indicate that Net1A acetylation regulates its subcellular
localization to impact on RhoA activity and actin cytoskeletal organization.
PMID- 25588832
TI - Dimerization drives EGFR endocytosis through two sets of compatible endocytic
codes.
AB - We have shown previously that epidermal growth factor (EGF) receptor (EGFR)
endocytosis is controlled by EGFR dimerization. However, it is not clear how the
dimerization drives receptor internalization. We propose that EGFR endocytosis is
driven by dimerization, bringing two sets of endocytic codes, one contained in
each receptor monomer, in close proximity. Here, we tested this hypothesis by
generating specific homo- or hetero-dimers of various receptors and their
mutants. We show that ErbB2 and ErbB3 homodimers are endocytosis deficient owing
to the lack of endocytic codes. Interestingly, EGFR-ErbB2 or EGFR-ErbB3
heterodimers are also endocytosis deficient. Moreover, the heterodimer of EGFR
and the endocytosis-deficient mutant EGFRDelta1005-1017 is also impaired in
endocytosis. These results indicate that two sets of endocytic codes are required
for receptor endocytosis. We found that an EGFR-PDGFRbeta heterodimer is
endocytosis deficient, although both EGFR and PDGFRbeta homodimers are
endocytosis-competent, indicating that two compatible sets of endocytic codes are
required. Finally, we found that to mediate the endocytosis of the receptor
dimer, the two sets of compatible endocytic codes, one contained in each receptor
molecule, have to be spatially coordinated.
PMID- 25588833
TI - Cavin3 interacts with cavin1 and caveolin1 to increase surface dynamics of
caveolae.
AB - Caveolae are invaginations of the cell surface thought to regulate membrane
tension, signalling, adhesion and lipid homeostasis owing to their dynamic
behaviour ranging from stable surface association to dynamic rounds of fission
and fusion with the plasma membrane. The caveolae coat is generated by
oligomerisation of the membrane protein caveolin and the family of cavin
proteins. Here, we show that cavin3 (also known as PRKCDBP) is targeted to
caveolae by cavin1 (also known as PTRF) where it interacts with the scaffolding
domain of caveolin1 and promote caveolae dynamics. We found that the N-terminal
region of cavin3 binds a trimer of the cavin1 N-terminus in competition with a
homologous cavin2 (also known as SDPR) region, showing that the cavins form
distinct subcomplexes through their N-terminal regions. Our data shows that
cavin3 is enriched at deeply invaginated caveolae and that loss of cavin3 in
cells results in an increase of stable caveolae and a decrease of caveolae that
are only present at the membrane for a short time. We propose that cavin3 is
recruited to the caveolae coat by cavin1 to interact with caveolin1 and regulate
the duration time of caveolae at the plasma membrane.
PMID- 25588834
TI - Brca2-Pds5 complexes mobilize persistent meiotic recombination sites to the
nuclear envelope.
AB - Homologous recombination is required for reciprocal exchange between homologous
chromosome arms during meiosis. Only select meiotic recombination events become
chromosomal crossovers; the majority of recombination outcomes are noncrossovers.
Growing evidence suggests that crossovers are repaired after noncrossovers. Here,
I report that persisting recombination sites are mobilized to the nuclear
envelope of Drosophila pro-oocytes during mid-pachytene. Their number correlates
with the average crossover rate per meiosis. Proteomic and interaction studies
reveal that the recombination mediator Brca2 associates with lamin and the
cohesion factor Pds5 to secure persistent recombination sites at the nuclear
envelope. In Rad51(-/-) females, all persistent DNA breaks are directed to the
nuclear envelope. By contrast, a reduction of Pds5 or Brca2 levels abolishes the
movement and has a negative impact on crossover rates. The data suggest that
persistent meiotic DNA double-strand breaks might correspond to crossovers, which
are mobilized to the nuclear envelope for their repair. The identification of
Brca2-Pds5 complexes as key mediators of this process provides a first
mechanistic explanation for the contribution of lamins and cohesins to meiotic
recombination.
PMID- 25588831
TI - The heterotrimeric kinesin-2 complex interacts with and regulates GLI protein
function.
AB - GLI transport to the primary cilium and nucleus is required for proper Hedgehog
(HH) signaling; however, the mechanisms that mediate these trafficking events are
poorly understood. Kinesin-2 motor proteins regulate ciliary transport of cargo,
yet their role in GLI protein function remains unexplored. To examine a role for
the heterotrimeric KIF3A-KIF3B-KAP3 kinesin-2 motor complex in regulating GLI
activity, we performed a series of structure-function analyses using biochemical,
cell signaling and in vivo approaches that define novel specific interactions
between GLI proteins and two components of this complex, KAP3 and KIF3A. We find
that all three mammalian GLI proteins interact with KAP3 and we map specific
interaction sites in both proteins. Furthermore, we find that GLI proteins
interact selectively with KIF3A, but not KIF3B, and that GLI interacts
synergistically with KAP3 and KIF3A. Using a combination of cell signaling assays
and chicken in ovo electroporation, we demonstrate that KAP3 interactions
restrict GLI activator function but not GLI repressor function. These data
suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for
proper GLI transcriptional activity.
PMID- 25588835
TI - Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the
activity of Tead family proteins and Myc.
AB - Cell competition is a short-range communication originally observed in
Drosophila. Relatively little is known about cell competition in mammals or in
non-epithelial cells. Hippo signaling and its downstream transcription factors of
the Tead family, control cell proliferation and apoptosis. Here, we established
an in vitro model system that shows cell competition in mouse NIH3T3 embryo
fibroblast cells. Co-culture of Tead-activity-manipulated cells with normal (wild
type) cells caused cell competition. Cells with reduced Tead activity became
losers, whereas cells with increased Tead activity became super-competitors. Tead
directly regulated Myc RNA expression, and cells with increased Myc expression
also became super-competitors. At low cell density, cell proliferation required
both Tead activity and Myc. At high cell density, however, reduction of either
Tead activity or Myc was compensated for by an increase in the other, and this
increase was sufficient to confer 'winner' activity. Collectively, NIH3T3 cells
have cell competition mechanisms similar to those regulated by Yki and Myc in
Drosophila. Establishment of this in vitro model system should be useful for
analyses of the mechanisms of cell competition in mammals and in fibroblasts.
PMID- 25588837
TI - Loss of LKB1 leads to impaired epithelial integrity and cell extrusion in the
early mouse embryo.
AB - LKB1/PAR-4 is essential for the earliest polarization steps in Caenorhabditis
elegans embryos and Drosophila oocytes. Although LKB1 (also known as STK11) is
sufficient to initiate polarity in a single mammalian intestinal epithelial cell,
its necessity in the formation and maintenance of mammalian epithelia remains
unclear. To address this, we completely remove LKB1 from mouse embryos by
generating maternal-zygotic Lkb1 mutants and find that it is dispensable for
polarity and epithelia formation in the early embryo. Instead, loss of Lkb1 leads
to the extrusion of cells from blastocyst epithelia that remain alive and can
continue to divide. Chimeric analysis shows that Lkb1 is cell-autonomously
required to prevent these extrusions. Furthermore, heterozygous loss of Cdh1
exacerbates the number of extrusions per blastocyst, suggesting that LKB1 has a
role in regulating adherens junctions in order to prevent extrusion in epithelia.
PMID- 25588836
TI - Specific interaction of KIF11 with ZBP1 regulates the transport of beta-actin
mRNA and cell motility.
AB - ZBP1-modulated localization of beta-actin mRNA enables a cell to establish
polarity and structural asymmetry. Although the mechanism of beta-actin mRNA
localization has been well established, the underlying mechanism of how a
specific molecular motor contributes to the transport of the ZBP1 (also known as
IGF2BP1) complex in non-neuronal cells remains elusive. In this study, we report
the isolation and identification of KIF11, a microtubule motor, which physically
interacts with ZBP1 and is a component of beta-actin messenger ribonucleoprotein
particles (mRNPs). We show that KIF11 colocalizes with the beta-actin mRNA, and
the ability of KIF11 to transport beta-actin mRNA is dependent on ZBP1. We
characterize the corresponding regions of ZBP1 and KIF11 that mediate the
interaction of the two proteins in vitro and in vivo. Disruption of the in vivo
interaction of KIF11 with ZBP1 delocalizes beta-actin mRNA and affects cell
migration. Our study reveals a molecular mechanism by which a particular
microtubule motor mediates the transport of an mRNP through direct interaction
with an mRNA-binding protein.
PMID- 25588838
TI - PDK1 regulates focal adhesion disassembly by modulating endocytosis of
alphavbeta3 integrin.
AB - Non-amoeboid cell migration is characterised by dynamic competition among
multiple protrusions to establish new adhesion sites at the cell's leading edge.
However, the mechanisms that regulate the decision to disassemble or to grow
nascent adhesions are not fully understood. Here we show that, in endothelial
cells, 3-phosphoinositide-dependent protein kinase 1 (PDK1) promotes focal
adhesion (FA) turnover by controlling endocytosis of integrin alphavbeta3 in a
PI3K-dependent manner. We demonstrate that PDK1 binds and phosphorylates integrin
alphavbeta3. Downregulation of PDK1 increases FA size and slows down their
disassembly. This process requires both PDK1 kinase activity and PI3K activation
but does not involve Akt. Moreover, PDK1 silencing stabilises FA in membrane
protrusions decreasing migration of endothelial cells on vitronectin. These
results indicate that modulation of integrin endocytosis by PDK1 hampers
endothelial cell adhesion and migration on extracellular matrix, thus unveiling a
novel role for this kinase.
PMID- 25588840
TI - TOM1 is a PI5P effector involved in the regulation of endosomal maturation.
AB - Phosphoinositides represent a major class of lipids specifically involved in the
organization of signaling cascades, maintenance of the identity of organelles and
regulation of multiple intracellular trafficking steps. We previously reported
that phosphatidylinositol 5-monophosphate (PI5P), produced by the Shigella
flexneri phosphatase IpgD, is implicated in the endosomal sorting of the
epidermal growth factor receptor (EGFR). Here, we show that the adaptor protein
TOM1 is a new direct binding partner of PI5P. We identify the domain of TOM1
involved in this interaction and characterize the binding motif. Finally, we
demonstrate that the recruitment of TOM1 by PI5P on signaling endosomes is
responsible for the delay in EGFR degradation and fluid-phase bulk endocytosis.
Taken together, our data strongly suggest that PI5P enrichment in signaling
endosomes prevents endosomal maturation through the recruitment of TOM1, and
point to a new function of PI5P in regulating discrete maturation steps in the
endosomal system.
PMID- 25588839
TI - IQGAP1 controls tight junction formation through differential regulation of
claudin recruitment.
AB - IQGAP1 is a scaffolding protein previously implicated in adherens junction
formation. However, its role in the establishment or maintenance of tight
junctions (TJs) has not been explored. We hypothesized that IQGAP1 could regulate
TJ formation by modulating the expression and/or localization of junctional
proteins, and we systematically tested this hypothesis in the model Madin-Darby
canine kidney (MDCK) cell line. We find that IQGAP1 silencing enhances a
transient increase in transepithelial electrical resistance (TER) observed during
the early stages of TJ formation (Cereijido et al., 1978). Quantitative
microscopy and biochemical experiments suggest that this effect of IQGAP1 on TJ
assembly is accounted for by reduced expression and TJ recruitment of claudin 2,
and increased TJ recruitment of claudin 4. Furthermore, we show that IQGAP1 also
regulates TJ formation through its interactor CDC42, because IQGAP1 knockdown
increases the activity of the CDC42 effector JNK and dominant-negative CDC42
prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide
evidence that IQGAP1 modulates TJ formation by a twofold mechanism: (1)
controlling the expression and recruitment of claudin 2 and recruitment of
claudin 4 to the TJ, and (2) transient inhibition of the CDC42-JNK pathway.
PMID- 25588842
TI - TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney
field establishment in Xenopus.
AB - In Xenopus laevis embryos, kidney field specification is dependent on retinoic
acid (RA) and coincides with a dramatic increase of Ca(2+) transients, but the
role of Ca(2+) signaling in the kidney field is unknown. Here, we identify TRPP2,
a member of the transient receptor potential (TRP) superfamily of channel
proteins encoded by the pkd2 gene, as a central component of Ca(2+) signaling in
the kidney field. TRPP2 is strongly expressed at the plasma membrane where it
might regulate extracellular Ca(2+) entry. Knockdown of pkd2 in the kidney field
results in the downregulation of pax8, but not of other kidney field genes (lhx1,
osr1 and osr2). We further show that inhibition of Ca(2+) signaling with an
inducible Ca(2+) chelator also causes downregulation of pax8, and that pkd2
knockdown results in a severe inhibition of Ca(2+) transients in kidney field
explants. Finally, we show that disruption of RA results both in an inhibition of
intracellular Ca(2+) signaling and of TRPP2 incorporation into the plasma
membrane of kidney field cells. We propose that TRPP2-dependent Ca(2+) signaling
is a key component of pax8 regulation in the kidney field downstream of RA
mediated non-transcriptional control of TRPP2.
PMID- 25588841
TI - ESCRT-0 marks an APPL1-independent transit route for EGFR between the cell
surface and the EEA1-positive early endosome.
AB - Endosomal sorting complexes required for transport (ESCRT)-0 sorts ubiquitylated
EGFR within the early endosome so that the receptor can be incorporated into
intralumenal vesicles. An important question is whether ESCRT-0 acts solely upon
EGFR that has already entered the vacuolar early endosome (characterised by the
presence of EEA1) or engages EGFR within earlier compartments. Here, we employ a
suite of software to determine the localisation of ESCRT-0 at subpixel resolution
and to perform particle-based colocalisation analysis with other endocytic
markers. We demonstrate that although some of the ESCRT-0 subunit Hrs (also known
as HGS) colocalises with the vacuolar early endosome marker EEA1, most localises
to a population of peripheral EEA1-negative endosomes that act as intermediates
in transporting EGFR from the cell surface to more central early endosomes. The
peripheral Hrs-labelled endosomes are distinct from APPL1-containing endosomes,
but co-label with the novel endocytic adaptor SNX15. In contrast to ESCRT-0,
ESCRT-I is recruited to EGF-containing endosomes at later times as they move to
more a central position, whereas ESCRT-III is also recruited more gradually. RNA
silencing experiments show that both ESCRT-0 and ESCRT-I are important for the
transit of EGF to EEA1 endosomes.
PMID- 25588845
TI - Pistagremic acid, a novel beta-secretase enzyme (BACE1) inhibitor from Pistacia
integerrima Stewart.
AB - A new triterpenic compound named pistagremic acid (PA) was once again isolated
from Pistaciaintegerrima. The beta-secretase inhibition study was carried out.
Compound PA was found significantly active against beta-secretase enzyme (BACE1)
with IC50 value of 350 +/- 2 nM in comparison to the standard inhibitors [Asn670,
Sta671, Val672]-amyloid-beta/A4 precursor protein 770 fragment 662-675 (IC50 =
290.71 +/- 1 nM). The selectivity of this compound was also evaluated against the
acetylcholinesterase and butyrylcholinesterase enzymes. Interestingly compound PA
was found to be inactive against them and showed selectivity towards beta
secretase enzyme (BACE1).
PMID- 25588843
TI - S1PR1 Tyr143 phosphorylation downregulates endothelial cell surface S1PR1
expression and responsiveness.
AB - Activation of sphingosine-1-phosphate receptor 1 (S1PR1) plays a key role in
repairing endothelial barrier function. We addressed the role of phosphorylation
of the three intracellular tyrosine residues of S1PR1 in endothelial cells in
regulating the receptor responsiveness and endothelial barrier function regulated
by sphingosine 1-phosphate (S1P)-mediated activation of S1PR1. We demonstrated
that phosphorylation of only Y143 site was required for S1PR1 internalization in
response to S1P. Maximal S1PR1 internalization was seen in 20 min but S1PR1
returned to the cell surface within 1 h accompanied by Y143-dephosphorylation.
Cell surface S1PR1 loss paralleled defective endothelial barrier enhancement
induced by S1P. Expression of phospho-defective (Y143F) or phospho-mimicking
(Y143D) mutants, respectively, failed to internalize or showed unusually high
receptor internalization, consistent with the requirement of Y143 in regulating
cell surface S1PR1 expression. Phosphorylation of the five S1PR1 C-terminal
serine residues did not affect the role of Y143 phosphorylation in signaling
S1PR1 internalization. Thus, rapid reduction of endothelial cell surface
expression of S1PR1 subsequent to Y143 phosphorylation is a crucial mechanism of
modulating S1PR1 signaling, and hence the endothelial barrier repair function of
S1P.
PMID- 25588844
TI - Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges
polarizes neutrophils.
AB - A hallmark of neutrophil polarization is the back localization of active RHOA and
phosphorylated myosin light chain (pMLC, also known as MYL2). However, the
mechanism for the polarization is not entirely clear. Here, we show that FAM65B,
a newly identified RHOA inhibitor, is important for the polarization. When FAM65B
is phosphorylated, it binds to 14-3-3 family proteins and becomes more stable. In
neutrophils, chemoattractants stimulate FAM65B phosphorylation largely depending
on the signals from the front of the cells that include those mediated by
phospholipase Cbeta (PLCbeta) and phosphoinositide 3-kinase gamma (PI3Kgamma),
leading to FAM65B accumulation at the leading edge. Concordantly, FAM65B
deficiency in neutrophils resulted in an increase in RHOA activity and
localization of pMLC to the front of cells, as well as defects in chemotaxis
directionality and adhesion to endothelial cells under flow. These data together
elucidate a mechanism for RHOA and pMLC polarization in stimulated neutrophils
through direct inhibition of RHOA by FAM65B at the leading edge.
PMID- 25588846
TI - Giant resonance tuning of micro and nanomechanical oscillators.
AB - We present a method to tune the resonance frequency and the Q-factor of micro and
nano-metric mechanical oscillators. A counteracting loop drives a capacitive
force applied to the oscillator. The proportional and differential gains are used
to shift the resonance frequency up to 75% and to tune the Q-factor of the
oscillator, by changing its effective stiffness and damping ratio. The oscillator
position is monitored in a large bandwidth with a fiber-optic based
interferometer. We applied this simple operational scheme with different
oscillators for modifying easily their dynamical properties. Compared to
alternative methods requiring external fields, our method can either increase or
decrease the resonance frequency in a frequency range much more extended. This
opens up a wide range of applications, from force sensors with extremely low
elastic constants but high quality factor to tunable energy harvesters or to high
frequency tuning of radio frequency filters. The control scheme can work in
different media, and is then suitable to be applied to biological sensors and
actuators.
PMID- 25588847
TI - Intramedullary nailing versus proximal plating in the management of closed extra
articular proximal tibial fracture: a randomized controlled trial.
AB - BACKGROUND: Extra-articular proximal tibial fractures account for 5-11 % of all
tibial shaft fractures. In recent years, closed reduction and minimally invasive
plating and multidirectional locked intramedullary nailing have both become
widely used treatment modalities for proximal and distal tibial metaphyseal
fractures. This study was performed to compare plating and nailing options in
proximal tibia extra-articular fractures. MATERIALS AND METHODS: This randomized
prospective clinical study was conducted on 58 skeletally mature patients with a
closed extra-articular fracture of the proximal tibia treated with minimally
invasive proximal tibial plating (PTP) or intramedullary nailing (IMN) by trained
surgeons at a tertiary trauma center. RESULTS: Postoperative hospital stay (p =
0.035), time to full weight-bearing, and union time (p = 0.004) were
significantly less in the IMN group than in the PTP group, but there was no clear
advantage of either technique in terms of operative time (p = 0.082), infection
rate (p = 0.738), range of motion of the knee (p = 0.462), or degrees of malunion
and nonunion. CONCLUSION: Both implants have shown promising results in extra
articular proximal tibial fractures, and provide rigid fixation that prevents
secondary fracture collapse. LEVEL OF EVIDENCE: Level 2, randomized controlled
trial.
PMID- 25588848
TI - Coloduodenal fistula due to signet-ring cells adenocarcinoma.
PMID- 25588849
TI - Other nanoparticles: general discussion.
PMID- 25588851
TI - Antiasthmatic Effects of Eugenol in a Mouse Model of Allergic Asthma by
Regulation of Vitamin D3 Upregulated Protein 1/NF-kappaB Pathway.
AB - The aim of the study was to investigate the antiasthmatic effects of eugenol
(EUG) and the possible mechanisms. Asthma model was established by ovalbumin
induction. A total of 50 mice were randomly assigned to five experimental groups:
control, OVA, OVA + dexamethasone (2 mg/kg), OVA + EUG (10 mg/kg), and OVA + EUG
(20 mg/kg). Airway resistance (Raw) were measured, histological studies were
evaluated by the hematoxylin and eosin (HE) staining, interleukin-4 (IL-4) and
interleukin-5 (IL-5) were evaluated by enzyme-linked immunosorbent assay (ELISA),
Vitamin D3 upregulated protein 1 (VDUP1), IkappaBalpha, P-IkappaBalpha, NF
kappaBP65, and p-NF-kappaBP65 were measured by Western blotting. Our study
demonstrated that EUG inhibited OVA-induced increases in Raw and eosinophil
count; IL-4 and IL-5 were recovered. Histological studies demonstrated that EUG
substantially inhibited OVA-induced eosinophilia in the lung tissue. Western
blotting studies demonstrated that EUG substantially inhibited P-IkappaBalpha, NF
kappaBP65, and p-NF-kappaBP65 protein levels and increased VDUP1 and IkappaBalpha
protein levels. These findings suggest that EUG may effectively ameliorate the
progression of asthma and could be used as a therapy for patients with allergic
asthma.
PMID- 25588852
TI - Biocontrol of Salmonella Enteritidis in spiked chicken cuts by lytic
bacteriophages PhiSP-1 and PhiSP-3.
AB - The ability of host specific bacteriophages PhiSP-1 and PhiSP-3 to lyse
Salmonella in artificially contaminated cuts of pressure cooked chicken meat was
evaluated at different temperatures -4 degrees C, room temperature (28 +/- 0.5
degrees C) and 37 degrees C applying low and high multiplicity of infection
(MOI). Bacteriophages were able to significantly reduce the bacterial counts at
all the temperatures studied. At 4 degrees C, individual application of Phi SP-1
and Phi SP-3 resulted in significant drop in bacterial counts (log10 2.46 and 2.1
CFU/ml, respectively) at high MOI and (log10 0.98 and 0.52 CFU/ml, respectively)
at low MOI, when compared to the untreated control on day 3. Similarly at room
temperature the drop was log10 3.99 and 3.46 CFU/ml at high MOI and log10 2.51
and 2.3 CFU/ml at low MOI. At 37 degrees C the drop was log10 1.98 and 2.38 at
high MOI and at low MOI it was log10 1.52 and 1.98 CFU/ml. Increased efficiency
was observed when phages where applied as cocktail at high MOI as the bacterial
counts at the end of day 3 dropped by log10 3.52 CFU/ml at 37 degrees C and to
beyond detectable level at 4 degrees C and room temperature. The average
reduction of bacterial load in the same group was -4 degrees C (79%), room
temperature (92%) and 37 degrees C (78%).
PMID- 25588850
TI - Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during
the development of salt-dependent hypertension in rats.
AB - A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4)
inhibitors have antihypertensive effects. Here, we aim to examine the effect of
vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian
dipping pattern during the development of salt-dependent hypertension in Dahl
salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl)
plus vehicle or vildagliptin (3 or 10 mg kg(-1) twice daily by oral gavage) for 7
days. Blood pressure was measured by the telemetry system. High-salt diet for 7
days significantly increased the mean arterial pressure (MAP), systolic blood
pressure (SBP) and were also associated with an extreme dipping pattern of blood
pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased
plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels
and attenuated the development of salt-induced hypertension. Furthermore,
vildagliptin significantly increased urine sodium excretion and normalized the
dipping pattern of blood pressure. In contrast, intracerebroventricular infusion
of vildagliptin (50, 500 or 2500 MUg) did not alter MAP and heart rate in DSS
rats. These data suggest that salt-dependent hypertension initially develops with
an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may
elicit beneficial antihypertensive effects, including the improvement of abnormal
circadian blood pressure pattern, by enhancing urinary sodium excretion.
PMID- 25588853
TI - Short-term diabetes- and diuresis-induced alterations of the bladder are mostly
reversible in rats.
AB - OBJECTIVES: To determine whether diabetes mellitus- and diuresis-induced
alterations in the bladder can be reversed in rats. METHODS: Male Sprague-Dawley
rats were randomly distributed into eight groups (n = 16 per group): 3 weeks and
11 weeks age-matched controls, 3 weeks and 11 weeks after streptozotocin-induced
diabetes mellitus, 3 weeks after diabetes mellitus induction then treated with
insulin for 8 weeks, 3 weeks and 11 weeks after 5% sucrose-induced diuresis, and
3 weeks after 5% sucrose-induced diuresis followed by removal of 5% sucrose for 8
weeks. Bodyweight, blood glucose and glycated hemoglobin A1c were monitored. At
the designated time-points, 24-h urinary habits were examined, and cystometry was
carried out in half of the animals. The bladders from the remaining animals were
harvested for histological examination, and quantification of smooth muscle,
urothelium and collagen components. RESULTS: Insulin treatment reversed
hyperglycemia and polyuria in diabetic animals successfully, which was shown by
normalization of blood glucose, glycated hemoglobin A1c and 24-h urinary habits.
Subsequently, bodyweight, bladder weight and percentage change of bladder
components (smooth muscle, collagen, urothelium) in total bladder cross-sectional
area were reversed to almost normal levels, and the bladder dysfunction was
mostly reversed by 8 weeks of glycemic control, seen in the cystometry study.
Similar alterations and reversed effects were seen in diuretic rats without and
with 5% sucrose removal, respectively. CONCLUSIONS: Short-term (3-week induction)
diabetes- and polyuria-induced functional and morphological alterations of the
bladder can mostly be reversed in rats.
PMID- 25588854
TI - Prognostic value of Bcl-2 expression in squamous cell carcinoma of the larynx: a
systematic review.
AB - The aim of this systematic review was to determine the prognostic value of Bcl-2
immunostaining in patients affected by laryngeal squamous cell carcinoma. An
appropriate search was conducted on PubMed to retrieve articles dealing with this
topic. A double cross-check was performed on citations and full-text articles by
2 investigators independently to review all manuscripts and perform a
comprehensive quality assessment. Of 115 abstracts identified, 15 articles were
included. These studies reported on 1,150 patients with histologically confirmed
diagnosis of laryngeal squamous cell carcinoma. Only a few studies showed a
statistical correlation between Bcl-2 immunohistochemical expression and at least
1 of the clinical and histopathological parameters considered by the authors.
Moreover, these findings were also discordant between them. Overall the studies
analyzed suggested that Bcl-2 expression was statistically connected with N stage
(2/14), grading (2/14), disease-free survival (3/14) and overall survival (5/14).
Interestingly, all of the 3 studies investigating the relation between Bcl-2 and
radioresistance showed significant results in terms of recurrence-free survival
and overall survival. Our review strongly suggests that the immunohistochemical
staining of Bcl-2 does not correlate with tumoral aggressiveness and prognosis of
patients affected by laryngeal squamous cell carcinoma and treated with primary
surgery. However, an interesting connection of this protein could be demonstrated
with tumoral radioresistance. Further, high-quality prospective studies should be
carried out to confirm this hypothesis.
PMID- 25588855
TI - Clinical significance of subtype classification in metastatic lymph nodes of
breast cancer patients undergoing neoadjuvant chemotherapy.
AB - BACKGROUND: Neoadjuvant chemotherapy has been increasingly utilized in the
treatment of breast cancer patients. However, there are no established surrogate
markers predicting the response to subsequent adjuvant therapy and clinical
outcome of patients. In particular, whether primary or lymph nodes metastasis
should be evaluated for these analyses has remained unknown. Therefore, in this
study, we first evaluated the differences in biomarkers between primary and
metastatic cancer tissues in the patients undergoing neoadjuvant chemotherapy. We
then correlated the findings with the clinical outcomes of these patients.
METHODS: We examined 49 patients receiving neoadjuvant chemotherapy and
subsequent surgery with lymph node metastasis. Estrogen receptor (ER),
progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) and
Ki-67 were all immunohistochemically evaluated in core needle biopsy samples from
primary and metastatic tumors following chemotherapy. RESULTS: No statistically
significant differences in these markers were detected between the primary tumor
and metastatic lymph nodes following therapy, but the Ki-67 labeling index was
significantly higher in metastatic lymph nodes than in primary tumor (p = 0.017).
The patients associated with luminal A type carcinoma in their lymph nodes
following chemotherapy demonstrated significantly better clinical outcomes
(disease-free survival: p = 0.0045, overall survival: p = 0.0006) than those who
were not. CONCLUSION: These data indicate that subtype classification following
chemotherapy, in the metastatic lymph nodes rather than primary tumor could
predict long-term outcomes of patients undergoing neoadjuvant chemotherapy.
PMID- 25588856
TI - MGMT promoter methylation and glioblastoma: a comparison of analytical methods
and of tumor specimens.
AB - It is already well known that hypermethylation of the O6-methylguanine DNA
methyltransferase (MGMT) gene promoter is a predictive biomarker of response to
temozolomide treatment and of favorable outcomes in terms of overall survival
(OS) and progression-free survival (PFS) in glioblastoma (GBM) patients.
Nevertheless, MGMT methylation status has not currently been introduced into
routine clinical practice, as the choice of the ideal technique and tissue sample
specimen is still controversial. The aim of this study was to compare 2
analytical methods, methylation-specific polymerase chain reaction (MSP) and
pyrosequencing (PSQ), and their use on 2 different tissue type samples, snap
frozen and formalin-fixed paraffin-embedded (FFPE), obtained from a single-center
and uniformly treated cohort of 46 GBM patients. We obtained methylation data
from all frozen tissues, while no results were obtained for 5 FFPE samples. The
highest concordance for methylation was found on frozen tissues (88.5%, 23/26
samples), using PSQ (76.7%, 23/30 samples). Moreover, we confirmed that OS and
PFS for patients carrying methylation of the MGMT promoter were longer than for
patients with an unmethylated promoter. In conclusion, we considered MSP a
limited technique for FFPE tissues due to the high risk of false-positive
results; in contrast, our data indicated PSQ as the most powerful method to
stratify methylated/unmethylated patients as it allows reaching quantitative
results with high sensitivity and specificity. Furthermore, frozen tumor tissues
were shown to be the best specimens for MGMT methylation analysis, due to the low
DNA degradation and homogeneity in methylation throughout the tumor.
PMID- 25588857
TI - Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in
triple-negative breast cancer.
AB - BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by the absence
of estrogen receptor, progesterone receptor and HER2. TNBCs are a diverse
subgroup, but one promising marker and therapeutic target of this breast cancer
is the androgen receptor (AR). Previously we demonstrated that AR and cognate
intracrine pathways are associated with decreased proliferation in invasive
ductal carcinoma with their decrease also detected between organ-confined and
invasive diseases. Therefore, in this study, we examined the status of AR and
androgen-producing enzymes during the process of metastasis to lymph nodes and
cancer recurrence. MATERIALS AND METHODS: We studied 2 series of patients with
TNBC, one from Kumamoto University Hospital composed of 16 matched cases of
primary and locally or distal recurrences and the other from Tohoku University
Hospital examining 46 lymph node metastasis from 23 patients. In addition to
studying concordance in AR expression, we also examined the interactions between
AR and Ki-67 labeling index and AR and site of distal metastasis. RESULTS: In
both series, AR status was concordant between primary and recurrent/metastatic
disease, but coordinated expression of AR and androgenic enzymes was lost during
the process. The inverse association between AR and Ki-67, previously reported in
invasive ductal carcinoma (IDC), was markedly potentiated in both lymph node and
recurrent cancers. In addition, AR expression appeared to have little effect on
visceral metastasis but was associated directly with bone metastasis and
inversely with brain metastasis. CONCLUSIONS: The results of our present study
demonstrated that AR remained in the majority of metastatic samples from AR
positive primary TNBCs and that AR manipulation could be exploited in the
metastatic settings of TNBC.
PMID- 25588858
TI - The relation between CA 19-9 level and early-phase insulin secretion in
normoglycemic and prediabetic subjects.
AB - BACKGROUND: Carbohydrate antigen (CA) 19-9 is used as a clinical tumor marker of
pancreatic cancer; recent studies report that CA 19-9 is also associated with
changes in blood glucose levels. The aim of the present study was to investigate
the relationship between serum CA 19-9 levels and early-phase insulin secretion
in nondiabetic individuals. METHODS: We enrolled 269 normoglycemic participants
and 172 prediabetic participants who had undergone the 75-g oral glucose
tolerance test during their annual health examination. Insulin secretion was
estimated using the disposition index (DI) [(Deltainsulin(0-30
min)/Deltaglucose(0-30 min) * (1/HOMA-IR)], which is an adjusted measure of
relationship between beta-cell sensitivity and insulin sensitivity. RESULTS:
Serum CA 19-9 level was significantly higher in the prediabetic participants than
in the normoglycemic participants. Simple linear regression analysis showed a
negative correlation between CA 19-9 levels and DI for all participants and
prediabetic participants (r = -0.126, p = 0.009, and r = -0.189, p = 0.002,
respectively). However, in the normoglycemic participants, CA 19-9 levels did not
correlate with DI. For all participants, and prediabetic subjects, multivariate
linear regression analysis revealed that serum CA 19-9 levels were one of the
independent predictors of DI (adjusted beta = -0.098, p = 0.025, and adjusted
beta = -0.177, p = 0.004, respectively). CONCLUSIONS: Serum CA 19-9 levels
significantly correlate with early-phase insulin secretion in the prediabetic
individuals. Our results indicate that CA 19-9 may be involved in the endocrine
function of pancreas.
PMID- 25588859
TI - Lung adenocarcinoma with concurrent KRAS mutation and ALK rearrangement
responding to crizotinib: case report.
AB - Chromosomal translocation resulting in the fusion between the echinoderm
microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma
kinase (ALK) gene was recently identified as a novel genetic alteration in a
subset of non-small cell lung cancer (NSCLC). EML4-ALK translocations are rare
events associated with specific clinicopathological features, such as never or
light smoking history, young age and adenocarcinoma with signet ring or acinar
histology. Reports suggest ALK gene arrangements are mutually exclusive with EGFR
and KRAS mutations. To the best of to our knowledge, this is the first case
report of a patient with concurrent KRAS mutation and ALK translocation. This
patient had an excellent response to crizotinib, suggesting that the ALK
translocation was the oncogenic driver.
PMID- 25588860
TI - Measurement of a urinary marker (8-hydroxydeoxy-guanosine, 8-OHdG) of DNA
oxidative stress in epidemiological surveys: a pilot study.
AB - BACKGROUND: 8-Hydroxydeoxyguanosine (8-OHdG) is a commonly used marker of DNA
oxidative stress in epidemiological studies. The aim of this study was to
establish whether the urinary concentration of 8-OHdG varies during the first
part of the day, when clinical tests are usually performed, and whether it can
therefore be measured without bias in spot urine samples. MATERIAL AND METHODS:
Spot urine samples were collected using a convenience sample. A linear mixed
effects model for repeated measurements was used to analyze 8-OHdG levels.
RESULTS: A significant increasing trend in time in the 8-OHdG concentration was
found among smokers, but not in the case of nonsmokers. CONCLUSIONS: In
epidemiological studies on oxidative stress, all participants should collect
their early morning urine specimens - before their first cigarette if they are
smokers - to gather information on individual background oxidation levels.
PMID- 25588861
TI - Change of hemopexin level is associated with the severity of sepsis in
endotoxemic rat model and the outcome of septic patients.
AB - PURPOSE: The purpose of the study is to uncover the role of hemopexin (HPX) as
anti-inflammatory mediator in animals and humans. MATERIALS AND METHODS: We
injected rats with 5 and 10 mg/kg of lipopolysaccharide to induce low- and high
grade endotoxemia (LGE and HGE), respectively, and we measured serum levels of
tumor necrosis factor alpha, interleukin 6, and HPX at 0, 1, 3, and 6 hours after
the injection. In a clinical study, we measured the initial serum HPX
concentrations of septic shock patients. We evaluated the correlation between HPX
levels and sepsis severity in rats and the predictive value of the HPX level for
28-day mortality of patients. RESULTS: In rats, serum interleukin 6 and tumor
necrosis factor alpha concentrations were lower in LGE than in HGE, whereas the
HPX level in HGE at 6 hours was significantly lower than in LGE (0.88,
interquartile range [0.79-1.00] vs 1.33, interquartile range [1.29-1.49] mg/mL,
P= .002). In patients, the initial serum HPX level in nonsurvivors was
significantly lower than in survivors (0.75 vs 1.02 mg/mL, P< .001). Multivariate
logistic regression analysis revealed that HPX exhibited independent prognostic
value for 28-day mortality, and its levels were closely related to Acute
Physiology and Chronic Health Evaluation II scores. CONCLUSIONS: Low serum HPX
levels are related to sepsis severity and could indicate poor prognosis for
septic shock patients.
PMID- 25588862
TI - Chronic liver disease and 90-day mortality in 21,359 patients following peptic
ulcer bleeding--a Nationwide Cohort Study.
AB - BACKGROUND: Bleeding is a serious and frequent complication of peptic ulcer
disease. Hepatic dysfunction can cause coagulopathy and increases the risk of
peptic ulcer bleeding. However, whether chronic liver disease increases mortality
after peptic ulcer bleeding remains unclear. AIM: To examine the prognostic
impact of chronic liver disease on mortality after peptic ulcer bleeding.
METHODS: We used population-based medical registries to conduct a cohort study of
all Danish residents hospitalised with incident peptic ulcer bleeding from 2004
through 2011. We identified patients diagnosed with liver cirrhosis or non
cirrhotic chronic liver disease before their admission for peptic ulcer bleeding.
We then computed 90-day mortality after peptic ulcer bleeding based on the Kaplan
Meier method (1 - survival function) and used a Cox regression model to estimate
mortality rate ratios (MRRs), controlling for potential confounders. RESULTS: We
identified 21,359 patients hospitalised with peptic ulcer bleeding. Among these,
653 (3.1%) had a previous diagnosis of liver cirrhosis and 474 (2.2%) had a
history of non-cirrhotic chronic liver disease. Patients with liver cirrhosis and
non-cirrhotic chronic liver disease had a cumulative 90-day mortality of 25.3%
and 20.7%, respectively, compared to 18.3% among patients without chronic liver
disease. Liver cirrhosis was associated with an adjusted 90-day MRR of 2.38 (95%
CI: 2.02-2.80), compared to 1.49 (95% CI: 1.22-1.83) among patients with non
cirrhotic chronic liver disease. CONCLUSION: Patients with chronic liver disease,
particularly liver cirrhosis, are at increased risk of death within 90 days after
hospitalisation for peptic ulcer bleeding compared to patients without chronic
liver disease.
PMID- 25588863
TI - Confinement of massless Dirac fermions in the graphene matrix induced by the B/N
heteroatoms.
AB - In this work, the systems are constructed with the defect lines of B-B or N-N
dimers embedded in a graphene matrix using density functional theory. It is found
that the Dirac-cone dispersions appear at the Fermi level in the bands introduced
by the B or N heteroatom, linear B-B or N-N dimers, demonstrating that the
carrier mobility is ~10(6) m s(-1) which is comparable with that of the pristine
graphene. Most importantly, such dimer lines act as the quasi-1-D conducting
nanowires whose charge carriers are confined around the linear defects in these
dimers while the charge carriers in pristine graphene are dispersed two
dimensionally. Such systems suggest that heteroatoms in graphene can indeed
contribute to the Dirac cone. In addition, the type of carriers (p-type or n
type) can be manipulated using the B or N heteroatoms, respectively. This will
greatly enrich the electronic properties of Dirac semimetals.
PMID- 25588864
TI - Autophagy inhibition by caffeine increases toxicity of methamphetamine in SH-SY5Y
neuroblastoma cell line.
AB - Methamphetamine (METH) is a highly addictive CNS stimulant that its long-term use
is associated with the loss of neurons in substantia nigra and development of
Parkinson's disease later in life. Common form of METH is Ya-Ba tablet, in which,
large portion of caffeine is added to the mass to enhance the stimulatory effect.
Previous study demonstrated that caffeine potentiates the toxic effect of METH in
association with the production of reactive oxygen species and the induction of
apoptosis. Since METH causes induction of autophagy, the question was raised
whether this pathway participates in the potentiating effect of caffeine on METH
neurotoxicity. We used SH-SY5Y, a neuroblastoma cell line, as an in vitro model
to study the effect of METH and caffeine. Co-treatment of non-toxic
concentrations of METH, at 0.5 mM, and caffeine, at 1 mM, caused reduction of the
cell viability. Reduction of the cell viability was associated with attenuation
of autophagy, demonstrated by reduction of LC3-II levels and the number of
autophagosome puncta, together with increase of caspase-3 activation. Similar
effect was produced by treatment with autophagy inhibitors, 3-MA and wortmanin.
Our results suggested that caffeine potentiates METH toxicity through inhibition
of autophagy and that autophagy serves as a protective mechanism. In conclusion,
we proposed the augmented hazard associated with caffeine and METH combination in
Ya-Ba abusers.
PMID- 25588865
TI - Toxic effects of bortezomib on primary sensory neurons and Schwann cells of adult
mice.
AB - The proteasome inhibitor bortezomib is nowadays first line treatment for multiple
myeloma. One of the most significant adverse events is peripheral neuropathy,
mainly involving sensory nerve fibers that can lead to withdrawal of treatment.
Here we develop an in vitro model to compare the effects of bortezomib on primary
sensory neurons and Schwann cells of adult mice. We observed that sensory neurons
were more susceptible to bortezomib, and their viability was reduced at a
concentration of 6 nM, that only affected Schwann cell proliferation but not
survival. At concentration higher than 8 nM Schwann cell viability was also
compromised. Already at low concentrations, surviving neurons presented
alterations in neurite outgrowth. Neurites were shorter and had dystrophic
appearance, with alterations in neurofilament staining. However, neurites were
able to regrow after removing bortezomib from the medium, thus indicating
reversibility of the neurotoxicity. We confirmed in vivo that bortezomib produced
alterations in neurofilaments at early stages of the treatment. After an
accumulated dose of 2 mg/kg bortezomib, dorsal root ganglia neurons of treated
animals showed accumulation of neurofilament in the soma. To evaluate if this
accumulation was related with alterations in axonal transport, we tested the
ability of sensory neurons to retrogradely transport a retrotracer applied at the
distal nerve. Treated animals showed a lower amount of retrotracer in the soma 24
h after its application to the tibial nerve, therefore suggesting that axonal
transport was affected by bortezomib.
PMID- 25588866
TI - Mesenchymal stem cells inhibit Th17 cells differentiation via IFN-gamma-mediated
SOCS3 activation.
AB - Mesenchymal stem cells (MSCs) are immunoregulatory, and the administration of
them has been shown to ameliorate inflammation caused by Th17 cells. However, the
mechanisms that contribute to MSC regulation on Th17 cell development are
unclear. Here, we found that MSCs could inhibit Th17 cell differentiation through
the activation of suppressors of cytokine signaling 3 (SOCS3) when coculture of
MSCs and CD4(+)CD25(low)CD44(low)CD62L(high) T cells. Further analysis
demonstrated that the inhibitory action was mediated via interferon gamma (IFN
gamma), which activated signal transducer and activator of transcription-1
(STAT1) to enhance the expression of SOCS3, leading to STAT3 inhibition.
Moreover, stable and reciprocal changes in H3K4me3 and H3K27me3 at the promoters
of STAT1, STAT3 and RORgammat determined the fate of Th17 cells. These results
demonstrate that MSCs may inhibit Th17 differentiation via IFN-gamma that
activates SOCS3 leading to immunomodulatory effects, suggesting a possible
mechanism by which MSCs could act as a cellular approach to attenuate the
clinical and pathological manifestations of some autoimmune diseases.
PMID- 25588867
TI - c-kit plays a critical role in induction of intravenous tolerance in experimental
autoimmune encephalomyelitis.
AB - c-kit (CD117) is a tyrosine kinase receptor found in various types of immune
cells. It has been shown that c-kit plays a role in the pathogenesis of multiple
sclerosis, an inflammatory demyelinating disorder of the CNS. Recent data have
suggested an immunoregulatory effect of c-kit. We therefore examined the role of
c-kit in autoantigen-induced i.v. tolerance in experimental autoimmune
encephalomyelitis (EAE), an animal model of MS. Our results show that induction
of intravenous tolerance against EAE in B6 mice is characterized by increased
numbers of CD117(+) cells and altered mast cell-associated molecules in the
periphery and in the CNS. W(-sh) (c-kit-deficient) mice were resistant to i.v
autoantigen-induced tolerance, with increased proinflammatory cytokine production
in the periphery. I.v. autoantigen in WT mice suppressed the production of
proinflammatory cytokines IFN-gamma and IL-6 and up-regulated the expression of
FoxP3, a transcription factor of Tregs; however, in W(-sh) mice, IFN-gamma and IL
6 were increased with a failure of FoxP3 induction upon i.v. autoantigen
injection and is thus a mechanism for resistance to i.v. tolerance induction in
these mice. We conclude that c-kit signaling has a regulatory role in i.v.
tolerance and could be a target for potential immunotherapy in autoimmune
disorders.
PMID- 25588871
TI - Ethical issues in isolating people treated for Ebola.
PMID- 25588870
TI - Evidence for shared deficits in identifying emotions from faces and from voices
in autism spectrum disorders and specific language impairment.
AB - BACKGROUND: While autism spectrum disorder (ASD) and specific language impairment
(SLI) have traditionally been conceptualized as distinct disorders, recent
findings indicate that the boundaries between these two conditions are not clear
cut. While considerable research has investigated overlap in the linguistic
characteristics of ASD and SLI, relatively less research has explored possible
overlap in the socio-cognitive domain, particularly in terms of the emotion
recognition abilities of these two groups of children. AIMS: To investigate
facial and vocal emotion recognition in children with ASD, children with SLI and
typically developing (TD) children. To do so, the ASD group was subdivided into
those with 'normal' (ALN) and those with 'impaired' (ALI) language to explore the
extent to which language ability influenced performance on the emotion
recognition task. METHODS & PROCEDURES: Twenty-nine children with ASD (17 ALN and
12 ALI), 18 children with SLI and 66 TD children completed visual and auditory
versions of an emotion recognition task. For the visual version of the task, the
participants saw photographs of people expressing one of six emotions (happy,
sad, scared, angry, surprised, disgusted) on the whole face. For the auditory
modality, the participants heard a neutral sentence that conveyed one of the six
emotional expressions in the tone of the voice. In both conditions, the children
were required to indicate how the person they could see/hear was feeling by
selecting a cartoon face that was presented on the computer screen. OUTCOMES &
RESULTS: The results showed that all clinical groups were less accurate than the
TD children when identifying emotions on the face and in the voice. While the ALN
children were less accurate than the TD children only when identifying
expressions that require inferring another's mental state (surprise, disgust)
emotional expressions, the ALI and the SLI children were less accurate than the
TD children when identifying the basic (happy, sad, scared, angry) as well as the
inferred emotions. CONCLUSIONS & IMPLICATIONS: The results indicate that children
with ALI and children with SLI share emotion recognition deficits, which are
likely to be driven by the poor language abilities of these two groups.
PMID- 25588868
TI - SEW2871 protects from experimental colitis through reduced epithelial cell
apoptosis and improved barrier function in interleukin-10 gene-deficient mice.
AB - Loss of intestinal epithelial barrier function including typical tight junction
changes and epithelial cell apoptosis plays an important role in Crohn's disease.
SEW2871, a selective sphingosine-1-phosphate type-1 receptor agonist, has been
proven to be efficient in protecting against colitis in IL-10(-/-) mice in our
previous study. Here we performed additional studies to investigate whether
treatment with SEW2871 was associated with an improved epithelial barrier
function in IL-10(-/-) mice. SEW2871 was administered by gavage at a dose of 20
mg/kg/day for 2 weeks to IL-10(-/-) mice. Severity of colitis, CD4+ T cells in
colon lamina propria and proinflammatory cytokine productions were evaluated.
Furthermore, intestinal permeability, tight junction (occludin and ZO-1)
expressions and distributions, as well as epithelial cell apoptosis, were also
assessed. SEW2871 treatment attenuated established colitis associated with
decreased CD4+ T cells in colon lamina propria and reduced TNF-alpha and IFN
gamma levels. Moreover, enhanced barrier function, which resulted from
ameliorated tight junction (occludin and ZO-1) expressions and suppressed
epithelial cell apoptosis, was found to contribute to the therapeutic effects.
SEW2871 treatment protects from colitis in IL-10(-/-) mice through reduced
epithelial cell apoptosis and improved barrier function. Thus, targeting
sphingosine-1-phosphate may represent a new therapeutic approach in Crohn's
disease.
PMID- 25588872
TI - Many older people may be overtreated for diabetes, US study finds.
PMID- 25588873
TI - Model for a patient-centered comparative effectiveness research center.
AB - This special report describes the systematic approach the University of
Pittsburgh and the University of Pittsburgh Medical Center (UPMC) undertook in
creating an infrastructure for comparative effectiveness and patient-centered
outcomes research resources. We specifically highlight the administrative
structure, communication and training opportunities, stakeholder engagement
resources, and support services offered.
PMID- 25588874
TI - Inhibitory role of REV-ERBalpha in the expression of bone morphogenetic protein
gene family in rat uterus endometrium stromal cells.
AB - Uterus circadian rhythms have been implicated in the gestation processes of
mammals through entraining of the clock proteins to numerous downstream genes.
Bone morphogenetic proteins (BMPs), having clock-controlled regulatory sites in
their gene promoters, are expressed in the uterus during decidualization, but the
regulation of the Bmp gene expression is poorly understood. The present study was
designed to dissect the physiological roles of the uterus oscillators in the Bmp
expression using the uterus endometrial stromal cells (UESCs) isolated from Per2
dLuc transgenic rats on day 4.5 of gestation. The in vitro decidualization of
UESCs was induced by medroxyprogesterone acetate and 2-O-dibutyryl cAMP. A
significant decline of Per2-dLuc bioluminescence activity was induced in decidual
cells, and concomitantly, the expression of canonical clock genes was
downregulated. Conversely, the expression of the core Bmp genes Bmp2, Bmp4, Bmp6,
and Bmp7 was upregulated. In UESCs transfected with Bmal1-specific siRNA, in
which Rev-erbalpha expression was downregulated, Bmp genes, such as Bmp2, Bmp4,
and Bmp6 were upregulated. However, Bmp1, Bmp7, and Bmp8a were not significantly
affected by Bmal1 silencing. The expression of all Bmp genes was enhanced after
treatment with the REV-ERBalpha antagonist (SR8278), although their rhythmic
profiles were differed from each other. The binding of REV-ERBalpha to the
proximal regions of the Bmp2 and Bmp4 promoters was revealed by chromatin
immunoprecipitation-PCR analysis. Collectively, these results indicate that the
Bmp genes are upregulated by the attenuation of the cellular circadian clock; in
particular, its core component REV-ERBalpha functions as a transcriptional
silencer in the Bmp gene family.
PMID- 25588876
TI - Functional analysis of matriptase-2 mutations and domains: insights into the
molecular basis of iron-refractory iron deficiency anemia.
AB - Mutations in the TMPRSS6 gene are associated with severe iron-refractory iron
deficiency anemia resulting from an overexpression of hepcidin, the key regulator
of iron homeostasis. The matriptase (MT)-2 protein (encoded by the TMPRSS6 gene)
regulates hepcidin expression by cleaving hemojuvelin [HJV/hemochromatosis type 2
(HFE2)], a bone morphogenetic protein (BMP) coreceptor in the hepcidin regulatory
pathway. We investigated the functional consequences of five clinically
associated TMPRSS6 variants and the role of MT-2 protein domains by generating
epitope-tagged mutant and domain-swapped MT-2-MT-1 (encoded by the ST14 gene)
chimeric constructs and expressing them in HepG2/C3A cells. We developed a novel
cell culture immunofluorescence assay to assess the effect of MT-2 on cell
surface HJV expression levels, compatible with HJV cleavage. The TMPRSS6 variants
Y141C, I212T, G442R, and C510S were retained intracellularly and were unable to
inhibit BMP6 induction of hepcidin. The R271Q variant, although it has been
associated with iron-refractory iron deficiency anemia, appears to remain
functional. Analysis of the chimeric constructs showed that replacement of sperm
protein, enterokinase, and agrin (SEA), low-density-lipoprotein receptor class A
(LDLRA), and protease (PROT) domains from MT-2 with those from MT-1 resulted in
limited cell surface localization, while the complement C1r/C1s, Uegf, Bmp1 (CUB)
domain chimera retained localization at the cell surface. The SEA domain chimera
was able to reduce cell surface HJV expression, while the CUB, LDLRA, and PROT
domain chimeras were not. These studies suggest that the SEA and LDLRA domains of
MT-2 are important for trafficking to the cell surface and that the CUB, LDLRA,
and PROT domains are required for cleavage of HJV.
PMID- 25588877
TI - Lipolytic inhibitor G0/G1 switch gene 2 inhibits reactive oxygen species
production and apoptosis in endothelial cells.
AB - G0/G1 switch gene 2 (G0S2), a novel target gene of peroxisome proliferator
activated receptor, is highly expressed in fat tissues. G0S2 acts as proapoptotic
factor toward human cancer cells. Endothelial cell (EC) apoptosis may be an
initiating event in the development of atherosclerosis. However, the expression
and function of G0S2 in vascular ECs remain unknown. Here, we reported for the
first time that G0S2 is expressed in arterial ECs. Ectopic expression of G0S2
increased neutral lipid accumulation in cultured ECs. However, G0S2 prevented ECs
from serum-free starvation stress- and hydrogen peroxide (H2O2)-induced
apoptosis. G0S2 blocked the H2O2-induced dissipation of mitochondrial membrane
potential. G0S2 decreased the release of cytochrome c from mitochondria into the
cytosol, followed by activation of caspase-9 and caspase-3. The anti-apoptotic
effect of G0S2 was Bcl-2 and adipose triglyceride lipase independent. In
contrast, gene silence of G0S2 increased serum-free starvation stress-induced EC
apoptosis and decreased the formation of capillary-like structures. We further
found that G0S2 couples with the F0F1-ATP synthase in ECs. Levels of ATP were
elevated, whereas reactive oxygen species levels were reduced in G0S2-expressing
ECs. G0S2 can inhibit endothelial denudation secondary to H2O2-induced injury to
ECs in vivo. These results indicate that G0S2 acts as a prosurvival molecule in
ECs. Taken together, our results indicate that G0S2 has a protective function in
ECs and may be a potential target for the treatment of cardiovascular diseases
associated with reactive oxygen species-induced EC injury, such as
atherosclerosis and restenosis.
PMID- 25588875
TI - P2X7 receptor inhibition protects against ischemic acute kidney injury in mice.
AB - Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the
development of experimental nephritis and diabetic and hypertensive nephropathy.
However, its role in acute kidney injury (AKI) remains unknown. In this study, we
examined the effects of P2X7R inhibition in a murine model of ischemia
reperfusion (I/R)-induced AKI using A438079, a selective inhibitor of P2X7R. At
24 h after I/R, mice developed renal dysfunction and renal tubular damage, which
was accompanied by elevated expression of P2X7R. Early administration of A438079
immediately or 6 h after the onset of reperfusion protected against renal
dysfunction and attenuated kidney damage whereas delayed administration of
A438079 at 24 h after restoration of perfusion had no protective effects. The
protective actions of A438079 were associated with inhibition of renal tubule
injury and cell death and suppression of renal expression of monocyte chemotactic
protein-1 and regulated upon expression normal T cell expressed and secreted
(RANTES). Moreover, I/R injury led to an increase in phosphorylation (activation)
of extracellular signal-regulated kinases 1/2 in the kidney; treatment with
A438079 diminished this response. Collectively, these results indicate that early
P2X7R inhibition is effective against renal tubule injury and proinflammatory
response after I/R injury and suggest that targeting P2X7R may be a promising
therapeutic strategy for treatment of AKI.
PMID- 25588878
TI - Increasing the number of patients receiving information about transition to end
of-life care: the effect of a half-day physician and nurse training.
AB - INTRODUCTION: Honest prognostication and information for patients are important
parts of end-of-life care. This study examined whether an educational
intervention could increase the proportion of patients who received information
about the transition to end-of-life (ITEOL care). METHOD: Two municipalities (in
charge of nursing homes) and two hospitals were randomised to receive an
interactive half-day course about ITEOL for physicians and nurses. The proportion
of patients who received ITEOL was measured with data from the Swedish Register
of Palliative Care (SRPC). Patients were only included if they died an expected
death and maintained their ability to express their will until days or hours
before their death. Four hospitals and four municipalities were assigned
controls, matched by hospital size, population and proportion of patients
receiving ITEOL at baseline. RESULTS: The proportion of patients in the
intervention group who received ITEOL increased from 35.1% (during a 6-month
period before the intervention) to 42% (during a 6-month period after the
intervention). The proportion in the control group increased from 30.4% to 33.7%.
The effect of the intervention was significant (p=0.005) in a multivariable model
adjusted for time, age, gender and cause of death. CONCLUSION: More patients at
end-of-life received ITEOL after an educative half-day intervention directed to
physicians and nurses.
PMID- 25588879
TI - Reversible catalytic dehydrogenation of alcohols for energy storage.
AB - Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an
elusive target for homogeneous catalysis. In this report, reversible acceptorless
dehydrogenation of secondary alcohols and diols on iron pincer complexes and
reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes
with separate transfer of protons and electrons on iridium complexes are shown.
This reactivity suggests a strategy for the development of reversible fuel cell
electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing
fuels.
PMID- 25588880
TI - Correction for Lewis et al., Angelman syndrome imprinting center encodes a
transcriptional promoter.
PMID- 25588881
TI - Hierarchical assembly of a dual-responsive macroscopic insulated molecular wire
bundle in a gradient system.
AB - Here, we report the hierarchical self-assembly of a cationic gemini amphiphile,
Azo 1, in a composition gradient solution generated using solvent evaporation. As
the gradient solution is formed, Azo 1 forms nanorods in the lower region of the
solution. Depending on solvent composition, these nanorods can further develop
into nanofibres, which can then intertwine to form double helices and other types
of nanohelices in the upper region of the solution. Finally, a macroscopic wire
bundle is formed via the fusion of nanohelices; this ribbon-like bundle exhibits
elasticity and linear ohmic resistance properties. More intriguingly, this bundle
exhibits photoresponsive properties that affect its deformation and conductivity,
as well as a rapid electroresponse that affects its conductivity, indicating that
it is feasible to control the charge pathway.
PMID- 25588882
TI - Factor structure and temporal stability of the Vancouver Obsessional Compulsive
Inventory-Mental Contamination Scale (VOCI-MC) and psychometric properties of its
Italian version.
AB - OBJECTIVE: The Vancouver Obsessional Compulsive Inventory-Mental Contamination
Scale (VOCI-MC) is a self-report instrument that assesses symptoms of mental
contamination. The aim of this study was to investigate the psychometric
properties of the Italian version of the VOCI-MC in non-clinical and clinical
samples. METHOD: Factor structure, internal consistency, temporal stability,
construct and criterion validity were investigated in 541 participants from the
general population, 120 participants diagnosed with OCD and 31 participants
diagnosed with other anxiety disorders (OAD). For some of these analyses, our OCD
sample was subdivided into those with contamination-related symptoms and concerns
(n=39) and those whose OCD excluded concerns related to contamination fear
(n=81). Exploratory and confirmatory factor analyses supported the expected one
factor structure of the VOCI-MC both in non-clinical and OCD sample. RESULTS:
VOCI-MC scores showed good internal consistency, temporal stability, construct
validity and criterion validity. In particular, the VOCI-MC successfully
discriminated between those with OCD who reported contamination-related concerns
and all other groups of participants. CONCLUSION: These findings suggest that the
Italian version of the VOCI-MC retains the adequate psychometric properties of
the original, provide preliminary evidence of its one-factor structure and
temporal stability, and suggest that it can be confidently used as an assessment
tool of mental contamination symptoms in both clinical and research settings.
PMID- 25588883
TI - Seaweed cultivation: potential and challenges of crop domestication at an
unprecedented pace.
PMID- 25588884
TI - Temperament and Parenting Styles in Early Childhood Differentially Influence
Neural Response to Peer Evaluation in Adolescence.
AB - Behavioral inhibition (BI) is a temperament characterized by social reticence and
withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety
disorder. Developmental outcomes associated with this temperament can be
influenced by children's caregiving context. The convergence of a child's
temperamental disposition and rearing environment is ultimately expressed at both
the behavioral and neural levels in emotional and cognitive response patterns to
social challenges. The present study used functional neuroimaging to assess the
moderating effects of different parenting styles on neural response to peer
rejection in two groups of adolescents characterized by their early childhood
temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21
without BI). The moderating effects of authoritarian and authoritative parenting
styles were examined in three brain regions linked with social anxiety:
ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth
characterized with BI in childhood, but not in those without BI, diminished
responses to peer rejection in vlPFC were associated with higher levels of
authoritarian parenting. In contrast, all youth showed decreased caudate response
to peer rejection at higher levels of authoritative parenting. These findings
indicate that BI in early life relates to greater neurobiological sensitivity to
variance in parenting styles, particularly harsh parenting, in late adolescence.
These results are discussed in relation to biopsychosocial models of development.
PMID- 25588886
TI - Bringing down the host: enteropathogenic and enterohaemorrhagic Escherichia coli
effector-mediated subversion of host innate immune pathways.
AB - Enteric bacterial pathogens commonly use a type III secretion system (T3SS) to
successfully infect intestinal epithelial cells and survive and proliferate in
the host. Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC; EHEC)
colonize the human intestinal mucosa, form characteristic histological lesions on
the infected epithelium and require the T3SS for full virulence. T3SS effectors
injected into host cells subvert cellular pathways to execute a variety of
functions within infected host cells. The EPEC and EHEC effectors that subvert
innate immune pathways--specifically those involved in phagocytosis, host cell
survival, apoptotic cell death and inflammatory signalling--are all required to
cause disease. These processes are reviewed within, with a focus on recent work
that has provided insights into the functions and host cell targets of these
effectors.
PMID- 25588885
TI - Thromboresistant/anti-biofilm catheters via electrochemically modulated nitric
oxide release.
AB - Inexpensive nitric oxide (NO) release strategies to prevent thrombosis and
bacterial infections are desirable for implantable medical devices. Herein, we
demonstrate the utility of electrochemically modulated NO release from a catheter
model using an inner copper wire working electrode and an inorganic nitrite salt
solution reservoir. These catheters generate NO surface fluxes of >1.0 * 10(
10)mol min(-1) cm(-2) for more than 60 h. Catheters with an NO flux of 1.1 * 10(
10)mol min(-1) cm(-2) are shown to significantly reduce surface thrombus
formation when implanted in rabbit veins for 7h. Further, the ability of these
catheters to exhibit anti-biofilm properties against bacterial species commonly
causing bloodstream and urinary catheter infections is examined. Catheters
releasing NO continuously during the 2d growth of Staphylococcus aureus exhibit a
6 log-unit reduction in viable surface bacteria. We also demonstrate that
catheters generating NO for only 3h at a flux of 1.0 * 10(-10)mol min(-1) cm(-2)
lower the live bacterial counts of both 2d and 4d pre-formed Escherichia coli
biofilms by >99.9%. Overall, the new electrochemical NO-release devices could
provide a cost-effective strategy to greatly enhance the biocompatibility and
antimicrobial properties of intravascular and urinary catheters, as well as other
implantable medical devices.
PMID- 25588887
TI - Transforming health professions' education through in-country collaboration:
examining the consortia among African medical schools catalyzed by the Medical
Education Partnership Initiative.
AB - BACKGROUND: African medical schools have historically turned to northern partners
for technical assistance and resources to strengthen their education and research
programmes. In 2010, this paradigm shifted when the United States Government
brought forward unprecedented resources to support African medical schools. The
grant, entitled the Medical Education Partnership Initiative (MEPI) triggered a
number of south-south collaborations between medical schools in Africa. This
paper examines the goals of these partnerships and their impact on medical
education and health workforce planning. METHODS: Semi-structured interviews were
conducted with the Principal Investigators of the first four MEPI programmes that
formed an in-country consortium. These interviews were recorded, transcribed and
coded to identify common themes. RESULTS: All of the consortia have prioritized
efforts to increase the quality of medical education, support new schools in
country and strengthen relations with government. These in-country partnerships
have enabled schools to pool and mobilize limited resources creatively and
generate locally-relevant curricula based on best-practices. The established
schools are helping new schools by training faculty and using grant funds to
purchase learning materials for their students. The consortia have strengthened
the dialogue between academia and policy-makers enabling evidence-based health
workforce planning. All of the partnerships are expected to last well beyond the
MEPI grant as a result of local ownership and institutionalization of
collaborative activities. CONCLUSIONS: The consortia described in this paper
demonstrate a paradigm shift in the relationship between medical schools in four
African countries. While schools in Africa have historically worked in silos,
competing for limited resources, MEPI funding that was leveraged to form in
country partnerships has created a culture of collaboration, overriding the
history of competition. The positive impact on the quality and efficiency of
health workforce training suggests that future funding for global health
education should prioritize such south-south collaborations.
PMID- 25588888
TI - Breastfeeding.
PMID- 25588890
TI - Interest of high-definition optical coherent tomography (HD-OCT) for non-invasive
imaging of dermatofibroma: a pilot study.
PMID- 25588889
TI - Distribution of yeast isolates from invasive infections and their in vitro
susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to
2012) surveillance study.
AB - Invasive yeast infections cause significant morbidity and mortality. Surveillance
for the infection is necessary to detect trends in species distribution and
antifungal resistance. We performed this retrospective study of yeast infection
at Jinling Hospital, Nanjing in China, from year of 2010 to 2012. A total of 341
yeast isolates were obtained from patients with invasive infections in the
period. Among these isolates, Candida spp. comprised of the highest percentage of
yeast strains (91.8 %), followed by Cryptococcus neoformans (5.9 %) and other non
Candida yeast strains (2.3 %). Bloodstream isolates made up 41.3 % of yeast
strains and the isolates from CVC made up 17.3 %. Among Candida spp., C. albicans
was the most common species identified from non-blood clinical specimens (42.9
%), but appeared in only 20.8 % of blood isolates (P < 0.001). C. tropicalis was
the most prevalent Candida species in the blood samples (28.5 %). Candida spp.
was mainly isolated from specimens of the ICU patients, while C. neoformans was
mainly isolated from specimens in medical wards. Resistance to FLC occurred in
3.7 % of C. albicans, 9.9 % of C. tropicalis, 74.0 % of C. glabrata, and 4.4 % of
C. parapsilosis. Most (>92 %) isolates of C. albicans, C. tropicalis, C.
parapsilosis, and C. neoformans strains were susceptible to VRC; However, 26.7 %
of isolates of C. glabrata were VRC resistant.
PMID- 25588891
TI - Discovery of Novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole Derivatives as
Potential Anti-Inflammatory Agents.
AB - A novel 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 5 with good anti
inflammatory activity was identified from our in-house library. Based on hit
compound 5, two series of 2-(piperidin-4-yl)-1H-benzo[d]imidazole derivative 6a-g
and 7a-h were designed and synthesized as novel anti-inflammatory agents. Most of
synthesized compounds exhibited good inhibitory activity on NO and TNF-alpha
production in LPS-stimulated RAW 264.7 macrophages, in which the compound 6e
showed most potent inhibitory activity on NO (IC50 = 0.86 MUm) and TNF-alpha
(IC50 = 1.87 MUm) production. Further evaluation revealed that compound 6e
displayed more potent in vivo anti-inflammatory activity than ibuprofen did on
xylene-induced ear oedema in mice. Additionally, Western blot analysis revealed
that compound 6e could restore phosphorylation level of IkappaBalpha and protein
expression of p65 NF-kappaB in LPS-stimulated RAW 264.7 macrophages.
PMID- 25588893
TI - Measurement of human rotation behavior for psychological and neuropsychological
investigations.
AB - The investigation of rotation behavior in human beings enjoys a longstanding and
enduring interest in laterality research. While in animal studies the issue of
accurately measuring the number of rotations has been solved and is widely
applied in practice, it is still challenging to assess the rotation behavior of
humans in daily life. We propose a robust method to assess human rotation
behavior based on recordings from a miniature inertial measurement unit that can
be worn unobtrusively on a belt. We investigate the effect of different
combinations of low-cost sensors-including accelerometers, gyroscopes, and
magnetometers-on rotation measurement accuracy, propose a simple calibration
procedure, and validate the method on data from a predefined path through and
around buildings. Results suggest that a rotation estimation based on the fusion
of accelerometer, gyroscope, and magnetometer measurements outperforms methods
based solely on earth magnetic field measurements, as proposed in previous
studies, by a drop in error rate of up to 32 %. We further show that magnetometer
signals do not significantly contribute to measurement accuracy in short-term
measurements, and could thus be omitted for improved robustness in environments
with magnetic field disturbances. Results also suggest that our simple
calibration procedure can compete with more complex approaches and reduce the
error rate of the proposed algorithm by up to 38 %.
PMID- 25588892
TI - Nencki Affective Word List (NAWL): the cultural adaptation of the Berlin
Affective Word List-Reloaded (BAWL-R) for Polish.
AB - In the present article, we introduce the Nencki Affective Word List (NAWL),
created in order to provide researchers with a database of 2,902 Polish words,
including nouns, verbs, and adjectives, with ratings of emotional valence,
arousal, and imageability. Measures of several objective psycholinguistic
features of the words (frequency, grammatical class, and number of letters) are
also controlled. The database is a Polish adaptation of the Berlin Affective Word
List-Reloaded (BAWL-R; Vo et al., Behavior Research Methods 41:534-538, 2009),
commonly used to investigate the affective properties of German words. Affective
normative ratings were collected from 266 Polish participants (136 women and 130
men). The emotional ratings and psycholinguistic indexes provided by NAWL can be
used by researchers to better control the verbal materials they apply and to
adjust them to specific experimental questions or issues of interest. The NAWL is
freely accessible to the scientific community for noncommercial use as
supplementary material to this article.
PMID- 25588896
TI - Is exaggeration in academic press releases related to investigators' conflicts of
interests?
PMID- 25588894
TI - The electromyographic threshold in boys and men.
AB - BACKGROUND: Children have been shown to have higher lactate (LaTh) and
ventilatory (VeTh) thresholds than adults, which might be explained by lower
levels of type-II motor-unit (MU) recruitment. However, the electromyographic
threshold (EMGTh), regarded as indicating the onset of accelerated type-II MU
recruitment, has been investigated only in adults. PURPOSE: To compare the
relative exercise intensity at which the EMGTh occurs in boys versus men.
METHODS: Participants were 21 men (23.4 +/- 4.1 years) and 23 boys (11.1 +/- 1.1
years), with similar habitual physical activity and peak oxygen consumption
(VO2pk) (49.7 +/- 5.5 vs. 50.1 +/- 7.4 ml kg(-1) min(-1), respectively). Ramped
cycle ergometry was conducted to volitional exhaustion with surface EMG recorded
from the right and left vastus lateralis muscles throughout the test (~10 min).
The composite right-left EMG root mean square (EMGRMS) was then calculated per
pedal revolution. The EMGTh was then determined as the exercise intensity at the
point of least residual sum of squares for any two regression line divisions of
the EMGRMS plot. RESULTS: EMGTh was detected in 20/21 of the men (95.2 %) and
only in 18/23 of the boys (78.3 %). The boys' EMGTh was significantly higher than
the men's (86.4 +/- 9.6 vs. 79.7 +/- 10.0 % of peak power output at exhaustion; p
< 0.05). The pattern was similar when EMGTh was expressed as percentage of VO2pk.
CONCLUSIONS: The boys' higher EMGTh suggests delayed and hence lesser utilization
of type-II MUs in progressive exercise, compared with men. The boys-men EMGTh
differences were of similar magnitude as those shown for LaTh and VeTh, further
suggesting a common underlying factor.
PMID- 25588897
TI - Macular pigment optical density in a healthy Chinese population.
AB - PURPOSE: To measure the macular pigment optical density (MPOD) values in a
healthy Chinese population using the one-wavelength reflectometry method and to
investigate the relationships of MPOD with age, sex, body mass index (BMI),
smoking and lens opacities. METHODS: A total of 441 healthy participants, aged 3
81 years old (242 male and 199 female subjects), were enrolled in this study.
Demographic and lifestyle data were recorded based on physical examinations and
questionnaires. Lens opacities were measured according to the Lens Opacities
Classification System III (LOCS III). MPOD values were measured at 7 degrees of
eccentricity, using the one-wavelength reflectometry method (Visucam 200; Carl
Zeiss Meditec). MPOD values were reported in parameters including 'max' and
'mean' optical density (OD). The original MPOD values without automated
correction were used for analysis. RESULTS: The average values were 0.303 +/-
0.097 d.u. (initials of density units) for the max OD and 0.109 +/- 0.031 d.u.
for the mean OD. A significant inverse relationship was found between age and
MPOD (for max OD, beta = -0.716, p < 0.001; for mean OD, beta = -0.669, p <
0.001). Participants with no lens opacities had higher MPOD values than those
with moderate lens opacities (p < 0.001). The MPOD values were not associated
with sex, BMI or smoking status. CONCLUSION: MPOD within 7 degrees of
eccentricity, as measured by one-wavelength reflectometry, was found to decrease
with increasing age in a healthy Chinese population, and lens opacities had an
impact on these measurements. These results provide a reference value for future
studies in the Chinese population.
PMID- 25588899
TI - A survey of anthropometry of rural agricultural workers in Enugu State, south
eastern Nigeria.
AB - In developed countries, large amount of anthropometric data are available for
reference purposes; however, anthropometric data of Nigerian populace are
lacking. As a result, most agricultural machines and equipment used are designed
using anthropometric data from other populations of the world. A total of 377
rural agricultural workers within the age limit of 18-45 years, who are involved
in different agricultural activities, were selected from six rural agriculture
based communities in Enugu state. Thirty-six anthropometric body dimensions were
measured including age and body weight. A comparison between the male and female
data indicated that data obtained from male agricultural workers were higher than
that obtained from their female counterparts in all body dimensions except chest
(bust) depth, abdominal breadth and hip breadth (sitting). In terms of design
parameters, it was observed that the data from Nigerian agricultural workers were
different from that obtained from agricultural workers in north-eastern India.
Practitioner Summary. Anthropometric data of Nigeria populace are lacking. As a
result, most agricultural machines and equipment used are designed using
anthropometric data from other populations of the world. It was observed that the
data from Nigerian agricultural workers were different from that obtained from
agricultural workers in north-eastern India.
PMID- 25588900
TI - John Appleby: hoping for the "Appleby paradox".
PMID- 25588898
TI - Identification of molecular signature of head and neck cancer stem-like cells.
AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer
in the world. HNSCC remains difficult to treat, and despite advances in
treatment, overall survival rate has modestly improved over the past several
years. Poor survival rate is attributed to high frequency of local recurrence and
distant metastasis. Cancer stem-like cells (CSCs) have been implicated in tumor
recurrence and confer resistance to anti-cancer therapy treatment. In this study,
we have characterized genes that are modulated in HNSCC-CSCs and can be targeted
in future as potential therapeutics. CSCs were isolated from HNSCC cells
(oralspheres) and examined for tumorigenicity in immunodeficient mice. We
observed aggressive tumor growth with oralspheres as compared to parental cells.
The CSC-derived tumors were grossly extremely vascularized and expressed VEGFR1.
We next analyzed the molecular determinant of oralspheres. In addition to CD133
and Nanog, we observed significant higher expression of Notch1 protein in the
oralspheres. There was differential expression of angiogenesis and invasive
marker genes such as angiopoietin1, integrin beta3, MMP9 and THBS1.
Interestingly, c-Fos was upregulated in oralspheres as compared to parental
cells. Our observations suggest that understanding the molecular determinant of
oralspheres will help in developing future therapeutic modalities against
treatment resistant HNSCC.
PMID- 25588901
TI - Feasibility, efficacy, and safety of radiofrequency ablation of atrial
fibrillation guided by monitoring of the initial impedance decrease as a
surrogate of catheter contact.
AB - BACKGROUND: The initial impedance decrease during radiofrequency (RF) ablation is
an indirect marker of catheter contact and lesion formation. We aimed to assess
feasibility, efficacy, and safety of an ablation approach guided by initial
impedance decrease. METHODS: A total of 25 patients with paroxysmal AF had point
by-point, wide antral pulmonary vein (PV) isolation. RF applications were aborted
if a decrease of at least 5 Omega did not occur in the first 10 seconds;
otherwise, ablation was continued for at least 20 seconds. Power was 30 Watts and
reduced to 15-25 Watts on the posterior wall. RESULTS: A total of 28% of RF
applications were terminated because of inadequate impedance decrease. The
remaining lesions showed a median decrease of 7.6 Omega (IQR 5.0-10.7) at 10
seconds and median duration of RF lesions was 38 seconds. Note that, 100 PVs were
isolated with 49 rings. PVI occurred before anatomic completion of the ablation
ring of adequate lesions in 39/49 (80%) and concurrent with ring completion in
7/49 (14%). Additional lesions were required in 3/49 (6%) rings. After PVI,
additional lesions were required to eliminate dormant conduction in 2/47 (4%) and
pace-capture on the ablation line in 24/49 vein pairs (49%). During short-term
follow-up, 3 nonfatal esophageal injuries and 2 late pericardial effusions
occurred. During a mean follow-up of 431 +/- 87 days, 21/25 patients (84%)
remained free of recurrent symptomatic atrial arrhythmias. CONCLUSIONS: PVI
guided by initial impedance decrease is feasible and results in PVI concurrent
with or before completion of the ablation ring in 94% of patients. Single
procedure efficacy after one year of follow-up was 84%. Near-term complications
suggest that deeper lesions are created, indicating that further reduction of RF
power and duration is warranted.
PMID- 25588902
TI - Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative
colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies.
AB - BACKGROUND: Conventional oral corticosteroids are effective at reducing
inflammation associated with ulcerative colitis (UC); however, systemic adverse
effects limit their use. Budesonide MMX is an extended-release, second-generation
corticosteroid that targets delivery of budesonide to the entire colon. AIM: To
analyse efficacy and safety outcomes from two phase 3 studies of budesonide MMX
in patients with mild-to-moderate active UC. METHODS: Patients were assigned to
budesonide MMX 9 mg, budesonide MMX 6 mg, or placebo once daily in two
randomised, double-blind, placebo-controlled, 8-week studies (CORE I and II).
Pooled data were analysed for pre-defined primary (combined clinical and
colonoscopic remission), secondary and exploratory endpoints. Primary endpoint
data were analysed to evaluate the potential influence of demographical and
baseline disease characteristics on remission. RESULTS: Modified intent-to-treat
population (histological evidence of baseline inflammation) had 232, 230 and 210
patients in budesonide MMX 9 mg, budesonide MMX 6 mg and placebo groups
respectively. Combined clinical and colonoscopic remission rates were
significantly greater than placebo (6.2%) for the budesonide MMX 9 mg group
(17.7%; P = 0.0002), but not the budesonide MMX 6 mg group (10.9%). The primary
endpoint of remission with budesonide MMX 9 mg was significantly greater than
placebo in most subgroups analysed. Symptom resolution and colonoscopic
improvement rates were significantly greater with budesonide MMX 9 mg vs.
placebo. Budesonide MMX was safe and well tolerated. CONCLUSION: This pooled
analysis showed that budesonide MMX 9 mg is efficacious, safe and well tolerated
for inducing remission of mild-to-moderate UC.
PMID- 25588903
TI - Welfare measurements of finishing pigs on the day of slaughter: a review.
AB - Animal welfare on the day of slaughter is of increasing concern to the
authorities and consumers alike, creating a need not only to optimize the welfare
of the animals but also to document the level of welfare. The day of slaughter is
composed of a variety of stages, initiated when the pigs leave the home pen and
including pick-up facilities, transport, lairage, stunning and sticking. At each
of these stages, the animals are exposed to different stressors that, both
individually and in interaction with one another, can compromise welfare. As part
of the initial work aiming to document the welfare of finishing pigs on the day
of slaughter, this paper provides an overview of the individual stages including
a discussion of potential stressors and potential welfare measurements. These
measurements are discussed with regard to their relevance and suitability for
documentation of animal welfare on the day of slaughter for development of on
site tools for continuous automatic monitoring of animal welfare.
PMID- 25588904
TI - Tracheobronchial fistula during the perioperative period of esophagectomy for
esophageal cancer.
AB - BACKGROUND: Tracheobronchial (TB) injury and fistula formation during the
perioperative period of esophagectomy is a rare but life-threatening
complication. METHODS: We examined the development of intraoperative TB injury
and postoperative TB fistulas in consecutive 763 patients with esophageal cancer
who underwent esophagectomy, including 494 patients who underwent transthoracic
subtotal esophagectomy. RESULTS: TB injury and fistulas developed in two (0.4 %)
and four patients (0.8 %), respectively, who received transthoracic
esophagectomy. TB injury developed during the dissection of a tumor invading a
major airway. Direct suturing of the laceration and covering it using a muscle
flap was effective for one patient, while additional repair with a major pectoral
muscle flap was needed in another patient. Postoperative TB fistulas developed
due to peri-tracheal infection in two patients, and conservative treatment with
drainage was performed. In another two patients, gastro-tracheal fistulas
developed due to mechanical compression of staplers on the gastric tube, which
was elevated via the posterior mediastinal route. The direct repair of the
gastric tube and covering it with a major pectoral muscle flap resulted in the
resolution of these fistulas. CONCLUSION: Careful dissection with direct vision
of the esophagus, as well as oversewing of the staplers on the gastric tube, is
mandatory for preventing TB injury and fistula formation. Appropriate drainage is
effective in cases with peri-tracheal abscesses. If the TB fistula fails to heal
within a 4- to 6-week period, conservative management should be abandoned. Direct
surgical intervention with coverage by a muscle flap is important for TB
fistulas.
PMID- 25588905
TI - Conformational features and binding affinities to Cripto, ALK7 and ALK4 of Nodal
synthetic fragments.
AB - Nodal, a member of the TGF-beta superfamily, is a potent embryonic morphogen also
implicated in tumor progression. As for other TGF-betas, it triggers the
signaling functions through the interaction with the extracellular domains of
type I and type II serine/threonine kinase receptors and with the co-receptor
Cripto. Recently, we reported the molecular models of Nodal in complex with its
type I receptors (ALK4 and ALK7) as well as with Cripto, as obtained by homology
modeling and docking simulations. From such models, potential binding epitopes
have been identified. To validate such hypotheses, a series of mutated Nodal
fragments have been synthesized. These peptide analogs encompass residues 44-67
of the Nodal protein, corresponding to the pre-helix loop and the H3 helix, and
reproduce the wild-type sequence or bear some modifications to evaluate the hot
spot role of modified residues in the receptor binding. Here, we show the
structural characterization in solution by CD and NMR of the Nodal peptides and
the measurement of binding affinity toward Cripto by surface plasmon resonance.
Data collected by both conformational analyses and binding measurements suggest a
role for Y58 of Nodal in the recognition with Cripto and confirm that previously
reported for E49 and E50. Surface plasmon resonance binding assays with
recombinant proteins show that Nodal interacts in vitro also with ALK7 and ALK4
and preliminary data, generated using the Nodal synthetic fragments, suggest that
Y58 of Nodal may also be involved in the recognition with these protein partners.
PMID- 25588906
TI - Reproducibility of pharmacological ASL using sequences from different vendors:
implications for multicenter drug studies.
AB - OBJECT: The current study assesses the multicenter feasibility of pharmacological
arterial spin labeling (ASL) by comparing a caffeine-induced relative cerebral
blood flow decrease (%CBF?) measured with two pseudo-continuous ASL sequences as
provided by two major vendors. MATERIALS AND METHODS: Twenty-two healthy
volunteers were scanned twice with both a 3D spiral (GE) and a 2D EPI (Philips)
sequence. The inter-session reproducibility was evaluated by comparisons of the
mean and within-subject coefficient of variability (wsCV) of the %CBF?, both for
the total cerebral gray matter and on a voxel level. RESULTS: The %CBF? was
larger when measured with the 3D spiral sequence (23.9 +/- 5.9 %) than when
measured with the 2D EPI sequence (19.2 +/- 5.6 %) on a total gray matter level
(p = 0.02), and on a voxel level in the posterior watershed area (p < 0.001).
There was no difference between the gray matter wsCV of the 3D spiral (57.3 %)
and 2D EPI sequence (66.7 %, p = 0.3), whereas on a voxel level, the wsCV was
visibly different between the sequences. CONCLUSION: The observed differences
between ASL sequences of both vendors can be explained by differences in the
employed readout modules. These differences may seriously hamper multicenter
pharmacological ASL, which strongly encourages standardization of ASL
implementations.
PMID- 25588909
TI - Unravelling the quenching mechanisms of a luminescent Ru(II) probe for Cu(II).
AB - We have investigated the photophysical and photochemical features of a
luminescent heteroleptic Ru(II)-polypyridyl probe and of its corresponding Ru(II)
Cu(II) dinuclear complex formed upon the analyte binding through extensive
density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The
molecular probe contains the tailored imidazo[4,5-f]-1,10-phenanthroline (IIP)
ligand for simultaneously binding the Ru(II) core and the target metal ion in
aqueous solution. We have rationalized the static photoluminescence quenching
observed upon the Cu(II) coordination, on the grounds of distinct excited state
deactivation mechanisms which are absent in the free Ru(II) complex probe.
Additionally, the emission quenching found upon increasing the solution pH has
also been investigated. When coordinated IIP deprotonates, the nature of the
lowest excited state of its complex changes from (3)MLCT to (3)LLCT/(3)IL. The
strong base-induced emission quenching can be understood in terms of both the
energy-gap law, since the (3)LLCT/(3)IL states lie at a significantly lower
energy than the (3)MLCT state increasing the contribution of non-radiative
mechanisms, and the expected slower radiative rates from such (3)LLCT/(3)IL
states. After Cu(II) binding, the lowest triplet excited state is similar to the
analyte-free probe in both energy and electronic nature. However, Cu-centered non
radiative excited states, populated after photoinduced electron transfer and
intersystem crossing processes, are responsible for the population drainage of
the emissive state.
PMID- 25588908
TI - Laparoscopic reconstruction of an iatrogenic perforation of the neovagina and
urinary bladder by a neovaginal dilator in a patient with Mayer-Rokitansky-Kuster
Hauser syndrome.
AB - INTRODUCTION AND HYPOTHESIS: Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is a
rare genital aplasia syndrome. Patients with MRKH regularly dilate their
neovagina with vaginal dilatators. METHODS: A 23-year-old MRKH syndrome patient
came to our department complaining of a lost vaginal dilator, which she had
inserted 2 days previously. She had no bleeding or abdominal pain, but did have
occasional urine loss. She had a history of abdominal exploration for an acute
abdomen and the creation of a neovagina at the age of 16. An abdominal CT scan
located the dislocated dilator intravesically. After diagnostic laparoscopy, the
dilator was removed through the vesico-neovaginal perforation. The vagina was
closed and covered by a pedicled peritoneal flap, followed by closure of the
urinary bladder. An omental J-flap was then fixed between the vagina and bladder.
RESULTS: The operative time was 185 min, with no significant blood loss, injuries
or need for conversion/revision. The indwelling catheter was removed 7 days later
after cystography, followed by normal micturition and an adequate bladder
capacity. Vaginal dilation and sexual activity was resumed 1 month
postoperatively. Follow-up was uneventful. CONCLUSIONS: Laparoscopic vaginal
dilator removal with immediate repair of the perforation of the neovagina and the
urinary bladder directly after an acute trauma in a patient with MRKH syndrome
may be a management option. It is a feasible, safe and viable operation in the
hands of experienced laparoscopists.
PMID- 25588907
TI - Evaluating the effects of increasing physical activity to optimize rehabilitation
outcomes in hospitalized older adults (MOVE Trial): study protocol for a
randomized controlled trial.
AB - BACKGROUND: Older adults who have received inpatient rehabilitation often have
significant mobility disability at discharge. Physical activity levels in
rehabilitation are also low. It is hypothesized that providing increased physical
activity to older people receiving hospital-based rehabilitation will lead to
better mobility outcomes at discharge. METHODS/DESIGN: A single blind, parallel
group, multisite randomized controlled trial with blinded assessment of outcome
and intention-to-treat analysis. The cost effectiveness of the intervention will
also be examined. Older people (age >60 years) undergoing inpatient
rehabilitation to improve mobility will be recruited from geriatric
rehabilitation units at two Australian hospitals. A computer-generated blocked
stratified randomization sequence will be used to assign 198 participants in a
1:1 ratio to either an 'enhanced physical activity' (intervention) group or a
'usual care plus' (control) group for the duration of their inpatient stay.
Participants will receive usual care and either spend time each week performing
additional physical activities such as standing or walking (intervention group)
or performing an equal amount of social activities that have minimal impact on
mobility such as card and board games (control group). Self-selected gait speed
will be measured using a 6-meter walk test at discharge (primary outcome) and 6
months follow-up (secondary outcome). The study is powered to detect a 0.1 m/sec
increase in self-selected gait speed in the intervention group at discharge.
Additional measures of mobility (Timed Up and Go, De Morton Mobility Index),
function (Functional Independence Measure) and quality of life will be obtained
as secondary outcomes at discharge and tertiary outcomes at 6 months follow-up.
The trial commenced recruitment on 28 January 2014. DISCUSSION: This study will
evaluate the efficacy and cost effectiveness of increasing physical activity in
older people during inpatient rehabilitation. These results will assist in the
development of evidenced-based rehabilitation programs for this population. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000884707
(Date of registration 08 August 2013); ClinicalTrials.gov Identifier NCT01910740
(Date of registration 22 July 2013).
PMID- 25588910
TI - Synthesis and Photophysical Properties of Two Diazaporphyrin-Porphyrin Hetero
Dimers in Polar and Nonpolar Solutions.
AB - Two diazaporphyrin (DAP)-porphyrin hetero dimers, in beta-meso and beta-beta
configurations, were prepared to study their photoinduced intramolecular electron
transfer properties. The two meso nitrogen atoms in the porphyrin ring of DAP
change its redox potential, making DAP more easily reduced, compared to its
porphyrin counterpart. A charge-transfer from porphyrin to DAP in both hetero
dimers was verified by versatile optical spectroscopic methods. The steady-state
fluorescence spectra indicated an efficient intramolecular exciplex formation for
both dimers. For the beta-meso dimer, ultrafast time-resolved spectroscopic
methods revealed the subpicosecond formation of two types of primary short-living
(1-18 ps) intramolecular exciplexes, which relaxed in toluene to form a long
living final exciplex (1.4 ns) followed by a longer-living charge transfer
complex (>5 ns). However, in benzonitrile, the lifetime of the final exciplex was
longer (660 ps) as was that of the charge transfer complex (180 ps). The beta
beta analogue formed similar short-living exciplexes in both solvents, but the
final exciplex and the charge transfer state had significantly shorter lifetimes.
The electrochemical redox potential measurements and density functional theory
calculations supported the proposed mechanism.
PMID- 25588911
TI - Provider advice on exercise and diet among adults with comorbid serious
psychological distress and diabetes or diabetes risk factors.
AB - PURPOSE: To examine the lifetime prevalence and correlates of provider advice to
increase exercise and reduce dietary fat intake among adults with comorbid
serious psychological distress (SPD) and diabetes or diabetes risk factors.
METHODS: Study sample (n = 5942) was selected from the Medical Expenditure Panel
Survey Household Component (MEPS-HC) series of 2007-2011. SPD was defined as a
score of >=13 on the Kessler Psychological Distress Scale (K6). Multivariate
logistic regression was used to examine correlates of lifetime provider advice.
RESULTS: Less than half of adults with SPD had been advised to increase exercise
(49.4%) or reduce dietary fat intake (45.6%). The prevalence of receiving
provider advice increased in a linear fashion as the number of diabetes risk
factors increased and was the highest among those with diabetes. Provision of
provider advice was strongly associated with clinical factors rather than
individuals' sociodemographic characteristics and current health behaviors.
CONCLUSIONS: Health care providers are missing opportunities to provide exercise
and low-fat dietary advice to patients with SPD before they manifest clinical
risk factors associated with diabetes. It is important that providers counsel
them as early as possible about exercise and nutritional changes that reduce the
risks associated with diabetes.
PMID- 25588913
TI - Population-based healthcare: the experience of a regional health system.
PMID- 25588914
TI - Clinician scientists in public sector hospitals--why and how?
PMID- 25588915
TI - Oncologic outcomes of neoadjuvant chemoradiation for locally advanced rectal
cancer: a single-institution experience.
AB - INTRODUCTION: This study reports the outcomes of patients with locally advanced
rectal cancer treated with neoadjuvant chemoradiation followed by surgery in a
local population of Singapore. MATERIALS AND METHODS: The records of 85 patients
who underwent neoadjuvant chemoradiation for locally advanced rectal cancer
followed by surgery at the Tan Tock Seng Hospital (TTSH) between November 2002
and January 2012 were reviewed. The treatment protocol comprised radiotherapy to
a total dose of 50.4 Gy concurrent with 5-fluorouracil-based chemotherapy.
Patients underwent total mesorectal excision surgery following the completion of
neoadjuvant chemoradiation. Local control, disease-free survival and overall
survival were analysed using Kaplan-Meier methods. RESULTS: Median age of the
patients was 61 years. All of them completed radiotherapy. One patient did not
complete neoadjuvant chemotherapy. The median time to surgery was 52 days. Fifty
five percent (47 of 85) of patients achieved pathological downstaging and 13% (11
of 85) of patients had a pathologic complete response to preoperative treatment.
The neoadjuvant chemoradiation was well tolerated. Four percent of patients had
grade 3 diarrhoea and 4% of them had grade 3 dermatitis. There were no grade 4
toxicities. With a median follow-up of 41 months, the 5-year actuarial local
recurrence, disease-free survival and overall survival rates were 7%, 71.9%, and
83.2% respectively. Univariate analysis showed that patients with positive
surgical margins had significantly worse disease-free survival and overall
survival (P=0.012 and P<0.001 respectively) and a trend towards a higher rate of
local recurrence (P=0.08). CONCLUSION: Our study provides evidence that
neoadjuvant chemoradiation is an effective treatment for locally advanced rectal
cancer. Our outcomes are comparable with internationally published data and
demonstrate the reproducibility of the neoadjuvant approach in an Asian
population.
PMID- 25588912
TI - Skilled forelimb movements and internal copy motor circuits.
AB - Mammalian skilled forelimb movements are remarkable in their precision, a feature
that emerges from the continuous adjustment of motor output. Here we discuss
recent progress in bridging the gap between theory and neural implementation in
understanding the basis of forelimb motor refinement. One influential theory is
that feedback from internal copy motor pathways enables fast prediction, through
a forward model of the limb, an idea supported by behavioral studies that have
explored how forelimb movements are corrected online and can adapt to changing
conditions. In parallel, neural substrates of forelimb internal copy pathways are
coming into clearer focus, in part through the use of genetically tractable
animal models to isolate spinal and cerebellar circuits and explore their
contributions to movement.
PMID- 25588916
TI - Association of Socioeconomic Status (SES) and Social Support with Depressive
Symptoms among the Elderly in Singapore.
AB - INTRODUCTION: Depression in the elderly is a major public health issue.
Socioeconomic status (SES) and social support are strong risk factors for
depression. This study aimed to investigate the influence of SES and social
support in elderly depression, and the modifying effect of social support on the
relationship between SES and depression. MATERIALS AND METHODS: A community-based
survey was conducted on residents>=60 years old. Depressive symptoms were
determined with scores>=5 using the 15-item Geriatric Depression Scale (GDS).
Multivariable logistic regression was performed to determine the odds ratio (OR)
of depressive symptoms with respect to SES and social support, and interaction
terms between the two variables. RESULTS: Of 2447 responses analysed, 188 (7.8%)
respondents had depressive symptoms. Living in 2-room housing, living alone/with
a domestic helper, infrequent leisure time with children/grandchildren or being
childless, and feeling socially isolated were independently associated with
depressive symptoms. Relative to residents living with spouse and children in 4
/5-room housing, the highest ORs for depressive symptoms were those living with
spouse and children in 2-room (OR: 3.06, P<0.05), followed by living with
children only in 3-room (OR: 2.98, P<0.05), and living alone/with a domestic
helper in 4-/5-room (OR: 2.73, P<0.05). Living with spouse only appears to buffer
against depressive symptoms across socioeconomic classes, although the effect was
not statistically significant. CONCLUSION: Low social support and low SES
significantly increased the odds of depressive symptoms. The moderating effect of
social support on depression was however not consistent across SES groups.
Specific interventions need to target different SES groups to better help older
adults at risk of developing depression.
PMID- 25588917
TI - Overcoming Barriers to Mammography Screening: A Quasi-randomised Pragmatic Trial
in a Community-based Primary Care Setting.
AB - INTRODUCTION: Breast cancer is the leading cancer among women in Singapore. Five
years after a population-wide breast cancer screening programme was introduced,
screening rates remained relatively low at 41%. Studies have shown decreased
screening propensity among medically underserved women typically of minority or
socioeconomically disadvantaged status. We conducted a quasi-randomised pragmatic
trial aimed at encouraging mammography screening among underscreened or
unscreened women in a publicly funded primary care facility in Singapore.
MATERIALS AND METHODS: The study was conducted from May to August 2010.
Components of intervention included (1) tailored education, (2) doctor's
reminder, and (3) cost reduction. Researchers administered a structured
questionnaire to eligible female polyclinic attendees and patient companions aged
40 to 69 years. Individual knowledge, attitudes, beliefs, and barriers towards
mammography screening were identified and educational messages tailored. Doctor's
reminder and cost reduction were implemented additively. RESULTS: Overall, out of
448 participants, 87 (19.4%, 95% confidence interval (CI), 15.8% to 23.1%)
completed mammography screening across 3 arms of study. Participants who received
a cost reduction were more likely to attend screening compared to participants in
other intervention arms (adjusted odds ratio (OR) 2.4, 95% CI, 1.2 to 4.5, P =
0.009). Cost of screening, ethnicity, prior screening history, and attitudes
towards mammography screening were identified as significant factors predicting
mammogram attendance. CONCLUSION: Including a cost reduction component was the
most effective intervention that increased mammography screening rates. Women's
underlying beliefs, attitudes, and other predisposing factors should also be
considered for integration into existing breast cancer screening programmes.
PMID- 25588918
TI - Physiologically-guided Balanced Resuscitation: An Evidence-based Approach for
Acute Fluid Management in Paediatric Major Trauma.
AB - Trauma is a major cause of death, and haemorrhage represents an important target
for improving outcomes after severe injury. Volume replacement with crystalloids
in resuscitation might become harmful in large amounts because of coagulopathy. A
fine balance must be achieved between haemodynamic and haemostatic resuscitation.
Permissive hypotension refers to permitting some degree of hypotension in such
adult patients in an attempt to attain this fine balance. For patients who
require a significant volume of blood product resuscitation, the term 'massive
transfusion protocol' (MTP) is used. There is very little data on transfusion
protocols for paediatric trauma patients, and children respond to hypovolemic
shock in a different physiological manner compared to adults. Hence, concepts
such as permissive hypotension may not be appropriate when treating children
involved in major trauma. We recently embarked on a plan to streamline the
management of blood transfusion in massive bleeding during paediatric trauma, to
reduce the logistical problems associated with the transport of blood products
from the blood bank to the patient. From this, we evolved a MTP for paediatric
major trauma. Nonetheless, further studies will be needed to see if there is
indeed improved outcome after MTP in paediatric major trauma as current evidence
is extrapolated from adult studies.
PMID- 25588919
TI - Probing the brain white matter in psychotic disorders using neuroimaging.
PMID- 25588921
TI - The mechanism of a ligand-promoted C(sp3)-H activation and arylation reaction via
palladium catalysis: theoretical demonstration of a Pd(II)/Pd(IV) redox manifold.
AB - Density functional theory (DFT) computations (BP86 and M06-L) have been utilized
to elucidate the detailed mechanism of a palladium-catalyzed reaction involving
pyridine-type nitrogen-donor ligands that significantly expands the scope of
C(sp(3))-H activation and arylation. The reaction begins with precatalyst
initiation, followed by substrate binding to the Pd(II) center through an amidate
auxiliary, which directs the ensuing bicarbonate-assisted C(sp(3))-H bond
activation producing five-membered-ring cyclopalladate(II) intermediates. These
Pd(II) complexes further undergo oxidative addition with iodobenzene to form
Pd(IV) complexes, which proceed by reductive C-C elimination/coupling to give
final products of arylation. The base-assisted C(sp(3))-H bond cleavage is found
to be the rate-determining step, which involves hydrogen bond interactions. The
mechanism unravels the intimate involvement of the added 2-picoline ligand in
every phase of the reaction, explains the isolation of the cyclopalladate
intermediates, agrees with the observed kinetic hydrogen isotope effect, and
demonstrates the Pd(II)/Pd(IV) redox manifold.
PMID- 25588920
TI - A questionnaire survey of pediatric inflammatory bowel disease in India.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is not uncommon in children and is
an important cause of morbidity. Since information on IBD in Indian children is
sparse, the study aimed at highlighting the salient features in them. MATERIALS
AND METHODS: A questionnaire survey was done among 221 children and adolescents
with IBD [ulcerative colitis (UC) 93 (42.1 %); Crohn's disease (CD) 122 (55.2 %);
unclassified (IBD-U) 6 (2.7 %)] across seven centers in India. The cut-off age
was 18 years and below. RESULTS: The mean age of presentation for UC and CD was
10.2 +/- 4.4 and 11.0 +/- 4.5 years, respectively, with no gender difference.
Diarrhea (69.9 %, p = 0.001) and blood in the stools (90.3 %, p = 0.0001) were
common in UC, whereas abdominal pain (73.8 %, p = 0.01), fever (39.3 %, p =
0.0001), anemia (64.7 %, p = 0.001), and growth failure (76.2 %, p = 0.0001) were
common in CD. Extraintestinal manifestations (EIM) were a feature in 23.6 % and
36.1 % of UC and CD, respectively. Pancolitis (E3) was predominant in UC (70.9 %)
and 88 % required steroids. Ileocolonic CD (L3) was common in 72.9 %; 76.2 %
required azathioprine for maintenance. Of the children with UC, 11.8 % had
complications like massive hemorrhage and toxic megacolon, while 27 % of CD had
fistulae, perianal abscess, stricture, and perforation. Biologicals were used in
0.8 % of severe UC and in 12.2 % of CD. In UC, 4.3 % required surgical
intervention. CONCLUSION: Pediatric inflammatory bowel disease (P-IBD) in India
shares similarities with adult-onset IBD. Distinctive features were growth
failure and more severe forms of the disease necessitating immunomodulators.
PMID- 25588922
TI - An evaporation-induced tri-consistent assembly route towards nitrogen-doped
carbon microfibers with ordered mesopores for high performance supercapacitors.
AB - Nitrogen-doped mesoporous carbon microfibers (NMCMFs) were prepared via an
evaporation-induced tri-consistent assembly of a triblock copolymer, resols and
prehydrolyzed tetraethoxy silane on natural silk followed by pyrolysis. The
resultant NMCMFs inherit the advantages of both order mesoporous carbons (OMCs)
and carbon microfibers (CMFs), such as uniform meso-channels, high surface area,
high nitrogen content, excellent electronic conductivity as well as good
flexibility. Owing to the well-designed nanostructure and the synergistic effects
of the strongly coupled components, the binder-free electrodes based on NMCMFs
exhibit enhanced capacity (189 F g(-1) at 5 mV s(-1)), excellent rate capability
(107 F g(-1) at 100 mV s(-1)) and durability (maintained over 96% of the initial
capacitance after 10,000 cycles) in electric double-layer capacitors,
outperforming those of OMCs and CMFs derived from pristine silk.
PMID- 25588923
TI - Two-photon imaging with longer wavelength excitation in intact Arabidopsis
tissues.
AB - In vivo imaging of living organisms is an important tool to investigate
biological phenomena. Two-photon excitation microscopy (2PEM) is a laser-scanning
microscopy that provides noninvasive, deep imaging in living organisms based on
the principle of multiphoton excitation. However, application of 2PEM to plant
tissues has not been fully developed, as plant-specific autofluorescence,
optically dense tissues, and multiple light-scattering structures diminish the
clarity of imaging. In this study, the advantages of 2PEM were identified for
deep imaging of living and intact Arabidopsis thaliana tissues. When compared to
single-photon imaging, near-infrared 2PEM, especially at 1000 nm, reduced
chloroplast autofluorescence; autofluorescence also decreased in leaves, roots,
pistils, and pollen grains. For clear and deep imaging, longer excitation
wavelengths using the orange fluorescent proteins (FPs) TagRFP and tdTomato gave
better results than with other colors. 2PEM at 980 nm also provided multicolor
imaging by simultaneous excitation, and the combination of suitable FPs and
excitation wavelengths allowed deep imaging of intact cells in root tips and
pistils. Our results demonstrated the importance of choosing both suitable FPs
and excitation wavelengths for clear two-photon imaging. Further advances in in
vivo analysis using 2PEM will facilitate more extensive studies in the plant
biological sciences.
PMID- 25588924
TI - RBMS3 is a tumor suppressor gene that acts as a favorable prognostic marker in
lung squamous cell carcinoma.
AB - Recent research indicates that RBMS3 may act as a tumor suppressor gene (TSG) in
nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). It
has been reported that RBMS3 directly binds to the promoter region of c-Myc in
ESCC and that beta-catenin from both whole cell extracts and nuclear
fractionation was significantly downregulated in RBMS3-transfected NPC cells
compared to control cells. The aim of this study was to evaluate the clinical
significance of the RBMS3 gene expression in relation to the expression of Wnt
pathway components in patients with lung squamous cell carcinoma (LSCC). RBMS3, c
Myc and cytoplasmic beta-catenin were detected in 39.76, 56.63 and 89.16 % of 83
LSCC samples by immunohistochemistry, respectively, in 83 primary LSCC samples.
Semiquantitative reverse transcriptase-polymerase chain reaction and Western
blotting demonstrated decreased RBMS3 mRNA and expression in 33.33 % (10/30) and
36.67 % (11/30) tumor tissues, respectively. Statistical correlation analysis
showed RBMS3 to be negatively correlated with c-Myc (r = -0.384, p < 0.001) and
not correlated with cytoplasmic beta-catenin in the LSCC samples. Multivariate
Cox proportional hazards model analysis showed that the combined marker RBMS3/c
Myc was an independent prognostic indicator of overall survival (p = 0.001; HR
3.470; IC 95 %, 1.652-7.290), and c-Myc was a prognostic indicator of disease
free survival (p < 0.001; HR 3.182; IC 95 %, 1.961-8.920). RBMS3 is a novel TSG
in LSCC, and its downregulation facilitates development and progression of LSCC.
Therefore, it is suggested that Rbms3 as a tumor marker may play an important
role in diagnosis of LSCC.
PMID- 25588925
TI - Outcomes of peripheral blood stem cell transplantation patients from HLA
mismatched unrelated donor with antithymocyte globulin (ATG)-Thymoglobulin versus
ATG-Fresenius: a single-center study.
AB - Although antithymocyte globulin (ATG) had been widely used in hematopoietic stem
cell transplantation from unrelated donor due to its ability to prevent acute and
chronic graft-versus-host disease (GVHD), the comparative efficacy and safety of
ATG-Thymoglobulin (ATG-T) and ATG-Fresenius (ATG-F) in patients undergoing HLA
mismatched allogeneic peripheral blood stem cell transplantation from unrelated
donors (UR-PBSCT) has not been evaluated. Retrospective analysis of patients who
underwent HLA-mismatched UR-PBSCT between January 2003 and December 2013 and
received pre-transplant ATG-T at a total dose of 10 mg/kg or ATG-F at a total
dose of 20 mg/kg was performed. Patients who received ATG-T (n = 23) or ATG-F (n
= 28) had similar baseline demographic, disease, and transplant characteristics.
There were no significant between-groups differences in the probability of acute
GVHD (P = 0.721) and chronic GVHD (P = 0.439). ATG-F was associated with
nonsignificant trends toward higher disease-free survival at 3-year follow-up
compared with ATG-T (45.7 +/- 11.1 vs 61.3 +/- 9.7 %, respectively, P = 0.07). A
significantly greater proportion of ATG-T patients experienced high fever than
ATG-F patients (P < 0.01) during ATG infusion. There was no difference in the
rate of infection between the two treatment groups. There were less adverse
effects comparing ATG-F with ATG-T. ATG-T at a total dose of 10 mg/kg and ATG-F
at a total dose of 20 mg/kg had a similar clinical outcome in the setting of HLA
mismatched UR-PBSCT.
PMID- 25588926
TI - Survivorship in untreated breast cancer patients.
AB - In any disease, the knowledge of the natural history of untreated cases provides
a real background against which the real advantages of a new treatment itself are
judged. Fortunately, in the present days, there are scant data on outcomes in
patients with untreated breast cancer. In an attempt to provide this background
against which the virtues of current curative and palliative treatments can be
more accurately assessed, we have reviewed the literature regarding published
untreated breast cancer series. Taking into consideration all the difficulties of
analyzing reports written on the last half of the nineteenth century or on the
first half of the twentieth century, in most reports, patients survived almost 3
4 years without any type of treatment. Worth mentioning, approximately 5-10 % of
untreated patients lived longer than 10 years. Thus, the spectrum of clinical
aggressiveness of untreated breast cancer varies between virulence and chronic
disease. These facts should be taken into account when considering the value of
current treatments for early-stage disease.
PMID- 25588928
TI - Attentional focus during exposure in spider phobia: the role of schematic versus
non-schematic imagery.
AB - Research has provided controversial results regarding the role of distraction
(vs. attentional focus) during exposure therapy. In the present study, we
manipulated the nature of the concepts activated during exposure. Sixty-six
spider phobics were exposed to pictures of spiders and asked, or not, to form
mental images of concepts that were either related or unrelated to spiders. At
pre-exposure, mid-exposure, post-exposure, and follow-up, subjective distress,
heart rate variability, and skin conductance responses were measured and the Fear
of Spiders Questionnaire and a Behavioural Avoidance Test were performed. Results
showed that the activation of concepts unrelated to spiders led to return of
distress at follow-up. Moreover, the activation of concepts related to spiders
decreased emotional and avoidance responses between sessions. This pattern of
results suggests that the nature of the activated concepts does not influence
subjective distress during exposure, but plays an important role in the
maintenance of distress reduction between sessions.
PMID- 25588927
TI - A systematic review and meta-analysis of the association between OGG1 Ser326Cys
polymorphism and cancers.
AB - The oxyguanine glycosylase 1 (OGG1) gene has an important role in DNA repair, and
the polymorphism of the gene may alter cancer susceptibility. This study aims to
examine the association between the OGG1 Ser326Cys polymorphism and cancer risk
based on meta-analysis. Relevant studies were identified through a search of
PubMed and Weipu databases, and a total of 109 studies including 111 comparisons
containing 34,041 cases and 42,730 controls were enrolled. Overall, significant
association was observed between OGG1 Ser326Cys polymorphism and cancer risk in
all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser:
OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI
1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308). In stratified
analysis by cancer type, significantly increased cancer risk was observed in
digestive system cancer, head and neck cancer and lung cancer. For gynecologic
cancer, significantly increased cancer risk was also observed in homozygote model
(OR 1.974, 95 % CI 1.254-3.107). In addition, in stratified analysis by
ethnicities, increased cancer risk was found in Asians (Cys/Cys vs Cys/Ser +
Ser/Ser: OR 1.195, 95 % CI 1.088-1.313; Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.115,
95 % CI 1.045-1.190; Cys/Cys vs Ser/Ser: OR 1.273, 95 % CI 1.149-1.410). The OGG1
Ser326Cys polymorphism may be a risk factor for cancers of lung, digestive system
and head and neck.
PMID- 25588929
TI - Molecular characteristics of endometrial cancer coexisting with peritoneal
malignant mesothelioma in Li-Fraumeni-like syndrome.
AB - BACKGROUND: Endometrial cancer that occurs concurrently with peritoneal malignant
mesothelioma (PMM) is difficult to diagnose preoperatively. CASE PRESENTATION: A
postmenopausal woman had endometrial cancer extending to the cervix, vagina and
pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple
peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy.
Targeted, massively parallel DNA sequencing and molecular inversion probe
microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni
like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a
somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications
and some deletions were found in the endometrial cancer. The patient has been
stable for 24 months after therapy. One of her four children was also found to
carry the germline TP53 mutation. CONCLUSIONS: Molecular characterization of the
coexistent tumors not only helps us make the definite diagnosis, but also
provides information to select targeted therapies if needed in the future.
Identification of germline TP53 mutation further urged us to monitor future
development of malignancies in this patient and encourage cancer screening in her
family.
PMID- 25588930
TI - Sustained-release methylphenidate in methamphetamine dependence treatment: a
double-blind and placebo-controlled trial.
AB - BACKGROUND: The objective of this randomized, double-blind, placebo-controlled
study was to evaluate the efficacy of sustained-release methylphenidate (MPH-SR)
in treatment of methamphetamine dependence. METHODS: Fifty-six individuals who
met DSM-IV-TR criteria for methamphetamine dependence participated in this 10
week trial. The participants were randomly allocated into two groups and received
18 to 54 mg/day sustained-released methylphenidate or placebo for 10 weeks.
Craving was evaluated by a visual analogue craving scale every week. Urinary
screening test for methamphetamine was carried out each week. The Beck Depression
Inventory-II (BDI-II) was used to monitor participant depressive symptoms at
baseline and bi-weekly during the treatment period. RESULTS: At the end of the
trial, the MPH-SR group was less methamphetamine positive compared to the placebo
group and the difference was significant (p = 0.03). By the end of the study, MPH
SR group showed significantly less craving scores compared to the placebo group
[MD (95% CI) = -10.28(0.88-19.18), t(54) = 2.19, p = 0.03]. There was greater
improvement in the depressive symptoms scores in the intervention group compared
to the placebo group [MD (95% CI) =2.03(0.31-3.75), t (54) =2.37, p = 0.02].
CONCLUSION: Sustained-released methylphenidate was safe and well tolerated among
active methamphetamine users and significantly reduced methamphetamine use,
craving and depressive symptoms. TRIAL REGISTRATION: IRCT201202281556N38.
PMID- 25588931
TI - Subthalamic deep brain stimulation differently alters striatal dopaminergic
receptor levels in rats.
AB - High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized
as an effective treatment for the motor symptoms of Parkinson's disease (PD), but
its mechanisms, particularly as concern dopaminergic transmission, remain
unclear. The aim of this study was to evaluate changes in the expression of
dopaminergic receptors (D1, D2, and D3 receptors) after prolonged (4 h)
unilateral STN-HFS in anesthetized intact rats and rats with total dopaminergic
denervation. We used [(3)H]SCH 23390, [(125)I]iodosulpride, and [(125)I]OH-PIPAT
to assess the densities of D1R, D2R, and D3R, respectively, within different
areas of the striatum-a major input structure of the basal ganglia-including the
nucleus accumbens. We found that STN-HFS increased D1 R levels in almost all of
the striatal areas examined, in both intact and denervated rats. By contrast, STN
HFS led to a large decrease in D2 R and D3R levels, limited to the nucleus
accumbens and independent of the dopaminergic state of the animals. These data
suggest that the influence of STN-HFS on striatal D1 R expression may contribute
to its therapeutic effects on motor symptoms, whereas its impact on D2R/D3 R
levels in the nucleus accumbens may account for the neuropsychiatric side effects
often observed in stimulated PD patients, such as postoperative apathy.
PMID- 25588932
TI - HealthMpowerment.org: Building Community Through a Mobile-Optimized, Online
Health Promotion Intervention.
AB - BACKGROUND: Both young Black men who have sex with men as well as young Black
transgender women (YBMSM/TW) continue to experience a significant increase in HIV
incidence. HealthMpowerment.org (HMP) is a mobile phone-optimized, online
intervention for both YBMSM/TW to build community and facilitate supportive
relationships. METHODS: To assess the feasibility, acceptability, and preliminary
outcomes, a 1-month pilot trial of HMP among 15 YBMSM/TW was conducted. RESULTS:
Retention was 100%. Mean age was 26 years, 60% were HIV-infected, 87% earned
<$21,000, and 67% were uninsured. Despite the small sample size and limited
intervention length, statistically significant improvements were seen in social
support (p = .012), social isolation (p = .050), and depressive symptoms (p =
.045). CONCLUSION: The HMP pilot trial demonstrated feasibility and
acceptability. Given the burden of the epidemic among YBMSM/TW, there is an
imperative to develop, test, and scale up culturally appropriate interventions to
both prevent HIV acquisition and limit onward transmission.
PMID- 25588933
TI - Perceptions that influence the maintenance of scientific integrity in community
based participatory research.
AB - Scientific integrity is necessary for strong science; yet many variables can
influence scientific integrity. In traditional research, some common threats are
the pressure to publish, competition for funds, and career advancement. Community
based participatory research (CBPR) provides a different context for scientific
integrity with additional and unique concerns. Understanding the perceptions that
promote or discourage scientific integrity in CBPR as identified by professional
and community investigators is essential to promoting the value of CBPR. This
analysis explores the perceptions that facilitate scientific integrity in CBPR as
well as the barriers among a sample of 74 professional and community CBPR
investigators from 25 CBPR projects in nine states in the southeastern United
States in 2012. There were variations in perceptions associated with team member
identity as professional or community investigators. Perceptions identified to
promote and discourage scientific integrity in CBPR by professional and community
investigators were external pressures, community participation, funding, quality
control and supervision, communication, training, and character and trust. Some
perceptions such as communication and training promoted scientific integrity
whereas other perceptions, such as a lack of funds and lack of trust could
discourage scientific integrity. These results demonstrate that one of the most
important perceptions in maintaining scientific integrity in CBPR is active
community participation, which enables a co-responsibility by scientists and
community members to provide oversight for scientific integrity. Credible CBPR
science is crucial to empower the vulnerable communities to be heard by those in
positions of power and policy making.
PMID- 25588935
TI - Impact of Fruit Smoothies on Adolescent Fruit Consumption at School.
AB - We examine the impact of serving fruit smoothies during school breakfast on fruit
consumption among middle school and high school students. We draw on
observational plate-waste data over a 10-week period during which fruit smoothies
were introduced for breakfast at two Utah schools. Our total sample includes
2,760 student-day observations. We find that the fraction of students eating a
full serving of whole fruit increased from 4.3% to 45.1%. As such, school
districts should consider offering fruit smoothies as part of a set of
interventions designed to increase fruit consumption at school.
PMID- 25588934
TI - The U.S. National Tips From Former Smokers Antismoking Campaign: Promoting
Awareness of Smoking-Related Risks, Cessation Resources, and Cessation Behaviors.
AB - OBJECTIVE: Evaluate the second flight of the U.S. Tips From Former Smokers (Tips)
campaign. METHOD: Data were analyzed from an online consumer panel of U.S. adult
smokers before (n = 1,404) and after (n = 1,401) the 2013 Tips campaign launch.
Generalized estimating equation models assessed whether the Tips advertisement
recall was associated with knowledge about smoking-related risks in the Tips
advertisements, awareness and use of a toll-free quitline and cessation websites,
and quit attempts. RESULTS: Seventy-one percent of participants at Wave 2
reported that they recalled seeing at least one Tips advertisement. Smokers who
recalled seeing a Tips advertisement were more likely to (a) show increases over
baseline in knowledge of health risks such as amputation: 65% versus 34%, p <
.001; blindness: 27% versus 12%, p < .001; and (b) to be aware of a quitline (41%
vs. 30%, p < .001) and cessation website (28% vs. 20%, p < .001). Recall of Tips
advertisements was also associated with greater likelihood of reporting having
visited cessation websites (odds ratio [OR] = 1.62, 95% confidence interval [CI]
= 1.27-2.06), having called a quitline (OR = 2.28, 95% CI = 1.61-3.24), and
having made a quit attempt (OR = 1.18, 95% CI = 1.00-1.39), although these
results were only statistically significant in the unadjusted models.
CONCLUSIONS: The 2013 Tips campaign was successful in increasing knowledge of
health risks and awareness of tobacco cessation resources.
PMID- 25588936
TI - Early Success Is Vital in Minimal Worksite Wellness Interventions at Small
Worksites.
AB - INTERVENTION: In an effort to increase physical activity, 15 workplaces
participated in a minimal-contact 10,000-steps-a-day program sponsored by the
Sedgwick County Health Department in 2007 and 2008. Pedometers were provided to
measure participants' weekly steps for the 10-week intervention. METHOD:
Participants were defined as those who completed the preregistration survey and
logged at least 1 week of results. Registrants were defined as those who
completed a registration survey but did not log any weekly results. The primary
dependent variable was whether or not participants achieved weekly success, as
measured by achieving at least 70,000 steps in a week. A secondary dependent
variable was participants' number of steps each week during the weeks they logged
results. Repeated measures logistic regression analysis was conducted to identify
factors associated with weekly success. RESULTS: Of the 2,515 registrants, 1,292
(51%) were participants. The average number of weeks of participation for this 10
week intervention was 5.6 weeks (SD = 3.4). Those from small employers (n < 750)
were more likely (OR = 2.0) than those from large organizations (n > 750) to
become participants. Participants who achieved at least 70,000 steps in the first
week of the intervention were 7.3 times more likely than participants who walked
less than 70,000 steps in the first week to achieve 70,000 steps each week for
all 10 weeks. CONCLUSIONS: Results from implementing a minimal-contact 10,000
step intervention can be maximized by targeting small worksites and supporting
employees to achieve 70,000 steps in their first week.
PMID- 25588937
TI - Physical and Social-Motivational Contextual Correlates of Youth Physical Activity
in Underresourced Afterschool Programs.
AB - Afterschool programs (ASPs) have become increasingly recognized as a key context
to support youth daily physical activity (PA) accrual. The purpose of the present
study was to assess the physical and social-motivational climate characteristics
of ASPs associated with youth PA, and variations in contextual correlates of PA
by youth sex. Systematic observations of 7 ASPs serving underserved youth
(minority, low income) was conducted using the System for Observing Play and
Leisure Activity in Youth and a social-motivational climate observation tool
founded on self-determination theory. For five program days at each site, teams
of two coders conducted continuous observations of youth PA (sedentary, moderate,
vigorous), five physical features (e.g., equipment availability), eight staff
interactions (e.g., encourage PA), and seven motivational climate components
(e.g., inclusive). Aligned with previous research, regressions controlling for
variations by site indicated that organized PA, provision of portable equipment,
and staff PA participation and supervision are key correlates of youth PA.
Moreover, as the first study to systematically observe motivational-context
characteristics of ASPs, we identified several key modifiable motivational
features that are necessary to address in order to increase youth engagement in
PA during the out-of-school hours. Among motivational features assessed,
"relatedness" components (positive peer relations, inclusive/cooperative
activities) were primary correlates of girls' PA. In contrast, all three
motivational features specified by self-determination theory (support for
autonomy, mastery/competence, and inclusion/relatedness) were correlated with
boys' PA. Findings are discussed in terms of policy and practice for
understanding strengths and needs of ASPs to effectively engage youth in PA.
PMID- 25588939
TI - An iron-catalyzed cascade approach to benzo[b]carbazole synthesis followed by 1,4
sulfonyl migration.
AB - A simple and straightforward approach was developed to construct 5H
benzo[b]carbazole derivatives by iron catalysis in a cascade sequence. The
notable features of this work include an atom-economical cascade sequence,
unprecedented 1,4-sulfonyl migration, tolerance of a variety of functional
groups, good yields, and an economical catalytic system.
PMID- 25588938
TI - Intermediate Catheters Reduce the Length of Mechanical Thrombectomy Procedures in
Acute Basilar Artery Occlusions.
AB - BACKGROUND AND PURPOSE: In the past years, technical developments have raised
recanalization rates of endovascular treatments of intracerebral artery
occlusions in acute ischemic stroke. By using stent retrievers, several
prospective trials have reported recanalization rates up to 79 % as well as good
neurological outcome in up to 58 % of the cases. The degree of the recanalization
and the length of the procedure are factors known to influence the clinical
outcome of patients treated endovascularly. Yet, still little is known about
factors influencing the angiographic results of thrombectomy procedures. The
purpose of this study was to investigate whether the use of intermediate
catheters affects the angiographic results of thrombectomy procedures in basilar
artery occlusions. MATERIALS AND METHODS: A total of 47 consecutive patients with
acute basilar artery occlusions who underwent endovascular treatment with stent
retrievers in our department were retrospectively identified. We analyzed the
angiographic data regarding the use of intermediate catheters, the lengths of the
procedures, the number of passes of the stent retrievers, the angiographic
results, and the site of access to the basilar artery. RESULTS: Recanalization
with modified thrombolysis in cerebral infarction (mTICI) >= 2b was achieved in
74.5 %. Intermediate catheters were used in 13 cases. The mean length of the
procedures was significantly shorter when intermediate catheters were used (44.8
+/- 27.6 vs. 70.7 +/- 41.4 min, P = .043). There were no significant differences
in the number of passes or in the final mTICI scores. CONCLUSIONS: The use of
intermediate catheters significantly reduces the length of mechanical
thrombectomy procedures in acute basilar artery occlusions.
PMID- 25588941
TI - Effect of alternate-day fasting therapy combined with Linggui Zhugan Decoction ()
on hepatic oxidative stress in hyperlipidemic rat.
AB - OBJECTIVE: To observe the effect of alternate-day fasting (ADF) therapy combined
with Linggui Zhugan Decoction (, LZD) on hepatic oxidative stress and blood
lipids in hyperlipidemic rats. METHODS: Fifty-two Wistar rats were randomly
assigned to two groups: the high-fat-diet (HF) group and the normal-diet (ND)
group. Hyperlipidemia was induced by feeding rats with high-cholesterol-diet for
5 weeks. Then the HF group was randomized to the model-control (MC) group, the
alternate-day-fasting (ADF) group, and the ADF combined with LZD (AL) group. The
ND group was regarded as the negative control (NC) group. The AL and ADF groups
were put on fast for 24 h on alternate days for 4 weeks. The AL group was
administrated with LZD on the fast days. Body weight and food intake were
measured once a week. After 4-week ADF, blood sample was collected for
determination of plasma total cholesterol (TC), triglyceride (TG), low-density
lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C).
Liver oxidative stress parameters including total superoxide dismutase (T-SOD)
activity, malondialdehyde (MDA) level and glutathione (GSH) content were also
tested. RESULTS: Body weight in the HF group decreased significantly (P<0.01).
TC, TG, HDL-C, and LDL-C concentrations in the HF group were higher than those in
the NC group (P<0.01), respectively. T-SOD in the HF group was clearly lower than
that in the NC group (P<0.05). After 4-week intervention, body weight, TC and TG
concentrations in the ADF and AL groups declined significantly, respectively,
compared to MC group (P<0.05). GSH in the ADF and AL groups were much higher than
those in the MC group (P<0.01). MDA level was also greatly higher in the ADF
group as compared with the NC group (P<0.05). CONCLUSION: ADF therapy combined
with LZD may be used as an effective combination approach for treatment of
hyperlipidemia and oxidative stress damage.
PMID- 25588940
TI - Protective effect of propyl gallate against oxidized low-density lipoprotein
induced injury of endothelial cells.
AB - OBJECTIVE: To evaluate the protective effect of propyl gallate (PG), an alkyl
ester of gallic acid which is an active ingredient of Radix Paeoniae, against
oxidized low-density lipoprotein (ox-LDL)-induced apoptosis and death in
endothelial cells (ECs) and to find out its preliminary mechanism. METHODS: The
cultured endothelial cells were divided into normal, model (ox-LDL), control
(fetal bovine serum), PG high dose (20 MUg/mL), PG middle dose (10 MUg/mL), and
PG low dose (5 MUg/mL) groups, each derived from three different pools of
umbilical cords. The model of injured human umbilical vein endothelial cells
(HUVECs) was induced by ox-LDL. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H
tetrazolium bromide (MTT) assay, Hoechst 33258 staining, flow cytometry and
measurement of nitrogen monoxidum (NO) release were used to evaluate the
protective effect of PG against ox-LDL-induced apoptosis and death in HUVECs. To
find out the mechanism of this protective effect, the expression of endothelial
nitric oxide synthase (eNOS) mRNA, eNOS protein expression, immunofluorescence of
intracellular reactive oxygen species (ROS) and activities of malondialdehyde
(MDA), superoxidedismutase (SOD) and glutathione peroxidase (GPx) were observed.
RESULTS: PG significantly reduced ox-LDL-induced apoptosis and cell death. The
percentage of cells death and apoptosis was significantly higher in the ox-LDL
group than that in the control group (P<0.05). Compared with the control group,
the cells death and apoptosis of PG group was no different (P>0.05). As compared
with the ox-LDL group, results of the PG high dose group showed that cell
viability was significantly increased (P<0.05), the level of NO release,
expression of eNOS mRNA, densitometric value of eNOS protein expression, as well
as the activities of SOD and GPx were all significantly higher (all P<0.05).
CONCLUSION: PG could potentially serve as a novel endothelial protective agent
against ox-LDL-induced injury of endothelial cell.
PMID- 25588942
TI - Cytotoxicity of syringin and 4-methoxycinnamyl alcohol isolated from Foeniculum
vulgare on selected human cell lines.
AB - This study was carried out to determine the cytotoxic effect of seven plant
extracts and the isolated compounds - syringin and 4-methoxycinnamyl alcohol - on
cancerous and non-cancerous cells. The ethanol extract of Foeniculum vulgare was
found to exhibit the most significant toxicity with an IC50 value of 19.97 MUg/mL
on HeLa cells. Bioassay-guided fractionation led to the isolation of two
compounds, syringin (1) and 4-methoxycinnamyl alcohol (2). Both compounds showed
toxicity against MCF-7, HeLa and DU145 cancer cell line. The results showed that
compound 2 showed high toxicity against all the cancer cell lines with IC50
values of 14.24, 7.82 and 22.10 MUg/mL, respectively. 4-Methoxycinnamyl alcohol
also showed no apoptotic effect in cell cycle analysis after 48 h at a
concentration of 10 MUg/mL. However, DNA fragmentation study revealed that
necrosis took place at a concentration of 10 MUg/mL after 48 h exposure.
PMID- 25588943
TI - Canine atopic dermatitis diagnostic criteria: evaluation of four sets of
published criteria among veterinary students.
AB - Canine atopic dermatitis (cAD) is a major teaching point as its diagnosis and
treatment are difficult. During 11 weeks, 140 dogs and students (third, fourth,
and fifth years) were recruited and paired. One of the four lists of diagnostic
criteria was randomly attributed to each student. Concordance results, calculated
with Cohen's kappa, ranged from slight (kappa=0.07) to moderate (kappa=0.53).
Favrot's diagnostic criteria received the best results. It has been observed that
results are improved with clinical experience. We observed that students often
forgot that Favrot's criteria apply only to pruritic dogs and that the
fulfillment of the criteria allows only a suspicion, not a diagnosis, of cAD.
Primary pruritus and corticosteroid-responsive pruritus were often misunderstood.
PMID- 25588944
TI - A Tetrahymena Hsp90 co-chaperone promotes siRNA loading by ATP-dependent and ATP
independent mechanisms.
AB - The loading of small interfering RNAs (siRNAs) and microRNAs into Argonaute
proteins is enhanced by Hsp90 and ATP in diverse eukaryotes. However, whether
this loading also occurs independently of Hsp90 and ATP remains unclear. We show
that the Tetrahymena Hsp90 co-chaperone Coi12p promotes siRNA loading into the
Argonaute protein Twi1p in both ATP-dependent and ATP-independent manners in
vitro. The ATP-dependent activity requires Hsp90 and the tetratricopeptide repeat
(TPR) domain of Coi12p, whereas these factors are dispensable for the ATP
independent activity. Both activities facilitate siRNA loading by counteracting
the Twi1p-binding protein Giw1p, which is important to specifically sort the 26-
to 32-nt siRNAs to Twi1p. Although Coi12p lacking its TPR domain does not bind to
Hsp90, it can partially restore the siRNA loading and DNA elimination defects of
COI12 knockout cells, suggesting that Hsp90- and ATP-independent loading of siRNA
occurs in vivo and plays a physiological role in Tetrahymena.
PMID- 25588946
TI - Isolation and characterization of an antimicrobial lipopeptide produced by
Paenibacillus ehimensis MA2012.
AB - In this study, a novel lipopeptide antibiotic was isolated from the culture
supernatant of Paenibacillus ehimensis strain MA2012. After analyses by mass
spectrometry (MS), nuclear magnetic resonance (NMR), and high resolution mass
spectrometry (HR-MS/MS) the compound was identified to be polypeptin C consisting
of 3-hydroxy-4-methyl-hexanoic acid moiety and nine amino acids as peptide body.
It has the same molecular mass (1115 Da) with that of polypeptin A and B but the
amino acid positions differ. A relatively low concentration (125 ppm) of
polypeptin C lowered the surface tension of water from 72.2 to 36.4 mN/m. It
showed antimicrobial activity against several plant pathogenic bacteria and
fungi. When the polypeptin C was applied to the ripe pepper fruits previously
inoculated with conidia of Colletotrichum gloeosporioides, the hyphal growth on
the fruit was significantly suppressed. Moreover, the hyphal morphology of C.
gloeosporioides was greatly affected by the purified compound. All these data
suggest the great potential of P. ehimensis MA2012 to control plant fungal and
bacterial diseases.
PMID- 25588947
TI - A murine model of lung ischemia and reperfusion injury: tricks of the trade.
AB - BACKGROUND: Pulmonary ischemia-reperfusion injury (IRI) causes postoperative
morbidity in patients undergoing lung transplantation, isolated lung perfusion,
and cardiopulmonary bypass and may lead to potentially lethal pathologies such as
respiratory shock. In-depth study of this pathology requires a reliable animal
model. Mice are a popular species to develop experimental models because of their
logistic advantages and the availability of knock outs. However, their small size
warrants microsurgical techniques and a skilled surgeon. MATERIALS AND METHODS:
We developed a murine model of pulmonary anoxic IRI through hilar clamping using
adult female Swiss mice. After left thoracotomy, we expose the pulmonary hilum
keeping the ribs and the muscles of back and forepaw intact. A microvascular
clamp is placed over the entire hilum, occluding bronchus, pulmonary artery, and
vein. RESULTS: Our model proved to be simple, reliable, and reproducible, showing
minimal preoperative and postoperative mortality. Histopathologic analysis
indicated all characteristic features of pulmonary IRI, such as an early
recruitment of lymphocytes followed by neutrophil influx. CONCLUSIONS: This
article presents a murine surgery model for pulmonary IRI based on a muscle
sparing thoracotomy. The minimal approach limits manipulation of lung tissue,
minimizing mortality and non-IRI-induced injury.
PMID- 25588945
TI - LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal
sorting, and degradation.
AB - Lysosomal degradation is essential for the termination of EGF-stimulated EGF
receptor (EGFR) signaling. This requires EGFR sorting to the intraluminal
vesicles (ILVs) of multi-vesicular endosomes (MVEs). Cytosolic proteins including
the ESCRT machineries are key regulators of EGFR intraluminal sorting, but roles
for endosomal transmembrane proteins in receptor sorting are poorly defined.
Here, we show that LAPTM4B, an endosomal transmembrane oncoprotein, inhibits EGF
induced EGFR intraluminal sorting and lysosomal degradation, leading to enhanced
and prolonged EGFR signaling. LAPTM4B blocks EGFR sorting by promoting
ubiquitination of Hrs (an ESCRT-0 subunit), which inhibits the Hrs association
with ubiquitinated EGFR. This is counteracted by the endosomal PIP kinase,
PIPKIgammai5, which directly binds LAPTM4B and neutralizes the inhibitory
function of LAPTM4B in EGFR sorting by generating PtdIns(4,5)P2 and recruiting
SNX5. PtdIns(4,5)P2 and SNX5 function together to protect Hrs from
ubiquitination, thereby promoting EGFR intraluminal sorting. These results reveal
an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2
signaling, and the ESCRT complex and define a mechanism by which the oncoprotein
LAPTM4B can transform cells and promote tumor progression.
PMID- 25588948
TI - Celecoxib inhibits early cutaneous wound healing.
AB - BACKGROUND: Cyclooxygenase-2 (COX-2) is an inducible enzyme that is rapidly
upregulated in response to injury, resulting in the production of prostaglandin
E2 (PGE2), a primary mediator of inflammation and wound healing. The selective
COX-2 inhibitor, celecoxib, is was used to treat pain and inflammation. When used
to treat injuries, we postulated that loss of PGE2 activity by COX-2 inhibition
would have detrimental effects on wound healing. Our objective was to study the
effect of selective COX-2 inhibition with celecoxib on cutaneous wound healing.
MATERIALS AND METHODS: C57BL/6J mice with uniform full-thickness wounds (1 cm(2))
to their dorsum were fed diet with or without celecoxib (1500 ppm). Wound closure
analysis measured wound contraction, reepithelialization, and open wound as a
percentage of the initial wound area, and was quantified by planimetry. Wounds
were excised en bloc at day 7 to examine cellular proliferation, angiogenesis,
cytokine production, and extracellular matrix (ECM) formation. RESULTS: Celecoxib
induced reduction in wound PGE2 levels was documented by enzyme-linked
immunosorbent assay on day 7 after wounding. Wound contraction and
reepithelialization were significantly reduced by celecoxib treatment, resulting
in a 20% greater open wound area at day 7 (P < 0.05). In response to celecoxib
treatment, immunohistochemistry analysis showed epithelial cell proliferation,
angiogenesis, and ECM components including collagen and myofibroblasts were
significantly decreased. CONCLUSIONS: Wound healing is significantly delayed by
celecoxib treatment. These data indicate that COX-2 and its downstream product
PGE2 modulate the activity of multiple essential functions of the inflammatory
stroma, including epithelial proliferation, angiogenesis, and ECM production. As
a result, reepithelialization and wound closure are delayed by celecoxib
treatment. These findings have potential clinical implications in postoperative
wound management.
PMID- 25588949
TI - Hydrogen-rich saline attenuates ischemia-reperfusion injury in skeletal muscle.
AB - BACKGROUND: To investigate the potential beneficial effect of hydrogen-rich
saline (HRS) in ischemia-reperfusion (IR) injury of skeletal muscle. METHODS:
Three experimental groups were established in male Sprague-Dawley rats: (1) sham
group, (2) IR with normal saline group, (3) and IR with HRS group. A rat model of
skeletal muscle IR injury was induced by 3-h tourniquet occlusion on its left
hind limb and 4-h reperfusion. Normal saline and HRS (1.0 mL/100 g) were
administered intraperitoneally at 10 min before reperfusion, respectively. Muscle
and serum samples were analyzed for detecting the levels of myeloperoxidase
(MPO), superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyl radical
(*OH). Muscle samples were assessed by wet/dry rate, hematoxylin and eosin
histologic assessment, Bcl2, Bax, cytochrome C, LC3B, terminal deoxynucleotidyl
transferase-mediated dUTP-biotin nick end labeling, and electron microscopy.
RESULTS: The wet/dry ratio increased significantly in the IR group (P < 0.01
compared with that in the sham group) and decreased significantly in IR with HRS
groups (4.12 +/- 0.14 versus 4.12 +/- 0.14, P < 0.01 compared with that in the IR
group). Muscle tissues and serum of the IR group had significantly increased
levels of MPO, MDA, *OH content, and decreased SOD activities compared with the
sham group (P < 0.01). The activity of SOD in the IR with HRS group was greatly
elevated compared with that in the IR group (295.028 +/- 9.288 versus 249.190 +/-
5.450 in muscle tissues; 91.627 +/- 2.604 versus 73.4045 +/- 6.487 in serum; P <
0.01), whereas the levels of MPO, MDA, and *OH content were clearly reduced (MPO:
0.5649 +/- 0.0724 versus 1.0984 +/- 0.0824 in muscle tissues; 0.7257 +/- 0.1232
versus 1.3147 +/- 0.0531 in serum. MDA: 4.457 +/- 0.650 versus 7.107 +/- 0.597 in
muscle tissues; 2.531 +/- 0.434 versus 4.626 +/- 0.237 in serum. *OH: 16.451 +/-
0.806 versus 19.871 +/- 0.594 in muscle tissues; 500.212 +/- 7.387 versus 621.352
+/- 7.591 in serum, P < 0.01). The integrated optical density of positive
amethyst staining increased significantly in the IR group (P < 0.01 compared with
that in the sham group) and decreased significantly in IR with HRS group (928.79
+/- 234.537 versus 3005.972 +/- 83.567, P < 0.01 compared with that in the IR
group). Muscle tissues of the IR group had significantly increased levels of Bax,
cytochrome C, LC3B content, and decreased Bcl2 activities compared with those in
the sham group (P < 0.01). The activity of Bcl2 in the IR with HRS group was
greatly elevated compared with that in the IR group (0.2635 +/- 0.0704 versus
0.1242 +/- 0.0662; P < 0.01), whereas the levels of Bax, cytochrome C, and LC3B
content were clearly reduced (Bax: 0.3103 +/- 0.0506 versus 0.5122 +/- 0.0148;
cytochrome C: 0.4194 +/- 0.1116 versus 0.8127 +/- 0.0166; LC3B: 0.5884 +/- 0.0604
versus 1.3758 +/- 0.0319; respectively, P < 0.01). CONCLUSIONS: HRS seems to be
effective in attenuating IR injury in skeletal muscle via its antioxidant, anti
apoptosis, and anti-autophagy effect.
PMID- 25588951
TI - Sexual health is another commissioning crisis.
PMID- 25588950
TI - Increasing diversity of the biomedical workforce through community engagement:
The University of Utah Native American Summer Research Internship.
PMID- 25588952
TI - Magnetic nanoparticles: general discussion.
PMID- 25588953
TI - Rhodium nanoparticle-mesoporous silicon nanowire nanohybrids for hydrogen
peroxide detection with high selectivity.
AB - Developing nanostructured electrocatalysts, with low overpotential, high
selectivity and activity has fundamental and technical importance in many fields.
We report here rhodium nanoparticle and mesoporous silicon nanowire (RhNP@mSiNW)
hybrids for hydrogen peroxide (H2O2) detection with high electrocatalytic
activity and selectivity. By employing electrodes that loaded with RhNP@mSiNW
nanohybrids, interference caused from both many electroactive substances and
dissolved oxygen were eliminated by electrochemical assaying at an optimal
potential of +75 mV. Furthermore, the electrodes exhibited a high detection
sensitivity of 0.53 MUA/mM and fast response (< 5 s). This high-performance
nanohybrid electrocatalyst has great potential for future practical application
in various oxidase-base biosensors.
PMID- 25588954
TI - Effective half-lives of 137Cs in giant butterbur and field horsetail, and the
distribution differences of potassium and 137Cs in aboveground tissue parts.
AB - Concentrations of (137)Cs and (40)K in different tissues of edible wild
herbaceous plants, that is, leaf blade and petiole for giant butterbur (Petasites
japonicas (Siebold et Zucc.) Maxim.), and leaf, stem and strobilus for fertile
shoot of field horsetail (Equisetum arvense L.) were measured in 2012-2014 to
clarify the effect in Japan from the Fukushima Daiichi Nuclear Power Plant
accident. The concentrations of (137)Cs decreased with time with effective half
lives of ca. 450 d and 360 d for giant butterbur and field horsetail,
respectively. The ANOVA test revealed that (40)K and (137)Cs distributions in
leaf blade and petiole for giant butterbur and leaf and stem for field horsetail
were different. Therefore, other plants, leaf and stem for Japanese knotweed
(Fallopia japonica (Houtt.) Ronse Decr.) and Canada goldenrod (Solidago
canadensis L.), and leaf blade and petiole for gingko (Ginkgo biloba L.) and
Someiyoshino cherry (Cerasus * yedoensis (Matsum.) A.V.Vassil. 'Somei-yoshino')
were collected from the same sampling field and their (137)Cs and (40)K
concentrations were compared to those in the giant butterbur and field horsetail
parts. For (137)Cs, concentrations in leaf blade and leaf parts were 1.1-6.0
times higher than those in petiole and stem parts for all six plants. On the
other hand, (40)K concentrations in leaf blade and leaf parts were 0.40-0.97 of
those observed in petiole and stem parts. Discrimination ratios of (40)K/(137)Cs
of leaf blade to petiole or leaf to stem were then calculated and they ranged
from 0.09 to 0.57. These results suggested that Cs and K did not behave similarly
in these plants. Thus, to understand the radiocesium fate in plants, K
measurement results should not be used as an analog for Cs behavior although Cs
is known to have a similar chemical reactivity to that of K.
PMID- 25588955
TI - The role of endoplasmic reticulum-related BiP/GRP78 in interferon gamma-induced
persistent Chlamydia pneumoniae infection.
AB - Direct interaction of Chlamydiae with the endoplasmic reticulum (ER) is essential
in intracellular productive infection. However, little is known about the
interplay between Chlamydiae and the ER under cellular stress conditions that are
observed in interferon gamma (IFN-gamma) induced chlamydial persistent infection.
ER stress responses are centrally regulated by the unfolded protein response
(UPR) under the control of the ER chaperone BiP/GRP78 to maintain cellular
homeostasis. In this study, we could show that the ER directly contacted with
productive and IFN-gamma-induced persistent inclusions of Chlamydia pneumoniae
(Cpn). BiP/GRP78 induction was observed in the early phase but not in the late
phase of IFN-gamma-induced persistent infection. Enhanced BiP/GRP78 expression in
the early phase of IFN-gamma-induced persistent Cpn infection was accompanied by
phosphorylation of the eukaryotic initiation factor-2alpha (eIF2alpha) and down
regulation of the vesicle-associated membrane protein-associated protein B. Loss
of BiP/GRP78 function resulted in enhanced phosphorylation of eIF2alpha and
increased host cell apoptosis. In contrast, enhanced BiP/GRP78 expression in IFN
gamma-induced persistent Cpn infection attenuated phosphorylation of eIF2alpha
upon an exogenous ER stress inducer. In conclusion, ER-related BiP/GRP78 plays a
key role to restore cells from stress conditions that are observed in the early
phase of IFN-gamma-induced persistent infection.
PMID- 25588956
TI - Erratum to: The lipidome of the photosynthetic bacterium Rhodobacter sphaeroides
R26 is affected by cobalt and chromate ions stress.
PMID- 25588958
TI - Rapid, sensitive, and reusable detection of glucose by a robust radiofrequency
integrated passive device biosensor chip.
AB - Tremendous demands for sensitive and reliable label-free biosensors have
stimulated intensive research into developing miniaturized radiofrequency
resonators for a wide range of biomedical applications. Here, we report the
development of a robust, reusable radiofrequency resonator based integrated
passive device biosensor chip fabricated on a gallium arsenide substrate for the
detection of glucose in water-glucose solutions and sera. As a result of the
highly concentrated electromagnetic energy between the two divisions of an
intertwined spiral inductor coupled with an interdigital capacitor, the proposed
glucose biosensor chip exhibits linear detection ranges with high sensitivity at
center frequency. This biosensor, which has a sensitivity of up to 199 MHz/mgmL(
1) and a short response time of less than 2 sec, exhibited an ultralow detection
limit of 0.033 MUM and a reproducibility of 0.61% relative standard deviation. In
addition, the quantities derived from the measured S-parameters, such as the
propagation constant (gamma), impedance (Z), resistance (R), inductance (L),
conductance (G) and capacitance (C), enabled the effective multi-dimensional
detection of glucose.
PMID- 25588957
TI - The Photosystem II D1-K238E mutation enhances electrical current production using
cyanobacterial thylakoid membranes in a bio-photoelectrochemical cell.
AB - The conversion of solar energy (SEC) to storable chemical energy by
photosynthesis has been performed by photosynthetic organisms, including oxygenic
cyanobacteria for over 3 billion years. We have previously shown that crude
thylakoid membranes from the cyanobacterium Synechocytis sp. PCC 6803 can reduce
the electron transfer (ET) protein cytochrome c even in the presence of the PSII
inhibitor DCMU. Mutation of lysine 238 of the Photosystem II D1 protein to
glutamic acid increased the cytochrome reduction rates, indicating the possible
position of this unknown ET pathway. In this contribution, we show that D1-K238E
is rather unique, as other mutations to K238, or to other residues in the same
vicinity, are not as successful in cytochrome c reduction. This observation
indicates the sensitivity of ET reactions to minor changes. As the next step in
obtaining useful SEC from biological material, we describe the use of crude
Synechocystis membranes in a bio-photovoltaic cell containing an N-acetyl
cysteine-modified gold electrode. We show the production of significant current
for prolonged time durations, in the presence of DCMU. Surprisingly, the presence
of cytochrome c was not found to be necessary for ET to the bio-voltaic cell.
PMID- 25588959
TI - Prospective evaluation of early postoperative male and female sexual function
after radical prostatectomy with erectile nerves preservation.
AB - Prostate cancer screening has led to the diagnosis of localized prostate cancer
in increasingly young and sexually active men. Accordingly, the impact of cancer
treatment on sexual function is gaining more attention. To prospectively evaluate
the impact of radical prostatectomy (RP) on male, female and conjugal sexual
function. Patients were prospectively assessed by an urologist and a sexologist
before and 6 months after robot-assisted laparoscopic RP (RALP). RALP was
performed with uni- or bilateral neurovascular bundle preservation by a single
surgeon. Postoperatively, all patients were prescribed tadalafil 20 mg, 3 times a
week during 6 months. Male and female sexual functions were evaluated by using
the International Index of Erectile Function (IIEF-5), the Female Sexual Function
Index (FSFI) and the Lock-Wallace Marital Adjustment Test (MAT). Continuous
variables were analyzed with rank-sum and t-tests, as needed, and categorical
variables with chi-squared tests. All tests were two-sided, with a P-value ? 0.05
considered significant. Twenty-one couples were included. Mean patient male and
female age was 62.4 and 60.7 years, respectively. Bilateral nerve sparing was
performed in 12/21 (57%) patients. Median preoperative IIEF-5 was 20/25,
corresponding to mild erectile dysfunction (ED). Median preoperative FSFI and MAT
were both within normal range (28/36 and 114/158, respectively). Six months
following surgery, both IIEF-5 (11/25) and FSFI (25/36) had significantly dropped
(P=0.007 and 0.003, respectively). Postoperative decreases in IIEF-5 and FSFI
scores were associated within couples. MAT scores (115/158), however, remained
unaffected by RALP, showing an unmodified relationship satisfaction
postoperatively. Finally, bilateral nerve sparing surgery preserved not only male
but also female sexual function. This study shows that the expected short-term
post-RALP ED is associated with a worsening of female sexual function, whereas
nerve sparing surgery has a protective effect on both the patient's and his
partner's sexual function with a significant effect of bilateral over unilateral
neurovascular bundle preservation. Furthermore, we found that conjugal complicity
remains stable throughout the first semestrial postoperative period despite the
decrease in sexual function.
PMID- 25588960
TI - Molecular recognition in protein modification with rhodium metallopeptides.
AB - Chemical manipulation of natural, unengineered proteins is a daunting challenge
which tests the limits of reaction design. By combining transition-metal or other
catalysts with molecular recognition ideas, it is possible to achieve site
selective protein reactivity without the need for engineered recognition
sequences or reactive sites. Some recent examples in this area have used
ruthenium photocatalysis, pyridine organocatalysis, and rhodium(II)
metallocarbene catalysis, indicating that the fundamental ideas provide
opportunities for using diverse reactivity on complex protein substrates and in
complex cell-like environments.
PMID- 25588961
TI - Bio-inspired mechanistic insights into CO2 reduction.
AB - The global energy and environmental concerns related to the excess CO2
concentration in the atmosphere have intensified the research and development
regarding CO2 utilization. Due to the high stability and inertness of CO2, CO2
functionalization under mild conditions has been proven to be extremely
challenging. Nature has, however, evolved efficient pathways to achieve this
difficult transformation. Herein, we compare the mechanisms of CO2 two-electron
reduction followed by synthetic catalysts and those by carbon monoxide
dehydrogenase and formate dehydrogenase in order to provide more mechanistic
insights into future catalyst design.
PMID- 25588962
TI - Pre- to postsleep change in psychophysiological reactivity to emotional films:
Late-night REM sleep is associated with attenuated emotional processing.
AB - Rapid eye movement (REM) sleep has been postulated to facilitate emotional
processing of negative stimuli. However, empirical evidence is mixed and
primarily based on self-report data and picture-viewing studies. This study used
a full-length aversive film to elicit intense emotion on one evening, and an
emotionally neutral control film on another evening while psychophysiological and
experiential responses were measured. Subsequent sleep was monitored
polysomnographically, and specific film scenes were presented again on the next
morning. Correlation analyses revealed that participants with longer late-night
REM sleep after the aversive film showed higher increase of electrodermal
reactivity and less reduction of facial corrugator muscle reactivity to negative
film scenes on the next morning. This indicates that REM sleep may be associated
with attenuated emotional processing of prolonged and intense emotional stimuli
from pre- to postsleep.
PMID- 25588964
TI - Criminalization of pregnant women with substance use disorders.
PMID- 25588963
TI - Efficacy and safety of late-start Corifollitropin-alfa administration for
controlled ovarian hyperstimulation in IVF: a cohort, case-control study.
AB - OBJECTIVE: To investigate efficacy and safety of a controlled ovarian stimulation
(COS) protocol in which a single dose of Corifollitropin-alfa (CFalpha) was
administered on day 4 of a GnRH-antagonist cycle. DESIGN: Cohort case-control
study. SETTING: University Hospital. PATIENTS: One hundred twenty-two normally
cycling women expected to be normal responders to COS. INTERVENTIONS: In 61
patients, CFalpha (100-150 MUg) was injected subcutaneously on day 4 of a
spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed
protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant
FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control
group of 61 matched women was stimulated with daily subcutaneous injections of
rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25
mg/day) from day 8. IVF or ICSI was performed according to the sperm
characteristics, and 1-2 embryos were transferred in utero under US guidance on
day 2. MAIN OUTCOME MEASURES: Number of retrieved cumulus-oocyte complexes
(COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10
weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate.
RESULTS: No cycle was cancelled and the mean number of retrieved COCs was
comparable in patients and controls. About 60% of CF-alfa treated women had no
need of daily rFSH addition, and the mean number of injections/cycle was
significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing
PR/transfer was 36.8% in CF-alfa group and 37.5% in controls. No patient
developed severe OHSS, and the incidence of moderate OHSS was similar in cases
and controls. CONCLUSIONS: CFalpha may be started on day 4 of the cycle obtaining
results comparable to those of a COS using day 4-start daily rFSH, with
significantly less injections and a similar risk of OHSS.
PMID- 25588965
TI - Matrix metalloproteinases (MMP-1, MMP-2, MMP-3 and MMP-9, and TIMP-1, TIMP-2 and
TIMP-3) and markers for vascularization in functioning and non-functioning bleb
capsules of glaucoma drainage implants.
AB - PURPOSE: To investigate and compare functioning versus non-functioning glaucoma
drainage implant (GDI) capsules for selective markers of extracellular matrix
degradation and vascularity. METHODS: In three samples of both functioning and
non-functioning blebs, immunohistochemistry was used to determine the expression
of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3 and CD31. A non-functioning
bleb was defined as IOP >21 mmHg or <20% reduction in IOP from baseline with
maximal tolerated medication. The samples were classified into five grades based
on immunostaining: no staining, no significant staining, mild, moderate or marked
staining. RESULTS: Expression of MMP-1, MMP-2 and MMP-3 was mostly low in both
functioning and non-functioning blebs. However, immunostaining of MMP-9 was
marked in samples taken from functioning GDIs and correlated with the presence of
vascular profiles in the luminal bleb. CD31 immunoreactivity was more intense in
the outer layers of the bleb than in the inner layers. In non-functioning blebs,
immunoreactivity for TIMP-3 was significant through the whole bleb wall, but only
mild in the inner zone of functioning blebs. TIMP-1 and TIMP-2 were barely
detectable. CONCLUSION: Staining of TIMP-3 was seen to be lower in the vicinity
of the small blood vessels. In avascular bleb wall, increased expression of TIMP
3 suggests its potential role in the inhibition of angiogenesis as reported
previously in vivo. The abundance of MMP-9 in bleb capsule wall of relatively old
patients might lead to weakened bleb capsule wall architecture and increasing
filtration of aqueous humour through the capsule, which are reflected in a lower
IOP.
PMID- 25588966
TI - Effect of the number of presentations on listener transcriptions and reliability
in the assessment of speech intelligibility in children.
AB - BACKGROUND: The assessment of intelligibility is an essential part of
establishing the severity of a speech disorder. The intelligibility of a speaker
is affected by a number of different variables relating, inter alia, to the
speech material, the listener and the listener task. AIMS: To explore the impact
of the number of presentations of the utterances on assessments of
intelligibility based on orthographic transcription of spontaneous speech,
specifically the impact on intelligibility scores, reliability and intra-listener
variability. METHODS & PROCEDURES: Speech from 12 children (aged 4:6-8:3 years;
mean = 5:10 years) with percentage consonants correct (PCC) scores ranging from
49 to 81 was listened to by 18 students on the speech-language pathology (SLP)
programme and by two recent graduates from that programme. Three conditions were
examined during the transcription phase: (1) listening to each utterance once;
(2) listening to each utterance a second time; and (3) listening to all
utterances from a given child a third time after having heard all of its
utterances twice. OUTCOMES & RESULTS: Statistically significant differences
between intelligibility scores were found across the three conditions, i.e. the
intelligibility score increased with the number of presentations while inter
judge reliability was unchanged. The results differed markedly across listeners,
but each individual listener's results were very consistent across conditions.
CONCLUSIONS & IMPLICATIONS: Information about the number of times an utterance is
presented to the listener is important and should therefore always be included in
reports of research involving intelligibility assessment. There is a need for
further research and discussion on listener abilities and strategies.
PMID- 25588967
TI - Novel Potent and Selective Acetylcholinesterase Inhibitors as Potential Drugs for
the Treatment of Alzheimer's Disease: Synthesis, Pharmacological Evaluation, and
Molecular Modeling of Amino-Alkyl-Substituted Fluoro-Chalcones Derivatives.
AB - A new series of-fluoro chalcones-substituted amino-alkyl derivatives (3a~3l) were
designed, synthesized, characterized and evaluated for the inhibitory activity
against acetylcholinesterase and butyrylcholinesterase. The results showed that
the alteration of fluorine atom position and amino-alkyl groups markedly
influenced the activity and the selectivity of chalcone derivates in inhibiting
acetylcholinesterase and butyrylcholinesterase. Among them, compound 3l possesses
the most potent inhibitory against acetylcholinesterase (IC50 = 0.21 +/- 0.03
MUmol/L), and the highest selectivity for acetylcholinesterase over
butyrylcholinesterase (IC50 (BuChE)/IC50 (AChE) = 65.0). Molecular modeling and
enzyme kinetic study on compound 3l supported its dual acetylcholinesterase
inhibitory profile, simultaneously binding at the catalytic active and peripheral
anionic site of the enzyme.
PMID- 25588969
TI - PCR assay for pathogen detection in ventriculostomy-related meningitis in
neurosurgery patients: unanswered questions?
PMID- 25588968
TI - Antibiotic consumption after implementation of a procalcitonin-guided
antimicrobial stewardship programme in surgical patients admitted to an intensive
care unit: a retrospective before-and-after analysis.
AB - PURPOSE: To analyse antibiotic use density (AD)--World Health Organization
defined daily doses/1,000 patient-days--before and after implementation of a
local antimicrobial stewardship programme (ASP) in conjunction with a
procalcitonin (PCT)-guided protocol in a surgical intensive care unit (ICU).
METHODS: In this retrospective observational study, data on 2,422 ICU patients
between 2010 and 2012 were analysed. In 2011, an ASP in conjunction with a PCT
protocol had been introduced into clinical practice. In a multivariate analysis,
hospital mortality, length of stay (LOS) in hospital and ICU LOS were adjusted
for effects from effective cost weight, gender, and age. AD and changes in the
use of antibiotic classes were analysed. RESULTS: AD decreased from 1,005.0 in
2010 to 791.9 in 2012 which is a total reduction of 21.2%. Consumption of
aminoglycosides, cephalosporins and quinolones showed a marked reduction, whereas
the use of penicillins did not change significantly. The multivariate models
revealed no relevant changes in mortality rate, ICU LOS and hospital LOS.
CONCLUSIONS: Implementation of an ASP in conjunction with a PCT protocol in 2011
was associated with a marked decrease in total AD and led to a significant change
in the spectrum of antibiotics. Clinical outcomes appeared to remain unchanged
over the study period.
PMID- 25588972
TI - Successful management of refractory angiolymphoid hyperplasia with eosinophilia
with thalidomide.
PMID- 25588971
TI - Effects of total fibre or resistant starch-rich diets within lifestyle
intervention in obese prediabetic adults.
AB - PURPOSE: Starting from the evidence-based health benefits that resistant starch
(RS) shows when added to the diet, our aim in this study was to evaluate the
effects of increased fibre intake with two different levels of RS coming from
regular daily consumed foods on normalization of glycaemia within lifestyle
intervention in the population with risk factors for developing diabetes.
METHODS: Study included 47 overweight and obese men and women with disordered
glucoregulation and dyslipidaemia, aged between 45-74, divided into RS and Fibre
group. Participants were subjected to the lifestyle and dietary intervention with
low-fat and high-fibre (>25 g/day) diet for 12 months and were offered two
different dietary advices aimed at increasing total fibre intake in Fibre group
and at increasing RS intake in RS group. RESULTS: The intake of macronutrients
and total fibre was similar between groups at the end of the study, but achieved
RS intake was two times higher in the RS group. Decrease in total cholesterol and
non-HDL-cholesterol was more pronounced in RS group in comparison with Fibre
group (p = 0.010, p = 0.031, respectively), whereas in Fibre group, a more
pronounced effect on glucoregulation was observed: significant fall in glycaemia
after 2-h oral glucose tolerance test (7.93 vs 6.96 mmol/L, p = 0.034).
CONCLUSION: At the end of the study, RS-rich diet failed to affect glycaemic
control in prediabetic obese individuals in contrast to the regular fibre-rich
diet, which indicated that fibre profile could be an important determinant of the
effect of dietary intervention.
PMID- 25588973
TI - Health workers' experiences, barriers, preferences and motivating factors in
using mHealth forms in Ethiopia.
AB - BACKGROUND: Mobile health (mHealth) applications, such as innovative electronic
forms on smartphones, could potentially improve the performance of health care
workers and health systems in developing countries. However, contextual evidence
on health workers' barriers and motivating factors that may influence large-scale
implementation of such interfaces for health care delivery is scarce. METHODS: A
pretested semistructured questionnaire was used to assess health workers'
experiences, barriers, preferences, and motivating factors in using mobile health
forms on smartphones in the context of maternal health care in Ethiopia. Twenty
five health extension workers (HEWs) and midwives, working in 13 primary health
care facilities in Tigray region, Ethiopia, participated in this study. RESULTS:
Over a 6-month period, a total of 2,893 electronic health records of 1,122 women
were submitted to a central computer through the Internet. Sixteen (69.6%)
workers believed the forms were good reminders on what to do and what questions
needed to be asked. Twelve (52.2%) workers said electronic forms were
comprehensive and 9 (39.1%) workers saw electronic forms as learning tools. All
workers preferred unrestricted use of the smartphones and believed it helped them
adapt to the smartphones and electronic forms for work purposes. With regards to
language preference, 18 (78.3%) preferred using the local language (Tigrinya)
version of the forms to English. Indentified barriers for not using electronic
forms consistently include challenges related to electronic forms (for example,
problem with username and password setting as reported by 5 (21.7%), smartphones
(for example, smartphone froze or locked up as reported by 9 (39.1%) and health
system (for example, frequent movement of health workers as reported by 19
(82.6%)). CONCLUSIONS: Both HEWs and midwives found the electronic forms on
smartphones useful for their day-to-day maternal health care services delivery.
However, sustainable use and implementation of such work tools at scale would be
daunting without providing technical support to health workers, securing mobile
network airtime and improving key functions of the larger health system.
PMID- 25588974
TI - Optic Neuritis and the Visual Pathway: Evaluation of Neuromyelitis Optica
Spectrum by Resting-State fMRI and Diffusion Tensor MRI.
AB - BACKGROUND AND PURPOSE: Optic neuritis (ON) is an acute episode of inflammation
in the visual pathway (VP). It may occur as part of a demyelinating disease,
which can affect white matter (WM) throughout the VP. Compensatory cortical
adaptations may occur following WM damage to maintain visual integrity. Our aim
was to investigate whether resting-state functional MRI (rsfMRI) can detect
cortical adaptations following ON attacks and to correlate rsfMRI with diffusion
tensor imaging (DTI) of WM within the VP. MATERIALS AND METHODS: Neuromyelitis
optica spectrum patients were compared to healthy controls at least 6 months
after ON onset. DTI and rsfMRI were performed and post-processed using FSL tools
(TBSS for DTI and MELODIC for fMRI). RESULTS: Ptients had higher synchronization
values than controls in the visual network (3.48 vs. 2.12, P < .05). A weak trend
of correlation was revealed between fMRI and structural analysis by DTI using
fractional anisotropy (right side: R = -.36, P < .08; left side: R = .075, P <
.73). CONCLUSIONS: The rsfMRI detected cortical reorganization following ON
attack, but WM was considerably preserved in the posterior VP.
PMID- 25588976
TI - Doctors are sceptical about Indian Medical Association's new code of conduct for
hospitals.
PMID- 25588977
TI - ERRATUM: A reduction in reactive oxygen species contributes to dihydromyricetin
induced apoptosis in human hepatocellular carcinoma cells.
PMID- 25588978
TI - Lead and cadmium in raw buffalo, cow and ewe milk from west Azerbaijan, Iran.
AB - In this study, 300 raw buffalo, cow and ewe milk samples from five townships in
west Azerbaijan, Iran, were analysed. Lead and cadmium were determined using
atomic absorption spectrophotometry. Mean concentration of lead and cadmium in
buffalo milk samples was 0.018 +/- 0.001 and 0.003 +/- 0.001 mg/kg, respectively.
Mean concentration of lead and cadmium in cow milk samples was 0.007 +/- 0.001
and 0.001 +/- 0.001 mg/kg, respectively, and in ewe milk, these mean values were
0.010 +/- 0.001 and 0.002 +/- 0.001 mg/kg, respectively. Statistical analyses
showed that lead and cadmium concentrations in buffalo milk were significantly
higher than those in cow and ewe milk. Moreover, the concentration of these heavy
metals in ewe milk was significantly higher than that in cow milk. It was also
found that concentration of these selected toxic metals in milk increased with
increasing age of the animals.
PMID- 25588975
TI - Regulation of vascular tone and arterial blood pressure: role of chloride
transport in vascular smooth muscle.
AB - Recent studies suggest that primary changes in vascular resistance can cause
sustained changes in arterial blood pressure. In this review, we summarize
current knowledge about Cl(-) homeostasis in vascular smooth muscle cells. Within
vascular smooth muscle cells, Cl(-) is accumulated above the electrochemical
equilibrium, causing Cl(-) efflux, membrane depolarization, and increased
contractile force when Cl(-) channels are opened. At least two different
transport mechanisms contribute to raise [Cl(-)] i in vascular smooth muscle
cells, anion exchange, and cation-chloride cotransport. Recent work suggests that
TMEM16A-associated Ca(2+)-activated Cl(-) currents mediate Cl(-) efflux in
vascular smooth muscle cells leading to vasoconstriction. Additional proteins
associated with Cl(-) flux in vascular smooth muscle are bestrophins, which
modulate vasomotion, the volume-activated LRRC8, and the cystic fibrosis
transmembrane conductance regulator (CFTR). Cl(-) transporters and Cl(-) channels
in vascular smooth muscle cells (VSMCs) significantly contribute to the
physiological regulation of vascular tone and arterial blood pressure.
PMID- 25588979
TI - Dynamics of Radical Ion Pairs following Photoinduced Electron Transfer in
Solvents with Low and Intermediate Polarities.
AB - Fluorescence quenching of p-xylene, naphthalene, or pyrene by fumaronitrile in
apolar solvents and in solvents of intermediate polarities leads to weakly
fluorescent radical ion pairs. This emission is assigned to ion pairs in close
contact on the basis of their solvent polarity dependence, kinetics, and
thermodynamics. The temperature-dependence of the intensity and fluorescence
emission maxima of ion pairs in methyl acetate reveals that they have decay
channels competitive with their thermal equilibration. The results presented in
this work are consistent with the direct formation of contact ion pairs in weakly
polar solvents and in solvents of intermediate polarities as the result of
bimolecular photoinduced electron transfer reactions between aromatic
hydrocarbons and nitriles. The implications of these findings in free-energy
relationships of electron transfer reactions are discussed.
PMID- 25588980
TI - Inhibition of MiR-199a-5p reduced cell proliferation in autosomal dominant
polycystic kidney disease through targeting CDKN1C.
AB - BACKGROUND: With a prevalence of about 1:500 to 1:1,000, autosomal dominant
polycystic kidney disease (ADPKD) often causes renal failure, with many serious
complications. However, there is no Food and Drug Administration (FDA) approved
therapy available. MATERIAL/METHODS: MiR-199a-5p level in ADPKD patient samples,
rat model, and cell lines were determined with Realtime PCR assay. After miR-199a
5p inhibitor was transfected, we detected the cell proliferation and apoptosis
using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally,
TargetScan version 5.1 was used to predict the miRNA target and the target gene
of miR-199a-5p was proved by a Luciferase assay. RESULTS: We identified a
dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines.
Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation
and induced cell apoptosis. We found that miR-199a-5p might exert this effect
through targeting CDKN1C/p57. CONCLUSIONS: Up-regulation of miR-199a-5p in ADPKD
tissues might promote cell proliferation through suppressing CDKN1C, suggesting
miR-199a-5p as a novel target for ADPKD treatment.
PMID- 25588981
TI - Radiologic assessment of glenohumeral relationship: reliability and
reproducibility of lateral humeral offset.
AB - BACKGROUND: It has been shown that anatomical reconstruction is an important step
in achieving good function after shoulder arthroplasty. It is essential to
reconstruct the distance between the coracoid process and greater tubercle as
this relates to the moment arm of the deltoid and rotator cuff muscles. This
study evaluated the reliability of measurement of the lateral humeral offset
(LHO) on plain radiographs and on computed tomography (CT). METHODS: Four
independent observers performed measurements of LHO on radiographs and CT from 26
patients awaiting shoulder reconstruction. The interobserver reliability and
intraobserver reproducibility were assessed. RESULTS: Interobserver reliability
and intraobserver reproducibility of LHO in axial CT scans were excellent. Plain
radiography showed fair to excellent interobserver reliability and variable
intraobserver reproducibility. CONCLUSION: CT is a reliable tool to measure LHO
supporting its use in preoperative planning. When AP radiography is used for
preoperative planning the examiner should be aware of its limitations and
standardisation protocols should be considered.
PMID- 25588982
TI - Molecular characterization of a defensin gene from a hard tick, Dermacentor
silvarum.
AB - BACKGROUND: Ticks are distributed worldwide and considered as vectors of many
human diseases. Tick defensins, a family of antimicrobial peptides, form the
first line of defense against pathogens. FINDINGS: A defensin-like gene, named Ds
defensin, was identified from a cDNA library of the hard tick Dermacentor
silvarum collected from northeast China. The full-length cDNA of Ds-defensin was
225 bp, encoding a 74 amino acid peptide. The nucleotide sequence of Ds-defensin
shared 98.2% similarity to putative defensin from Dermacentor marginatus. RT-PCR
results suggested that Ds-defensin was extensively expressed in tick salivary
gland and midgut, with a higher expression level in midgut. Ds-defensin showed
broad antimicrobial activity against various Gram-positive and Gram-negative
bacteria, as well as the fungus Candida albicans. CONCLUSIONS: We characterized a
functional defensin from D. silvarum of China. Ds-defensin showed bactericidal
activity against various Gram-positive and Gram-negative bacteria. Ds-defensin
can be expected to be introduced to the medical field as a new molecule with
antibacterial activity.
PMID- 25588983
TI - External validation of the HIT Expert Probability (HEP) score.
AB - The diagnosis of heparin-induced thrombocytopenia (HIT) can be challenging. The
HIT Expert Probability (HEP) Score has recently been proposed to aid in the
diagnosis of HIT. We sought to externally and prospectively validate the HEP
score. We prospectively assessed pre-test probability of HIT for 51 consecutive
patients referred to our Consultative Service for evaluation of possible HIT
between August 1, 2012 and February 1, 2013. Two Vascular Medicine fellows
independently applied the 4T and HEP scores for each patient. Two independent HIT
expert adjudicators rendered a diagnosis of HIT likely or unlikely. The median
(interquartile range) of 4T and HEP scores were 4.5 (3.0, 6.0) and 5 (3.0, 8.5),
respectively. There were no significant differences between area under receiver
operating characteristic curves of 4T and HEP scores against the gold standard,
confirmed HIT [defined as positive serotonin release assay and positive anti
PF4/heparin ELISA] (0.74 vs 0.73, p = 0.97). HEP score >= 2 was 100 % sensitive
and 16 % specific for determining the presence of confirmed HIT while a 4T score
> 3 was 93 % sensitive and 35 % specific. In conclusion, the HEP and 4T scores
are excellent screening pre-test probability models for HIT, however, in this
prospective validation study, test characteristics for the diagnosis of HIT based
on confirmatory laboratory testing and expert opinion are similar. Given the
complexity of the HEP scoring model compared to that of the 4T score, further
validation of the HEP score is warranted prior to widespread clinical acceptance.
PMID- 25588984
TI - Expression of basolateral organic anion and cation transporters in experimental
cadmium nephrotoxicity in rat kidney.
AB - Cadmium (Cd)-intoxicated experimental animals exhibit impaired renal secretion of
organic anions (OA) and cations (OC), indicating their transporters (Oats and
Octs) in the proximal tubule (PT) basolateral membrane as possible targets of Cd.
To correlate transport data from the literature with the expression of relevant
transporters, we performed immunochemical and RT-PCR studies of renal Oats and
Octs in the subchronic (treatment with CdCl2; 2 mg Cd/kg b.m./day, for 2 weeks)
and acute (treatment with Cd-metallothionein (CdMT); 0.4 mg Cd/kg b.m., 6 or 12 h
before killing) models of Cd nephrotoxicity. In the subchronic model, PT
exhibited a minor loss of basolateral invaginations and overall unchanged
expression of Na(+)/K(+)-ATPase and GAPDH proteins and mRNAs, while the
expression of Oat and Oct proteins and their mRNAs was strongly downregulated. In
the acute model, a time-related redistribution of basolateral transporters to the
intracellular vesicular compartment was a major finding. However, 6 h following
CdMT treatment, the total abundance of Oat and Oct proteins in the renal tissue
remained unchanged, the expression of mRNAs decreased only for Oats, while a
limited Oat1 and Na(+)/K(+)-ATPase immunoreactivity in the PT apical membrane
indicated loss of cell polarity. As tested in rats treated with colchicine, the
observed loss/redistribution of basolateral transporters in both models may be
independent on microtubules. Therefore, the diminished renal secretion of OA and
OC via PT in Cd nephrotoxicity may result from (a) limited loss of secretory
surface (basolateral invaginations), (b) selective loss of Oats and Octs, and
PMID- 25588986
TI - A bright future for Hormones and Cancer: farewell comments of Dr. Carol A. Lange,
recent past Editor-in-Chief.
PMID- 25588985
TI - Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture
effects in rats.
AB - Humans are simultaneously exposed to several chemicals that act jointly to induce
mixture effects. At doses close to or higher than no-observed adverse effect
levels, chemicals usually act additively in experimental studies. However, we are
lacking knowledge on the importance of exposure to complex real-world mixtures at
more relevant human exposure levels. We hypothesised that adverse mixture effects
occur at doses approaching high-end human exposure levels. A mixture (Mix) of 14
chemicals at a combined dose of 2.5 mg/kg bw/day was tested in combination with
perfluorononanoic acid (PFNA) at doses of 0.0125 (Low PFNA), 0.25 (Mid PFNA) and
5 (High PFNA) mg/kg bw/day by oral administration for 14 days in juvenile male
rats. Indication of a toxicokinetic interaction was found, as simultaneous
exposure to PFNA and the Mix caused a 2.8-fold increase in plasma PFNA
concentrations at Low PFNA. An increase in testosterone and dihydrotestosterone
plasma concentrations was observed for Low PFNA + Mix. This effect was considered
non-monotonic, as higher doses did not cause this effect. Reduced LH plasma
concentrations together with increased androgen concentrations indicate a
disturbed pituitary-testis axis caused by the 15-chemical mixture. Low PFNA by
itself increased the corticosterone plasma concentration, an effect which was
normalised after simultaneous exposure to Mix. This combined with affected ACTH
plasma concentrations and down-regulation of 11beta HSD mRNA in livers indicates
a disturbed pituitary-adrenal axis. In conclusion, our data suggest that mixtures
of environmental chemicals at doses approaching high-end human exposure levels
can cause a hormonal imbalance and disturb steroid hormones and their regulation.
These effects may be non-monotonic and were observed at low doses. Whether this
reflects a more general phenomenon that should be taken into consideration when
predicting human mixture effects or represents a rarer phenomenon remains to be
shown.
PMID- 25588987
TI - Influence of the beta-sheet content on the mechanical properties of aggregates
during amyloid fibrillization.
AB - Amyloid fibrils associated with neurodegenerative diseases, such as Parkinson's
and Alzheimer's, consist of insoluble aggregates of alpha-synuclein and Abeta-42
proteins with a high beta-sheet content. The aggregation of both proteins occurs
by misfolding of the monomers and proceeds through the formation of intermediate
oligomeric and protofibrillar species to give the final fibrillar cross-beta
sheet structure. The morphological and mechanical properties of oligomers,
protofibrils, and fibrils formed during the fibrillization process were
investigated by thioflavin T fluorescence and circular dichroism in combination
with AFM peak force quantitative nanomechanical technique. The results reveal an
increase in the Young's modulus during the transformation from oligomers to
mature fibrils, thus inferring that the difference in their mechanical properties
is due to an internal structural change from a random coil to a structure with
increased beta-sheet content.
PMID- 25588988
TI - Breadfruit (Artocarpus altilis): a source of high-quality protein for food
security and novel food products.
AB - Protein deficiency has been observed as a leading cause of malnutrition and child
death in the tropics. The current study evaluated the protein quality of 49
important breadfruit cultivars (41 Artocarpus altilis and 8 hybrids of A. altilis
* A. mariannensis). While significant differences were found between cultivars,
all varieties contained a full spectrum of the essential amino acids and are
especially rich in phenylalanine, leucine, isoleucine, and valine. The cultivar
Ma'afala contained significantly higher total essential amino acid content than
other varieties and higher-quality protein than staples such as corn, wheat,
rice, soybean, potato, and pea.
PMID- 25588989
TI - Use of medication algorithms in first episode psychosis: a naturalistic
observational study.
AB - AIMS: Medical algorithms are evidence-based guidelines which help physicians to
make their decisions regarding treatment. Non-adherence to medical algorithms is
a matter of concern. The aims of this study were to investigate physicians'
adherence to an algorithm for antipsychotics, patients' adherence to the
physicians' recommendations and whether these factors influence one year outcome.
METHOD: An extensive file audit survey was conducted among 55 consecutively first
admitted inpatients and outpatients from three units of a university hospital;
looking at the prescription of antipsychotics to patients (15-65 years)
experiencing first episode psychosis (F19.5, F20.0-F29.0 according to ICD-10).
Inclusion period was 2 years. Data on clinical condition and use of drugs were
collected from the electronic patient administrative record system and from each
patient's medical record for 12 months. RESULTS: Only 62% of the physicians
adhered to the medical algorithm, although all first choices of drugs were made
according to international standards. Fifty-six percent of patients used their
medicine more than 75% of the time, 22% had between 26% and 74% adherence and 22%
adhered less than 25%. Patient adherence was significantly associated with good
outcome. Older patients and inpatients had more favourable outcomes than younger
patients and outpatients. Physicians at inpatient wards initiated pharmacological
treatment significantly earlier than physicians in outpatient departments. The
most common first antipsychotic drug to prescribe was olanzapine followed by
risperidone. CONCLUSION: Initial medical intervention followed international
standards, but the physicians failed to adhere to algorithms in their follow-up
of medication regimes. Adherence was associated with outcome.
PMID- 25588991
TI - The ligand field of the azido ligand: insights into bonding parameters and
magnetic anisotropy in a Co(II)-azido complex.
AB - The azido ligand is one of the most investigated ligands in magnetochemistry.
Despite its importance, not much is known about the ligand field of the azido
ligand and its influence on magnetic anisotropy. Here we present the electronic
structure of a novel five-coordinate Co(II)-azido complex (1), which has been
characterized experimentally (magnetically and by electronic d-d absorption
spectroscopy) and theoretically (by means of multireference electronic structure
methods). Static and dynamic magnetic data on 1 have been collected, and the
latter demonstrate slow relaxation of the magnetization in an applied external
magnetic field of H = 3000 Oe. The zero-field splitting parameters deduced from
static susceptibility and magnetizations (D = -10.7 cm(-1), E/D = 0.22) are in
excellent agreement with the value of D inferred from an Arrhenius plot of the
magnetic relaxation time versus the temperature. Application of the so-called N
electron valence second-order perturbation theory (NEVPT2) resulted in excellent
agreement between experimental and computed energies of low-lying d-d
transitions. Calculations were performed on 1 and a related four-coordinate
Co(II)-azido complex lacking a fifth axial ligand (2). On the basis of these
results and contrary to previous suggestions, the N3(-) ligand is shown to behave
as a strong sigma and pi donor. Magnetostructural correlations show a strong
increase in the negative D with increasing Lewis basicity (shortening of the Co-N
bond distances) of the axial ligand on the N3(-) site. The effect on the change
in sign of D in going from four-coordinate Co(II) (positive D) to five-coordinate
Co(II) (negative D) is discussed in the light of the bonding scheme derived from
ligand field analysis of the ab initio results.
PMID- 25588997
TI - Theranostic mercury: (197(m))Hg with high specific activity for imaging and
therapy.
AB - The no carrier added (NCA) radionuclide (197(m))Hg is accessible through proton
induced nuclear reactions on gold. The decay properties of both simultaneous
produced nuclear isomers (197m)Hg and (197)Hg like convenient half life, low
energy gamma radiations for imaging, Auger and conversion electrons for therapy
are combined with unique chemical and physical properties of mercury and its
compounds. Gold as a monoisotopic element has a natural abundance of 100% (197)Au
superseding expensive enrichment for the target material. Additionally, the high
thermal conductivity of gold enables high beam current irradiations. For
separation of target material a liquid-liquid extraction method was applied.
PMID- 25588998
TI - Relationships between dipole moments of diatomic molecules.
AB - The dipole moment is one of the most important physical properties of a molecule.
We present a combination rule for the dipole moments of related diatomic
molecules. For molecules AB, AX, BY, and XY from two different element groups in
the periodic table, if their elements make a small parallelogram, reliable
predictions can be obtained. Our approach is particularly useful for systems with
heavy atoms. For a large set of molecules tested, the average difference of the
prediction from experimental data is less than 0.2 debye (D). The dipole moments
for heavy molecules such as GaCl, InBr, SrCl, and SrS, for which no experimental
data are available at present, are predicted to be 3.17, 3.76, 3.85 and 11.54 D,
respectively.
PMID- 25588992
TI - Increased locomotor and thermogenic activity in mice with targeted ablation of
the GHRH gene.
AB - OBJECTIVE: Growth hormone (GH) 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 examine
the factors that contribute to energy imbalance in the GH releasing hormone knock
out (GHRHKO) mice, a well established model of GHD. DESIGN: We evaluated food
intake (of standard laboratory chow), total body weight (TBW), locomotor
activity, body temperature and interscapular brown adipose tissue (BAT) weight in
8 adult male mice homozygous for the GHRHKO allele (-/-) and 8 heterozygous (+/-)
animals as controls. The gene expression of uncoupling protein-1 (UCP-1) in BAT
and the levels of norepinephrine (NE), dopamine (DA), and serotonin (5
hydroxytryptamine, 5-HT) in the ventral striatum were measured by real-time
reverse transcription polymerase chain reaction (RT-PCR) and high performance
liquid chromatography (HPLC) analysis, respectively. RESULTS: Throughout 2 months
of observation -/- mice consumed approximately 40% more food (normalized to TBW;
P<0.001), and showed increased locomotor activity in 24h time compared to
controls (P<0.05). Moreover, -/- animals showed increased body temperature
(P<0.001), BAT weight (P<0.001), and UCP-1 gene expression (P<0.001), while NE
levels in the striatum area were lower (P<0.05) than controls. CONCLUSIONS: The
present study demonstrates that the increased food intake observed in GHRH
ablated animals is associated with increased locomotor and thermogenic activity.
PMID- 25588999
TI - Promoting Ecohealth through Geography and Governmental Partnerships.
PMID- 25588990
TI - Disruption of SUMO-targeted ubiquitin ligases Slx5-Slx8/RNF4 alters RecQ-like
helicase Sgs1/BLM localization in yeast and human cells.
AB - RecQ-like helicases are a highly conserved protein family that functions during
DNA repair and, when mutated in humans, is associated with cancer and/or
premature aging syndromes. The budding yeast RecQ-like helicase Sgs1 has
important functions in double-strand break (DSB) repair of exogenously induced
breaks, as well as those that arise endogenously, for example during DNA
replication. To further investigate Sgs1's regulation, we analyzed the
subcellular localization of a fluorescent fusion of Sgs1 upon DNA damage.
Consistent with a role in DSB repair, Sgs1 recruitment into nuclear foci in
asynchronous cultures increases after ionizing radiation (IR) and after exposure
to the alkylating agent methyl methanesulfonate (MMS). Yet, despite the
importance of Sgs1 in replicative damage repair and in contrast to its elevated
protein levels during S-phase, we find that the number of Sgs1 foci decreases
upon nucleotide pool depletion by hydroxyurea (HU) treatment and that this
negative regulation depends on the intra S-phase checkpoint kinase Mec1.
Importantly, we identify the SUMO-targeted ubiquitin ligase (STUbL) complex Slx5
Slx8 as a negative regulator of Sgs1 foci, both spontaneously and upon
replicative damage. Slx5-Slx8 regulation of Sgs1 foci is likely conserved in
eukaryotes, since expression of the mammalian Slx5-Slx8 functional homologue,
RNF4, restores Sgs1 focus number in slx8 cells and furthermore, knockdown of RNF4
leads to more BLM foci in U-2 OS cells. Our results point to a model where RecQ
like helicase subcellular localization is regulated by STUbLs in response to DNA
damage, presumably to prevent illegitimate recombination events.
PMID- 25589000
TI - Age at Vaccination May Influence Response to Sylvatic Plague Vaccine (SPV) in
Gunnison's Prairie Dogs (Cynomys gunnisoni).
AB - Gunnison's prairie dogs (Cynomys gunnisoni) have been considered at greater risk
from Yersinia pestis (plague) infection in the montane portion of their range
compared to populations at lower elevations, possibly due to factors related to
flea transmission of the bacteria or greater host susceptibility. To test the
latter hypothesis and determine whether vaccination against plague with an oral
sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a
C. g. gunnisoni or "montane" population and a C. g. zuniensis or "prairie"
population for vaccine efficacy and challenge studies. No differences (P = 0.63)
were found in plague susceptibility in non-vaccinated animals between these two
populations; however, vaccinates from the prairie population survived plague
challenge at significantly higher rates (P < 0.01) than those from the montane
population. Upon further analysis, we determined that response to immunization
was most likely associated with differences in age, as the prairie group was much
younger on average than the montane group. Vaccinates that were juveniles or
young adults survived plague challenge at a much higher rate than adults (P <
0.01 and P = 0.02, respectively), but no difference (P = 0.83) was detected in
survival rates between control animals of different ages. These results suggest
that host susceptibility is probably not related to the assumed greater risk from
plague in the C. g. gunnisoni or "montane" populations of Gunnison's prairie
dogs, and that SPV could be a useful plague management tool for this species,
particularly if targeted at younger cohorts.
PMID- 25589002
TI - Second Morning ACR Could Be the Alternative to First Morning ACR to Assess
Albuminuria in Elderly Population.
AB - BACKGROUND: Albumin/creatinine ratio (ACR) from a first morning urine is
recommended as a early indicator for diabetic nephropathy. However, it is not
always feasible to collect the first morning urine for outpatients. We aimed to
explore whether ACR from a second morning urine had a good consistency with that
from a first morning urine to predict albuminuria in Chinese elderly citizens.
METHOD: One hundred and ninety-one elderly citizens (?60 years old) from
Junliangcheng community, Dongli district, Tianjin, China were included. A first
and second morning urine was collected from each participants, successfully and
detected the urinary albumin and creatinine of each urine sample. Albumin to
creatinine ratio from a first morning urine (ACR1) was compared with that from a
second morning urine (ACR2), and the ability of ACR1 and ACR2 to predict
albuminuria was assessed. RESULT: ACR1 and ACR2 were highly correlated (r =
0.901), especially in male and hypertension group (r = 0.938 and 0.904). The
slope and intercept were 0.93 and 0.11 after log-transformed. And there was no
statistical difference between values of ACR1 and ACR2 (P = 0.271). Overall,
26.2% participants were detected with albuminuria when judged by ACR1 and 28.3%
by ACR2. A good concordance of ACR category (normal or albuminuria) was found
between ACR1 and ACR2 (Kappa value = 0.815 in overall; in male and hypertension
group were 0.900 and 0.850). CONCLUSION: A second morning urine ACR could be the
alternative to a first morning urine ACR for albuminuria detection in elderly
population.
PMID- 25589001
TI - Body weight and risk of atrial fibrillation in 7,169 patients with newly
diagnosed type 2 diabetes; an observational study.
AB - BACKGROUND: Obesity, type 2 diabetes and atrial fibrillation (AF) are closely
associated, but the underlying mechanisms are not fully understood. We aimed to
explore associations between body mass index (BMI) or weight change with risk of
AF in patients with type 2 diabetes. METHODS: A total of 7,169 participations
with newly diagnosed type 2 diabetes were stratified according to baseline BMI,
and after a second BMI measurement within 18 months, further grouped according to
relative weight change as "weight gain" (>1 BMI unit), "stable weight" (+/- 1 BMI
unit) and "weight loss" (<1 BMI unit). The mean follow-up period was 4.6 years,
and the risk of AF was estimated using adjusted Cox regression models. RESULTS:
Average age at diabetes diagnosis was 60 years and the patients were slightly
obese (mean BMI 30.2 kg/m(2)). During follow-up, 287 patients developed incident
AF, and those with overweight or obesity at baseline had 1.9-fold and 2.9-fold
higher risk of AF, respectively, than those with normal BMI. The 14% of the
patients with subsequent weight gain had 1.5-fold risk of AF compared with those
with stable weight or weight loss. CONCLUSIONS: In patients with newly diagnosed
type 2 diabetes, baseline overweight and obesity, as well as modest weight
increase during the first 18 months after diagnosis, were associated with a
substantially increased risk of incident AF. Patients with type 2 diabetes may
benefit from efforts to prevent weight gain in order to reduce the risk of
incident AF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01121315.
PMID- 25589003
TI - Sporadic hemangioblastomas are characterized by cryptic VHL inactivation.
AB - Hemangioblastomas consist of 10-20% neoplastic "stromal" cells within a vascular
tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial
cases of central nervous system hemangioblastoma uniformly result from mutations
in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been
previously observed in only a minority of sporadic hemangioblastomas, suggesting
an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32
sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n =
22), followed by analysis of clonality, copy number alteration, and somatic
mutation. We identified somatic mutation, loss of heterozygosity and/or deletion
of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were
ultimately detected in 78% (25/32) of cases. No other gene was significantly
mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL
alterations within the neoplastic fraction of these tumors at higher frequencies
than previously reported. Our findings support the central role of VHL
inactivation in the molecular pathogenesis of both familial and sporadic
hemangioblastomas.
PMID- 25589004
TI - Clinicopathological and Prognostic Significance of CD133 in Glioma Patients: A
Meta-Analysis.
AB - In recent years, CD133 has been identified as a cancer stem cell (CSC) marker in
gliomas. Nevertheless, the clinical and prognostic value of CD133 in glioma
patients remains controversial. Therefore, we conducted a systematic meta
analysis to evaluate the correlation of CD133 with World Health Organization
(WHO) grade, age, gender, overall survival (OS), and progression-free survival
(PFS) in glioma patients. Eligible studies on this subject were included, and
then pooled odd ratios (ORs) and hazard ratios (HRs) with 95 % confidence
intervals (95 % CIs) were estimated. Publication bias was assessed by the funnel
plots, and heterogeneity and sensitivity were analyzed as well. In the present
study, 21 articles with the total number of 1535 patients were included. High
expression of CD133 in glioma patients was associated with high WHO grade (III +
IV) (n = 11, OR 5.10, 95 % CI 2.99-8.69; p = 0.000), rather than age (n = 4, OR
2.54, 95 % CI 0.68-9.52; p = 0.167) and gender (n = 4, OR 0.71, 95 % CI 0.21
2.45; p = 0.587). In addition, survival analysis demonstrated a significant
association between CD133 high expression and poor 2-year OS (n = 11, HR 2.18, 95
% CI 1.29-3.7; p = 0.004), 5-year OS (n = 4, HR 10.39, 95 % CI 2.59-41.63; p =
0.001), as well as PFS (n = 10, HR 2.34, 95 % CI 1.62-3.37; p = 0.000). Taken
together, this study suggests that CD133 expression correlates to higher grade of
gliomas and worse prognosis in glioma patients. Thus, CD133 could be recommended
as a useful pathological and prognostic biomarker in clinical practice.
PMID- 25589006
TI - [The hospital emergency plan].
AB - STRUCTURE: The hospital emergency plan consists of a basic plan and an appendix.
The basic plan deals with the general aspects of emergency operation and the
special aspects of external and internal emergencies. The appendix contains
special instructions, e.g., emergency action orders, staff alert lists, material
lists, and situation plans. CONTENT AND IMPLEMENTATION: External emergencies
(e.g., mass casualty incidents) and internal emergencies (e.g., fire and other
environmental threats) should be regarded. Once a defined experienced physician
decides to activate the emergency plan, the hospital changes from routine to
emergency service. Due to its security significance, the emergency plan should be
regarded as confidential. MANDATORY REQUIREMENTS: A two-tier chain of command is
implemented: the hospital staff deals with administrational and organizational
aspects, whereas the subsequent medical staff is in charge of immediate patient
care. Repeated updating and exercises are necessary. Furthermore, a basic
logistic autonomy of the hospital is essential.
PMID- 25589007
TI - Practical synthesis of anti-beta-hydroxy-alpha-amino acids by Pd(II) -catalyzed
sequential C(sp(3) )-H functionalization.
AB - An improved and practical procedure for the stereoselective synthesis of anti
beta-hydroxy-alpha-amino acids (anti-betahAAs), by palladium-catalyzed sequential
C(sp(3) )-H functionalization directed by 8-aminoquinoline auxiliary, is
described. followed by a previously established monoarylation and/or alkylation
of the beta-methyl C(sp(3) )-H of alanine derivative, beta-acetoxylation of both
alkylic and benzylic methylene C(sp(3) )-H bonds affords various anti-beta
hydroxy-alpha-amino acid derivatives. As an example, the synthesis of beta
mercapto-alpha-amino acids, which are highly important to the extension of native
chemical ligation chemistry beyond cysteine, is described. The synthetic
potential of this protocol is further demonstrated by the synthesis of diverse
beta-branched alpha-amino acids. The observed diastereoselectivities are strongly
influenced by electronic effects of aromatic AAs and steric effects of the linear
side-chain AAs, which could be explained by the competition of intramolecular C
OAc bond reductive elimination from Pd(IV) intermediates vs. intermolecular
attack by an external nucleophile (AcO(-) ) in an SN 2-type process.
PMID- 25589005
TI - Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A
Receptors.
AB - Exposure to UV radiation is the principal cause of nonmelanoma skin cancer, a
process in which serotonin (5-HT) is intimately involved. This review focuses on
the potential of serotonin receptors, namely 5-HT1/2A, as therapeutic targets for
prevention of photocarcinogenesis. UV-induced immunosuppression is triggered by a
cascade of events initiated when cis-urocanic acid, a UV photoreceptor present in
the skin, binds to the serotonin receptor. Serotonin receptor antagonists will
therefore attempt to block this association, and in turn, prevent skin cancer
induction. In addition, 5-HT2A receptor antagonists are also capable of
regulating DNA repair, including the acceleration of nucleotide excision repair.
At the same time, UV-induced formation of reactive oxygen species is also reduced
by these agents. Since the involvement of serotonin in photocarcinogenesis
process is somewhat underexplored as a pertinent therapeutic effect, this review
intends to reveal the use of serotonergic drugs as an important strategy to
prevent and/or inhibit photocarcinogenesis. Considering the emergency of
developing novel therapeutic strategies for skin cancer management, the use of
these agents, whose benefits have partially been studied, may be crucial
especially if topically applied. Topical nanoformulations containing serotonin
receptor agonists and/or antagonists also represent a pioneer concept in this
area. Graphical Abstract ?.
PMID- 25589008
TI - Fungistatic activity of Zanthoxylum rhoifolium Lam. bark extracts against fungal
plant pathogens and investigation on mechanism of action in Botrytis cinerea.
AB - Plant-derived compounds are emerging as an alternative choice to synthetic
fungicides. Chloroform-methanol extract, obtained from the bark of Zanthoxylum
rhoifolium, a member of Rutaceae, showed a fungistatic effect on Botrytis
cinerea, Sclerotinia sclerotiorum, Alternaria alternata, Colletotrichum
gloeosporioides and Clonostachys rosea, when added to the growth medium at
different concentrations. A fraction obtained by gel separation and containing
the alkaloid O-Methylcapaurine showed significant fungistatic effect against B.
cinerea and S. sclerotiorum, two of the most destructive phytopathogenic fungi.
The underlying mechanism of such an inhibition was further investigated in B.
cinerea, a fungus highly prone to develop fungicide resistance, by analysing the
expression levels of a set of genes (BcatrB, P450, CYP51 and TOR). O
Methylcapaurine inhibited the expression of all the analysed genes. In
particular, the expression of BcatrB gene, encoding a membrane drug transporter
involved in the resistance to a wide range of xenobiotic compounds, was strongly
inhibited (91%).
PMID- 25589009
TI - An observational study of social and emotional support in smoking cessation
Twitter accounts: content analysis of tweets.
AB - BACKGROUND: Smoking continues to be the number one preventable cause of premature
death in the United States. While evidence for the effectiveness of smoking
cessation interventions has increased rapidly, questions remain on how to
effectively disseminate these findings. Twitter, the second largest online social
network, provides a natural way of disseminating information. Health
communicators can use Twitter to inform smokers, provide social support, and
attract them to other interventions. A key challenge for health researchers is
how to frame their communications to maximize the engagement of smokers.
OBJECTIVE: Our aim was to examine current Twitter activity for smoking cessation.
METHODS: Active smoking cessation related Twitter accounts (N=18) were
identified. Their 50 most recent tweets were content coded using a schema adapted
from the Roter Interaction Analysis System (RIAS), a theory-based, validated
coding method. Using negative binomial regression, the association of number of
followers and frequency of individual tweet content at baseline was assessed. The
difference in followership at 6 months (compared to baseline) to the frequency of
tweet content was compared using linear regression. Both analyses were adjusted
by account type (organizational or not organizational). RESULTS: The 18 accounts
had 60,609 followers at baseline and 68,167 at 6 months. A total of 24% of tweets
were socioemotional support (mean 11.8, SD 9.8), 14% (mean 7, SD 8.4) were
encouraging/engagement, and 62% (mean 31.2, SD 15.2) were informational. At
baseline, higher frequency of socioemotional support and encouraging/engaging
tweets was significantly associated with higher number of followers
(socioemotional: incident rate ratio [IRR] 1.09, 95% CI 1.02-1.20;
encouraging/engaging: IRR 1.06, 95% CI 1.00-1.12). Conversely, higher frequency
of informational tweets was significantly associated with lower number of
followers (IRR 0.95, 95% CI 0.92-0.98). At 6 months, for every increase by 1 in
socioemotional tweets, the change in followership significantly increased by
43.94 (P=.027); the association was slightly attenuated after adjusting by
account type and was not significant (P=.064). CONCLUSIONS: Smoking cessation
activity does exist on Twitter. Preliminary findings suggest that certain content
strategies can be used to encourage followership, and this needs to be further
investigated.
PMID- 25589010
TI - Temperate bacteriophages collected by outer membrane vesicles in Komagataeibacter
intermedius.
AB - The acetic acid bacteria have mainly relevance for bacterial cellulose production
and fermented bio-products manufacture. The purpose of this study was to identify
temperate bacteriophages in a cellulose-producing bacterial strain
Komagataeibacter intermedius IMBG180. Prophages from K. intermedius IMBG180 were
induced with mitomycin C and nalidixic acid. Transmission electron microscopy
analysis exhibited tailed bacteriophages belonging to Myoviridae. A PCR assay
targeting the capsid gene of the myoviruses proved phylogenetic position of
induced phages. Nalidixic acid was poor inducer of prophages, however, it induced
the OMV-like particles release. Size of OMVs depended on an antibiotic applied
for phage induction and varied in the range of 30-80 and 120-200 nm. Inside some
of them, tails of phages have been visible. Under conditions, inducing prophages,
OMVs acted as the collectors of formed phage particles, using outer membrane
receptors for phage detection (in this case, outer membrane siderophore
receptor), and fulfilled therefore "a cleaning," as well as defensive functions,
preventing bacteriophage spread outside population. This is the first description
of myoviruses affiliated to K. intermedius, as well as outer membrane vesicles
interaction with phages within this host.
PMID- 25589011
TI - How much is too much? Threshold dose distributions for 5 food allergens.
AB - BACKGROUND: Precautionary labeling is used to warn consumers of the presence of
unintended allergens, but the lack of agreed allergen thresholds can result in
confusion and risk taking by patients with food allergy. The lack of data on
threshold doses below which subjects are unlikely to react is preventing the
development of evidence-based allergen management strategies that are understood
by clinician and patient alike. OBJECTIVE: We sought to define threshold dose
distributions for 5 major allergenic foods in the European population. METHODS:
Patients with food allergy were drawn from the EuroPrevall birth cohort,
community surveys, and outpatient clinic studies and invited to undergo a food
challenge. Low-dose, double-blind, placebo-controlled food challenges were
undertaken with commercially available food ingredients (peanut, hazelnut,
celery, fish, and shrimp) blinded into common matrices. Dose distributions were
modeled by using interval-censoring survival analysis with 3 parametric
approaches. RESULTS: Of the 5 foods used for challenge, 4 produced similar dose
distributions, with estimated doses eliciting reactions in 10% of the allergic
population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut,
and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher
(27.3 mg of protein), although the CIs were wide and overlapping between fish and
plant foods. Shrimp provided radically different dose distributions, with an ED10
value of 2.5 g of protein. CONCLUSION: This evidence base will contribute to the
development of reference doses and action levels for allergens in foods below
which only the most sensitive subjects might react.
PMID- 25589012
TI - Synthesis and characterization of the anticancer and metal binding properties of
novel pyrimidinylhydrazone derivatives.
AB - Three novel pyrimidinylhydrazones substituted at either the aromatic moiety or at
the imine carbon atom were synthesized and characterized by standard analytical
methods. All compounds were found to be toxic in the micro- to submicromolar
range against a diverse panel of cancer cell lines including multidrug resistant
(MDR) derivatives expressing P-glycoprotein (Pgp). UV-visible spectrophotometry
experiments demonstrated that the most active compound (3) forms highly stable
complexes with iron(III) and copper(II) in a wide pH range with a stronger
preference towards iron(III). The redox activity of the iron and copper complexes
of ligand 3 was investigated using cyclic voltammetry and was tested with
cellular reductants. The impact of reactive oxygen species (ROS) on the mechanism
of toxicity was assessed using the ROS-sensitive cell permeable dye 2',7'
dichlorofluorescin diacetate (DCFDA). Our results demonstrate that the studied
pyrimidinylhydrazones form redox-active iron and copper complexes that are
capable of producing intracellular ROS, which might lead to cellular damage and
cell death in cancer cells regardless of their resistance status.
PMID- 25589013
TI - Regulation of nonclassical renin-angiotensin system receptor gene expression in
the adrenal medulla by acute and repeated immobilization stress.
AB - The involvement of the nonclassical renin-angiotensin system (RAS) in the
adrenomedullary response to stress is unclear. Therefore, we examined basal and
immobilization stress (IMO)-triggered changes in gene expression of the classical
and nonclassical RAS receptors in the rat adrenal medulla, specifically the
angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor
[(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2
receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A
receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor
mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also
transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient
decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following
single or repeated IMO. Because of its abundance, the function of the (P)RR was
explored in PC-12 cells. Prorenin activation of the (P)RR increased
phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine
hydroxylase at Ser(31), likely increasing its enzymatic activity and
catecholamine biosynthesis. Together, the broad and dynamic changes in gene
expression of the nonclassical RAS receptors implicate their role in the
intricate response of the adrenomedullary catecholaminergic system to stress.
PMID- 25589014
TI - A cholinergic contribution to the circulatory responses evoked at the onset of
handgrip exercise in humans.
AB - A cholinergic (muscarinic) contribution to the initial circulatory response to
exercise in humans remains controversial. Herein, we posit that this may be due
to exercise mode with a cholinergic contribution being important during isometric
handgrip exercise, where the hyperemic response of the muscle is relatively small
compared with the onset of leg cycling, where a marked increase in muscle blood
flow rapidly occurs as a consequence of multiple redundant mechanisms. We
recorded blood pressure (BP; brachial artery), stroke volume (pulse contour
analysis), cardiac output, and systemic vascular resistance (SVR) in young
healthy males, while performing either 20 s of isometric handgrip contraction at
40% maximum voluntary contraction (protocol 1; n = 9) or 20 s of low-intensity
leg cycling exercise (protocol 2; n = 8, 42 +/- 8 W). Exercise trials were
conducted under control (no drug) conditions and following cholinergic blockade
(glycopyrrolate). Under control conditions, isometric handgrip elicited an
initial increase in BP (+5 +/- 2 mmHg at 3 s and +3 +/- 1 mmHg at 10 s, P <
0.05), while SVR dropped after 3 s (-27 +/- 6% at 20 s; P < 0.05). Cholinergic
blockade abolished the isometric handgrip-induced fall in SVR and, thereby,
augmented the pressor response (+13 +/- 3 mmHg at 10 s; P < 0.05 vs. control). In
contrast, cholinergic blockade had a nonsignificant effect on changes in BP and
SVR at the onset of leg cycling exercise. These findings suggest that a
cholinergic mechanism is important for the BP and SVR responses at the onset of
isometric handgrip exercise in humans.
PMID- 25589015
TI - Using ecology to inform physiology studies: implications of high population
density in the laboratory.
AB - Conspecific density is widely recognized as an important ecological factor across
the animal kingdom; however, the physiological impacts are less thoroughly
described. In fact, population density is rarely mentioned as a factor in
physiological studies on captive animals and, when it is infrequently addressed,
the animals used are reared and housed at densities far above those in nature,
making the translation of results from the laboratory to natural systems
difficult. We survey the literature to highlight this important ecophysiological
gap and bring attention to the possibility that conspecific density prior to
experimentation may be a critical factor influencing results. Across three taxa:
mammals, birds, and fish, we present evidence from ecology that density
influences glucocorticoid levels, immune function, and body condition with the
intention of stimulating discussion and increasing consideration of population
density in physiology studies. We conclude with several directives to improve the
applicability of insights gained in the laboratory to organisms in the natural
environment.
PMID- 25589016
TI - Hemorrhagic hypotension-induced hypersensitivity of vagal pulmonary C-fibers to
chemical stimulation and lung inflation in anesthetized rats.
AB - This study was carried out to investigate whether hemorrhagic hypotension (HH)
altered the sensitivity of vagal pulmonary C-fibers. The fiber activity (FA) of
single vagal pulmonary C-fiber was continuously recorded in anesthetized rats
before, during, and after HH was induced by bleeding from the femoral arterial
catheter into a blood reservoir and lowering the mean systemic arterial pressure
(MSAP) to ~40 mmHg for 20 min. Our results showed the following. First, after
MSAP reached a steady state of HH, the peak FA response to intravenous injection
of capsaicin was elevated by approximately fivefold. The enhanced C-fiber
sensitivity continued to increase during HH and sustained even after MSAP
returned to baseline during the recovery, but slowly returned to control ~20 min
later. Second, responses of FA to intravenous injections of other chemical
stimulants of pulmonary C-fibers (phenylbiguanide, lactic acid, and adenosine)
and a constant-pressure lung hyperinflation were all significantly potentiated by
HH. Third, infusion of sodium bicarbonate alleviated the systemic acidosis during
HH, and it also attenuated, but did not completely prevent, the HH-induced C
fiber hypersensitivity. In conclusion, the pulmonary C-fiber sensitivity was
elevated during HH, probably caused by the endogenous release of chemical
substances (e.g., lactic acid) that were produced by tissue ischemia during HH.
This enhanced C-fiber sensitivity may heighten the pulmonary protective reflexes
mediated through these afferents (e.g., cough, J reflex) during hemorrhage when
the body is more susceptible to other hazardous insults and pathophysiological
stresses.
PMID- 25589017
TI - Incidence of Gallstone Formation and Cholecystectomy 10 Years After Bariatric
Surgery.
AB - PURPOSE: Rapid weight loss is a risk factor for gallstone formation, and
postoperative treatment options for gallstone formation are still part of
scientific discussion. No prospective studies monitored the incidence for
gallstone formation and subsequent cholecystectomy after bariatric surgery longer
than 5 years. The aim of the study was to determine the incidence of gallstone
formation and cholecystectomy in bariatric patients over 10 years. MATERIALS AND
METHODS: One hundred nine patients were observed over 10 years after laparoscopic
gastric banding or gastric bypass/gastric sleeve. The incidence of gallstone
formation and cholecystectomy was correlated to longitudinal changes in
anthropometric parameters. RESULTS: In total, 91 female and 18 male patients were
examined. Nineteen patients had postoperative gallstone formation, and 12 female
patients required cholecystectomy. The number needed to harm for gallstone
formation was 7.1 and 2.3 cases in the banding group and gastric bypass/gastric
sleeve group, respectively. The number needed to harm for cholecystectomy was
11.6 and 2.5 cases in the banding group and the gastric bypass/gastric sleeve
group, respectively. Weight loss was higher in patients requiring subsequent
cholecystectomy. Mean follow-up to cholecystectomy was 21.5 months with the
latest operation after 51 months. CONCLUSION: Female gender and rapid weight loss
were major risk factors for postoperative cholelithiasis. Ultrasound examinations
within 2 to 5 years are recommended in every patient, independent of bariatric
procedure. Pharmacologic treatment should be considered in high risk patients
within 2 to 5 years to prevent postoperative cholelithiasis. This helps to
optimize patient care and lowers postoperative morbidity.
PMID- 25589018
TI - Mood disorders are highly prevalent but underdiagnosed among patients seeking
bariatric surgery.
PMID- 25589019
TI - Outcome of leaks after sleeve gastrectomy based on a new algorithm adressing leak
size and gastric stenosis.
AB - BACKGROUND: Leaks after laparoscopic sleeve gastrectomy (LSG) are estimated to be
the most serious complication of this procedure due to difficult healing process
using non-standardized endoscopic approaches. Initially, endoscopic management
recommended the use of stents. METHODS: A total of 19 patients received
endoscopic treatment after LSG to manage leaks. The leak was classified depending
on the primary orifice's size (more or less than 10 mm) or on the presence of
gastric stenosis. The primary aim was to develop a therapeutic algorithm in order
to reduce the number of endoscopic procedures. RESULTS: The average number of
endoscopic procedures was 2.8 (range 2-5) in group A (leak size <10 mm) and 4
(range 3-7) in group B (leak size >10 mm). Two out of 13 patients had stent
migration (15.4 %) and required an additional procedure, one in group A and
another in group B. The average duration to achieve complete healing was 3.4
months (range 2-14 months), 2.8 months for group A and 3.9 months for group B.
CONCLUSIONS: Limited data can be found in the literature on leaks after LSG. A
new algorithm based on leak size permits standardization of endoscopic management
and reduces procedures after LSG.
PMID- 25589020
TI - Clinical effectiveness of exenatide in diabetic patients waiting for bariatric
surgery.
AB - BACKGROUND: Bariatric surgery constitutes the most effective treatment for
severely obese type 2 diabetic patients. Exenatide is a glucagon-like peptide 1
receptor agonist that can improve glycemic control and cause weight loss in
patients with type 2 diabetes. Clinical experience with exenatide in obese
patients with type 2 diabetes waiting for bariatric surgery has not been
reported. The aim of the study was to evaluate, in clinical practice, weight and
metabolic effects of exenatide (after 3 and 6 months) in patients with type 2
diabetes and obesity waiting for bariatric surgery. METHODS: A total of 100
diabetic adult subjects with a BMI >= 35 kg/m(2) were included. Primary endpoints
were changes in weight and HbA1c after 6 months of treatment. Secondary endpoints
were changes from baseline of a variety of clinical measures (triglycerides
levels, blood pressure, and waist circumference). Data were analyzed at 3 and 6
months of follow-up. RESULTS: Treatment for 6 months with exenatide decreased
significantly body weight (-12.5 kg) and waist circumference (-13 cm). Twenty
percent of patients reduced their BMI under 35 kg/m(2) and significantly improved
their metabolic profile (HbA1c <7 %). Significant and maintained decreases in
HbA1c of 1 % were observed in the 3 and 6 months cohorts. Triglycerides levels
and blood pressure also decreased from baseline to the end of the study.
Treatment was discontinued in 19 % of patients mainly due to drug inefficacy (6
%) or adverse events (4 %). CONCLUSIONS: Exenatide twice daily (BID) leads to
early, robust, and significant weight loss in a subset of patients with diabetes
and severe obesity before bariatric surgery. Clinical trials are needed to
confirm the benefits of GLP-1 agonists in type 2 diabetic obese patients or high
risk super-obese patients waiting for bariatric surgery.
PMID- 25589021
TI - External focus and autonomy support: two important factors in motor learning have
additive benefits.
AB - We examined whether the combination of two factors that have consistently been
found to enhance motor learning - an external focus (EF) of attention and
autonomy support (AS) - would produce additive benefits. Participants practiced
throwing with their non-dominant arm. In a 2*2 design, they were or were not
asked to focus externally (i.e., on the target), and were or were not given a
choice (autonomy support). The latter involved choosing 2 5-trials blocks during
practice on which they used their dominant arm. All four groups - EF/AS, EF, AS,
and C (control) - completed a practice phase consisting of 60 trials. The
distance to the target (bull's eye) was 7.5m. One day later, participants
performed retention (same target distance) and transfer tests (8.5m). Both
external focus instructions and autonomy support enhanced retention and transfer
performance. Importantly, the combination of these factors resulted in additive
learning advantages. The EF/AS group showed the greatest throwing accuracy, and
the EF and AS groups outperformed the C group. In addition, self-efficacy
measured after practice and before retention and transfer was increased by both
factors. Thus, promoting an external focus of attention and supporting learners'
need for autonomy seem to independently influence learning.
PMID- 25589023
TI - Optical nanoparticles: general discussion.
PMID- 25589022
TI - Upgrading Preschool Environment in a Swedish Municipality: Evaluation of an
Implementation Process.
AB - Redesigning outdoor preschool environment may favorably affect multiple factors
relevant to health and reach many children. Cross-sectional studies in various
landscapes at different latitudes have explored the characteristics of preschool
outdoor environment considering the play potential triggering combined physical
activity and sun-protective behavior due to space, vegetation, and topography.
Criteria were pinpointed to upgrade preschool outdoor environment for multiple
health outcomes to be applied in local government in charge of public preschools.
Purposeful land use policies and administrative management of outdoor land use
may serve to monitor the quality of preschool outdoor environments (upgrading and
planning). This study evaluates the process of implementing routines for
upgrading outdoor preschool environments in a medium-sized municipality, Sweden,
2008-2011, using qualitative and quantitative analysis. Recorded written material
(logs and protocols) related to the project was processed using thematic
analysis. Quantitative data (m(2) flat/multileveled, overgrown/naked surface, and
fraction of free visible sky) were analyzed to assess the impact of
implementation (surface, topography, greenery integrated in play). The preschool
outdoor environments were upgraded accordingly. The quality of implementation was
assessed using the theory of policy streams approach. Though long-term impact
remains to be confirmed the process seems to have changed work routines in the
interior management for purposeful upgrading of preschool outdoor environments.
The aptitude and applicability of inexpensive methods for assessing, selecting,
and upgrading preschool land at various latitudes, climates, and outdoor play
policies (including gender aspects and staff policies) should be further
discussed, as well as the compilation of data for monitoring and evaluation.
PMID- 25589024
TI - Semi-automatic organelle detection on transmission electron microscopic images.
AB - Recent advances in the acquisition of large-scale datasets of transmission
electron microscope images have allowed researchers to determine the number and
the distribution of subcellular ultrastructures at both the cellular level and
the tissue level. For this purpose, it would be very useful to have a computer
assisted system to detect the structures of interest, such as organelles. Using
our original image recognition framework CARTA (Clustering-Aided Rapid Training
Agent), combined with procedures to highlight and enlarge regions of interest on
the image, we have developed a successful method for the semi-automatic detection
of plant organelles including mitochondria, amyloplasts, chloroplasts,
etioplasts, and Golgi stacks in transmission electron microscope images. Our
proposed semi-automatic detection system will be helpful for labelling organelles
in the interpretation and/or quantitative analysis of large-scale electron
microscope imaging data.
PMID- 25589025
TI - [Surgery for male urinary incontinence: where are we now and what is in the
pipeline?].
AB - Male stress urinary incontinence, which has radical prostatectomy as the main
aetiology, affects about 39% of the adult male population and is one of the
complications of radical prostatectomy with the greatest impact on the quality of
life of patients. There are a wide range of treatments for stress urinary
incontinence available to the urologist, ranging from conservative treatments to
surgical treatments, from minimally invasive procedures to the implant of
artificial sphincter prosthesis. The aim of this work is to define the state-of
the-art of surgical treatments for male stress urinary incontinence, analyzing
the most recent studies in the literature and evaluating the available scientific
evidence.
PMID- 25589026
TI - Robotic-assisted partial nephrectomy: experience on 60 cases.
AB - INTRODUCTION: Laparoscopic partial nephrectomy is still one of the more
challenging procedures in urology. Minimizing warm ischemia time (WIT) and
bleeding requires efficient intracorporeal suturing. In addition, achieving
negative surgical margins requires complete excision of the tumor. Robotic
assisted partial nephrectomy (RALPN) adds the advantages offered by the "Da Vinci
system" to laparoscopy, such as the 3-D vision, and the better degree of freedom
of surgical instruments. OBJECTIVE: The objective of this study is to report our
experience with RALPN. METHODS: From August 2009 to October 2012, 60 patients
underwent RALPN for kidney cancer. The average age of the patients (35 female, 25
male) was 63 (range 48-80) years. Average BMI was 25 (range 21.8-29.7) kg/m2.
Average tumor size was 3.2 cm (range 2-6.7 cm). All the procedures were performed
by a transperitoneal approach. Ilar clamping was used in all cases: in 47
patients by one intracorporeal tourniquet for the artery and one for the vein; in
three cases, ilar clamping was "en block" by Satinsky. RESULTS: Mean operative
time was 167.2 min (140-250) with a WIT of 23.8 min (15-28). The mean estimated
blood loss was 260 mL (50-300). In one case, nephrectomy was necessary because
the tumor involved the renal pedicle. One patient had pulmonary embolism and one
urinary leakage conservatively managed.Pathologic examination revealed clear cell
renal cell carcinoma in 58 patients, oncocytoma in one patient, and
angiomyolipoma in one patient. All resection margins were free from tumor.
CONCLUSIONS: Partial nephrectomy, facilitated by robotic technology, is more and
more frequently performed as a safe and effective minimally invasive procedure.
PMID- 25589027
TI - Endourethral migration of a Hem-o-Lok Clip after robot-assisted laparoscopic
radical prostatectomy.
AB - Hem-o-Lok clips (Weck Surgical Instruments, Teleflex Medical, Durham, North
Carolina, USA) are widely used in robot-assisted laparoscopic radical
prostatectomy because of their easy application and secure clamping. To date,
there have been some reports of their migration into the urinary tract, causing
urethral erosion, bladder neck contractures orcalculus formation. We report a
case of endourethral migration of a hem-o-lok after robot-assisted laparoscopic
prostatectomy. The hem-o-lok was almost completely endoluminal and attached to
one end at the vesico-urethral anastomosis. The hem-o-lok was easily removed
cystoscopically by using an endoscopic forceps.
PMID- 25589028
TI - [Female incontinence surgery: state of the art].
AB - Female urinary incontinence represents a medical and social problem with huge
impact regarding both patient's quality of life and social costs. The diagnosis
is important for therapeutic choice and should consider some factors: the degree
of urethral mobility, urodynamics parameters, patient's will and expectations,
information about surgical complications and risks. Nowadays suburethral sling
evolution and bulking therapy for selected cases consent to perform miniinvasive
surgery; the most relevant problem concerns the management of postoperative
complications: in this sense autologous slings are used after urethrolisis. In
most difficult cases, it is possible to consider artificial sphincter as the best
option.
PMID- 25589029
TI - Urinary incontinence and neuropathy after radical prostatectomy: diagnosis and
treatment.
AB - INTRODUCTION AND OBJECTIVE: The urinary incontinence after radical prostatectomy
is secondary to neuropathy with various degrees from neurapraxia to neurotmesis.
We propose to apply therapeutic and rehabilitative models appropriate to the
diagnosis and to evaluate the results. MATERIALS AND METHODS: We examined 79
homogeneous patients with urinary incontinence after radical prostatectomy. After
having defined the diagnosis by a urodynamic examination, the study of pudendal
nerve somatosensory-evoked potentials (SEPs) and perineal electromyography (EMG),
patients were divided into four groups (A; B; C; D) and submitted to different
clinical drug protocols and rehabilitation. After 3 months, patients were
reevaluated. RESULTS: Twenty-eight patients with idiopathic overactive bladder
(Group A) have been treated with anticholinergics: two unchanged (7%); 14
improved (50%); and 12 recovered (43%). Sixteen patients with overactive bladder
and sphincter incompetence (Group B) have practiced physiokinesis therapy (FKT)
of pelvic floor and anticholinergic therapy: one unchanged (6%); eight improved
(50%); and seven recovered (44%). Fourteen patients with perineal incompetence to
continence (Group C) have been treated with FES, FKT of pelvic floor, and
Biofeedback: three patients were unchanged (21%); five improved (36%); and six
recovered (43%). Twenty-one patients with sphincter denervation (Group D)
performed FES, FKT of pelvic floor, and Biofeedback: 16 unchanged (76%); five
improved (24%); and zero recovered (0%). Of these 16 patients, six non-responders
have placed a transobturator tape (TOT) sling and four an artificial sphincter.
CONCLUSIONS: A therapy adherent to the diagnosis increases success rate.
PMID- 25589030
TI - Association of Concurrent fNIRS and EEG Signatures in Response to Auditory and
Visual Stimuli.
AB - Functional near-infrared spectroscopy (fNIRS) has been proven reliable for
investigation of low-level visual processing in both infants and adults. Similar
investigation of fundamental auditory processes with fNIRS, however, remains only
partially complete. Here we employed a systematic three-level validation approach
to investigate whether fNIRS could capture fundamental aspects of bottom-up
acoustic processing. We performed a simultaneous fNIRS-EEG experiment with visual
and auditory stimulation in 24 participants, which allowed the relationship
between changes in neural activity and hemoglobin concentrations to be studied.
In the first level, the fNIRS results showed a clear distinction between visual
and auditory sensory modalities. Specifically, the results demonstrated area
specificity, that is, maximal fNIRS responses in visual and auditory areas for
the visual and auditory stimuli respectively, and stimulus selectivity, whereby
the visual and auditory areas responded mainly toward their respective stimuli.
In the second level, a stimulus-dependent modulation of the fNIRS signal was
observed in the visual area, as well as a loudness modulation in the auditory
area. Finally in the last level, we observed significant correlations between
simultaneously-recorded visual evoked potentials and deoxygenated hemoglobin
(DeoxyHb) concentration, and between late auditory evoked potentials and
oxygenated hemoglobin (OxyHb) concentration. In sum, these results suggest good
sensitivity of fNIRS to low-level sensory processing in both the visual and the
auditory domain, and provide further evidence of the neurovascular coupling
between hemoglobin concentration changes and non-invasive brain electrical
activity.
PMID- 25589031
TI - The effect of unemployment on self-reported health and mental health in Greece
from 2008 to 2013: a longitudinal study before and during the financial crisis.
AB - The current study uses six annual waves of the Longitudinal Labor Market Study
(LLMS) covering the 2008-2013 period to obtain longitudinal estimations
suggesting statistically significant negative effects from unemployment on self
reported health and mental health in Greece. The specifications suggest that
unemployment results in lower health and the deterioration of mental health
during the 2008-2009 period compared with the 2010-2013 period, i.e., a period in
which the country's unemployment doubled as a consequence of the financial
crisis. Unemployment seems to be more detrimental to health/mental health in
periods of high unemployment, suggesting that the unemployment crisis in Greece
is more devastating as it concerns more people. Importantly, in all
specifications, comparable qualitative patterns are found by controlling for
unemployment due to firm closure, which allows us to minimize potential bias due
to unemployment-health related reverse causality. Moreover, in all cases, women
are more negatively affected by unemployment in relation to their health and
mental health statuses than are men. Greece has been more deeply affected by the
financial crisis than any other EU country, and this study contributes by
offering estimates for before and during the financial crisis and considering
causality issues. Because health and mental health indicators increase more
rapidly in a context of higher surrounding unemployment, policy action must place
greater emphasis on unemployment reduction and supporting women's employment.
PMID- 25589032
TI - Attitudes towards legalising physician provided euthanasia in Britain: the role
of religion over time.
AB - Hastening the death of another whether through assisted suicide or euthanasia is
the subject of intense debate in the UK and elsewhere. In this paper we use a
nationally representative survey of public attitudes - the British Social
Attitudes survey - to examine changes in attitudes to the legalisation of
physician provided euthanasia (PPE) over almost 30 years (1983-2012) and the role
of religious beliefs and religiosity in attitudes over time. Compatible questions
about attitudes to euthanasia were available in the six years of 1983, 1984,
1989, 1994, 2005, and 2012. We study the trends in the support for legalisation
through these time points and the relationship between attitudes, religious
denomination and religiosity, controlling for a series of covariates. In total,
8099 individuals provided answers to the question about PPE in the six years of
the study. The support for legalisation rose from around 76.95% in 1983 to 83.86%
in 2012. This coincided with an increase in secularisation exhibited in the
survey: the percentage of people with no religious affiliation increasing from
31% to 45.4% and those who do not attend a religious institution (e.g. church)
increasing from 55.7% to 65.03%. The multivariate analysis demonstrates that
religious affiliation and religiosity as measured by religious institution
attendance frequency are the main contributors to attitudes towards euthanasia,
and that the main increase in support happened among the group with least
religious affiliation. Other socio-demographic characteristics do not seem to
alter these attitudes systematically across the years. Our study demonstrates an
increase in the support of euthanasia legalisation in Britain in the last 30
years coincided with increased secularisation. It does not follow, however, that
trends in public support are immutable nor that a change in the law would improve
on the current pragmatic approach toward hastening death by a physician adopted
in England and Wales in terms of the balance between compassion and safeguards
against abuse offered.
PMID- 25589033
TI - Examining individual and school characteristics associated with child obesity
using a multilevel growth model.
AB - The childhood obesity epidemic continues to be a serious concern in the U.S.,
disproportionately affecting low socioeconomic and minority groups. Because many
interventions are based in schools, both individual and school factors
contributing to obesity were examined in this study. Employing data from the
Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999 (ECLS-K), a
three level hierarchical linear model was used to estimate children's body mass
index (BMI) growth trajectories within their school contexts. Results indicated
an inverse relationship between BMI and socioeconomic status (SES), except for
black males. Additionally, results showed that low school SES and rural locality
of the school were school-level risk factors of obesity. Lastly, a major portion
of the between-schools variance was explained by aggregated student
characteristics, indicating that students were more likely to attend schools with
peers of similar BMI who had similar SES and race/ethnicity, supporting a school
level compositional effect associated with obesity.
PMID- 25589034
TI - Ethnic discrimination predicts poor self-rated health and cortisol in pregnancy:
insights from New Zealand.
AB - Despite growing research emphasis on understanding the health effects of ethnic
discrimination, little work has focused on how such exposures may influence a
woman's biology and health during pregnancy. Understanding such effects is
important given evidence that maternal stress experience in pregnancy can have
long term effects on offspring health. Here we present data evaluating the
relationship between perceived discrimination, self-rated health, and the stress
hormone cortisol measured in late pregnancy among a diverse sample of women
living in Auckland, New Zealand (N = 55). We also evaluated possible
intergenerational impacts of maternal discrimination on stress reactivity in a
subset of offspring (N = 19). Pregnant women were recruited from two antenatal
care clinics in Auckland. Women were met in their homes between 34 and 36 weeks
gestation, during which time a prenatal stress questionnaire was administered and
saliva samples (morning and evening from two days) were obtained. Offspring
cortisol reactivity was assessed at the standard six week postnatal vaccination
visit. We found that 34% of women reported having experienced ethnic
discrimination, with minority and immigrant women being more likely to report
being angry or upset in response to discrimination experience compared with NZ
born women of European descent. Women reporting discrimination experience had
worse self-rated health, higher evening cortisol and gave birth to infants with
higher cortisol reactivity, all independent of ethnicity and material
deprivation. These findings suggest that discrimination experience can have
biological impacts in pregnancy and across generations, potentially contributing
to the ethnic gradient in health.
PMID- 25589035
TI - Psychiatrists' Perceptions of Role-Playing Games.
AB - The literature has seen a surge in research on the mental health impacts of
technologies such as Facebook, video games, and massively-multiplayer online role
playing games such as World of Warcraft, but little is known regarding the mental
health impact of non-video role-playing games, such as Dungeons & Dragons. The
present study examines how psychiatrists' perceive role-playing games and whether
they play them. Psychiatrists at a tertiary care centre in Canada completed a
questionnaire assessing history of playing role-playing games and whether they
associate them with psychopathology. Forty-eight psychiatrists responded. Twenty
three percent have played a role-playing game over their lifetimes. Twenty-two
percent believed there was an association between psychopathology and role
playing games. A majority of psychiatrists who responded do not associate role
playing games with psychopathology. Implications for clinical practice and future
research are discussed.
PMID- 25589036
TI - Confinement without boundaries: anisotropic diffusion on the surface of a
cylinder.
AB - Densely packed systems of thermal particles in curved geometries are frequently
encountered in biological and microfluidic systems. In 2D systems, at
sufficiently high surface coverage, diffusive motion is widely known to be
strongly affected by physical confinement, e.g., by the walls. In this work, we
explore the effects of confinement by shape, not rigid boundaries, on the
diffusion of discs by confining them to the surface of a cylinder. We find that
both the magnitude and the directionality of lateral diffusion is strongly
influenced by the radius of the cylinder. An anisotropy between diffusion in the
longitudinal and circumferential direction of the cylinder develops. We
demonstrate that the origin of this effect lies in the fact that screw-like
packings of mono- and oligodisperse discs on the surface of a cylinder induce
preferential collective motions in the circumferential direction, but also show
that even in polydisperse systems lacking such order an intrinsic finite size
confinement effect increases diffusivity in the circumferential direction.
PMID- 25589037
TI - Deaths after Fluad flu vaccine and the epidemic of panic in Italy.
PMID- 25589038
TI - Ultrafast room-temperature crystallization of TiO2 nanotubes exploiting water
vapor treatment.
AB - In this manuscript a near-room temperature crystallization process of anodic
nanotubes from amorphous TiO2 to anatase phase with a fast 30 minutes treatment
is reported for the first time. This method involves the exposure of as-grown
TiO2 nanotubes to water vapor flow in ambient atmosphere. The water vapor
crystallized samples are deeply investigated in order to gain a whole
understanding of their structural, physical and chemical properties. The
photocatalytic activity of the converted material is tested by dye degradation
experiment and the obtained performance confirms the highly promising properties
of this low-temperature processed material.
PMID- 25589039
TI - How should the legal framework for the protection of human genomic data be
formulated?-Implications from the revision processes of the Act on the Protection
of Personal Information (PPI Act).
PMID- 25589041
TI - Agnathia-otocephaly complex and asymmetric velopharyngeal insufficiency due to an
in-frame duplication in OTX2.
AB - Agnathia-otocephaly complex is a malformation characterized by absent/hypoplastic
mandible and abnormally positioned ears. Mutations in two genes, PRRX1 and OTX2,
have been described in a small number of families with this disorder. We
performed clinical and genetic testing in an additional family. The proband is a
healthy female with a complicated pregnancy history that includes two offspring
diagnosed with agnathia-otocephaly during prenatal ultrasound scans. Exome
sequencing was performed in fetal DNA from one of these two offspring revealing a
heterozygous duplication in OTX2: c.271_273dupCAG, p.(Gln91dup). This change
leads to the insertion of a glutamine within the OTX2 homeodomain region, and is
predicted to alter this signaling molecule's ability to interact with DNA. The
same variant was also identified in the proband's clinically unaffected 38-year
old husband and their 9-year-old daughter, who presented with a small mandible,
normal ears and velopharyngeal insufficiency due to a short hemi-palate. This
unusual presentation of OTX2-related disease suggests that OTX2 might have a role
in palatal hypoplasia cases. A previously unreported OTX2 variant associated with
extreme intrafamilial variability is described and the utility of exome
sequencing as a tool to confirm the diagnosis of agnathia-otocephaly and to
inform the reproductive decisions of affected families is highlighted.
PMID- 25589042
TI - A reply to a commentary on identification of the rare compound heterozygous
variants in the NEB gene in a Korean family with intellectual disability,
epilepsy and early-childhood-onset generalized muscle weakness.
PMID- 25589040
TI - Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal
dominant nonsyndromic hearing loss DFNA4B in a Chinese family.
AB - Autosomal dominant nonsyndromic hearing loss (ADNSHL/DFNA) is a highly
genetically heterogeneous disorder. Hitherto only about 30 ADNSHL-causing genes
have been identified and many unknown genes remain to be discovered. In this
research, genome-wide linkage analysis mapped the disease locus to a 4.3 Mb
region on chromosome 19q13 in SY-026, a five-generation nonconsanguineous Chinese
family affected by late-onset and progressive ADNSHL. This linkage region showed
partial overlap with the previously reported DFNA4. Simultaneously, probands were
analyzed using exome capture followed by next-generation sequencing.
Encouragingly, a heterozygous missense mutation, c.505G>A (p.G169R) in exon 3 of
the CEACAM16 gene (carcinoembryonic antigen-related cell adhesion molecule 16),
was identified via this combined strategy. Sanger sequencing verified that the
mutation co-segregated with hearing loss in the family and that it was not
present in 200 unrelated control subjects with matched ancestry. This is the
second report in the literature of a family with ADNSHL caused by CEACAM16
mutation. Immunofluorescence staining and western blots also prove CEACAM16 to be
a secreted protein. Furthermore, our studies in transfected HEK293T cells show
that the secretion efficacy of the mutant CEACAM16 is much lower than that of the
wild type, suggesting a deleterious effect of the sequence variant.
PMID- 25589043
TI - A commentary on identification of the rare compound heterozygous variants in the
NEB gene in a Korean family with intellectual disability, epilepsy and early
childhood-onset generalized muscle weakness.
PMID- 25589044
TI - Oxidative stress protection by polyphosphate--new roles for an old player.
AB - Inorganic polyphosphate is a universally conserved biopolymer whose association
with oxidative stress resistance has been documented in many species, but whose
mode of action has been poorly understood. Here we review the recent discovery
that polyphosphate functions as a protein-protective chaperone, examine the
mechanisms by which polyphosphate-metal ion interactions reduce oxidative stress,
and summarize polyphosphate's roles in regulating general stress response
pathways. Given the simple chemical structure and ancient pedigree of
polyphosphate, these diverse mechanisms are likely to be broadly relevant in many
organisms, from bacteria to mammalian cells.
PMID- 25589046
TI - Contact allergy to acrylates and methacrylates in consumers and nail artists -
data of the Information Network of Departments of Dermatology, 2004-2013.
AB - BACKGROUND: Allergic contact dermatitis caused by (meth)acrylates used in
artificial nails is a relevant problem in both nail artists and consumers.
OBJECTIVE: To analyse the frequency of this problem in the contact allergy
surveillance network Information Network of Departments of Dermatology in 2004
2013, and address possible time trends and patterns of co-sensitization. METHODS:
A retrospective analysis of patch test results with (meth)acrylates, along with
clinical and demographic data, was performed. These were used to subdivide
patients according to (i) a potentially exposed occupation and (ii) nail
cosmetics as the suspected cause of contact dermatitis. RESULTS: Among the 114
440 patients patch tested, 72 244 were female and were considered further. Eighty
seven patients both worked as nail artists/cosmetologists and suspected nail
cosmetics as the cause of dermatitis. Among these, 47.1% reacted to at least one
(meth)acrylate, most often to 2-hydroxyethyl methacrylate (n = 27), 2
hydroxypropyl methacrylate, and hydroxyethyl acrylate (n = 26 each), with marked
coupled reactivity. In other subgroups of interest, frequencies of sensitization
to (meth)acrylates were less elevated but higher than in all remaining female
patients (n = 69 419). CONCLUSIONS: The results indicate a not entirely common,
but potentially serious, problem, especially concerning occupationally exposed,
and sensitized, nail artists. Adequate protective measures should be taught as
part of the vocational training.
PMID- 25589047
TI - Role of the registered nurse in the care of the pregnant woman receiving
analgesia and anesthesia by catheter techniques.
PMID- 25589045
TI - Temporal and evolutionary dynamics of two-component signaling pathways.
AB - Bacteria sense and respond to numerous environmental signals through two
component signaling pathways. Typically, a given stimulus will activate a sensor
histidine kinase to autophosphorylate and then phosphotransfer to a cognate
response regulator, which can mount an appropriate response. Although these
signaling pathways often appear to be simple switches, they can also orchestrate
surprisingly sophisticated and complex responses. These temporal dynamics arise
from several key regulatory features, including the bifunctionality of histidine
kinases as well as positive and negative feedback loops. Two-component signaling
pathways are also dynamic on evolutionary time-scales, expanding dramatically in
many species through gene duplication and divergence. Here, we review recent work
probing the temporal and evolutionary dynamics of two-component signaling
systems.
PMID- 25589049
TI - Lyme disease update for the general dermatologist.
AB - Lyme disease is an Ixodes tick-borne illness that may arise from different
species of the Borrelia spirochete and may be propagated in various hosts. Humans
are considered dead-end hosts in this propagation cycle but may have a range of
Lyme disease characteristics as a result of borrelial infection. Lyme disease has
varied cutaneous manifestations, and the approach to diagnosis and treatment is
based on the patient, the region, and suspected coinfection with another tick
borne illness. An understanding of the distribution of the Ixodes tick, its
vectors, and the most likely dermatologic presentation based on these factors
allows the dermatologist to make appropriate testing and treatment
recommendations. Our aim is to simplify this approach for the treating
practitioner.
PMID- 25589048
TI - Synthesis and Biological Evaluation of Strictosamide Derivatives with Improved
Antiviral and Antiproliferative Activities.
AB - A series of novel derivatives of strictosamide were synthesized and biologically
evaluated. Most of the new compounds exhibited improved activities than the
parent compound strictosamide. Among them, compounds Ib and If possessed
antiviral activities against influenza A virus (A/Jinan/15/90) with IC50 values
of 4.12 and 12.35 MUg/mL, respectively. Compound Ie possessed antiviral activity
against respiratory syncytial virus (RSV) with an IC50 value of 9.58 MUg/mL. Both
compounds IIc and IId had moderate antiproliferative effects against five human
cancer cell lines. The preliminary structure-activity relationships were also
concluded. This study provides a promising new template with potential antiviral
activity.
PMID- 25589050
TI - Clinicopathological and diagnostic characterization of confluent and reticulate
papillomatosis of Gougerot and Carteaud: a retrospective study in a South-East
Asian population.
AB - BACKGROUND: Confluent and reticulate papillomatosis of Gougerot and Carteaud
(CRP) is a rare dermatological condition, which has not been reported widely in
Asian populations. AIM: To characterize the clinicopathological and diagnostic
features of CRP in a South-East Asian population. METHODS: The medical records of
29 patients accorded the diagnosis of CRP at the National Skin Centre, Singapore,
from 1990 to 2011, were analyzed. RESULTS: The male to female ratio was 2.6:1.
Eight patients were Indians. The mean age at the onset of skin eruptions was 29.1
years (range 16-55 years), while the mean duration was 19.9 months (range 0.5-120
months). CRP itself was the most common preliminary diagnosis. Fungal smears were
negative in all 22 instances. All 29 patients had received a trial of antifungal
therapy before being seen at our center. Antifungal therapy was repeated in three
subjects, and the response was uniformly poor. Conversely, the treatment response
with tetracyclines was excellent, yielding more than a 50% response in all 14
patients. Four patients suffered recurrence of CRP. According to the diagnostic
criteria set forth by Davis et al., 25/29 patients (86.2%) and 19/29 patients
(65.6%) fulfilled at least three and four criteria, respectively. CONCLUSION: A
predilection for male gender and Indian ethnicity were noted in our study. The
diagnosis of CRP was often made clinically, and investigations were mainly
ancillary. The treatment response was poor with antifungal agents but excellent
with tetracyclines. The diagnostic criteria proposed by Davis et al. were found
to be useful in our cohort of patients.
PMID- 25589051
TI - Enhancing patient satisfaction in dermatology.
AB - Patient satisfaction is an important component of dermatological care that
reflects patients' perspectives on the care they receive. While physicians'
expertise and judgment should always remain the foundation of providing
appropriate and effective care, the patient experience can also be influenced by
interpersonal relationships, expectations, and a sense of agency in the treatment
patients receive. Dermatology providers can use practical techniques such as
sitting rather than standing, reframing the concept of cure, and engaging
patients in treatment decisions to improve the patient-provider experience and
thereby optimize patient satisfaction.
PMID- 25589052
TI - Airborne hazards exposure and respiratory health of Iraq and Afghanistan
veterans.
AB - More than 2.6 million military personnel have been deployed to recent conflicts
in Iraq and Afghanistan and were likely exposed to a variety of airborne hazards
during deployment. Despite several epidemiologic reports of increased respiratory
symptoms, whether or not these respiratory illnesses lead to reductions in lung
function and/or specific pulmonary disease is unclear. We reviewed data published
from 2001 to 2014 pertaining to respiratory health in military personnel deployed
to Iraq and Afghanistan and found 19 unique studies. Study designs were primarily
retrospective and observational in nature with patient symptom reporting and
medical encounter data as primary outcome measures. Two case series reported on
rare respiratory diseases, and one performed a standardized evaluation of new
onset respiratory symptoms. Respiratory outcomes in relation to proximity to a
specific air pollution source (i.e., smoke from burning trash and sulfur mine
fire) were described in 2 separate studies. Only 2 longitudinal investigations
were identified comparing pre- and postdeployment measurement of exercise
capacity. In summary, published data based on case reports and retrospective
cohort studies suggest a higher prevalence of respiratory symptoms and
respiratory illness consistent with airway obstruction. However, the association
between chronic lung disease and airborne hazards exposure requires further
longitudinal research studies with objective pulmonary assessments.
PMID- 25589053
TI - Alcohol use and substance use disorders in Gulf War, Afghanistan, and Iraq War
veterans compared with nondeployed military personnel.
AB - Although recent veterans have been found to be at increased risk of psychiatric
disorders, limited research has focused on alcohol or substance use disorders.
This systematic review and meta-analysis examined whether alcohol or substance
use disorders were more common in Gulf War, Afghanistan, and Iraq War veterans
compared with military comparison groups nondeployed to the corresponding
conflict, including never deployed personnel. Literature was searched (1990-2014)
in multiple electronic databases. Studies were assessed for eligibility and
quality, including risk of bias. Eighteen studies (1997-2014) met inclusion
criteria. Pooled analysis based on a random-effects model yielded a summary odds
ratio of 1.33 (95% confidence interval (CI): 1.22, 1.46) for alcohol (7 studies)
and 2.13 (95% CI: 0.96, 4.72) for substance use (3 studies) disorders among Gulf
War veterans, as well as 1.36 (95% CI: 1.11, 1.66) for alcohol (7 studies) and
1.14 (95% CI: 1.04, 1.25) for substance use (4 studies) disorders among
Iraq/Afghanistan veterans; meta-regressions found no statistically significant
association between theater of war and alcohol use or substance use disorders.
Our findings indicate that Gulf and Iraq/Afghanistan war veterans are at higher
alcohol use disorder risk than nondeployed veterans, but further studies with
increased power are needed to assess substance use disorder risk in Gulf War
veteran populations.
PMID- 25589054
TI - Heart rate reduction and longevity in mice.
AB - Heart rate correlates inversely with life span across all species, including
humans. In patients with cardiovascular disease, higher heart rate is associated
with increased mortality, and such patients benefit from pharmacological heart
rate reduction. However, cause-and-effect relationships between heart rate and
longevity, notably in healthy individuals, are not established. We therefore
prospectively studied the effects of a life-long pharmacological heart rate
reduction on longevity in mice. We hypothesized, that the total number of cardiac
cycles is constant, and that a 15% heart rate reduction might translate into a
15% increase in life span. C57BL6/J mice received either placebo or ivabradine at
a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and
body weight were monitored. Autopsy was performed on all non-autolytic cadavers,
and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart
rate by 14% (median, interquartile range 12-15%) throughout life, and median life
span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were
not different between placebo and ivabradine. Life span was not increased to the
same extent as heart rate was reduced, but nevertheless significantly prolonged
by 6.2%.
PMID- 25589055
TI - Reduction of no-reflow and reperfusion injury with the synthetic 17beta
aminoestrogen compound Prolame is associated with PI3K/Akt/eNOS signaling
cascade.
AB - A high proportion of primary percutaneous coronary interventions performed in the
setting of acute myocardial infarction, concur with inadequate myocardial
perfusion at the microvascular level. This phenomenon, known as "no-reflow"
contributes to reperfusion injury, poor prognosis and to unfavorable clinical
outcome. In this study, we evaluated the hypothesis that the synthetic 17beta
aminoestrogen Prolame, may confer cardioprotection and prevent against no-reflow.
In an open-chest model of 30-min ischemia and 90-min reperfusion, male Wistar
rats were randomly assigned to different groups: Control, Prolame, Prolame
followed by the nitric oxide synthase inhibitor (L-NAME), and 17beta-estradiol.
Areas of risk, infarct size and no-reflow were determined by planimetry with
triphenyltetrazolium chloride and thioflavin-S stains. Structural damage of the
vasculature was measured as capillary compression in clarified tissue after intra
atrial injection of Microfil. Hemodynamic function was obtained at the end of
stabilization, ischemia and reperfusion; nitric oxide (NO.) content was
determined indirectly using the Griess reaction. Activation of the eNOS signaling
cascade was determined by western blot. Prolame reduced the infarcted area,
decreased the zones of no-reflow and capillary compression by activating the
PI3K/Akt/eNOS signaling pathway in correlation with NO. increase. Prolame also
activated endothelial cells augmenting NO. production, which was inhibited by
ICI182780 (a selective estrogen receptor down-regulator), supporting the notion
that the cardioprotective effect of Prolame involves the preservation of
endothelium through the activation of estrogen receptor downstream signaling. Our
results provide evidence that Prolame has potential therapeutic application in
patients with AMI, as it prevents from both vascular and cardiac tissue damage.
PMID- 25589056
TI - An update on photodynamic therapies in the treatment of onychomycosis.
AB - Onychomycosis is a common fungal infection of the nails that is increasing in
prevalence in the old, diabetics and immunocompromised. Onychomycosis presents a
therapeutic challenge that can lead to significant reductions in quality of life
leading to both physical and psychological consequences. Current treatment
modalities are difficult to implement due to the poor penetration of topical
treatments to the nail bed, the slow growing nature of nails and the need for
prolonged use of topical and/or oral medications. Standard of care medications
have cure rates of 63-76% that leads to a high propensity of treatment failures
and recurrences. Photodynamic therapy (PDT) offers an alternative treatment for
onychomycosis. Methylene blue dye, methyl-aminolevulinate (MAL) and
aminolevulinic acid (ALA) have been used as photosensitizers with approximately
630 nm light. These modalities are combined with pre-treatment of urea and/or
microabrasion for better penetration. PDT treatments are well tolerated with only
mild transient pain, burning and erythema. In addition, significant cure rates
for patients who have contraindications to oral medications or failed standard
medications can be obtained. With further enhancements in photosensitizer
permeability, decreased pre-treatment and photosensitizer incubation times, PDT
can be a more efficient and cost-effective in office based treatment for
onychomycosis. However, more large-scale randomized control clinical trials are
needed to access the efficacy of PDT treatments.
PMID- 25589057
TI - Feasibility of establishing a biosafety level 3 tuberculosis culture laboratory
of acceptable quality standards in a resource-limited setting: an experience from
Uganda.
AB - BACKGROUND: Despite the recent innovations in tuberculosis (TB) and multi-drug
resistant TB (MDR-TB) diagnosis, culture remains vital for difficult-to-diagnose
patients, baseline and end-point determination for novel vaccines and drug
trials. Herein, we share our experience of establishing a BSL-3 culture facility
in Uganda as well as 3-years performance indicators and post-TB vaccine trials
(pioneer) and funding experience of sustaining such a facility. METHODS: Between
September 2008 and April 2009, the laboratory was set-up with financial support
from external partners. After an initial procedure validation phase in parallel
with the National TB Reference Laboratory (NTRL) and legal approvals, the
laboratory registered for external quality assessment (EQA) from the NTRL, WHO,
National Health Laboratories Services (NHLS), and the College of American
Pathologists (CAP). The laboratory also instituted a functional quality
management system (QMS). Pioneer funding ended in 2012 and the laboratory
remained in self-sustainability mode. RESULTS: The laboratory achieved
internationally acceptable standards in both structural and biosafety
requirements. Of the 14 patient samples analyzed in the procedural validation
phase, agreement for all tests with NTRL was 90% (P <0.01). It started full
operations in October 2009 performing smear microscopy, culture, identification,
and drug susceptibility testing (DST). The annual culture workload was 7,636,
10,242, and 2,712 inoculations for the years 2010, 2011, and 2012, respectively.
Other performance indicators of TB culture laboratories were also monitored.
Scores from EQA panels included smear microscopy >80% in all years from NTRL,
CAP, and NHLS, and culture was 100% for CAP panels and above regional average
scores for all years with NHLS. Quarterly DST scores from WHO-EQA ranged from 78%
to 100% in 2010, 80% to 100% in 2011, and 90 to 100% in 2012. CONCLUSIONS: From
our experience, it is feasible to set-up a BSL-3 TB culture laboratory with
acceptable quality performance standards in resource-limited countries. With the
demonstrated quality of work, the laboratory attracted more research groups and
post-pioneer funding, which helped to ensure sustainability. The high skilled
experts in this research laboratory also continue to provide an excellent
resource for the needed national discussion of the laboratory and quality
management systems.
PMID- 25589060
TI - Abscisic acid and the key enzymes and genes in sucrose-to-starch conversion in
rice spikelets in response to soil drying during grain filling.
AB - MAIN CONCLUSION: Abscisic acid mediates the effect of post-anthesis soil drying
on grain filling through regulating the activities of key enzymes and expressions
of genes involved in sucrose-to-starch conversion in rice spikelets. This study
investigated if abscisic acid (ABA) would mediate the effect of post-anthesis
soil drying on grain filling through regulating the key enzymes in sucrose-to
starch conversion in rice (Oryza sativa L.) spikelets. Two rice cultivars were
field-grown. Three treatments, well-watered (WW), moderate soil drying (MD), and
severe soil drying (SD), were imposed from 6 days after full heading until
maturity. When compared with those under the WW, grain filling rate, grain
weight, and sink activity, in terms of the activities and gene expression levels
of sucrose synthase, ADP glucose pyrophosphorylase, starch synthase, and starch
branching enzyme, in inferior spikelets were substantially increased under the
MD, whereas they were markedly decreased in both superior and inferior spikelets
under the SD. The two cultivars showed the same tendencies. Both MD and SD
increased ABA content and expression levels of its biosynthesis genes in
spikelets, with more increase under the SD than the MD. ABA content was
significantly correlated with grain filling rate and sink activities under both
WW and MD, while the correlations were not significant under the SD. Application
of a low concentration ABA to WW plants imitated the results under the MD, and
applying with a high concentration ABA showed the effect of the SD. The results
suggest that ABA plays a vital role in grain filling through regulating sink
activity and functions in a dose-dependent manner. An elevated ABA level under
the MD enhances, whereas a too high level of ABA under the SD decreases, sink
activity.
PMID- 25589061
TI - Within-visit blood pressure variability is associated with prediabetes and
diabetes.
AB - We investigated the associations between within-visit blood pressure variability
(BPV) and risk factors for cardiovascular disease (CVD). The study subjects
included 17,795 people aged 40-74 years who underwent health check-ups in Aichi
Prefecture, Japan, and completed two blood pressure measurements. Subjects were
categorized into three groups according to the difference of systolic blood
pressure (DeltaSBP), namely, low-BPV (<= 10 mmHg), moderate-BPV (11-20 mmHg), and
high-BPV (> 20 mmHg). Subjects were also divided into three categories as those
without prediabetes (glycosylated hemoglobin A1c [HbA1c] < 5.7%), prediabetes
(HbA1c 5.7-6.4%) and diabetes (HbA1c >= 6.5% or under treatment for diabetes).
The proportion of prediabetes and diabetes were significantly higher in subjects
with high-BPV than in those with low-BPV after adjusting for age, sex, and mean
SBP (odds ratio [95% confidence interval] was 1.16 [1.01-1.33] for prediabetes
and 1.33 [1.06-1.66] for diabetes). Other CVD risk factors were not associated
with high-BPV after the adjustment. In conclusion, increased within-visit BPV was
significantly associated with the prevalence of prediabetes and diabetes,
independent of mean SBP, in a large general population. Therefore, assessing BPV
in a single visit may help to identify subjects at increased risk of impaired
glycemic control.
PMID- 25589062
TI - Influence of food condiments on the formation of carcinogenic heterocyclic amines
in cooked chicken and determination by LC-MS/MS.
AB - Heterocyclic amines (HCAs) are known to be suspected human carcinogens produced
by high-temperature cooking of protein-rich foods such as meat and fish. In the
present study, the influence of numerous food condiments on the formation of HCAs
in cooked chicken was investigated. Chicken samples were subjected to pan-frying
under controlled temperature. The levels of HCAs DMIP, MeIQx, 4,8-DiMeIQx, PhIP,
harman and norharman were found to be between 0.93 and 27.52 ng g(-1), whereas
IQ, MeIQ, AalphaC, MeAalphaC, Trp-P-1 and Trp-P-2 were found either below the
limit of quantification or not detected in the control sample. Nevertheless, for
samples cooked using food condiments, the amounts of HCAs (DMIP, MeIQx, 4,8
DiMeIQx and PhIP) were between 0.14 and 19.57 ng g(-1); harman and norharman were
detected at higher concentrations up to 17.77 ng g(-1) while IQ and MeIQ were at
levels below the limit of quantification; and AalphaC, MeAalphaC, Trp-P-1 and Trp
P-2 were not detected in any of the samples. The outcomes revealed that the
formation of HCAs (except harman and norharman) diminished after the addition of
food condiments. Edible oil contributed to the highest levels of HCA formation,
followed by garlic, paprika, pepper and tomato.
PMID- 25589063
TI - Personalized- and one- medicine: bioinformatics foundation in health and its
economic feasibility.
AB - Personalized medicine's foundation rests on the use of molecular technologies,
which are being used to identify genetic mutations, polymorphisms, and variants
that can be associated with an individual's genetic make up, revealing risk
factors and predictive data. Needless to say this same analysis can be performed
on various types of cancers, including samples stored for many years under the
right conditions. For the most part, these technologies employ microarray and RNA
Seq methodologies, which examine large numbers of gene expressions at a time,
providing clustering and patterns of this expression. The methodologies and their
evaluative outcomes further demonstrate that more than a single gene is involved
with various phenomena. However, given the mass of data emerging from this
analysis, and commonalities they reveal between various phenomena/disorders,
achieving 100% certainty may not be that easy. Another outcome from this massive
store of molecular data is the concept of one medicine. This field has been
developed by researchers in a variety of disciplines (e.g., medical and
veterinary science) that advocate for greater integration of animal and human
health. One medicine takes advantage of the fact that molecular commonalities in
major biochemical pathways occur because of evolutionary conservation, which is
dependent on stereospecificity. In this regard, the foci of personalized medicine
and one medicine are quite broad and require trained professionals, as well as a
lowering of cost in order to be better integrated into mainstream medical
practice.
PMID- 25589065
TI - Sharing clinical trial data should become the "expected norm," US panel says.
PMID- 25589064
TI - Tick-borne haemoparasites in African buffalo (Syncerus caffer) from two wildlife
areas in Northern Botswana.
AB - BACKGROUND: The African buffalo (Syncerus caffer) is a host for many pathogens
known to cause economically important diseases and is often considered an
important reservoir for livestock diseases. Theileriosis, heartwater, babesiosis
and anaplasmosis are considered the most important tick-borne diseases of
livestock in sub-Saharan Africa, resulting in extensive economic losses to
livestock farmers in endemic areas. Information on the distribution of tick-borne
diseases and ticks is scarce in Northern Botswana. Nevertheless, this data is
necessary for targeting surveillance and control measures in livestock production
at national level. METHODS: In order to address this gap, we analyzed 120 blood
samples from buffalo herds for the presence of common tick-borne haemoparasites
causing disease in livestock, collected in two of the main wildlife areas of
Northern Botswana: the Chobe National Park (CNP, n=64) and the Okavango Delta
(OD, n=56). RESULTS: Analysis of the reverse line blot (RLB) hybridization assay
results revealed the presence of Theileria, Babesia, Anaplasma and Ehrlichia
species, either as single or mixed infections. Among the Theileria spp. present,
T. parva (60%) and T. mutans (37%) were the most prevalent. Other species of
interest were Anaplasma marginale subsp. centrale (30%), A. marginale (20%),
Babesia occultans (23%) and Ehrlichia ruminantium (6%). The indirect fluorescent
antibody test (IFAT) indicated 74% of samples to be positive for the presence of
T. parva antibodies. Quantitative real-time PCR (qPCR) detected the highest level
of animals infected with T. parva (81% of the samples). The level of agreement
between the tests for detection of T. parva positive animals was higher between
qPCR and IFAT (kappa=0.56), than between qPCR and RLB (kappa=0.26) or the latter
and IFAT (kappa=0.15). CONCLUSIONS: This is the first report of tick-borne
haemoparasites in African buffalo from northern Botswana, where animals from the
CNP showed higher levels of infection than those from OD. Considering the absence
of fences separating wildlife and livestock in the CNP and the higher levels of
some parasite species in buffalo from that area, surveillance of tick-borne
diseases in livestock at the interface in the CNP should be prioritized.
PMID- 25589066
TI - High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa
keratitis.
AB - High-mobility group box 1 (HMGB1), a prototypic alarmin, mediates the systemic
inflammatory response syndrome. Treatment with vasoactive intestinal peptide, an
anti-inflammatory neuropeptide, downregulates proinflammatory cytokines and
promotes healing in a susceptible (cornea perforates) model of Pseudomonas
aeruginosa keratitis, and also significantly downregulates HMGB1 expression.
Therefore, we examined targeting HMGB1 for the treatment of P. aeruginosa
keratitis to avoid delivery and other issues associated with vasoactive
intestinal peptide. For this, HMGB1 was silenced using small interfering RNA,
whereas controls were treated with a nonspecific scrambled sequence small
interfering RNA. Less disease was seen postinfection in siHMGB1 compared with
control mice and was documented by clinical score and photographs with a slit
lamp. Real-time RT-PCR and ELISA confirmed HMGB1 knockdown. RT-PCR analysis also
revealed reduced mRNA levels of IL-1beta, MIP-2, TNF-alpha, TLR4, and receptor
for advanced glycation end products, whereas mRNA levels of anti-inflammatory
TLRs single Ig IL-1-related receptor and ST2 were increased significantly. HMGB1
knockdown also decreased IL-1beta and MIP-2 proteins, reducing polymorphonuclear
cell number in the infected cornea. mRNA and protein levels of CXCL12 and CXCR4,
as well as mononuclear cells, were reduced significantly after HMGB1 knockdown.
Ab neutralization of HMGB1, infection with a clinical isolate, and recombinant
HMGB1 treatment of resistant mice supported the silencing studies. These data
provide evidence that silencing HMGB1 promotes better resolution of P. aeruginosa
keratitis by decreasing levels of proinflammatory mediators (decreasing
polymorphonuclear cell infiltration), increasing anti-inflammatory TLRs, reducing
CXCL12 (preventing HMGB1/CXCL12 heterodimer formation), and signaling through
CXCR4, reducing monocyte/macrophage infiltration.
PMID- 25589067
TI - A novel regulatory macrophage induced by a helminth molecule instructs IL-10 in
CD4+ T cells and protects against mucosal inflammation.
AB - Immunomodulation is a common feature of chronic helminth infections and mainly
attributed to the secretion of bioactive molecules, which target and modify host
immune cells. In this study, we show that the helminth immunomodulator
AvCystatin, a cysteine protease inhibitor, induces a novel regulatory macrophage
(Mreg; AvCystatin-Mreg), which is sufficient to mitigate major parameters of
allergic airway inflammation and colitis in mice. A single adoptive transfer of
AvCystatin-Mreg before allergen challenge suppressed allergen-specific IgE
levels, the influx of eosinophils into the airways, local and systemic Th2
cytokine levels, and mucus production in lung bronchioles of mice, whereas
increasing local and systemic IL-10 production by CD4(+) T cells. Moreover, a
single administration of AvCystatin-Mreg during experimentally induced colitis
strikingly reduced intestinal pathology. Phenotyping of AvCystatin-Mreg revealed
increased expression of a distinct group of genes including LIGHT, sphingosine
kinase 1, CCL1, arginase-1, and costimulatory molecules, CD16/32, ICAM-1, as well
as PD-L1 and PD-L2. In cocultures with dendritic cells and CD4(+) T cells,
AvCystatin-Mreg strongly induced the production of IL-10 in a cell-contact
independent manner. Collectively, our data identify a specific suppressive
macrophage population induced by a single parasite immunomodulator, which
protects against mucosal inflammation.
PMID- 25589069
TI - Vaccine adjuvant MF59 promotes retention of unprocessed antigen in lymph node
macrophage compartments and follicular dendritic cells.
AB - Ag retention within lymph nodes (LNs) upon vaccination is critical for the
development of adaptive immune responses, because it facilitates the encounter of
the Ag with cognate lymphocytes. During a secondary exposure of the immune system
to an Ag, immune complexes (ICs) that contain the unprocessed Ag are captured by
subcapsular sinus macrophages and are transferred onto follicular dendritic
cells, where they persist for weeks, facilitating Ag presentation to cognate
memory B cells. The impact of adjuvants on Ag retention within the draining LNs
is unknown. In this article, we provide the first evidence, to our knowledge,
that the oil-in-water emulsion adjuvant MF59 localizes in subcapsular sinus and
medullary macrophage compartments of mouse draining LNs, where it persists for at
least 2 wk. In addition, we demonstrate that MF59 promotes accumulation of the
unprocessed Ag within these LN compartments and facilitates the consequent
deposition of the IC-trapped Ag onto activated follicular dendritic cells. These
findings correlate with the ability of MF59 to boost germinal center generation
and Ag-specific Ab titers. Our data suggest that the adjuvant effect of MF59 is,
at least in part, due to an enhancement of IC-bound Ag retention within the LN
and offer insights to improve the efficacy of new vaccine adjuvants.
PMID- 25589070
TI - 5-lipoxygenase is a direct target of miR-19a-3p and miR-125b-5p.
AB - 5-Lipoxygenase (5-LO) is the key enzyme in leukotriene biosynthesis. Leukotrienes
are mediators of the innate immune system and inflammatory processes, and they
might also be involved in cancer development. MicroRNAs (miRNAs) are important
translational regulators and have been shown to be involved in development,
differentiation, and cancer. Unraveling the miRNA network is important for
understanding the cellular regulation processes. We identified two new miRNAs,
miR-19a-3p and miR-125b-5p, regulating 5-LO and confirmed direct interaction by
reporter gene assays. Furthermore, we investigated the regulation of 5-LO by
these two miRNAs in several cell types. Inhibition of both miRNAs by antagomirs
during differentiation of the myeloid cell line Mono Mac 6 led to a significant
increase in 5-LO protein expression. Stimulation of human T lymphocytes with PHA
resulted in a strong downregulation of 5-LO mRNA expression and in the induction
of miR-19a-3p. The inhibition of miR-19a-3p with an antagomir led to a
significant increase in 5-LO mRNA expression in T lymphocytes. Taken together,
our data reveal that miR-19a-3p and miR-125b-5p target 5-LO in a cell type- and
stimulus-specific manner.
PMID- 25589068
TI - Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution
inflammatory syndrome.
AB - Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS)
frequently complicates combined antiretroviral therapy and antituberculosis
therapy in HIV-1-coinfected tuberculosis patients. The immunopathological
mechanisms underlying TB-IRIS are incompletely defined, and improved
understanding is required to derive new treatments and to reduce associated
morbidity and mortality. We performed longitudinal and cross-sectional analyses
of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB
coinfected patients commencing antiretroviral therapy who did not develop TB
IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium
tuberculosis H37Rv (hkH37Rv) were used for IFN-gamma ELISPOT and RNA extraction.
Stored RNA was used for microarray and RT-PCR, whereas corresponding stored
culture supernatants were used for ELISA. Stored PBMC were used for perforin and
granzyme B ELISPOT and flow cytometry. There were significantly increased IFN
gamma responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035).
Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the
most significantly upregulated gene, with granzyme B among the top five (log2
fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream
experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression
and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced
in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell
(CD3(+)Valpha24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and
were a source of perforin. Our data implicate the granule exocytosis pathway in
TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this
condition will facilitate development of specific diagnostic and improved
therapeutic options.
PMID- 25589071
TI - The unappreciated intracellular lifestyle of Blastomyces dermatitidis.
AB - Blastomyces dermatitidis, a dimorphic fungus and the causative agent of
blastomycosis, is widely considered an extracellular pathogen, with little
evidence for a facultative intracellular lifestyle. We infected mice with spores,
that is, the infectious particle, via the pulmonary route and studied
intracellular residence, transition to pathogenic yeast, and replication inside
lung cells. Nearly 80% of spores were inside cells at 24 h postinfection with
10(4) spores. Most spores were located inside of alveolar macrophages, with
smaller numbers in neutrophils and dendritic cells. Real-time imaging showed
rapid uptake of spores into alveolar macrophages, conversion to yeast, and
intracellular multiplication during in vitro coculture. The finding of multiple
yeast in a macrophage was chiefly due to intracellular replication rather than
multiple phagocytic events or fusion of macrophages. Depletion of alveolar
macrophages curtailed infection in mice infected with spores and led to a 26-fold
reduction in lung CFU by 6 d postinfection versus nondepleted mice. Phase
transition of the spores to yeast was delayed in these depleted mice over a time
frame that correlated with reduced lung CFU. Spores cultured in vitro converted
to yeast faster in the presence of macrophages than in medium alone. Thus,
although advanced B. dermatitidis infection may exhibit extracellular residence
in tissue, early lung infection with infectious spores reveals its unappreciated
facultative intracellular lifestyle.
PMID- 25589073
TI - Selective blockade of CD28-mediated T cell costimulation protects rhesus monkeys
against acute fatal experimental autoimmune encephalomyelitis.
AB - Costimulatory and coinhibitory receptor-ligand pairs on T cells and APC control
the immune response. We have investigated whether selective blockade of CD28
CD80/86 costimulatory interactions, which preserves the coinhibitory CTLA4
CD80/86 interactions and the function of regulatory T (Treg) cells, abrogates the
induction of experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys.
EAE was induced by intracutaneous immunization with recombinant human myelin
oligodendrocyte glycoprotein (rhMOG) in CFA on day 0. FR104 is a monovalent,
PEGylated-humanized Fab' Ab fragment against human CD28, cross-reactive with
rhesus monkey CD28. FR104 or placebo was administered on days 0, 7, 14, and 21.
FR104 levels remained high until the end of the study (day 42). Placebo-treated
animals all developed clinical EAE between days 12 and 27. FR104-treated animals
did not develop clinical EAE and were sacrificed at the end of the study
resulting in a significantly prolonged survival. FR104 treatment diminished T and
B cell responses against rhMOG, significantly reduced CNS inflammation and
prevented demyelination. The inflammatory profile in the cerebrospinal fluid and
brain material was also strongly reduced. Recrudescence of latent virus was
investigated in blood, spleen, and brain. No differences between groups were
observed for the beta-herpesvirus CMV and the polyomaviruses SV40 and SA12. Cross
sectional measurement of lymphocryptovirus, the rhesus monkey EBV, demonstrated
elevated levels in the blood of FR104-treated animals. Blocking rhesus monkey
CD28 with FR104 mitigated autoreactive T and B cell activation and prevented CNS
pathology in the rhMOG/CFA EAE model in rhesus monkeys.
PMID- 25589074
TI - Monitoring and cell-specific deletion of C5aR1 using a novel floxed GFP-C5aR1
reporter knock-in mouse.
AB - Many of the biological properties of C5a are mediated through activation of its
receptor (C5aR1), the expression of which has been demonstrated convincingly on
myeloid cells, such as neutrophils, monocytes, and macrophages. In contrast,
conflicting results exist regarding C5aR1 expression in dendritic cells (DCs) and
lymphoid lineage cells. In this article, we report the generation of a floxed GFP
C5aR1 reporter knock-in mouse. Using this mouse strain, we confirmed strong C5aR1
expression in neutrophils from bone marrow, blood, lung, and spleen, as well as
in peritoneal macrophages. Further, we show C5aR1 expression in lung eosinophils,
lung- and lamina propria-resident and alveolar macrophages, bone marrow-derived
DCs, and lung-resident CD11b(+) and monocyte-derived DCs, whereas intestinal and
pulmonary CD103(+) DCs stained negative. Also, some splenic NKT cells expressed
GFP, whereas naive NK cells and B2 cells lacked GFP expression. Finally, we did
not observe any C5aR1 expression in naive or activated CD4(+) Th cells in vitro
or in vivo. Mating the floxed GFP-C5aR1 mouse strain with LysMCre mice, we were
able to specifically delete C5aR1 in neutrophils and macrophages, whereas C5aR1
expression was retained in DCs. In summary, our findings suggest that C5aR1
expression in mice is largely restricted to cells of the myeloid lineage. The
novel floxed C5aR1 reporter knock-in mouse will prove useful to track C5aR1
expression in experimental models of acute and chronic inflammation and to
conditionally delete C5aR1 in immune cells.
PMID- 25589072
TI - TLR signaling modulates side effects of anticancer therapy in the small
intestine.
AB - Intestinal mucositis represents the most common complication of intensive
chemotherapy, which has a severe adverse impact on quality of life of cancer
patients. However, the precise pathophysiology remains to be clarified, and there
is so far no successful therapeutic intervention. In this study, we investigated
the role of innate immunity through TLR signaling in modulating genotoxic
chemotherapy-induced small intestinal injury in vitro and in vivo. Genetic
deletion of TLR2, but not MD-2, in mice resulted in severe chemotherapy-induced
intestinal mucositis in the proximal jejunum with villous atrophy, accumulation
of damaged DNA, CD11b(+)-myeloid cell infiltration, and significant gene
alterations in xenobiotic metabolism, including a decrease in ABCB1/multidrug
resistance (MDR)1 p-glycoprotein (p-gp) expression. Functionally, stimulation of
TLR2 induced synthesis and drug efflux activity of ABCB1/MDR1 p-gp in murine and
human CD11b(+)-myeloid cells, thus inhibiting chemotherapy-mediated cytotoxicity.
Conversely, TLR2 activation failed to protect small intestinal tissues
genetically deficient in MDR1A against DNA-damaging drug-induced apoptosis. Gut
microbiota depletion by antibiotics led to increased susceptibility to
chemotherapy-induced mucosal injury in wild-type mice, which was suppressed by
administration of a TLR2 ligand, preserving ABCB1/MDR1 p-gp expression. Findings
were confirmed in a preclinical model of human chemotherapy-induced intestinal
mucositis using duodenal biopsies by demonstrating that TLR2 activation limited
the toxic-inflammatory reaction and maintained assembly of the drug transporter p
gp. In conclusion, this study identifies a novel molecular link between innate
immunity and xenobiotic metabolism. TLR2 acts as a central regulator of
xenobiotic defense via the multidrug transporter ABCB1/MDR1 p-gp. Targeting TLR2
may represent a novel therapeutic approach in chemotherapy-induced intestinal
mucositis.
PMID- 25589075
TI - Cutting edge: stage-specific requirement of IL-18 for antiviral NK cell
expansion.
AB - Although NK cells are considered part of the innate immune system, recent studies
have demonstrated the ability of Ag-experienced NK cells to become long-lived and
contribute to potent recall responses similar to T and B cells. The precise
signals that promote the generation of a long-lived NK cell response are largely
undefined. In this article, we demonstrate that NK cells require IL-18 signaling
to generate a robust primary response during mouse CMV (MCMV) infection but do
not require this signal for memory cell maintenance or recall responses. IL-12
signaling and STAT4 in activated NK cells increased the expression of the adaptor
protein MyD88, which mediates signaling downstream of the IL-18 and IL-1
receptors. During MCMV infection, NK cells required MyD88, but not IL-1R, for
optimal expansion. Thus, an IL-18-MyD88 signaling axis facilitates the prolific
expansion of NK cells in response to primary viral infection, but not recall
responses.
PMID- 25589077
TI - Zoonotic bacterial pathogens and mixed crop-livestock farming.
AB - Use of mixed crop-livestock farms (MCLFs) is one of the oldest and most
traditional farming methods practiced all over the world, and MCLFs are still one
of the major systems of food production, particularly for organic foods. On these
typically small farms, livestock are reared primarily on grass and naturally
grown crops, while composted animal wastes are used to fertilize the soil for
growing crops. Specific to organic MCLFs, biosecurity challenges arise from the
fact that animals are reared outdoors, which increases potential for contact with
disease vectors including wild birds, rodents, and insects. Organic regulations
do not allow the use of chemicals and antibiotics; therefore, alternative methods
for control of disease and zoonotic pathogens must be used. Due to the
biosecurity challenges and the complexity of the MCLF environment, methods for
control of zoonotic pathogens need to be carefully considered in order to be
effective and to abide by organic regulations if required. The objectives of this
study are to define the complex routes of transmission, as well as the prevalence
of potential zoonotic and possible interruption strategies of these pathogens
among the food animals and crops produced on MCLFs.
PMID- 25589078
TI - Functional properties of bicarbonates and lactic acid on chicken breast retail
display properties and cooked meat quality.
AB - Whole chicken breast was injected with potassium bicarbonate (PB), sodium
bicarbonate (SB), and potassium lactate (K-lactate) and salt, alone or in
combination at different concentration levels. The objectives were to 1)
investigate the effects of different concentration of PB, SB, and PL on
instrumental color, water-holding capacity (WHC), objective tenderness,
expressible moisture, and moisture content and 2) evaluate whether sodium
containing ingredients can be replaced with potassium as a potential strategy to
reduce total sodium content in the finished product. Results showed that chicken
breast tissue marinated with SB and PB had greater moisture retention, display
characteristics, and cooked product qualities than chicken breast tissue injected
with water and the nonmarinated control. The L* values (lightness) did not change
over the period of retail display and were not different compared to the control
(P>0.05). The chicken breast enhanced with SB, PB, and K-lactate retained better
retail display color than the controls (marinated with water and nonmarinated).
Increasing the potassium bicarbonate concentration from 0.5 to 1.5% significantly
improved the water-holding capacity (82.17 to 92.61%; P<0.05) and led to better
cook yield (83.84 to 91.96%). Shear force values were lower at the 0.5% level for
both SB and PB compared to the control. PB performed better on retail display and
cooked meat quality than SB. This study suggests that chicken breast tissue can
be marinated with KB as a healthier alternative to phosphate or SB.
PMID- 25589079
TI - Genetic analysis of leg problems and growth in a random mating broiler
population.
AB - Improvement in growth has been widely reported as the cause of increased
incidence of leg problems in broiler chickens. We report herein the genetic
relationship between growth and leg problems in a random mating broiler control
population. The traits studied were valgus (VL), varus (VR), and tibial
dyschondroplasia (TD), which were expressed on a binary scale of 0 (normal) and 1
(abnormal); growth rates from 0 to 4 wk (BWG 0-4) and from 0 to 6 wk of age (BWG
0-6); and residual feed intake from 5 to 6 wk of age (RFI 5-6). A threshold
linear mixed model was employed for the joint analysis of the categorical and
linear traits. Incidences of VL, VR, and TD were 26, 4, and 2%, respectively.
Heritability of leg problems ranged from 0.11 to 0.13. Phenotypic correlations
alluded to an unfavorable relationship between growth and leg problems; however,
the genetic relationship between growth and leg problems was extremely weak,
ranging from 0.01 to 0.08. There is, therefore, a basis for genetic improvement
in leg problems. However, improved management practices would also be important
to reduce incidence of leg problems in broiler chickens.
PMID- 25589076
TI - Macronutrient deprivation modulates antigen trafficking and immune recognition
through HSC70 accessibility.
AB - B lymphocytes exploit macroautophagy to capture cytoplasmic and nuclear proteins
within autophagosomes. Fusion of autophagosomes with lysosomes and endosomes
facilitates content proteolysis, with the resulting peptides selectively binding
MHC class II (MHC II) molecules, which are displayed for recognition by T
lymphocytes. Nutrient deprivation or stress amplified this pathway, favoring
increased MHC II presentation of cytoplasmic Ags targeted to autophagosomes. By
contrast, this stress diminished MHC II presentation of membrane Ags including
the BCR and cytoplasmic proteins that use the chaperone-mediated autophagy
pathway. Whereas intracellular protease activity increased with nutrient stress,
endocytic trafficking and proteolytic turnover of the BCR was impaired. Addition
of macronutrients such as high molecular mass proteins restored endocytosis and
Ag presentation, evidence of tightly regulated membrane trafficking dependent on
macronutrient status. Altering cellular levels of the cytosolic chaperone HSC70
was sufficient to overcome the inhibitory effects of nutritional stress on BCR
trafficking and Ag presentation. Together, these results reveal a key role for
macronutrient sensing in regulating immune recognition and the importance of
HSC70 in modulating membrane trafficking pathways during cellular stress.
PMID- 25589080
TI - Photostimulation of Japanese quail.
AB - To adapt commercial poultry production to a new scenario of energy savings and to
develop specific practices for quail production aimed at reducing costs while
maintaining or improving productivity, four experiments were conducted. In the
first experiment, birds were allocated to four treatments (photoperiod duration):
T1: 14 L:10 D; T2: 15 L:9 D; T3: 16 L:8 D; and T4: 17 L:7 D. In the second
experiment, birds were subjected to four levels of brightness: T1: 5 lux; T2: 10
lux; T3:15 lux; and T4: 22 lux (control). In the third experiment, four types of
lamps were evaluated: T1: compact fluorescent lamp (color temperature: 6,500 K);
T2: compact fluorescent lamp (color temperature: 2,700 K); T3: incandescent lamp;
and T4: yellow LED. In the last experiment, four lighting programs were compared:
T1: continuous program (control), in which there was a single photoperiod of 15
h; the other treatments consisted of intermittent lighting programs, as follows:
T2: 1 h of light provided 1 h after dusk; T3: 1 h of light provided 2 h before
dawn; T4: half an hour of light provided 1 h after dusk and half an hour of light
provided 1.5 h before dawn. In each experiment, 1,296 Japanese quail were
evaluated for four 28-d cycles, totaling 112 experimental days. A completely
randomized experimental design of 4 treatments with 12 replicates of 27 birds
each was applied in all trials. Performance and egg quality were evaluated in
each experiment. Higher egg production and adequate egg quality, as well as
energy savings, can be obtained with Japanese quail using compact fluorescent
lamps or LEDs and a photoperiod of 15 h/d supplied using an intermittent lighting
program, with 1 h of artificial light 2 h before dawn at a brightness of 5 lux.
PMID- 25589081
TI - Development of intestinal mucin 2, IgA, and polymeric Ig receptor expressions in
broiler chickens and Pekin ducks.
AB - Intestinal mucin 2 (MUC2), a major gel-forming mucin, represents a primary
barrier component of mucus layers and a target site for secretory IgA. Polymeric
Ig receptor (pIgR) expressed on the basolateral surface of epithelium is used to
transport polymeric IgA from the lamina propria into luminal mucins to establish
the first lines of intestinal defense. To determine the spatio-temporal
expression of MUC2, IgA, and pIgR in broiler chickens and Pekin ducks, intestinal
tissues (n=6/age) were dissected from late embryonic days up to 21 d posthatch.
In the intestinal tissues, MUC2 was expressed with a rapid increase at hatching,
followed by steady expression through 21 d posthatch both in chickens and ducks.
IgA expression was low during the first week following hatching for both species.
From the second week posthatch, IgA was rapidly expressed in the chickens,
arriving at steady expression in the third week after hatching. However, in
ducks, IgA expression during the 2 to 3 wk posthatch period was relatively slow.
The expression of pIgR was greatly increased after hatching for both species, but
its expression in ducks was relatively delayed. In addition, intestinal pIgR
expression was highly correlated with MUC2 and IgA expressions in chickens but
just moderately correlated in ducks. The relatively slow and late expression of
IgA and pIgR as well as their moderate correlation may or may not account for the
susceptibility of ducklings to mucosal pathogens at a young age.
PMID- 25589082
TI - Genetic parameters for body weight in meat quail.
AB - The aim of this study was to estimate genetic parameters for BW in meat quail at
different ages. A total of 24,382 weight records from 3,652 quail, born between
2009 and 2011, were evaluated. Weekly BW was measured from hatch until 42 d of
age. The genetic parameters were estimated by the restricted maximum likelihood
method using a multivariate animal model. Heritability of BW ranged from 0.03 to
0.23. Genetic correlations were mainly high and positive. Selection for BW at 28
d of age yielded good indirect genetic progress in BW at 42 d of age.
PMID- 25589083
TI - Cloacal and surface temperatures of tom turkeys exposed to different rearing
temperature regimes during the first 12 weeks of growth.
AB - Years of genetic selection have caused an increase in growth rate and market body
mass in agricultural poultry species compared to earlier genetic strains,
potentially altering their physiological requirements. The objective of this
study was to expose Hybrid Converter tom turkeys on a weekly basis to the
recommended rearing temperature regime (TCON: control) or 4 degrees C below the
recommended standard (TTRT: treatment) to determine their thermal responses. Once
per week for 12 weeks, 12 turkeys were individually exposed to either TCON or
TTRT for a 2-h period. Surface temperatures of the breast (TBREAST), wing
(TWING), drumstick (TDRUM), head (THEAD), and shank (TSHANK) were measured at 20
min intervals using an infrared camera, while a thermal data logger measured the
skin surface temperature under the wing (TLOGGER) at 30-s intervals. The cloacal
temperature (TCORE) was measured using a medical thermometer at the start and end
of the exposure period. Regardless of exposure temperature, the TBREAST (TCON:
P<0.001 and TTRT: P<0.001), TWING (TCON: P<0.001 and TTRT: P<0.001), and TDRUM
(TCON: P<0.001 and TTRT: P<0.001) decreased from weeks 4 to 6 and remained
constant from weeks 1 to 3 and 8 to 12. THEAD was elevated in week 2 (TCON:
P<0.001) or week 3 (TTRT: P<0.001), TSHANK increased slightly during week 3 for
both TCON (P<0.001) and TTRT (P<0.001), and TLOGGER (TCON: P<0.001 and TTRT:
P=0.001) and TCORE (TCON: P<0.001 and TTRT: P<0.001) were lower during the first
week. Thereafter, THEAD, TSHANK, TLOGGER, and TCORE remained constant. Exposure
to TTRT resulted in lower TBREAST, TWING, and TDRUM compared to TCON. Generally,
THEAD, TSHANK, TLOGGER, and TCORE were not affected by the different exposure
temperatures. The data demonstrated that the degree of thermal response expressed
is dependent on the location of measurement, age, and exposure temperature.
PMID- 25589084
TI - Four Measures of Change in Physiologic State During the Feeding Period of Very
Premature Infants.
AB - Precise assessment of infants' ability to regulate feeding challenges requires
modeling of physiologic values across intervals of the feeding period without
smoothing too much of the data stream. Using a subset of data from a study of
physiologic stability and feeding performance in very preterm (<=30 weeks'
gestational age) infants fed in two different feeding positions, this exploratory
study compared mean heart rate (HR) and its coefficient of variation sampled
during the feeding period using four methods: (1) dividing the feeding period
into three equal intervals; (2) extracting 2-min intervals from the initial,
middle, and final third of the feeding period; (3) using successive 2-min
intervals during the first 6 min of feeding; and (4) using successive 2-min
intervals during the entire feeding period. Power analysis simulation was
conducted with varying numbers of subjects to determine the method that requires
the least number of subjects to detect a position effect for change in HR across
time with 80% power. Different patterns of HR change across the feeding period
were observed across the methods, which suggest potential advantages and
disadvantages of each method. Among the four methods, using the first 6 min of
the feeding period required the fewest subjects to detect significant differences
in changes in HR across time between the feeding positions.
PMID- 25589085
TI - The Efficacy of a Family-Based Intervention Program on Childhood Obesity: A Quasi
Experimental Design.
AB - The purpose of this quasi-experimental study was to assess the efficacy of a
family-based (FB) weight-loss and behavior-modification intervention among
overweight/obese children (age 9-11 years) and their parents in Taiwan. The
intervention group (52 child-parent dyads) participated in an FB program for 7
weeks. The control group (55 child-parent dyads) received an educational pamphlet
about obesity prevention. The children's body mass index (BMI) z-scores were the
primary outcome variable. The parents' BMI, high-calorie (HC) food-intake
behaviors, screen-related behaviors, and restrictions on children's consumption
of HC foods and screen-related behaviors and the availability of HC foods at home
were the secondary outcome variables. Outcome variables were measured at baseline
(T0), at the end of the intervention (T1), and 4 weeks after the end of the
intervention (T2). A linear mixed model was used to assess the efficacy of the FB
program. Results indicated that the children's BMI z-scores decreased
significantly more from T0 to T2 in the experimental group than in the control
group. The decreases in parents' HC food-intake behaviors and availability of HC
foods at home and the increase in parental restrictions on children's consumption
of HC foods were significantly greater in the experimental than in the control
group from T0 to T1 and T0 to T2. The FB program was effective in modifying
parental behaviors and the weight of overweight/obese children in a Taiwanese
population.
PMID- 25589087
TI - Tackling fears about exercise is important for ME treatment, analysis indicates.
PMID- 25589086
TI - Illness perception in Polish patients with chronic diseases: Psychometric
properties of the Brief Illness Perception Questionnaire.
AB - The study evaluates the psychometric properties of a Polish translation of the
Brief Illness Perception Questionnaire. A total of 276 patients with chronic
conditions (58.7% women) completed the Brief Illness Perception Questionnaire and
the Hospital Anxiety and Depression Scale. The internal consistency of the Polish
Brief Illness Perception Questionnaire measured with Cronbach's alpha was
satisfactory (alpha = 0.74). Structural validity was demonstrated by significant
inter-correlations between the Brief Illness Perception Questionnaire components.
Discriminant validity was supported by the fact that the Brief Illness Perception
Questionnaire enables patients with various conditions to be differentiated.
Significant correlations were found between Brief Illness Perception
Questionnaire and depression and anxiety levels. The Polish Brief Illness
Perception Questionnaire thus evaluated is a reliable and valid tool.
PMID- 25589088
TI - Under-representation of women on governing bodies: women general practitioners on
Clinical Commissioning Groups in England.
AB - Recently formed Clinical Commissioning Groups in the English National Health
Service have important responsibility for commissioning local health and care
services. Women are under-represented on the governing bodies of these
significant primary care based organizations despite the fact that they
constitute almost half of the general practitioner workforce in England. This
essay examines some of the reasons for this under-representation including the
predominance of women in the salaried and part-time sector of general practice
and gendered management styles within the National Health Service. It is argued
that the under-representation of women on Clinical Commissioning Group governing
bodies matters in terms of social justice, representation of the broader
community and role models.
PMID- 25589090
TI - Dermatology has been decimated by political meddling.
PMID- 25589089
TI - Prevalence of major depressive disorder among spouses of men who use alcohol in a
rural community in Central Sri Lanka.
AB - AIMS: To estimate the prevalence of major depressive disorder (MDD) among spouses
of men who use alcohol in two rural areas in Sri Lanka, and to examine whether
the severity of alcohol-related problems (ARPs) in men and presence of alcohol
related domestic violence are associated with MDD among these women. METHOD: In a
cross-sectional study, ARPs among men were assessed using Alcohol Use Disorders
Identification Test (AUDIT) questionnaire filled in by men, and domestic violence
and husbands' drinking pattern data obtained from the women. MDD among the women
was ascertained using the Structured Clinical Interview for DSM-IV Disorders for
major depression. Using logistic regression we examined whether age, past history
of depression, different indices of ARPs and domestic violence were associated
with current MDD among the women. RESULTS: Point prevalence of MDD in the sample
was 33.3% (95% CI: 25.93, 40.73%). Once adjusted for other factors, morning
drinking of the spouse (odds ratio = 4.11, 95% CI: 1.25, 13.47; P = 0.019) and
increasing age (odds ratio = 1.05, 95% CI: 1.01, 1.09; P = 0.003) significantly
increased the odds of MDD. Being subjected to domestic violence/arguments also
had a trend to be associated with MDD among women, but was not significant (odds
ratio = 2.29, 95% CI: 0.95, 5.48; P = 0.062). CONCLUSION: The prevalence of MDD
among spouses of men who use alcohol is markedly higher than that has been
observed among Sri Lankan women in previous studies. The prevalence of MDD in
women seems to increase when their husbands are morning drinkers, and with
increasing age.
PMID- 25589091
TI - The prevention and management of rabies.
PMID- 25589092
TI - Narratives of HIV: measuring understanding of HIV and the law in HIV-positive
patients.
AB - OBJECTIVE: This study aimed to identify the understanding of people living with
HIV and AIDS (PLWHA) regarding the application of the law around transmission of
HIV in England and Wales. DESIGN: A questionnaire was designed to prompt
participants attending a large HIV department to discuss their understanding of
the law with reference to HIV transmission. The design focused on qualitative
analysis as there were insufficient data available to inform a metric reflecting
quantitative data on PLWHA's understanding of the legal implications of
transmission. METHODS: The data were collected from PLWHA attending their HIV
outpatient appointment to ensure relevance of population to the analysis. The
answers were analysed using grounded theory and thematic analysis to identify key
themes and theories for further testing. RESULTS: Analysis demonstrated that
understanding of legal obligations and outcomes of prosecutions was poor and
patchy, with behavioural restrictions often overstated. There was a strong theme
of ownership of responsibility amongst PLWHA, and of reference to principles of
morality beyond legal restrictions. CONCLUSIONS: PLWHA remain at risk of
prosecution through poor understanding of the law. Clinical services and advocacy
agencies should strive to increase understanding in order to enable PLWHA to
comprehend the law and negotiate it successfully. This information should be
shared as a process, not an isolated event.
PMID- 25589093
TI - Clinical Characteristics and Outcome of Cardiovascular Implantable Electronic
Device Infections in Turkey.
AB - Infection is one of the most devastating outcomes of cardiovascular implantable
electronic device (CIED) implantation and is related to significant morbidity and
mortality. In our country, there is no evaluation about CIED infection.
Therefore, our aim was to investigate clinical characteristics and outcome of
patients who had infection related to CIED implantation or replacement. The study
included 144 consecutive patients with CIED infection treated at 11 major
hospitals in Turkey from 2005 to 2014 retrospectively. We analyzed the medical
files of all patients hospitalized with the diagnosis of CIED infection.
Inclusion criteria were definite infection related to CIED implantation,
replacement, or revision. Generator pocket infection, with or without bacteremia,
was the most common clinical presentation, followed by CIED-related endocarditis.
Coagulase-negative staphylococci and Staphylococcus aureus were the leading
causative agents of CIED infection. Multivariate analysis showed that infective
endocarditis and ejection fraction were the strongest predictors of in-hospital
mortality.
PMID- 25589096
TI - GPs are advised to cut back on extra work to defend core services.
PMID- 25589095
TI - Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.
AB - 3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to
assess potential environmental and human health effects. A 14-day oral toxicity
study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200
by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and
food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced
at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a
90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO.
There was no effect on food consumption, body mass, or neurobehavioral
parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with
associated tubular degeneration and atrophy. The testicular effects were the most
sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70
mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d.
PMID- 25589094
TI - Advancing the science of measurement of diagnostic errors in healthcare: the
Safer Dx framework.
AB - Diagnostic errors are major contributors to harmful patient outcomes, yet they
remain a relatively understudied and unmeasured area of patient safety. Although
they are estimated to affect about 12 million Americans each year in ambulatory
care settings alone, both the conceptual and pragmatic scientific foundation for
their measurement is under-developed. Health care organizations do not have the
tools and strategies to measure diagnostic safety and most have not integrated
diagnostic error into their existing patient safety programs. Further progress
toward reducing diagnostic errors will hinge on our ability to overcome
measurement-related challenges. In order to lay a robust groundwork for
measurement and monitoring techniques to ensure diagnostic safety, we recently
developed a multifaceted framework to advance the science of measuring diagnostic
errors (The Safer Dx framework). In this paper, we describe how the framework
serves as a conceptual foundation for system-wide safety measurement, monitoring
and improvement of diagnostic error. The framework accounts for the complex
adaptive sociotechnical system in which diagnosis takes place (the structure),
the distributed process dimensions in which diagnoses evolve beyond the doctor's
visit (the process) and the outcomes of a correct and timely "safe diagnosis" as
well as patient and health care outcomes (the outcomes). We posit that the Safer
Dx framework can be used by a variety of stakeholders including researchers,
clinicians, health care organizations and policymakers, to stimulate both
retrospective and more proactive measurement of diagnostic errors. The feedback
and learning that would result will help develop subsequent interventions that
lead to safer diagnosis, improved value of health care delivery and improved
patient outcomes.
PMID- 25589098
TI - Between the paper mills and the World Wide Web.
PMID- 25589097
TI - The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen-Activated
Protein Kinase Inhibitors.
AB - The identification, synthesis, biological activity, and binding mode prediction
of a series of pyrazolobenzothiazines as novel p38alpha MAPK inhibitors are
reported. Some of these compounds showed interesting activity in both p38alpha
MAPK and TNF-alpha release assays. Derivative 6 emerged as the most interesting
compound with IC50 (p38alpha) = 0.457 MUm, IC50 (TNF-alpha) = 0.5 MUm and a
promising kinase selectivity profile. The obtained results strongly indicate the
pyrazolobenzothiazine core as a new p38alpha inhibitor chemotype worthy of future
chemical optimization efforts directed toward identifying a new generation of
anti-inflammatory agents.
PMID- 25589099
TI - [Seclusion--punishment or support?].
PMID- 25589100
TI - [Paternalism on the rise?].
PMID- 25589101
TI - [Re: Detection of cerebrospinal fluid leakage with tinted chlorhexidine].
PMID- 25589102
TI - [Re: Detection of cerebrospinal fluid leakage with tinted chlorhexidine].
PMID- 25589103
TI - [L.B. Karlsen and colleagues reply].
PMID- 25589104
TI - [Re: The working environment continues to cause illness].
PMID- 25589105
TI - [T.O.B. Aasen & J. Kongerud reply].
PMID- 25589106
TI - [Re: The working environment continues to cause illness].
PMID- 25589110
TI - [Re: Medication Reconciliation--important measure for better treatment].
PMID- 25589111
TI - [S. Madsen and colleagues reply].
PMID- 25589112
TI - [Re: Listening to patient preferences].
PMID- 25589113
TI - [B. Gjelsvik replies].
PMID- 25589116
TI - [Re: An integrated understanding of subjective disorders in clinical practice].
PMID- 25589117
TI - [A. Tveramo and colleagues reply].
PMID- 25589118
TI - [Re: Implementation of guidelines for PSA testing in general practice].
PMID- 25589120
TI - "Ten commandments" for psychopharmacology.
PMID- 25589121
TI - [Best treatment in nursing homes].
PMID- 25589122
TI - [Guidelines or personal experience?].
PMID- 25589125
TI - Compulsory hospitalisation in mental health care in Ostfold in 2000 and 2010.
AB - BACKGROUND: For many years, it has been an objective of national public health
policy in Norway to reduce the number of compulsory hospitalisations under the
Norwegian Mental Health Care Act. Uncertain data quality and inadequate reporting
have made it difficult to obtain reliable measurements of hospitalisation trends.
We have examined changes in psychiatric emergency admissions and compulsory
hospitalisations under the Mental Health Care Act between 2000 and 2010 in the
county of Ostfold. MATERIAL AND METHOD: The material on which the study is based
was gathered during two three-month periods - from 1 September to 30 November in
the years 2000 and 2010 respectively. We compared emergency admissions in
accordance with the national care quality indicator for compulsory
hospitalisation in mental health care and examined whether there were changes in
the diagnostic composition. RESULTS: The number of emergency admissions per 1,000
population in Ostfold increased from a rate of 7.05 in 2000 to 8.86 in 2010 (p <
0.001). There was no significant change in the rate of compulsory hospitalisation
during this period, being 2.48 and 2.24 per 1,000 population, respectively. There
was a sharp increase in the number of admissions for mental disorders related to
alcohol and illicit drug abuse. INTERPRETATION: The study material showed that
there was a significant increase in psychiatric emergency admissions between 2000
and 2010. The rate of compulsory hospitalisation, measured among the population
over the age of 18, remained unchanged during the period. The Norwegian Board of
Health Supervision's care quality indicator for compulsory hospitalisation in
mental health care can contribute to providing information and a basis of
comparison for the use of compulsory hospitalisation, provided that the data
submitted is quality assured. The highest increase was seen in the group of
emergency admissions for mental disorders related to alcohol and illicit drug
abuse as the principal diagnosis.
PMID- 25589126
TI - [Seclusion in emergency psychiatry].
AB - BACKGROUND: In Norway, seclusion (also called "shielding" or "open-area
seclusion") is often used as an intervention in inpatient psychiatric wards as a
continuation of milieu therapy, but the method remains controversial in health
policy. A psychiatrist or occasionally a psychologist is responsible for making a
decision on seclusion pursuant to Section 4-3 of the Mental Health Care Act.
Because of the uncertainty regarding the content and academic legitimacy of this
model, we have undertaken a review of available literature on the justification,
practical application and effect of the Norwegian tradition of seclusion.
MATERIAL AND METHOD: The article is based on systematic searches in national and
international databases for the years 1930-2013. RESULTS: The seclusion method is
closely associated with the development of psychiatric institutions, especially
the establishment of emergency units and milieu therapy. The concept of seclusion
covers a variety of approaches, and its knowledge base is generally poor.
Clinical treatment studies are largely of older origin and most likely not
descriptive of current practices. The absence of efficacy studies means that as
of today, we have little knowledge on the benefits of using seclusion as
treatment. INTERPRETATION: We detected a major discrepancy between the clinical
ubiquity of the seclusion method and its knowledge basis. There is a clear need
for more research on various types of seclusion to be able to assess the effects
of seclusion in current practice.
PMID- 25589127
TI - [Aortic aneurysm in a young woman].
PMID- 25589128
TI - [How to prevent recurrent urinary tract infections after menopause?].
PMID- 25589129
TI - [Asylum seekers on hunger strike--how far does the patient's right to refuse
treatment go?].
PMID- 25589134
TI - [Pregnant no asset].
PMID- 25589141
TI - Photoluminescence-tunable carbon nanodots: surface-state energy-gap tuning.
AB - The photoluminescence of carbon nanodots (C-dots) can be tuned by changing their
surface chemistry or size because the photoluminescence is a function of the
surface-state electronic transitions. Increasing the degree of surface oxidation
leads to a narrowing of the energy gap of the surface; meanwhile, larger C-dots
with an extensive pi-electron system, which can couple with surface electronic
states, can also lead to a narrowing of the energy gap of the surface states.
PMID- 25589142
TI - We are all accountable for our professional actions.
PMID- 25589143
TI - Antidepressant-like effects induced by NMDA receptor blockade and NO synthesis
inhibition in the ventral medial prefrontal cortex of rats exposed to the forced
swim test.
AB - RATIONALE: Systemic treatment with NMDA receptor (NMDAR) antagonists, inhibitors
of neuronal nitric oxide synthase (nNOS) or of soluble guanylyl cyclase (sGC),
induce antidepressant-like effects in rats. Increased levels of glutamate and
nitric oxide (NO) in the medial prefrontal cortex (MPFC) of stressed animals have
been described in the literature. However, the role of the NMDAR-nNOS-sGC pathway
of the MPFC in the mediation of forced swim-induced behaviors remains unclear.
OBJECTIVE: The aim of this work was to test the hypothesis that the inhibition of
the NMDAR-nNOS-sGC pathway in the ventral MPFC (infralimbic (IL) or prelimbic
(PL)) would elicit antidepressant-like effects in the forced swim test (FST).
METHODS: Rats implanted with cannulae aimed at the PL or the IL were exposed to
the FST and injected with LY235959 (NMDAR antagonist), NPA (nNOS inhibitor), ODQ
(sGC inhibitor), or carboxy-PTIO (NO scavenger). Additional groups received the
AMPA antagonist, NBQX, before the effective doses of LY235959 or NPA. RESULTS:
LY235959 administration into PL or IL before the FS pretest produced no effects.
Administration of LY235959 (3 and 10 nmol/0.2 MUL) after pretest was effective
only when administered into the PL. However, the administration of NPA (0.01
nmol/0.2 MUL), c-PTIO (1.0 nmol/0.2 MUL), and ODQ (1.0 nmol/0.2 MUL) into the PL
or IL before the FST produced antidepressant-like effects. NBQX blocked the
antidepressant-like effect of LY235959 but not of NPA. CONCLUSION: Blocking NMDAR
or NO signaling in the vMPFC, either in the IL or the PL, induces antidepressant
like effects in the rat FST. These effects seemingly occur through independent
mechanisms, since NBQX blocked the former effect but not the latter.
PMID- 25589146
TI - Neuroleptic malignant syndrome and the catatonic dilemma.
PMID- 25589144
TI - Age-dependent changes in cocaine sensitivity across early ontogeny in male and
female rats: possible role of dorsal striatal D2(High) receptors.
AB - RATIONALE: Responsiveness to acute psychostimulant administration varies across
ontogeny. OBJECTIVE: The purpose of the present study was to determine if age
dependent changes in D2(High) receptors may be responsible for the ontogeny of
cocaine sensitivity in preweanling, adolescent, and adult rats. METHODS: [(3)H]
Domperidone/dopamine competition assays were used to determine ontogenetic
changes in the proportion of D2(High) receptors in male and female preweanling
[postnatal day (PD) 5, 10, 15, and 20], adolescent (PD 40), and adult (PD 80)
rats. In the behavioral experiment, responsiveness to cocaine (2.5, 5, 10, or 20
mg/kg) was assessed on PD 20, PD 40, and PD 80 for 60 min. Male and female rats
were habituated to the apparatus on the 2 days prior to testing. Distance
traveled data were presented both untransformed and as percent of saline
controls. RESULTS: Male and female preweanling rats (PD 5-PD 20) had a
significantly greater percentage of dorsal striatal D2(High) receptors than
adolescent or adult rats. Likewise, preweanling rats (PD 20) were more sensitive
to the behavioral effects of cocaine than the two older age groups. Adolescent
and adult rats responded in a generally similar manner; however, analysis of the
untransformed locomotor activity data suggested that adolescent rats were
hyporesponsive to 2.5 and 20 mg/kg cocaine when compared to adults. CONCLUSIONS:
Data from the present study are consistent with the hypothesis that ontogenetic
changes in D2(High) receptors are responsible for age-dependent differences in
psychostimulant sensitivity.
PMID- 25589145
TI - Nucleus accumbens AMPA receptor involvement in cocaine-conditioned place
preference under different dietary conditions in rats.
AB - RATIONALE: When ad libitum-fed (AL) rats undergo cocaine place preference
conditioning (CPP) but are switched to food restriction (FR) for testing, CPP is
enhanced and preference scores correlate with phosphorylation of alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 at Ser845 in
nucleus accumbens (NAc) core. OBJECTIVES: The present study tested whether a
similar association exists in AL rats and whether an inhibitor of Ca(2+)
permeable AMPARs blocks CPP expression in either diet group. MATERIALS AND
METHODS: In experiments 1-3, AL rats were conditioned with cocaine (12.0 mg/kg,
i.p.). Three weeks later, CPP was tested daily and brains were harvested after
the fifth test. Western analyses were used to probe for levels of AMPA receptors
in NAc. In experiment 4, AL rats were conditioned, half were switched to FR for
testing, and half in each diet group received NAc core microinjection of 1
naphthylacetyl spermine (NASPM (NASPM) (25.0 MUg) prior to each test. RESULTS: In
experiment 1, CPP expression in AL rats was associated with elevated pSer845
GluA1, GluA1, and GluA2 in NAc. In experiment 2, the correlation between pSer845
GluA1 and CPP was localized to NAc core. In experiment 3, pSer845-GluA1 following
a CPP test was higher in NAc synaptic membranes of FR relative to AL rats. In
experiment 4, NASPM blocked CPP expression in both diet groups. CONCLUSIONS:
Results support a scheme in which pSer845-GluA1 in NAc core underlies expression
of cocaine CPP and does so by stabilizing or trafficking Ca(2+)-permeable AMPARs
to the synaptic membrane. The more robust CPP of FR rats may result from
upregulation of stimulus-induced pSer845-GluA1.
PMID- 25589147
TI - Incidence and identification of inadvertent lumbar vein catheterisation in the
NICU.
PMID- 25589148
TI - Tadehaginoside modulates lipogenesis and glucose consumption in HepG2 cells.
AB - Tadehaginoside (TS) is a phenylpropanoid glycoside found in Tadehagi triquetrum,
a medicinal plant with multiple biological activities. This study investigated
the effect of TS on lipogenesis and glucose consumption in HepG2 cells. Treatment
with TS inhibited lipid accumulation in a dose-dependent manner. This inhibition
was closely associated with the downregulation of lipogenic genes such as SREBP
1a, SREBP-2 and their downstream targets (FAS, ACC, HMGR) and the upregulation of
lipolytic gene PPARalpha as revealed by real-time quantitative PCR. Further
investigation showed that TS significantly stimulated glucose consumption by
HepG2 cells and glucose uptake by C2C12 myotubes, which could be partially
explained by the upregulation of PPARgamma. Collectively, these results clearly
indicate that TS is an effective regulator of lipogenesis and glucose
consumption, which could be useful in treatment of obesity and diabetes.
PMID- 25589149
TI - The role of the body in end-stage kidney disease in young adults: Gender, peer
and intimate relationships.
AB - OBJECTIVES: To understand how the physical body, and changes in the physical
body, influence peer and intimate relationships and parenting in young adults on
renal replacement therapies (RRT). METHODS: Qualitative interview data from 40
young adults aged 16-30 years with end-stage kidney disease (ESKD), first
diagnosed aged 0-19 years, were analysed using modified grounded theory.
FINDINGS: Alternating modalities of RRT had a 'yo-yo' effect on the bodies of
interviewees, repeatedly reconstructing them as either 'transplanted' bodies,
often initially obese, or as 'dialysis' bodies', often underweight. Invisible
somatic changes had a major impact on gendered social identity, making intimate
social relationships and parenthood problematic. Prepubertal onset interviewees
were generally less successful in forming partnerships than those with
postpubertal onset; and interviewees on dialysis were likely to postpone
partnering until they were transplanted. Social networks were essential for
finding a partner, but male interviewees had fewer networks than females.
Parenthood was particularly challenging for female interviewees. CONCLUSIONS: In
ESKD, life-saving RRT brings major changes to the body. These adversely affect
social relationships and family formation during the crucial period of early
adulthood. Effects vary according to age of onset, RRT modality, and gender, with
those who were ill before puberty and those on dialysis worst affected.
PMID- 25589150
TI - State level variations in nephrology workforce and timing and incidence of
dialysis in the United States among children and adults: a retrospective cohort
study.
AB - BACKGROUND: Multiple factors influence timing of dialysis initiation. The impact
of supply of nephrology workforce on timing and incidence of dialysis initiation
is not well known. METHODS: We determined the number of pediatric and adult
nephrologists in each state using data from the American Medical Association and
American Boards of Internal Medicine and Pediatrics. We ascertained state
population data from the 2010 US Census. United States Renal Data System (USRDS)
data were used to determine estimated glomerular filtration rate (eGFR) at
dialysis initiation and dialysis incidence for adults (>=18 years) in 2008 and
children (<18 years) in 2007-2009 by state. RESULTS: Across all states, there
were a median of 3.0 (IQR 2.3 to 3.4) adult nephrologists per 100,000 adults and
0.5 (IQR 0.2 to 0.9) pediatric nephrologists per 100,000 children. The median
eGFR at start of dialysis was 9.8 mL/min/1.73 m2 (IQR 7.1-13.1) in adults and 8.5
mL/min/1.73 m2 (IQR 6.2-11.4) in children. Neither the number of adult (Spearman
r of 0.02 [95% CI -0.26-0.30], p = 0.88) nor pediatric (Spearman r of -0.13 [95%
0.39-0.15], p = 0.38) nephrologists per state population was associated with mean
eGFR across states. The number of nephrologists per state population was
associated with incident dialysis cases per state population in adults (Spearman
r of 0.50 [95% CI 0.26-0.68], p = 0.0002), but not in children (Spearman r of
0.06 [95% CI -0.33-0.22], p = 0.67). In linear regression models, the association
between nephrologists per state population and incident dialysis cases per state
population remained statistically significant (p = 0.006) after adjustment for
provider characteristics. CONCLUSIONS: Nephrology workforce supply is aligned
with demand but does not appear to be associated with timing of dialysis
initiation.
PMID- 25589151
TI - Prospective trial of breast MRI versus 2D and 3D ultrasound for evaluation of
response to neoadjuvant chemotherapy.
AB - BACKGROUND: Preoperative imaging to assess response to neoadjuvant chemotherapy
in breast cancer is routine but no single imaging modality is standard of
practice. Our hypothesis is that ultrasound (US) is comparable to magnetic
resonance imaging (MRI) in the prediction of residual disease. METHODS: A single
institution, Institutional Review Board-approved prospective trial of primary
invasive ductal breast cancer patients receiving neoadjuvant chemotherapy
enrolled women from 2008 to 2012. Two-dimensional (2D) and three-dimensional (3D)
US, as well as MRI images of pre- and post-neoadjuvant tumors were obtained. Skin
involvement or inadequate images were excluded. Residual tumor on imaging was
compared with surgical pathology. Differences of tumor volume on imaging and
pathology were compared using the non-parametric Wilcoxon signed-rank test. US to
MRI agreement was determined by the kappa coefficient. Tumor volumes in estrogen
receptor (ER), progesterone receptor (PR), and Her2neu subgroups were compared
using the Kruskal-Wallis test. ER/PR staining <5 % was considered negative;
Her2neu status was determined by in situ hybridization. RESULTS: Forty-two
patients were enrolled in the study; 39 had evaluable post-treatment data. Four
patients were Her2neu positive, and 17 (46 %) patients had triple-negative
tumors. Among 11 (28 %) patients with pathologic complete response (pCR), US
correctly predicted pCR in six (54.5 %) patients compared with eight (72.7 %)
patients when MRI was used. This is a substantial agreement between US and MRI in
predicting pCR (kappa = 0.62). There was no difference between 2D and 3D US
modalities. For the 39 patients, US and MRI had no significant difference in
volume estimation of pathology, even stratified by receptor status. CONCLUSION:
The estimation of residual breast tumor volume by US and MRI achieves similar
results, including prediction of pCR.
PMID- 25589152
TI - Incorporation of radiotherapy in the multidisciplinary treatment of isolated
retroperitoneal lymph node recurrence from colorectal cancer.
AB - PURPOSE: This article was designed to study the clinical outcomes and prognostic
factors following radiotherapy (RT) in the multidisciplinary management of
isolated retroperitoneal lymph node (RPLN) recurrence of colorectal cancer.
METHODS: We identified 52 patients treated consecutively with tumor-directed RT
for isolated RPLN recurrence. Twenty-five patients received upfront RT (Group 1).
Twenty-seven patients received RT after systemic therapy. The deferred RT was
administered either to locally controlled tumors (Group 2, n = 17) or to locally
progressive tumors in RPLNs (Group 3, n = 10). RESULTS: The median overall
survival and progression-free survival were 41 and 13 months, respectively, with
a median follow-up time of 34 months. Survival was not significantly different
among three groups. Local recurrence (32/52) was predominant and occurred earlier
than distant metastasis (31/52). Two-thirds of the local recurrences (21/32)
involved outfield recurrence, which was mostly in the cranial direction (15/21)
from the upper margin of the RT volume. Repeated RT successfully salvaged a
substantial number of patients. A shorter disease-free interval, low-dose
radiation, and a tumor location above the renal vein were independent risk
factors for local recurrence (all P < 0.05). A large gross tumor volume was an
independent risk factor for distant metastasis (P = 0.037). No acute or late RT
related toxicity >= grade 3 occurred. CONCLUSIONS: Our analysis suggests that
both upfront RT and deferred RT incorporated into multidisciplinary management
are potentially effective treatment strategies. We found that gross tumor volume,
tumor location, and disease-free interval are important prognostic factors and
should be taken into consideration to decide the timing of RT.
PMID- 25589153
TI - High levels of anomalous self-experience are associated with longer duration of
untreated psychosis.
AB - AIM: To investigate the relationship between anomalous self-experiences and
duration of untreated psychosis in a sample of patients with first-episode
schizophrenia spectrum disorders. METHODS: Anomalous self-experiences were
assessed by means of the Examination of Anomalous Self-Experience manual in 55
patients referred to their first adequate treatment for schizophrenia. Diagnoses,
symptom severity, functioning and childhood trauma were assessed using the
Structured Clinical Interview for the Positive and Negative Syndrome Scale,
Premorbid Adjustment Scale, Social Functioning Scale and Childhood Trauma
Questionnaire. Substance misuse was measured with the Drug Use Disorder
Identification Test, and alcohol use was measured with the Alcohol Use Disorder
Identification Test. Duration of untreated psychosis was measured in accordance
with a standardized procedure. RESULTS: High levels of anomalous self-experiences
are significantly associated with longer duration of untreated psychosis, an
association which held after correcting for other variables associated with long
duration of untreated psychosis. CONCLUSIONS: The field of early detection in
psychosis is in need of additional clinical perspectives to make further
progress. Improved understanding and assessment of anomalous self-experiences may
help clinicians to detect these important phenomena and provide earlier help, and
thus reduce treatment delay.
PMID- 25589154
TI - Surgery under general anaesthesia in severe hidradenitis suppurativa: a study of
363 primary operations in 113 patients.
AB - BACKGROUND: Treatment of hidradenitis suppurativa (HS) is a difficult
undertaking, especially as there is no consensus on what surgical technique is
preferred. At our centre severe HS (Hurley II/III) is operated under general
anaesthesia, mostly with the STEEP procedure. OBJECTIVES: To investigate
characteristics, surgical outcomes and patient satisfaction of HS patients who
underwent deroofing or STEEP under general anaesthesia. METHODS: A clinical
records-based retrospective analysis was conducted of all patients who had
surgery under general anaesthesia between 1999 and 2013. Patient satisfaction was
retrospectively investigated with questionnaires. RESULTS: A total of 482
operations (363 primary operations and 119 re-operations) were performed during
the study period. The proportion of women in the included population was 68%. The
median diagnostic delay (patient's and doctor's delay) was 6.5 years. Relapses
occurred after 29.2% of primary operations. Women had higher relapse rates than
men [odds ratio 2.85 (1.07;7.61)]. Hypergranulation of the wound was the most
common complication and occurred in 7% of all operations. The median score
patients attributed to the medical effect of surgery was eight of 10 (zero
corresponding to very dissatisfied and 10 to very satisfied). CONCLUSION: The
diagnostic delay in HS is long due to a lack of knowledge in both patients and
health care professionals, indicating that there is a need for education.
Deroofing and the STEEP are effective surgical procedures in severe cases of HS
and lead to a relatively high patient satisfaction. The postoperative relapse
risk is higher in women. Prospective studies are required for the development of
clear guidelines on the appropriate choice of surgery.
PMID- 25589156
TI - A molecular view of the role of chirality in charge-driven polypeptide
complexation.
AB - Polyelectrolyte molecules of opposite charge are known to form stable complexes
in solution. Depending on the system conditions, such complexes can be solid or
liquid. The latter are known as complex coacervates, and they appear as a second
liquid phase in equilibrium with a polymer-dilute aqueous phase. This work
considers the complexation between poly(glutamic acid) and poly(lysine), which is
of particular interest because it enables examination of the role of chirality in
ionic complexation, without changes to the overall chemical composition.
Systematic atomic-level simulations are carried out for chains of poly(glutamic
acid) and poly(lysine) with varying combinations of chirality along the backbone.
Achiral chains form unstructured complexes. In contrast, homochiral chains lead
to formation of stable beta-sheets between molecules of opposite charge, and
experiments indicate that beta-sheet formation is correlated with the formation
of solid precipitates. Changes in chirality along the peptide backbone are found
to cause "kinks" in the beta-sheets. These are energetically unfavorable and
result in irregular structures that are more difficult to pack together. Taken
together, these results provide new insights that may be of use for the
development of simple yet strong bioinspired materials consisting of beta-rich
domains and amorphous regions.
PMID- 25589155
TI - Sertraline and breastfeeding: review and meta-analysis.
AB - We examined the risk-benefit profile of sertraline treatment during
breastfeeding, summarized the available literature on sertraline use, presented
previously unpublished data, and performed a correlation-based meta-analysis of
sertraline serum levels in mother-infant pairs. We conducted a search of PubMed
and the National Library of Medicine LactMed database. We performed a meta
analysis to examine correlations between maternal and infant serum sertraline
levels in the existing literature and in previously unpublished data. Of 167
available infant sertraline levels, 146 (87.4 %) were below the limit of
detection, and the meta-analysis found no significant relationship between
maternal and infant sertraline concentrations. Of 150 infant desmethylsertraline
levels, 105 (70.0 %) were below the limit of detection. The correlation analysis
revealed a significant relationship between maternal and infant
desmethylsertraline concentrations, but this metabolite has only a fraction of
the activity of sertraline. A significant relationship was also found for the sum
of sertraline and desmethylsertraline, which stems primarily from the
contribution of desmethylsertraline. Sertraline is a first-line drug for
breastfeeding women due to documented low levels of exposure in breastfeeding
infants and very few adverse events described in case reports. Based on the
current literature, neither routine serum sampling nor genotyping is warranted
for breastfeeding mothers taking sertraline and/or their infants. Routine
pediatric care is appropriate monitoring for breastfed infants of women who take
sertraline monotherapy.
PMID- 25589157
TI - Nano/micro hybrid scaffold of PCL or P3HB nanofibers combined with silk fibroin
for tendon and ligament tissue engineering.
AB - A novel biodegradable nano/micro hybrid structure was obtained by electrospinning
P3HB or PCL nanofibers onto a twisted silk fibroin (SF) structure, with the aim
of fabricating a suitable scaffold for tendon and ligament tissue engineering.
The electrospinning (ES) processing parameters for P3HB and PCL were optimized on
2D samples, and applied to produce two different nano/micro hybrid constructs
(SF/ES-PCL and SF/ES-P3HB).Morphological, chemico-physical and mechanical
properties of the novel hybrid scaffolds were evaluated by SEM, ATR FT-IR, DSC,
tensile and thermodynamic mechanical tests. The results demonstrated that the
nanofibers were tightly wrapped around the silk filaments, and the crystallinity
of the SF twisted yarns was not influenced by the presence of the electrospun
polymers. The slightly higher mechanical properties of the hybrid constructs
confirmed an increase of internal forces due to the interaction between nano and
micro components. Cell culture tests with L929 fibroblasts, in the presence of
the sample eluates or in direct contact with the hybrid structures, showed no
cytotoxic effects and a good level of cytocompatibility of the nano/micro hybrid
structures in term of cell viability, particularly at day 1. Cell viability onto
the nano/micro hybrid structures decreased from the first to the third day of
culture when compared with the control culture plastic, but appeared to be higher
when compared with the uncoated SF yarns. Although additional in vitro and in
vivo tests are needed, the original fabrication method here described appears
promising for scaffolds suitable for tendon and ligament tissue engineering.
PMID- 25589158
TI - Microleakage of bacteria in different implant-abutment assemblies: an in vitro
study.
AB - PURPOSE: The aim of the present in vitro study was to evaluate the leakage
observed for 2 different microbial species at the level of the implant-abutment
(I-A) interface, and the marginal fit and size of microgap at the I-A interface
in 2 different implant connections. METHODS: Ten specimens of each group were
tested. The inner parts of 5 implants per group were inoculated with 0.1 MUL of a
viable Enterococcus faecalis suspension and 5 implants per group with
Aggregatibacter actinomycetemcomitans. All of the vials containing the control
specimens were incubated at 37 degrees C under aerobic condition for E. faecalis
and 37 degrees C in presence of 5% CO2 for A. actinomycetemcomitans. They were
maintained for 14 days, and the possible penetration of bacterial suspension into
the surrounding solution was determined by the observation of turbidity of the
broth. The I-A interface was evaluated for size of microgap and measured under
SEM. Five implants of each group were evaluated. The marginal fit between implant
and abutment was measured at 8 random locations in each assembly, under different
magnifications at the interface. RESULTS: No leakages through the I-A interface
were demonstrated for either type of connection evaluated. The microgap values of
all I-A interfaces ranged from 0.008 to 2.009 MUm; the differences between the 2
systems were statistically significant. CONCLUSIONS: The present study
demonstrated that a good marginal fit of implant components seemed to be able to
prevent bacterial leakage.
PMID- 25589159
TI - Local blood flow patterns in stented coronary bifurcations: an experimental and
numerical study.
AB - PURPOSE: Despite the atheroprone environment of blood flow in coronary
bifurcations, limited quantitative information is available on the hemodynamics
occurring in these geometries, both before and after their treatment with
endovascular stents. Previous studies have focused on computational fluid
dynamics (CFD) analyses and have bypassed the challenges associated with
experimentally representing the flow environment, providing no means for
validation. This study analyzed steady flow conditions in 3 bifurcation angles
and 4 different single- and double-stenting procedures, which are used clinically
in coronary bifurcations. METHODS: The numerical aspect of this study utilized
geometries derived from CAD models (nonstented cases) and finite element
simulations (stented cases). Digital particle image velocimetry (DPIV) testing
was conducted within compliant bifurcating models for which an uncertainty
analysis was performed at each measurement location for CFD validation purposes.
Results were analyzed in terms of velocity magnitude contour maps and axial
velocity profiles at several locations in the bifurcated vessels. RESULTS AND
CONCLUSIONS: Qualitatively, the 2 approaches showed agreement in the bulk flow
patterns. However, the velocity computed with CFD was outside the DPIV
uncertainty estimates, which can be attributed to the intrinsic difference and
modeling assumptions of the 2 approaches. The findings reveal that wider
bifurcation angles and double-stenting procedures are both characterized by
increased areas of low flow and recirculation. Additionally, inferior performance
in terms of viscous and wall shear stresses was observed in double-stented cases.
PMID- 25589160
TI - The efficacy of custom-made porous hydroxyapatite prostheses for cranioplasty:
evaluation of postmarketing data on 2697 patients.
AB - PURPOSE: Cranioplasty is a surgical intervention aimed at reestablishing the
integrity of skull defects. Autologous bone is still considered the treatment of
choice for cranioplasty. The aims of this study were to characterize and evaluate
the efficacy of porous hydroxyapatite (HA) to fill skull defects based on its
biomimetic characteristics. METHODS: The authors analyzed the postmarketing data
of all patients treated with custom-made porous HA prostheses (CustomBone
Service). Characterization data in terms of physicochemical analysis and
mechanical performance of the porous HA prostheses were also reported. RESULTS:
The low incidence of adverse events (5.72%) due to the use of HA porous custom
made prostheses for cranioplasty is related to the biomimetic performance of the
prostheses. The composition and morphology of the porosity enable it to be a
useful biomimetic prosthesis for the reconstruction of large and complex skull
defects, also able to promote osteointegration. CONCLUSIONS: These collected and
analyzed data demonstrate that porous HA is a suitable material to produce custom
made prostheses to repair craniolacunia. It is a biomimetic implant well
tolerated in both adult and pediatric patients and has been shown to be an
effective and good alternative for cranial reconstruction.
PMID- 25589161
TI - Synthetic, potentiometric and spectroscopic studies of chelation between Fe(III)
and 2,5-DHBA supports salicylate-mode of siderophore binding interactions.
AB - Catecholate type enterobactin, a prototype siderophore, comprises 2,3
dihydroxybenzoic acid (2,3-DHBA) cyclically linked to serine in E. coli. The
existence of iron-chelating ligands in humans is a recent discovery, however, the
basic chemical interactions between 2,5-dihydroxybenzoic acid and Fe(III) ion
remain poorly understood. Achieving an accurate description of the fundamental
Fe(III) binding properties of 2,5-DHBA is essential for understanding its role in
iron transport mechanisms. Here, we show that 2,5-DHBA binds iron in a salicylate
mode via a two-step kinetic mechanism by UV spectroscopy. Complexation between
Fe(III) salt and 2,5-DHBA initially occurs at 1:1 ratio (of ligand to metal) and
binding resulting in higher-order complexes continues at higher concentrations.
Through potentiometric measurements we quantify the distribution of Fe(III)-2,5
DHBA complexes with 1:1, 1:2 and 1:3 stoichiometry. The formation of 1:3
complexes is further supported through high-resolution mass spectrometry.
Further, using kinetic and equilibrium UV spectroscopy, we report Fe(III)-2,5
DHBA complex formation at a pH range of 2.5-9.0 at 298.15K in water. Maximum
complexation occurred at a pH range of 4.5-6.5 consistent with deprotonation of
the carboxylic acid proton. Equilibrium measurements and stopped-flow kinetics
show that complexation rate constants were independent of concentrations of 2,5
DHBA. Together the data supports a model in which the rate-determining step
involves rearrangement of ligands on an initial complex formed by reversible
binding between the carboxylate group of 2,5-DHBA and Fe(III).
PMID- 25589162
TI - Dietary protein influences the life-history characteristics across generations in
the African striped mouse Rhabdomys.
AB - The level of dietary protein determines the onset of reproduction, affects
offspring growth and maturation, and hence influences life-history traits and
fitness. However, to date, the long-term life-history consequences of protein
deficiency are not well understood. We studied the transgenerational effects of
different levels of dietary protein on the life-history and level of maternal
behavior of the striped mouse Rhabdomys dilectus chakae in captivity. Breeding
pairs were assigned to three treatments based on the percentage of dietary
protein: baseline (BP; 19%); high protein (HP; 24%); and low protein (LP; 10%).
Reproductive output and offspring ontogeny was diminished in the LP treatment
compared to the other treatments. Transgenerational effects were studied by
breeding F2 females raised on the LP or HP diets on the same (HP-HP, LP-LP) or
altered diets (HP-LP, LP-HP). The LP-LP treatment had no reproductive success,
while reproductive capacity in the remaining treatments was determined mainly by
the diet of mothers at breeding. Pups from protein-restricted females (LP, HP-LP)
showed post-weaning compensatory growth. Timing of sexual maturity was age
dependent in female and mass-dependent in male offspring. Females fed low protein
diets during breeding (LP, HP-LP) displayed lower levels of maternal behavior
than females from the other treatments. This study demonstrates that the level of
dietary protein influences the life-history of R. d. chakae in predictable ways.
The taxon responds to changes in dietary protein at breeding, largely regardless
of its nutrition during rearing. Such phenotypic flexibility in life-history
parameters allows Rhabdomys to adaptively respond to unpredictable environmental
changes.
PMID- 25589164
TI - Novel oral anticoagulants and valvular atrial fibrillation: are they always
contraindicated?
AB - Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia, and is
associated with an increased risk of death, stroke, and other thromboembolic
events. Valvular heart disease (VHD) frequently coexists with AF, mostly in
elderly patients. After the introduction of novel oral anticoagulants (NOACs)
approved for the prevention of stroke in non-valvular atrial fibrillation (NVAF)
on the basis of recent trials, the importance of a universal definition of NVAF
was raised in clinical practice. In the most recent guidelines, the term valvular
AF is used to imply that AF is related to rheumatic valvular disease
(predominantly mitral stenosis), or prosthetic heart valves. In all the trials
comparing NOACs and warfarin, a significant percentage of patients presented any
type of VHD, excluding rheumatic mitral stenosis and mechanical heart valve. The
subgroups analysis performed, so far showed no significant differences in terms
of efficacy in the VHD subgroup compared to the general AF population. A
restrictive definition of valvular AF (i.e., rheumatic mitral stenosis and
mechanical heart valve) seems to be the most appropriate to contraindicate
treatment with NOACs for AF thromboprophylaxis. In the remaining AF patients with
significant valvular disease who per se would not require oral anticoagulation,
NOACs should be allowed.
PMID- 25589165
TI - Aortic dissection and stroke in a 37-year-old woman: discovering an emerging
heritable connective tissue disorder.
PMID- 25589166
TI - Do clinicians decide relying primarily on Bayesian principles or on Gestalt
perception? Authors' reply.
PMID- 25589163
TI - Transcript profiling of different types of multiple sclerosis lesions yields FGF1
as a promoter of remyelination.
AB - Chronic demyelination is a pathological hallmark of multiple sclerosis (MS). Only
a minority of MS lesions remyelinates completely. Enhancing remyelination is,
therefore, a major aim of future MS therapies. Here we took a novel approach to
identify factors that may inhibit or support endogenous remyelination in MS. We
dissected remyelinated, demyelinated active, and demyelinated inactive white
matter MS lesions, and compared transcript levels of myelination and inflammation
related genes using quantitative PCR on customized TaqMan Low Density Arrays. In
remyelinated lesions, fibroblast growth factor (FGF) 1 was the most abundant of
all analyzed myelination-regulating factors, showed a trend towards higher
expression as compared to demyelinated lesions and was significantly higher than
in control white matter. Two MS tissue blocks comprised lesions with adjacent de-
and remyelinated areas and FGF1 expression was higher in the remyelinated rim
compared to the demyelinated lesion core. In functional experiments, FGF1
accelerated developmental myelination in dissociated mixed cultures and promoted
remyelination in slice cultures, whereas it decelerated differentiation of
purified primary oligodendrocytes, suggesting that promotion of remyelination by
FGF1 is based on an indirect mechanism. The analysis of human astrocyte responses
to FGF1 by genome wide expression profiling showed that FGF1 induced the
expression of the chemokine CXCL8 and leukemia inhibitory factor, two factors
implicated in recruitment of oligodendrocytes and promotion of remyelination.
Together, this study presents a transcript profiling of remyelinated MS lesions
and identified FGF1 as a promoter of remyelination. Modulation of FGF family
members might improve myelin repair in MS.
PMID- 25589167
TI - Development of a walleye cell line and use to study the effects of temperature on
infection by viral haemorrhagic septicaemia virus group IVb.
AB - A cell line, WE-cfin11f, with a fibroblast-like morphology was developed from a
walleye caudal fin and used to study the intersection of thermobiology of
walleye, Sander vitreus (Mitchill), with the thermal requirements for replication
of viral haemorrhagic septicaemia virus (VHSV) IVb. WE-cfin11f proliferated from
10 to 32 degrees C and endured as a monolayer for at least a week at 1-34
degrees C. WE-cfin11f adopted an epithelial shape and did not proliferate at 4
degrees C. Adding VHSV IVb to cultures at 4 and 14 degrees C but not 26 degrees
C led to cytopathic effects (CPE) and virus production. At 4 degrees C, virus
production developed more slowly, but Western blotting showed more N protein
accumulation. Infecting monolayer cultures at 4 degrees C for 7 days and then
shifting them to 26 degrees C resulted in the monolayers being broken in small
areas by CPE, but with time at 26 degrees C, the monolayers were restored. These
results suggest that at 26 degrees C, the VHSV IVb life cycle stages responsible
for CPE can be completed, but the production of virus and the initiation of
infections cannot be accomplished.
PMID- 25589169
TI - C-C coupling of ketones with methanol catalyzed by a N-heterocyclic carbene
phosphine iridium complex.
AB - An N-heterocyclic carbene-phosphine iridium complex system was found to be a very
efficient catalyst for the methylation of ketone via a hydrogen transfer
reaction. Mild conditions together with low catalyst loading (1 mol %) were used
for a tandem process which involves the dehydrogenation of methanol, C=C bond
formation with a ketone, and hydrogenation of the new generated double bond by
iridium hydride to give the alkylated product. Using this iridium catalyst
system, a number of branched ketones were synthesized with good to excellent
conversions and yields.
PMID- 25589168
TI - New mass-spectrometry-compatible degradable surfactant for tissue proteomics.
AB - Tissue proteomics is increasingly recognized for its role in biomarker discovery
and disease mechanism investigation. However, protein solubility remains a
significant challenge in mass spectrometry (MS)-based tissue proteomics.
Conventional surfactants such as sodium dodecyl sulfate (SDS), the preferred
surfactant for protein solubilization, are not compatible with MS. Herein, we
have screened a library of surfactant-like compounds and discovered an MS
compatible degradable surfactant (MaSDeS) for tissue proteomics that solubilizes
all categories of proteins with performance comparable to SDS. The use of MaSDeS
in the tissue extraction significantly improves the total number of protein
identifications from commonly used tissues, including tissue from the heart,
liver, and lung. Notably, MaSDeS significantly enriches membrane proteins, which
are often under-represented in proteomics studies. The acid degradable nature of
MaSDeS makes it amenable for high-throughput MS-based proteomics. In addition,
the thermostability of MaSDeS allows for its use in experiments requiring high
temperature to facilitate protein extraction and solubilization. Furthermore, we
have shown that MaSDeS outperforms the other MS-compatible surfactants in terms
of overall protein solubility and the total number of identified proteins in
tissue proteomics. Thus, the use of MaSDeS will greatly advance tissue proteomics
and realize its potential in basic biomedical and clinical research. MaSDeS could
be utilized in a variety of proteomics studies as well as general biochemical and
biological experiments that employ surfactants for protein solubilization.
PMID- 25589170
TI - Work extraction from heat-powered quantized optomechanical setups.
AB - We analyze work extraction from an autonomous (self-contained) heat-powered
optomechanical setup. The initial state of the quantized mechanical oscillator
plays a key role. As the initial mean amplitude of the oscillator decreases, the
resulting efficiency increases. In contrast to laser-powered self-induced
oscillations, work extraction from a broadband heat bath does not require
coherence or phase-locking: an initial phase-averaged coherent state of the
oscillator still yields work, as opposed to an initial Fock-state.
PMID- 25589171
TI - Application of the combination index integrated with confidence intervals to
study the toxicological interactions of antibiotics and pesticides in Vibrio
qinghaiensis sp.-Q67.
AB - It is necessary to explore the effect of confidence intervals on the combination
index (CI) so that rationally evaluate the toxicological interaction (synergism
or antagonism) which is dependent on the concentration ratio, the mixture
concentration and the exposure time. To effectively detect the toxicological
interaction taking place in mixtures, we combined the CI with the observation
based confidence intervals (OCI) which can characterize the uncertainty in
toxicity test and in data fitting. In time scale, the short-term (15min) and long
term (12h) toxicities of three chemicals (imidacloprid (IMI), pirimicarb (PIR)
and streptomycin sulfate (STR)) and their binary mixtures on Vibrio qinghaiensis
sp.-Q67 were determined by the microplate toxicity analysis (MTA). The mixtures
of IMI, PIR and STR have additive actions all but four IMI-PIR rays (R2-R5) at
the effect levels above about 30-40% whose long-term toxicological interaction
are synergism.
PMID- 25589172
TI - Effect of COX-2 inhibitors and other non-steroidal inflammatory drugs on breast
cancer risk: a meta-analysis.
AB - Evidence on non-steroidal anti-inflammatory drugs (NSAID) use and breast cancer
risk shows a slightly protective effect of these drugs, but previous studies lack
randomized clinical trial results and present high heterogeneity in exposure
measurement. This systematic review and meta-analysis widens the knowledge about
NSAID use and breast cancer risk, updating the information from the last meta
analysis, focusing on evidence on specific effects of COX-2 inhibitors and
differential expression patterns of hormonal receptors. A PubMed-database search
was conducted to include all entries published with the keywords "BREAST CANCER
NSAID ANTI-INFLAMMATORY" until 10/24/2013 providing original results from cohort
studies, case-control studies, or randomized clinical trials with at least one
reported relative risk (RR) or odds ratio (OR) on the association between any
NSAID use and incidence of invasive breast cancer. This resulted in 49
publications, from which the information was retrieved about type of study,
exposure characteristics, breast cancer characteristics, and breast cancer-NSAID
association. Meta-analyses were performed separately for case-control and cohort
studies and for different hormone-receptor status. NSAID use reduced invasive
breast cancer risk by about 20 %. A similar effect was found for aspirin,
acetaminophen, COX-2 inhibitors and, to a lesser extent, ibuprofen. The effect of
aspirin was similar in preventing hormone-receptor-positive breast cancer. This
meta-analysis suggests a slightly protective effect of NSAIDs-especially aspirin
and COX-2 inhibitors- against breast cancer, which seems to be restricted to
ER/PR+tumors.
PMID- 25589175
TI - Erratum: CT signs, patterns and differential diagnosis of solitary fibrous tumors
of the pleura: Erratum.
AB - [This corrects the article on p. 21 in vol. 2, PMID: 22263012.].
PMID- 25589173
TI - Engineering synthetic antibody binders for allosteric inhibition of prolactin
receptor signaling.
AB - BACKGROUND: Many receptors function by binding to multiple ligands, each
eliciting a distinct biological output. The extracellular domain of the human
prolactin receptor (hPRL-R) uses an identical epitope to bind to both prolactin
(hPRL) and growth hormone (hGH), yet little is known about how each hormone
binding event triggers the appropriate response. FINDINGS: Here, we utilized a
phage display library to generate synthetic antibodies (sABs) that preferentially
modulate hPRL-R function in a hormone-dependent fashion. We determined the
crystal structure of a sAB-hPRL-R complex, which revealed a novel allosteric
mechanism of antagonism, whereby the sAB traps the receptor in a conformation
more suitable for hGH binding than hPRL. This was validated by examining the
effect of the sABs on hormone internalization via the hPRL-R and its downstream
signaling pathway. CONCLUSIONS: The findings suggest that subtle structural
changes in the extracellular domain of hPRL-R induced by each hormone determine
the biological output triggered by hormone binding. We conclude that sABs
generated by phage display selection can detect these subtle structural
differences, and therefore can be used to dissect the structural basis of
receptor-ligand specificity.
PMID- 25589174
TI - Synanthropic rodents and their ectoparasites as carriers of a novel haemoplasma
and vector-borne, zoonotic pathogens indoors.
AB - BACKGROUND: Despite their close association with human dwellings, the role of
synanthropic rodents in the epidemiology of vector-borne infections is seldom
studied. The aim of the present study was to compensate for this lack of
information, by the molecular investigation of vector-borne bacteria in
peridomestic rodents and their ectoparasites. FINDINGS: Fifty-two rodents (mainly
house mice and brown rats) were caught alive in buildings and checked for blood
sucking ectoparasites; followed by molecular analysis of these, together with
spleen samples, for the presence of vector-borne agents. Haemoplasma infection
was significantly more prevalent among brown rats, than among house mice. A novel
haemoplasma genotype (with only 92-93% similarity to Candidatus Mycoplasma
turicensis and M. coccoides in its 16S rRNA gene) was detected in a harvest mouse
and a brown rat. Sporadic occurrence of Rickettsia helvetica, Anaplasma
phagocytophilum, Borrelia burgdorferi s.l. and Bartonella sp. was also noted in
rodents and/or their ectoparasites. CONCLUSIONS: These results indicate that
synanthropic rodents, although with low prevalence, may carry zoonotic and vector
borne pathogens indoors.
PMID- 25589176
TI - [Results of surgical treatment of patients with internal carotid artery kinking
depending on methods of its reconstruction].
AB - It was analyzed the results of surgical treatment of 60 patients with internal
carotid artery kinking operated in the department of vascular surgery of acad.
B.V. Petrovsky Russian Scientific Center of Surgery of RAN. Indications for
surgery included symptoms of cerebrovascular insufficiency (CVI) and
instrumentally confirmed hemodynamically significant kinking of ICA. Criteria for
surgical treatment were linear flow velocity gradient more than 2 and turbulent
blood flow in the kinking segment diagnosed by ultrasonic scanning. All patients
were divided into 2 groups depending on methods of surgery. The first group
included 36 (60%) patients who underwent resection of ICA with orifice bringing
down. The second group included 8 (13%) patients after ICA replacement and 16
(27%) cases with eversion endarterectomy, resection of ICA and orifice bringing
down. The analysis of immediate surgery results did not reveal significant
differences in dynamics of CVI and velocity parameters in reconstructed ICA
(p>0.05). The index "stroke+mortality from stroke" was higher in the second group
(p<0.05). Thrombosis of ICA reconstruction area has been developing more frequent
(p<0.05) after ICA replacement (8%) in comparison with resection of ICA with
orifice bringing down (0) and eversion endarterectomy, resection of ICA and
orifice bringing down (0). Our data show that resection of ICA with orifice
bringing down is preferable for surgical treatment of ICA kinking. ICA
replacement is associated with significantly more frequent complications.
Eversion endarterectomy with resection of ICA is optimal in case of combination
of kinking with stenosis of ICA.
PMID- 25589177
TI - [Permanent vascular accesses in patients with chronic renal failure undergoing
hemodialysis].
AB - The article presents an experience of arteriovenous fistulas forming and using in
78 patients with end-stage chronic renal failure undergoing hemodialysis. New
methods for permanent vascular accesses forming were suggested. These techniques
increased the operation period of arteriovenous fistulas.
PMID- 25589178
TI - [Opportunities for volatile fatty acids using in early diagnostics of infected
pancreonecrosis].
AB - It was analyzed the treatment results of 108 patients with pancreonecrosis (PN).
Gas-liquid chromatography with definition of blood concentration of volatile
fatty acids (VFA) was used additionally for timely diagnostics of infected
pancreonecrosis. Volatile fatty acids are toxic metabolites of microorganisms.
Statistically significant threshold values of VFA were revealed. These values
allow to diagnose timely early phase of PN infection and the nature of the
microflora. It was defined changes of VFA depending on the severity of infectious
process in pancreas and retroperitoneal fiber.
PMID- 25589179
TI - [Experience of surgical treatment of abdominal and intraabdominal desmoid
fibromas].
AB - It is presented the treatment results of abdominal and intraabdominal desmoid
fibromas. Group of abdominal localization included 19 patients. 15 of them had
primary tumors, 4 - recurrent tumors after surgical treatment. Radical (R0)
operations were performed in all cases. Tumor removal was associated with plastic
of abdominal wall by synthetic implant in 17 patients. Wide excision of
surrounding tissues and musculo-aponeurotic layer of anterior abdominal wall
allows to achieve long-term disease-free period. There weren't recurrent symptoms
in terms from 4 to 60 months of observation. The second group included 28
patients with intraabdominal desmoid fibromas. Operations were performed in 11
(35.2%) patients including 3 cases of reoperations. There were 14 operations.
Radical (R0) volume was applied in 11 (78.6%) operations, cytoreductive (R2)
volume - in 1 (7%) operation. Explorative laparotomy was used in 3 (21.4%) cases
because of involvement of mesenteric vessels. Combined treatment was performed in
4 (14.3%) patients. 14 (50%) patients received conservative therapy because of
unresectable tumor including chemo-, hormone- and radiotherapy. Operated patients
were under observation in terms from 11 to 156 months, median was 63.2 months.
Recurrence developed in 4 of 10 (40%) patients after R0-surgery. Cytoreductive
(R1/R2) volume is admitted for intraabdominal desmoid fibromas. But even in case
of unresectable process and explorative intervention stabilization and regression
of tumor is possible by means of chemo-, hormone- and radiotherapy in different
combination. It allows to preserve a good life quality.
PMID- 25589180
TI - [Early complications after surgery for middle- and lower-ampullar cancer: total
mesorectumectomy or "blind" preparation of rectum?].
AB - It was performed a comparative analysis of parameters of early postoperative
period in 318 patients with middle- and lower-ampullar cancer of rectum who
underwent total mesorectumectomy and "blind" preparation of rectum. All patients
were divided into 2 groups. The main group included 202 patients after total
mesorectumectomy. The control group included 116 patients after "blind"
preparation of rectum. Statistically significant differences in frequency of
laparotomy wounds suppuration, urinary tract dysfunction and postoperative
mortality were revealed. These complications were diagnosed more frequent in case
of "blind" preparation of rectum. In the main group laparotomy wounds suppuration
depended on sex (p<0.001, r=0.65), in the control group - on surgeon's experience
(p=0.006, r=0.58), localization of tumor (p<0.001, r= -0.87) and type of surgery
(p<0.001, r= -0.76). Urinary tract dysfunction after total mesorectumectomy
depended on patient's sex (p<0.001, r=-0.77), after "blind" preparation of rectum
- sex (p=0.002, r= -0.39) and performing of preoperative radiation therapy
(p<0.001, r=0.46). In the main group none of the analyzed variables effected on
the postoperative mortality. In the control group age (p=0.006, r=0.48),
intraoperative blood loss (p=0.002, r=0.55), anastomosis failure (p=0.01,
r=0.61), postoperative bleeding (p<0.001, r=0.88), early adhesive intestinal
obstruction (p=0.006, r=0.77) effected on the mortality. It is considered that
total mesorectumectomy in comparison with "blind" preparation of rectum decreases
frequency of postoperative complications and mortality.
PMID- 25589181
TI - [The criteria for choose of treatment method of children with spleen injuries].
AB - It was performed cohort prospective study of treatment results of 69 children
with through-capsule spleen injuries for the period from 2002 to 2013. Patients
were divided into 2 groups. The first group included 63 patients after non
surgical treatment. The second group included 6 children who underwent surgery.
In the first group 95.3% of patients had stable hemodynamics at admission. In the
second group only 2 patients had the signs of deferred bleeding. Continuing
abdominal bleeding was the indication for surgery in 4 patients although stable
hemodynamics. Hemoperitoneum in case of spleen injury is not significant
prognostic factor defining the tactics of treatment. The physiological response
on bleeding but not the amount of blood in abdominal cavity determines tactics of
treatment. Hemodynamic status is single statistically significant criterion for
choose of surgical treatment of children with spleen injuries. Unstable
hemodynamics increases the risk of surgical treatment in 20 times (p<0.007).
PMID- 25589182
TI - [Comparative results of surgical treatment of patients with morbid obesity].
AB - It was performed a comparative analysis of treatment of 62 patients who were
operated for morbid obesity. Patients were divided into 3 groups depending on
kind of surgery: jejunal-iliac intestinal bypass, restrictive operations and
combined operations. The complications in early postoperative period were
diagnosed in 16.6% of patients after jejunal-iliac intestinal bypass and in 10%
of patients after combined operations. Regardless of the kind of surgery there
was rapid reduction of the body mass in the first year of observation with
gradual increase of weight by an average of 5% in the subsequent period. The
highest rate of weight loss by the second year was revealed after combined
operations (up to 73.4%). Thus it was 1.1 times more than after jejunal-iliac
intestinal bypass and 1.3 times more than after restrictive operations.
PMID- 25589183
TI - [Effect of hepatic functional activity of the liver and endogenous intoxication
in patients with ovarian cancer].
AB - The analysis of the clinical observations and the results of the study 70
patients with ovarian cancer stage III-IV, aged 30 to 70 years. After various
programs chemotherapy underwent surgical treatment stage under general
anesthesia. Investigated hematological indices of intoxication, protein-synthetic
liver function, transaminase, C-reactive protein, hemostasis in the perioperative
period. Analysis of the results revealed that the original premorbid background
characterized by severe hepatic dysfunction, endogenous intoxication, activation
of the systemic inflammatory response. The introduction of the treatment of
patients with ovarian cancer Remaxol promotes more pronounced and rapid reduction
in the degree of metabolic disorders, endogenous intoxication and systemic
inflammatory response, compared with ademethionine.
PMID- 25589184
TI - [Aspects of the practical application of direct oral anticoagulants in
traumatological and orthopedic hospital].
PMID- 25589185
TI - [Current concept of peptic ulcer disease: an endoscopist's view].
PMID- 25589186
TI - [Thoracoscopic lobectomy for giant pulmonary arterio-venous aneuryzm].
PMID- 25589187
TI - [Laparoscopic combined resection of sigmoid colon, panhysterectomy with removal
through vagina stump].
PMID- 25589188
TI - [Perfused bone autograft from medial epicondyle of femur in treatment of false
joint of navicular bone].
PMID- 25589189
TI - [Surgical treatment of patient with echinococcus cyst of left ventricle apex].
PMID- 25589190
TI - LUX-Lung: determining the best EGFR inhibitor in NSCLC?
PMID- 25589192
TI - Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for
patients with rectal cancer: a systematic review and meta-analysis of individual
patient data.
AB - BACKGROUND: The role of adjuvant chemotherapy for patients with rectal cancer
after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta
analysis of individual patient data to compare adjuvant chemotherapy with
observation for patients with rectal cancer. METHODS: We searched PubMed,
Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference
abstracts to identify European randomised, controlled, phase 3 trials comparing
observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and
surgery for patients with non-metastatic rectal cancer. The primary endpoint of
interest was overall survival. FINDINGS: We analysed data from four eligible
trials, including data from 1196 patients with (y)pTNM stage II or III disease,
who had an R0 resection, had a low anterior resection or an abdominoperineal
resection, and had a tumour located within 15 cm of the anal verge. We found no
significant differences in overall survival between patients who received
adjuvant chemotherapy and those who underwent observation (hazard ratio [HR]
0.97, 95% CI 0.81-1.17; p=0.775); there were no significant differences in
overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not
significantly improve disease-free survival (HR 0.91, 95% CI 0.77-1.07; p=0.230)
or distant recurrences (0.94, 0.78-1.14; p=0.523) compared with observation.
However, in subgroup analyses, patients with a tumour 10-15 cm from the anal
verge had improved disease-free survival (0.59, 0.40-0.85; p=0.005,
p(interaction)=0.107) and fewer distant recurrences (0.61, 0.40-0.94; p=0.025,
p(interaction)=0.126) when treated with adjuvant chemotherapy compared with
patients undergoing observation. INTERPRETATION: Overall, adjuvant fluorouracil
based chemotherapy did not improve overall survival, disease-free survival, or
distant recurrences. However, adjuvant chemotherapy might benefit patients with a
tumour 10-15 cm from the anal verge in terms of disease-free survival and distant
recurrence. Further studies of preoperative and postoperative treatment for this
subgroup of patients are warranted. FUNDING: None.
PMID- 25589191
TI - Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung
adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data
from two randomised, phase 3 trials.
AB - BACKGROUND: We aimed to assess the effect of afatinib on overall survival of
patients with EGFR mutation-positive lung adenocarcinoma through an analysis of
data from two open-label, randomised, phase 3 trials. METHODS: Previously
untreated patients with EGFR mutation-positive stage IIIB or IV lung
adenocarcinoma were enrolled in LUX-Lung 3 (n=345) and LUX-Lung 6 (n=364). These
patients were randomly assigned in a 2:1 ratio to receive afatinib or
chemotherapy (pemetrexed-cisplatin [LUX-Lung 3] or gemcitabine-cisplatin [LUX
Lung 6]), stratified by EGFR mutation (exon 19 deletion [del19], Leu858Arg, or
other) and ethnic origin (LUX-Lung 3 only). We planned analyses of mature overall
survival data in the intention-to-treat population after 209 (LUX-Lung 3) and 237
(LUX-Lung 6) deaths. These ongoing studies are registered with
ClinicalTrials.gov, numbers NCT00949650 and NCT01121393. FINDINGS: Median follow
up in LUX-Lung 3 was 41 months (IQR 35-44); 213 (62%) of 345 patients had died.
Median follow-up in LUX-Lung 6 was 33 months (IQR 31-37); 246 (68%) of 364
patients had died. In LUX-Lung 3, median overall survival was 28.2 months (95% CI
24.6-33.6) in the afatinib group and 28.2 months (20.7-33.2) in the pemetrexed
cisplatin group (HR 0.88, 95% CI 0.66-1.17, p=0.39). In LUX-Lung 6, median
overall survival was 23.1 months (95% CI 20.4-27.3) in the afatinib group and
23.5 months (18.0-25.6) in the gemcitabine-cisplatin group (HR 0.93, 95% CI 0.72
1.22, p=0.61). However, in preplanned analyses, overall survival was
significantly longer for patients with del19-positive tumours in the afatinib
group than in the chemotherapy group in both trials: in LUX-Lung 3, median
overall survival was 33.3 months (95% CI 26.8-41.5) in the afatinib group versus
21.1 months (16.3-30.7) in the chemotherapy group (HR 0.54, 95% CI 0.36-0.79,
p=0.0015); in LUX-Lung 6, it was 31.4 months (95% CI 24.2-35.3) versus 18.4
months (14.6-25.6), respectively (HR 0.64, 95% CI 0.44-0.94, p=0.023). By
contrast, there were no significant differences by treatment group for patients
with EGFR Leu858Arg-positive tumours in either trial: in LUX-Lung 3, median
overall survival was 27.6 months (19.8-41.7) in the afatinib group versus 40.3
months (24.3-not estimable) in the chemotherapy group (HR 1.30, 95% CI 0.80-2.11,
p=0.29); in LUX-Lung 6, it was 19.6 months (95% CI 17.0-22.1) versus 24.3 months
(19.0-27.0), respectively (HR 1.22, 95% CI 0.81-1.83, p=0.34). In both trials,
the most common afatinib-related grade 3-4 adverse events were rash or acne (37
[16%] of 229 patients in LUX-Lung 3 and 35 [15%] of 239 patients in LUX-Lung 6),
diarrhoea (33 [14%] and 13 [5%]), paronychia (26 [11%] in LUX-Lung 3 only), and
stomatitis or mucositis (13 [5%] in LUX-Lung 6 only). In LUX-Lung 3, neutropenia
(20 [18%] of 111 patients), fatigue (14 [13%]) and leucopenia (nine [8%]) were
the most common chemotherapy-related grade 3-4 adverse events, while in LUX-Lung
6, the most common chemotherapy-related grade 3-4 adverse events were neutropenia
(30 [27%] of 113 patients), vomiting (22 [19%]), and leucopenia (17 [15%]).
INTERPRETATION: Although afatinib did not improve overall survival in the whole
population of either trial, overall survival was improved with the drug for
patients with del19 EGFR mutations. The absence of an effect in patients with
Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be
distinct from Leu858Arg-positive disease and that these subgroups should be
analysed separately in future trials. FUNDING: Boehringer Ingelheim.
PMID- 25589193
TI - Hemophagocytic lymphohistiocytosis syndrome in dengue hemorrhagic Fever: authors'
reply.
PMID- 25589194
TI - Hemophagocytic lymphohistiocytosis syndrome in dengue hemorrhagic Fever:
correspondence.
PMID- 25589195
TI - Outcome of Rhino-Sinus Mucormycosis in Children with Type 1 Diabetes.
PMID- 25589196
TI - On Some Practical Considerations Regarding Community-Based Participatory Research
for Addressing Cancer Health Disparities.
AB - There is a consensus about the benefits of community-based participatory research
and the important role it can play in reducing cancer health disparities.
Although every community-based participatory research project is unique in many
ways, several fundamental issues deserve consideration. We discuss issues
concerning community representation, possible tensions within community-based
participatory research (CBPR) projects, and staffing CBPR projects. Flexibility,
open-mindedness, transparency, and above all, caring, are characteristics that
best ensure successful and rewarding outcomes.
PMID- 25589197
TI - Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery
Disease: The Influence of Diabetes.
AB - BACKGROUND: Patients with diabetes mellitus (DM) have a higher risk of sudden
cardiac death. Factors associated with the risk profiles of coronary artery
disease (CAD) patients with DM are not well established. Heart rate turbulence
(HRT) and T-wave alternans (TWA) are often used to predict arrhythmia events.
METHODS AND RESULTS: HRT and TWA were measured in two independent groups: the
ARTEMIS cohort study and the REFINE-ICD randomized trial. ARTEMIS assesses risk 3
12 months after coronary angiography in patients with CAD. The initial 1001
patients in ARTEMIS, 526 with and 475 without DM, are included in this analysis.
REFINE-ICD compares usual care versus usual care plus ICD therapy in patients
with left ventricular (LV) ejection fraction (EF) values of 36-50% assessed 2-15
months after myocardial infarction. The initial 275 patients screened in REFINE
ICD are included in this analysis. Abnormal HRT plus TWA was more common in
patients with versus without DM in ARTEMIS (125/526, 24% vs 63/475, 13%; P <
0.001) and REFINE-ICD (43/55, 78% vs 55/220, 25%; P < 0.001), respectively.
Abnormal HRT plus TWA was also more common in patients with LVEF values < 50%
(28%) vs >= 50% (18%; P < 0.001) in ARTEMIS and LVEF values below the population
median of 42% (60/138, 43%) versus above the median (38/137, 28%; P < 0.01) in
REFINE-ICD. CONCLUSIONS: Abnormal HRT plus TWA is more common in CAD patients
with DM compared with the patients without DM and is related to the severity of
LV dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION:
http://www.clinicaltrials.gov, NCT01426685; http://www.clinicaltrials.gov,
NCT00673842.
PMID- 25589199
TI - Effective combination of LED-based visible light, photosensitizer and
photocatalyst to combat Gram (-) bacteria.
AB - The aim of this study was to investigate antimicrobial efficiency of combined
treatments of visible light (405nm), chlorophyllin (Chl) and ZnO nanoparticles
(NPs). Results obtained indicate that incubation of the Gram (-) Escherichia coli
with Chl (1.5*10(-5)M) for 60min as well as illumination alone (405nm;
380kJ/m(2)) has no impact on the viability of E. coli. Just photosensitization
(60min incubation with 1.5*10(-5)M Chl and following illumination, 405nm;
380kJ/m(2)) slightly reduces their population (~1.5 log). ZnO NPs (5*10(-4)M) in
the dark have negligible effect on E. coli viability. However, photocatalytic
treatment (10min incubation with ZnO NPs (5*10(-4)M) and following illumination
with light (lambda=405nm; 380kJ/m(2)) resulted in significant reduction of viable
cell population (4.6 log). Scanning electron microscopy (SEM) images indicate
that cell surface-adhered NPs as well as chlorophyllin after illumination trigger
cell shrinkage and eventually death. Simultaneous (at the same time) incubation
30min. with Chl and ZnO NPs and following illumination (380kJ/m(2)) was less
effective than every treatment separately. Interaction of bacteria with
photosensitizer and photocatalyst in the sequence (photosensitizer->photocatalyst
>light) reduced the viability of bacteria by 3 log. But applying interaction of
bacteria with photosensitizer and photocatalyst in opposite order (photocatalyst
>photosensitizer->light) looks more promising as this reduced the Gram (-) E.
coli microbial population by 4.5 log using 5 times lower photocatalyst
concentration in comparison with efficiency of photoactivated ZnO NPs (4.6 log).
In this case ZnO NPs interact electrostatically with negatively-charged cell
surface and afterwards bind negatively charged Chl, thus act as mediators between
negatively-charged cell surface and negatively-charged photosensitizer.
PMID- 25589200
TI - Erratum to: Vedolizumab: A Review of Its Use in Adult Patients with Moderately to
Severely Active Ulcerative Colitis or Crohn's Disease.
PMID- 25589198
TI - Monitoring aspirin therapy in children after interventional cardiac
catheterization: laboratory measures, dose response, and clinical outcomes.
AB - Very few studies have investigated dose response of aspirin and agreement of
different platelet function assays in children. One hundred five children were
studied at baseline and after interventional cardiac catheterization during
aspirin treatment and, in cases of aspirin resistance (AR), after dose increase.
Results from arachidonate-induced aggregation (AA) were compared with aggregation
induced by ADP, PFA-100 closure times (CTs), urinary 11-dehydro-thromboxane B2
(urinary 11-dhTxB2) levels, and Impact-R % surface coverage. Aspirin at 2-5
mg/kg/day inhibited platelet function in a large majority. While 19 % showed
bruising and mild epistaxis, no thrombotic complications were recorded. AR was
detected by AA in seven children (6.7 %). After dose increase, the majority
showed inhibition by aspirin. Infants had higher urinary 11-dhTxB2 baseline
levels; this assay showed some correlation with AA. Both assays manifested high
sensitivity and specificity for aspirin while inferior results were found for the
other assays. With the PFA-100, 15.2 % of patients were found to have AR, but
this corresponded to AR by AA in only one of seven children. CONCLUSION: While
there was poor agreement among assays, AA and urinary 11-dhTxB2 show good
specificity for the monitoring of aspirin therapy in children. Aspirin at 2-5
mg/kg inhibits platelet function; AR in children is rare and can be overcome by
dose increase.
PMID- 25589201
TI - Apatite-forming PEEK with TiO2 surface layer coating.
AB - Polyetheretherketone (PEEK) is widely used in orthopedic implants, such as spinal
fusion devices, because of its moderate elastic modulus, as well as relatively
high mechanical strength. However, it does not bond to living bone, and hence it
needs autograft to be fixed to the bone. In this study, we attempted to add bone
bonding properties to PEEK by coating with TiO2 synthesized by the sol-gel
process. When a TiO2 sol solution consisting of titanium isopropoxide, water,
ethanol, and nitric acid was deposited on a PEEK substrate without any
pretreatment, the formed TiO2 gel layer was easily peeled off after subsequent
treatments. However, when the same solution was deposited on PEEK that was
preliminarily subjected to UV or O2 plasma treatment, the deposited TiO2 gel
layer strongly adhered to the substrate even after subsequent treatments. The
strong adhesion was attributed to the interaction among the C-O, C=O, and O-C=O
groups on the PEEK owing to the UV or O2 plasma treatment and the Ti-O bond of
the TiO2 gel. Apatite did not form on the as-formed TiO2 gel layer in a simulated
body fluid (SBF) even within 3 days; however, apatite formed after soaking in 0.1
M HCl solution at 80 degrees C for 24 h. This apatite formation was attributed
to positive surface charge of the TiO2 gel layer induced by the acid treatment.
The PEEK with the TiO2 gel layer coating formed by the proposed process is
expected to bond to living bone, because a positively charged titanium oxide
which facilitates the formation of apatite in SBF within a short period is known
to bond to living bone.
PMID- 25589202
TI - Elasticity and structure of the compounds in the wollastonite (CaSiO3)-Na 2SiO 3
system: from amorphous to crystalline state.
AB - The elastic properties and structure of four potential bioactive compounds in the
CaSiO3-Na2SiO3 system were characterized by Raman and Brillouin spectroscopy at
ambient conditions. The increase of Na2O content in the Na2O-CaO-SiO2 glass with
the same silica content and hence polymerization was found to lower the elastic
moduli with accompanied decrease of Q(0) and Q(2) species, increase of Q(1)
species and negligible change of Q(3) species, corresponding to a lower and
higher equilibrium constant for the disproportional reactions [Formula: see text]
and [Formula: see text] (without balance), respectively. The composition
dependent variation in the shear modulus (G) of the Na2O-CaO-SiO2 glass can be
attributed to the concentration change of Q(2) and probably Q(4) species; while
bulk modulus (K) ascribed to the cohesion factor. The elastic moduli of the
corresponding crystalline phases in this system also lower with the increase of
Na2O content following two general criteria as a function of Na2O/CaO molar
ratio: (1) K decreases faster than G for both the amorphous and crystalline
phases and (2) both K and G decreases faster for the crystals than the glasses.
PMID- 25589203
TI - Experimental self-etching HEMA-free adhesive systems: cytotoxicity and degree of
conversion.
AB - The aim of this study was to evaluate the effect of replacing 2-hydroxyethyl
methacrylate (HEMA) by methacrylate surfactant monomers on the cytotoxicity and
degree of conversion of two-step self-etching dentin adhesive systems. Five HEMA
free adhesive systems were tested: Bis-EMA 10, Bis-EMA 30, PEG400, PEG400UDMA,
PEG1000, and a HEMA group was used as positive control. The cytotoxicity of the
experimental primers, with different monomer concentrations (2 or 20 wt%), and
bond resins, containing 25 wt% surfactant, was assessed using murine fibroblast
cell line 3T3 and the tetrazolium assay (3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT)). The degree of conversion of the bond resins
was analyzed using Fourier transform infrared spectroscopy. The data were
submitted to statistical analysis using level of significance set at P < 0.05.
The PEG 1000 group obtained higher cell viability in comparison with HEMA in the
2 % primer. The cell survival rate using 20 % primer showed that PEG1000 and BIS
EMA 10 were less cytotoxic than HEMA. With regard to the eluate from bond resin,
the data showed that the groups BIS-EMA 10, BIS-EMA 30 and PEG400UDMA were less
cytotoxic than HEMA. No statistically significant difference was found among
degrees of conversion of the experimental groups and HEMA. PEG 1000, BIS-EMA 10
and 30 monomers showed the biological potential for use in new adhesive system
formulations since they showed lower cytotoxicity and similar degree of
conversion when compared with the HEMA-containing group.
PMID- 25589204
TI - New TiAg composite coating for bone prosthesis engineering shows promising
microvascular compatibility in the murine dorsal skinfold chamber model.
AB - The incorporation of antimicrobial substances like silver into implant surface
coatings is one promising concept against primary infections of endoprosthesis,
especially for immunocompromised patients as well as against reinfection after
revision operations. However, besides good antimicrobial and mechanical
properties it is equally important that the implant material does not disturb the
local microvascular perfusion of muscle tissue to enable microbial host defense
and tissue repair processes. In this study the biocompatibility of a newly
developed TiAg-composite coating applied on conventional titanium via physical
vapor deposition was analysed. To evaluate the local microvascular and
inflammatory response of striated muscle tissue upon implantation of TiAg-coated
plates the murine dorsal skinfold chamber model was used. We repetitively
examined local capillary and venular perfusion, endothelial integrity as well as
leucocyte activation by intravital fluorescence microscopy at 1 h, 24 h as well
as 3 and 7 days after implantation. TiAg-implants were well tolerated by the
vascular system as indicated by intact functional capillary density and
endothelial integrity compared to pure titanium plates and controls without a
metal implant. Furthermore, quantification of rolling and adherent leucocytes did
not reveal signs of inflammation upon TiAg-implantation.
PMID- 25589205
TI - Anticancer activity of fungal L-asparaginase conjugated with zinc oxide
nanoparticles.
AB - Demand for developing novel delivery system for cancer treatment has increased
due to the side effects present in intravenous injection of L-asparaginase.
Nanoparticles are used for delivering the drugs to its destination in cancer
cure. Nanobiocomposite of zinc oxide nanoparticles conjugated with L-asparaginase
was produced by Aspergillus terreus and was confirmed using maximum UV-Vis
absorption at 340 nm in the present work. The presence of functional groups like
OH, C-H, -C=N and C=O on the surface of nanobiocomposite was found from Fourier
transform infrared spectrum analysis. Size of the produced nanocomposite was
found in the range of 28-63 nm using scanning electron microscope. The
crystalline nature of the synthesized nanobiocomposites was confirmed by X-ray
diffraction analysis. The presence of zinc oxide on synthesized nanobiocomposite
was confirmed by energy dispersive spectrum analysis. The anti-cancerous nature
of the synthesized zinc oxide conjugated L-asparaginase nanobiocomposite on MCF-7
cell line was studied using MTT assay. The viability of the MCF-7 cells was
decreased to 35.02 % when it was treated with L-asparaginase conjugated zinc
oxide nanobiocomposite. Hence it is proved that the synthesized nanobiocomposites
of zinc oxide conjugated L-asparaginase has good anti-cancerous activity.
PMID- 25589206
TI - Structure and properties of porous films based on aliphatic copolyamide developed
for cellular technologies.
AB - The effect of concentration and viscosity of the copolyamide (copolymer of
epsilon-caprolactam and hexamethylendiaminadipate) solutions in aqueous/alcoholic
solvents on its phase state was studied. The films obtained by the coagulation
method were characterized by monodisperse pore distribution with an average pore
size of 1.3 MUm. The films processed by electrospinning from copolyamide
solutions were characterized by a bimodal distribution of macropores with one
peak of pore radius at 2.0 MUm and second peak of pore radius at 20 MUm. The
adhesion and proliferation of mesenchymal adhesion stem cells (ASCs) stem cells
to copolyamide matrix were studied. With the help of scanning electron microscopy
it was shown that both tapes porous films were characterized by good adhesion of
mesenchymal ASCs stem cells. It was shown that the porous structure, transport
and mechanical properties of these copolyamide films allow their use as two
dimensional matrices for cellular technology.
PMID- 25589207
TI - Effects of cathode design parameters on in vitro antimicrobial efficacy of
electrically-activated silver-based iontophoretic system.
AB - Post-operative infection is a major risk associated with implantable devices.
Prior studies have demonstrated the effectiveness of ionic silver as an
alternative to antibiotic-based infection prophylaxis and treatment. The focus of
this study is on an electrically activated implant system engineered for active
release of antimicrobial silver ions. The objective was to evaluate the effects
of the cathode design, especially the cathode material, on the in vitro
antimicrobial efficacy of the system. A modified Kirby-Bauer diffusion technique
was used for the antimicrobial efficacy evaluations (24 h testing interval). In
phase-1 of the study, a three-way ANOVA (n = 6, alpha = 0.05) was performed to
determine the effects of cathode material (silver, titanium, and stainless
steel), cathode surface area and electrode separation distance on the efficacy of
the system against Staphylococcus aureus. The results show that within the design
space tested, none of these parameters had a statistically significant effect on
the antimicrobiality of the system (P > 0.15). Subsequently, one-way ANOVA (n =
6, alpha = 0.05) was conducted in phase-2 to validate the inference regarding the
non-significance of the cathode material to the system efficacy using a broader
spectrum of pathogens (methicillin-resistant S. aureus, Escherichia coli,
Streptococcus agalactiae and Aspergillus flavus) responsible for osteomyelitis.
The results confirmed the lack of statistical difference between efficacies of
the three cathode material configurations against all pathogens tested (P >
0.58). Overall, the results demonstrate the ability to alter the cathode material
and related design parameters in order to minimize the silver usage in the system
without adversely affecting its antimicrobial efficacy.
PMID- 25589210
TI - Electrochemical preparation of nanostructured lanthanum using lanthanum chloride
as a precursor in 1-butyl-3-methylimidazolium dicyanamide ionic liquid.
AB - Nanostructured lanthanum was electrochemically prepared on a platinum (Pt)
substrate in the room temperature ionic liquid 1-butyl-3-methylimidazolium
dicyanamide (BMI-DCA) containing anhydrous LaCl3 at 333 K. The electrochemical
reduction behavior of La(iii) was investigated using cyclic voltammetry and
chronoamperometry techniques. Cyclic voltammogram revealed that the reduction of
La(iii) in BMI-DCA involved an irreversible process controlled by diffusion.
Chronoamperometric transient analysis confirmed the diffusion controlled
electrodeposition process with the diffusion coefficient of La(iii) species in
the range of 10(-10) cm(2) s(-1). The strong complexing capability of DCA(-)
anions facilitated the displacement of chloride ligands and induced the
solubility of LaCl3. The subsequent coordination of La(iii) and DCA(-) anions
forming [La(DCA)4](-) complex anions was monitored by designing amperometric
titration experiments. Potentiostatically deposited La-deposits with different
nanostructures were characterized by SEM, XRD and XPS analyses. The
electrodeposition potential was found to play an important role in controlling
the nucleation and growth kinetics of the nanocrystal during the
electrodeposition process. Depending on the deposition potential, metallic
lanthanum with either nanoparticles or nanoporous structures was obtained.
PMID- 25589208
TI - In vitro assessment of the soft tissue/implant interface using porcine gingival
explants.
AB - The biologic seal of peri-implant soft tissue is crucial for long-term prognosis
of oral implants. This in vitro study describes a novel tissue culture model
using porcine gingival explants to evaluate the soft tissue/implant interface.
Two different types of substrates were investigated: (a) plain polymer: BisGMA
TEGDMA (50-50 %) and (b) unidirectional fiber-reinforced composite (FRC). Porcine
gingival explants were obtained from a local slaughterhouse. The experimental
implants (n = 4) were inserted into the middle of freshly excised porcine
gingival explants and cultured at the air/liquid interface up to 14 days. Porcine
gingival explants with no implants served as baseline controls. The specimens
were fixed and processed for the preparation of undecalcified samples.
Histological analysis of the soft tissue/implant interface was carried out using
a light-microscope. Microscopic evaluation suggests that the gingival explants
established epithelial and connective tissue attachment to both implant types
over the incubation period. FRC surfaces seemed to have a favorable tissue
response with a sign of an outward epithelial migration. However, tissue
degeneration was observed at the end of the experiment. In conclusion, this in
vitro model maintains mucosal viability and ability to histologically evaluate
soft tissue attachment to biomaterials rendering it a time efficient and cost
effective model that may reduce the need for animal experiments.
PMID- 25589209
TI - In situ synthesis of hydroxyapatite nanocomposites using iron oxide nanofluids at
ambient conditions.
AB - This paper describes a simple method for the room temperature synthesis of
magnetite/hydroxyapatite composite nanocomposites using ferrofluids. The in situ
synthesis of magnetic-hydroxyapatite results in a homogenous distribution of the
two phases as seen both in transmission electron micrographs and assembled to a
micron range in the confocal micrographs. The selected area diffraction pattern
analysis shows the presence of both phases of iron oxide and hydroxyapatite. To
the dialyzed ferrofluid, the constituents of hydroxyapatite synthesis was added,
the presence of the superparamagnetic iron oxide particles imparts directionality
to the hydroxyapatite crystal growth. Electron probe microanalysis confirms the
co-existence of both iron and calcium atoms. Vibrating Sample magnetometer data
shows magnetization three times more than the parent ferrofluid, the local
concentration of iron oxide nanoparticles affects the strength of dipolar
interparticle interactions changing the energy barrier for determining the
collective magnetic behavior of the sample. The limitations inherent to the use
of external magnetic fields which can be circumvented by the introduction of
internal magnets located in the proximity of the target by a minimal surgery or
by using a superparamagnetic scaffold under the influence of externally applied
magnetic field inspires us to increase the magnetization of our samples. The
composite in addition shows anti-bacterial properties against the two gram (-ve)
bacteria tested. This work is significant as magnetite-hydroxyapatite composites
are attracting a lot of attention as adsorbents, catalysts, hyperthermia agents
and even as regenerative medicine.
PMID- 25589211
TI - Calcium intake and hypertension among obese adults in United States: associations
and implications explored.
AB - The relationship between calcium intake and hypertension is receiving increased
research attention. The prevalence of hypertension is high among the obese
populations. Calcium is a mineral that influences blood pressure. The aim of the
study was to examine the association between calcium intake and hypertension in a
large nationally representative sample of obese American adults. A total of
14,408 obese adults aged 20 years or older were obtained from the 1999-2010
National Health and Nutrition Examination Survey. Analysis of variance and linear
regression models were used to examine relationships between calcium intake and
systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple
logistic regression models were used to examine the association between calcium
intake and hypertension after adjusting for potential confounders and
interactions, including: age, race, education level, alcohol use, smoking,
diabetes status, sodium intake and potassium intake. Calcium intake was
significantly lower for the hypertensive group compared with the normotensive
group (P<0.0001), especially among those obese female young adults aged 20-44
years and among non-diabetic obese adults. Based on ordinary linear regression
analysis, a significant inverse relationship was detected, SBP and DBP decreased
if calcium intake increased (SBP: regression coefficient estimate=-0.015,
P<0.0001; DBP: regression coefficient estimate=-0.028, P<0.0001). Multiple
logistic regression showed that calcium intake was negatively associated with the
probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI):
0.74-0.87, P<0.0001). In stratified analysis, calcium intake in youngest adults
(age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI:
0.64-0.93, P<0.0001), the inverse relationship between calcium intake and
probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55
0.84, P<0.0001), when compared with the whole sample including all of 14,408
obese adults. The protective effect of calcium intake and hypertension was found
significantly in obese non-diabetic adults (OR: OR=0.77, 95% CI: 0.67-0.89,
P<0.0001) not in obese diabetic adults. SBP, DBP and calcium intake were log
transformed for both ordinary linear regression analysis and logistic regression
analysis. Our study findings underscore the need to explore the physiological
mechanism between calcium intake and hypertension. In this study, increased
calcium intake was associated with the lowest risk of hypertension. Future
studies utilizing longitudinal research designs are needed to quantify
therapeutic levels of calcium for control of hypertension among obese adults.
Increasing calcium intake among American adults may offer promise as a cost
effective strategy to improve hypertension among obese adults; however, further
scientific exploration is warranted.
PMID- 25589212
TI - Hypertension prevalence, awareness, treatment and control among Han and four
ethnic minorities (Uygur, Hui, Mongolian and Dai) in China.
AB - In the previous study, hypertension prevalence, awareness, treatment and control
for Han and others four ethnic minorities (Uygur, Hui, Mongolian and Dai) has not
been clearly documented in China. Therefore we used the baseline data of
Prospective Urban and Rural Epidemiology (PURE) for further detailed study.
Adjusted rate were estimated and compared through logistic regression after
adjustment of age, sex, location and education. Among the total of 7137
participants (Han: 1626, ethnic minorities: 5511), hypertension prevalence,
awareness, treatment and control were 2922(40.9%), 1199(41.0%), 873(29.9%) and
147(5.0%), respectively. The most commonly used antihypertensive drugs are
traditional compound drugs (6.2%) and calcium channel blockers (5.2%).
Hypertension prevalence in ethnic minorities was significantly higher than in Han
(42.4% vs 34.4%, P<0.0001), while control rate (1.6% vs 9.8%, P=0.0198) and
treated control rate (8.0% vs 25.0%, P=0.0200) were lower. Compared with Han
counterparts, Dai had a higher prevalence (50.8% vs 29.9%, P<0.0001). Uygur had a
lower treatment rate (33.2% vs 20.6%, P=0.0110). Mongolian had a lower control
(5.1% vs 16.1%, P=0.0046) and treated control rate (14.1% vs 50.3%, P=0.0013). In
conclusions, our study showed ethnic minorities had higher hypertension
prevalence, especially for Dai and lower control and treated control rate for
Mongolian. Hence, we need more attention with respect to hypertension in ethnic
minorities.
PMID- 25589213
TI - Weight reduction and aortic stiffness in obese children and adolescents: a 1-year
follow-up study.
AB - Little is known about the effect of weight reduction on aortic stiffness and
especially so in the young. The present study investigates whether weight
reduction influences aortic stiffness in obese children and adolescents. Carotid
femoral pulse wave velocity (cfPWV) and augmentation index at heart rate 75
(AIx@HR75) were measured in 72 obese patients aged 10-18 years at baseline and
after 1-year of lifestyle intervention (follow-up). We found that although the
degree of obesity decreased (Deltabody mass index z-score: -0.24+/-0.45,
P<0.0001), cfPWV was higher at follow-up (DeltacfPWV: 0.27+/-0.47 m s(-1),
P<0.0001), which was explained by the increase in age (beta=0.12 ms(-1) per
year, 95% confidence interval (CI) 0.07-0.17, P<0.0001) and partly by changes in
mean arterial pressure and heart rate. Changes in cfPWV were not related to
changes in obesity measures. No significant change was found in AIx@HR75
(DeltaAIx@HR75: 2.10+/-9.73%, P=0.072), but changes in AIx@HR75 were related to
changes in abdominal fat (Deltawaist/height ratio: beta=50.3, 95% CI 6.7-94.0,
P=0.02) and changes in total body fat percent by dual energy X-ray absorptiometry
scan (Deltatotal body fat (%): beta=0.7, 95% CI 0.1-1.3, P=0.02) when adjusted
for gender and relevant baseline confounders. In conclusion, no clear effect of
weight reduction was found on aortic stiffness, although changes in AIx@HR75 were
associated with changes in both abdominal fat and total body fat percent. The
higher cfPWV at follow-up was related to the older age.
PMID- 25589214
TI - Resistant hypertension: do all definitions describe the same patients?
AB - Resistant hypertension (RH) is defined as blood pressure (BP) that remains ?140
and/or 90 mm Hg despite therapy with ?3 full-dose antihypertensive drugs
(classical definition=CD). A definition proposed subsequently (new definition=ND)
includes patients requiring ?4 drugs irrespective of BP values. We aimed to
evaluate whether both definitions characterize the same kind of patients.One
hundred and twenty-four consecutively attended patients with RH were classified
into two groups according to their BP control: 66 patients had non-controlled BP
(all those who met the CD criteria plus a few patients who met the ND criteria);
58 patients had controlled BP (all with RH according to the ND). Clinical,
laboratory and office BP data were recorded. RH patients with non-controlled BP
were more frequently diabetic (72% vs 49%), and had higher plasmatic glucose (149
vs 130 mg dl(-1)), cholesterol (179 vs 164 mg dl(-1)), low-density lipoprotein
(LDL)-cholesterol (107 vs 95 mg dl(-1)) and triglyceride (169 vs 137 mg dl(-1))
levels; P<0.05 for all comparisons. In multivariate logistic regression analysis,
the variables that independently associated with non-controlled BP were diabetes
(P=0.001) and higher LDL-cholesterol (P=0.007).We conclude that, although both
cohorts of patients are phenotypically quite similar, uncontrolled RH patients
have higher prevalence of diabetes mellitus and higher LDL-cholesterol levels
than controlled RH patients.
PMID- 25589215
TI - Production benefits from pre- and post-lambing anthelmintic treatment of ewes on
commercial farms in the southern North Island of New Zealand.
AB - AIMS: To measure the magnitude and variability in production responses to
anthelmintic treatments administered to adult ewes around lambing. METHODS: Ewes
carrying twin lambs, from sheep and beef farms (eight in Year 1 and six in Year
2) in the Wairarapa region of New Zealand, were enrolled in 14 trials (part of an
experiment carried out on one farm in one year). Experiment 1 compared ewes
treated 2-4 weeks pre-lambing with a controlled release capsule (CRC) containing
abamectin, albendazole, Se and Co, to ewes injected pre-lambing with a long
acting Se plus vitamin B12 product, and to untreated ewes. Experiment 2 included
these treatments, plus a CRC administered at pregnancy scanning. Experiment 3
included the same treatments as Experiment 1, plus administration of a CRC
containing albendazole, Se and Co, injectable moxidectin or oral derquantel plus
abamectin, all administered pre-lambing, or oral derquantel plus abamectin
administered 4-6 weeks after lambing. Variables compared were ewe liveweight at
weaning and pre-mating, lamb liveweight at weaning, total weight of lamb weaned
per ewe and ewe dag score at weaning. RESULTS: Ewes treated with a CRC pre
lambing were heavier than untreated ewes (mean 3.2 kg) at weaning in 12/14
trials, and pre-mating (mean 2.8 kg) in 9/14 trials (p<0.001). Compared with
mineral-treated ewes the mean difference was 2.8 kg pre-lambing (9/14 trials) and
1.7 kg pre-weaning (6/14 trials). Lambs reared by treated ewes were heavier (mean
1.55 kg) at weaning in 6/14 trials (p<0.001), but there was no effect of CRC
treatment on total weight of lambs weaned per ewe (p=0.507). Variation in weight
of lamb weaned per ewe was largely explained by differences in lamb survival from
birth to weaning (p<0.001), with no effect of CRC treatment (p>0.65). Treatment
of ewes with a CRC at pregnancy scanning was neither better nor worse than a pre
lambing treatment (p=0.065). There was no difference in the response from
treatment with either of the two CRC or moxidectin. Treatment with short-acting
oral anthelmintics resulted in no consistent benefit. CONCLUSIONS: Anthelmintic
treatments administered to ewes around lambing resulted in variable responses
between farms and years, which in some trials were negative for some variables,
and some of the variability was due to the mineral component of the CRC. The
widespread perception amongst farmers and veterinarians that anthelmintic
treatment of ewes around lambing will always result in positive benefits is not
supported.
PMID- 25589216
TI - ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in
acute ischaemic stroke.
AB - Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be
insufficient to achieve recanalisation in certain patients. Predicting
probability of non-recanalisation after IVT may have the potential to influence
patient selection to more aggressive management strategies. We aimed at deriving
and internally validating a predictive score for post-thrombolytic non
recanalisation, using clinical and radiological variables. In thrombolysis
registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and
Geneva), patients were selected with large arterial occlusion on acute imaging
and with repeated arterial assessment at 24 hours. Based on a logistic regression
analysis, an integer-based score for each covariate of the fitted multivariate
model was generated. Performance of integer-based predictive model was assessed
by bootstrapping available data and cross validation (delete-d method). In 599
thrombolysed strokes, five variables were identified as independent predictors of
absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial
vessel STenosis (ST), decreased Range of visual fields (R), large Arterial
occlusion (A) and decreased Level of consciousness (L). All variables were
weighted 1, except for (L) which obtained 2 points based on beta-coefficients on
the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation
probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of
0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using
delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately
predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its
performance can be confirmed by external validation and its clinical usefulness
can be proven, the score may influence patient selection for more aggressive
revascularisation strategies in routine clinical practice.
PMID- 25589217
TI - Virulence-targeted Antibacterials: Concept, Promise, and Susceptibility to
Resistance Mechanisms.
AB - In view of the relentless increase in antibiotic resistance in human pathogens,
efforts are needed to safeguard our future therapeutic options against infectious
diseases. In addition to regulatory changes in our antibiotic use, this will have
to include the development of new therapeutic compounds. One area that has
received growing attention in recent years is the possibility to treat or prevent
infections by targeting the virulence mechanisms that render bacteria pathogenic.
Antivirulence targets include bacterial adherence, secretion of toxic effector
molecules, bacterial persistence through biofilm formation, quorum sensing and
immune evasion. Effective small-molecule compounds have already been identified
that suppress such processes. In this review, we discuss the susceptibility of
such compounds to the development of resistance, by comparison with known
resistance mechanisms observed for classical bacteriostatic or bacteriolytic
antibiotics, and by review of available experimental case studies. Unfortunately,
appearance of resistance mechanisms has already been demonstrated for some,
showing that the quest of new, lasting drugs remains complicated.
PMID- 25589218
TI - The modified quasi-quantum treatment of rotationally inelastic NO(X)-He
scattering.
AB - A modified quasi-quantum treatment (MQQT) of molecular scattering has been
developed to account for the softness of the repulsive part of the anisotropic
atom-molecule PES. A contour of the PES is chosen such that the barrier height is
just large enough to reflect the incoming kinetic energy, directed anti-parallel
to the hard shell normal at the site of impact. The resulting rotationally
inelastic quantum state resolved DCSs and ICSs of He + NO(X) at Ecol = 508 cm(-1)
are compared to those obtained from regular QQT and from quantum mechanically
exact calculations performed on the full highest quality ab initio Vsum PES. The
MQQT parity changing DCSs for Deltaj <= 4 exhibit much better agreement with the
QM DCSs than is obtained using regular QQT, particularly in the forward scattered
direction. The improvements upon the remaining MQQT DCSs with respect to the
regular QQT were minor, due to the near incompressible hard shell character of
the n ? 1 or 3 anisotropic Legendre polynomial terms of the PES.
PMID- 25589219
TI - Intermolecular enantioselective dearomatization reaction of beta-naphthol using
meso-aziridine: a bifunctional in situ generated magnesium catalyst.
AB - A direct, facile, and highly diastereo- and enantioselective dearomatization
reaction of beta-naphthol derivatives with aziridines has been developed for the
first time. A newly designed Box-OH ligand was employed for an in situ generated
magnesium catalyst and proved to be efficient. The corresponding dearomatization
product was transformed into a polycyclic scaffold and polyhydroxylated compound.
(1) H NMR studies revealed the activation mode of the dearomatization process of
beta-naphthols, and a clear positive nonlinear effect was observed in the
reaction, and provides insight into the coordination environment around the
Mg(II) center and the possible active species.
PMID- 25589221
TI - Erratum to: does saturable formation of gemcitabine triphosphate occur in
patients?
PMID- 25589220
TI - Effect of axitinib on the QT interval in healthy volunteers.
AB - PURPOSE: Axitinib is a potent and selective inhibitor of vascular endothelial
growth factor receptors 1-3, approved for second-line treatment of advanced renal
cell carcinoma (RCC). Preclinical studies did not indicate potential for axitinib
induced delayed cardiac repolarization. METHODS: The effect of axitinib on
corrected QT (QTc) prolongation was evaluated with one-stage concentration-QTc
response modeling using data from a definitive randomized crossover QT phase I
study in healthy volunteers administered one single 5-mg axitinib dose alone or
in the presence of steady-state ketoconazole (400 mg once daily). RESULTS:
Axitinib and ketoconazole had opposite effects on heart rate: Axitinib lowered
it, ketoconazole raised it. The final analysis showed a flat relationship between
QTc and axitinib concentration (slope -0.0314 ms.mL/ng) for axitinib alone. Mean
highest placebo-matched change from baseline in QTc was -3.0 [90 % confidence
interval (CI) -5.4, -0.6] ms. At supratherapeutic axitinib exposures achieved
with potent cytochrome P450 3A4/5 inhibition by ketoconazole, the model predicted
mean QTc change of 6.5 (90 % CI 4.4-8.5) ms. The slope population mean estimate
was -0.331 (95 % CI -0.860, 0.198) ms.mL/ug for ketoconazole alone and 0.0725
(0.0445-0.1005) ms.mL/ng for axitinib in the presence of ketoconazole. The
results were then compared with those obtained based on more widely used
Fridericia's, Bazett's, and study-specific correction methods. CONCLUSIONS: Since
axitinib plasma concentrations observed in this study exceeded the range of
concentrations observed in patients with RCC at the highest approved clinical
dose (10 mg twice daily), axitinib was not associated with clinically significant
QTc prolongation in target populations.
PMID- 25589222
TI - Therapeutic use of CCR5 antagonists is supported by strong expression of CCR5 on
CD8(+) T cells in progressive multifocal leukoencephalopathy-associated immune
reconstitution inflammatory syndrome.
PMID- 25589223
TI - Danon disease: a phenotypic expression of LAMP-2 deficiency.
AB - Danon disease is an X-linked disorder clinically characterized by the triad of
hypertrophic cardiomyopathy, myopathy, and intellectual disability.
Cardiomyopathy is a severe and life-threatening problem, for which cardiac
transplantation is the only therapeutic option. The most striking finding in
muscle biopsy samples is small basophilic granules scattered in myofibers, which
are in fact small autophagic vacuoles surrounded by membranes with sarcolemmal
features characterized by the recruitment of sarcolemmal proteins and
acetylcholine esterase and by the presence of basal lamina on its luminal side.
The mechanism underlying the formation of these autophagic vacuoles with unique
sarcolemmal features (AVSF) still remains a mystery and its origin is unknown. In
heart, cardiomyocytes show dramatically increased vacuolation and degenerative
features, including myofibrillar disruption and lipofuscin accumulation. In
brain, pale granular neurons and neurons with lipofuscin-like granules may be
seen. Danon disease is caused by loss-of-function mutations in the LAMP2 gene,
which encodes lysosome-associated membrane protein 2 (LAMP-2), a single-spanned
transmembrane protein localized in the limiting membranes of lysosomes and late
endosomes. Most mutations lead to splicing defects or protein truncation,
resulting in a loss of transmembrane and/or cytoplasmic domains, leading to LAMP
2 protein deficiency. LAMP-2 is required for the maturation of autophagosomes by
fusion with lysosomes; therefore, LAMP-2 deficiency leads to a failure in
macroautophagy. There are three LAMP-2 isoforms, LAMP-2A, -2B, and -2C. Clinical
features of Danon disease are thought to be mediated by loss of the LAMP-2B
isoform which is the major isoform expressed in muscle. It is also known that
LAMP-2 plays a role in chaperone-mediated autophagy and RNA- and DNA-targeting
autophagy. However, the precise pathophysiological mechanism through which LAMP-2
deficiency causes Danon disease is still not fully understood and its elucidation
would promote the development of new therapies.
PMID- 25589225
TI - Evaluating genetic diversity and constructing core collections of Chinese
Lentinula edodes cultivars using ISSR and SRAP markers.
AB - Genetic diversity among 89 Chinese Lentinula edodes cultivars was analyzed by
inter-simple sequence repeat (ISSR) and sequence-related amplified polymorphism
(SRAP) markers. A 123 out of 126 ISSR loci (97.62%) and 108 out of 129 SRAP loci
(83.73%) were polymorphic between two or more strains. A dendrogram constructed
by cluster analysis based on the ISSR and SRAP markers separated the L. edodes
strains into two major groups, of which group B was further divided into five
subgroups. Clustering results also showed a positive correlation with the main
agronomic traits of the strains, and that strains with similar traits clustered
together into the same groups or subgroups in most cases. The average coefficient
of pairwise genetic similarity was 0.820 (range: 0.576-0.988). Compared to the
wild strains, Chinese L. edodes cultivars indicated a lower level of genetic
diversity. Two preliminary core collections of L. edodes, Core1 and Core2, were
established based on the ISSR and SRAP data, respectively. Core1 was constructed
by the advanced M (maximization) strategy using the PowerCore version 1.0
software and contained 21 strains, whereas Core2 was created by the allele
preferred sampling strategy using the cluster method and contained 18 strains.
Both core collections were highly representative of the genetic diversity of the
original germplasm, as confirmed by the values of Na (observed number of
alleles), Ne (effective number of alleles), H (Nei's gene diversity) and I
(Shannon's information index), as well as results of principal coordinate
analysis. The loci retention ratio of Core1 (99.61%) was higher than that of
Core2 (97.65%). Moreover, Core1 contained strains with more types of agronomic
traits than those in Core2. This study builds the basis for further effective
protection, management and use of L. edodes germplasm resource.
PMID- 25589224
TI - Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and
intensity modulated radiotherapy (78/82 Gy) for prostate cancer.
AB - PURPOSE: The purpose of this work was to compare toxicity and cancer control
between patients with prostate cancer treated using three-dimensional conformal
radiotherapy (3D-CRT) and those treated using intensity-modulated radiation
therapy (IMRT). METHODS AND MATERIALS: A total of 553 patients with prostate
cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy
(IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT
criteria. Biochemical failure was defined using the Phoenix and ASTRO
definitions. RESULTS: The 5-year risk of grade 2-4 genitourinary toxicity was
26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB
82) without statistical differences. The 5-year risk of grade 2-4
gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 %
(IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT
70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p =
0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk,
intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5,
and 57.8 %, respectively. Patients treated with IMRT achieved the following
results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in
patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7
vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for
patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached
95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were
statistically significant, while C-RFS and DFS were marginally better.
CONCLUSION: Dose escalation with IMRT was associated with improved cancer control
in intermediate- and high-risk patients in comparison with 3D-CRT, without
compromising toxicity.
PMID- 25589226
TI - Leptin resistance in diet-induced obesity: the role of hypothalamic inflammation.
AB - The consumption of Western diets, high in sugar and saturated fat, is a crucial
contributor to the alarming incidence of obesity and its associated morbidities.
These diets have been reported to induce an inflammatory response in the
hypothalamus, which promotes the development of central leptin resistance and
obesity. This inflammatory signalling involves dynamic changes in the expression
and activity of several mediators of the innate immune system, including toll
like receptor 4, IkappaB kinase-beta/nuclear factor-kappaB, c-Jun N-terminal
kinase, suppressor of cytokine signalling 3 and pro-inflammatory cytokines, as
well as the induction of endoplasmic reticulum stress and autophagy defect.
Although the exact cellular mechanisms remain incompletely understood, recent
evidence suggests that the inflammatory response is at least mediated by
interactions between neurons and non-neuronal cells such as microglia and
astrocytes. Current evidence of the contribution of each inflammatory mediator to
leptin resistance and diet-induced obesity (DIO), including their reciprocal
interactions and cell-type-specific effects, is reviewed and integrated in a
conceptual model. Based upon this model and pharmacological intervention studies,
several inflammatory mediators are proposed to be promising therapeutic targets
for the treatment of DIO.
PMID- 25589227
TI - Updates on quick identification of acetic acid bacteria with a focus on the 16S
23S rRNA gene internal transcribed spacer and the analysis of cell proteins by
MALDI-TOF mass spectrometry.
AB - Acetic acid bacteria have attracted much attention over the past few years, due
mainly to their metabolic traits that are of interest to the biotechnology
industry. In addition, it turns out that their ecological habitats are almost
unlimited since they have been found as symbionts in different insects and also
as emerging opportunistic human pathogens. Very surprising is the finding that
they colonize niches considered anaerobic, disproving the generalized statement
that they are strict aerobes. Since they have taken on different biological roles
in our environment, more and more people are charged with the task of identifying
them. However, this turns out to be not always easy, especially if we are using
phenotypic approaches for identification. A substantial step forward in making
the identification of acetic acid bacteria easier was made possible using
molecular biological methods, which have been extensively tested since 2000.
However, some molecular methods require expensive machines and experienced staff,
and moreover the level of their discrimination varies. All these factors must be
considered when selecting the most appropriate approach for identifying acetic
acid bacteria. With this objective in mind, this review article discusses the
benefits and drawbacks of molecular biological methods for identification of
acetic acid bacteria, with a focus on the 16S-23S rRNA gene ITS regions and the
recently described alternative method for identification of acetic acid bacteria,
MALDI-TOF MS.
PMID- 25589228
TI - Early embryonic and endometrial regulation of tumor necrosis factor and tumor
necrosis factor receptor 2 in the cattle uterus.
AB - Tumor necrosis factor (TNF) alpha likely mediates embryomaternal communication in
mammals. In bovine, we have previously found that the uterine fluid of heifers
that carried early embryos shows downregulation in the TNF and nuclear factor
kappaB system. In this work, we assessed the expression of TNF and its receptor
TNFR2 in the bovine endometrium and embryos during blastocyst development.
Moreover, to explore the endometrial immune response to early embryos, we
analyzed the number of CD45 leukocytes in the bovine endometrium. Day 8
endometrium and blastocyst recovered from animals after transfer of Day 5 embryos
showed TNF and TNFR2 mRNA transcription and protein colocalization. The presence
of embryos increased endometrial TNF and TNFR2 protein, whereas endometrial
leukocytes decreased. Blastocysts exposed to the uterine tract had undetectable
levels of TNF and lower levels of TNFR2 mRNA. These results suggest that the
endometrium might lower the TNF concentration in the blastocyst by (1) regulating
TNF secretion into the uterine fluid and (2) inducing decreased TNF and TNFR2
mRNA transcription in the embryo. Thus, TNF and TNFR2 might participate in early
embryomaternal communication.
PMID- 25589229
TI - Functional characterization of aquaporins and aquaglyceroporins of the yellow
fever mosquito, Aedes aegypti.
AB - After taking vertebrate blood, female mosquitoes quickly shed excess water and
ions while retaining and concentrating the mostly proteinaceous nutrients.
Aquaporins (AQPs) are an evolutionary conserved family of membrane transporter
proteins that regulate the flow of water and in some cases glycerol and other
small molecules across cellular membranes. In a previous study, we found six
putative AQP genes in the genome of the yellow fever mosquito, Ae. aegypti, and
demonstrated the involvement of three of them in the blood meal-induced diuresis.
Here we characterized AQP expression in different tissues before and after a
blood meal, explored the substrate specificity of AQPs expressed in the
Malpighian tubules and performed RNAi-mediated knockdown and tested for changes
in mosquito desiccation resistance. We found that AQPs are generally down
regulated 24 hrs after a blood meal. Ae. aegypti AQP 1 strictly transports water,
AQP 2 and 5 demonstrate limited solute transport, but primarily function as water
transporters. AQP 4 is an aquaglyceroporin with multiple substrates. Knockdown of
AQPs expressed in the MTs increased survival of Ae. aegypti under dry conditions.
We conclude that Malpighian tubules of adult female yellow fever mosquitoes
utilize three distinct AQPs and one aquaglyceroporin in their osmoregulatory
functions.
PMID- 25589230
TI - Using magnetic levitation for non-destructive quality control of plastic parts.
AB - Magnetic levitation (MagLev) enables rapid and non-destructive quality control of
plastic parts. The feasibility of MagLev as a method to: i) rapidly assess
injection-molded plastic parts for defects during process optimization, ii)
monitor the degradation of plastics after exposure to harsh environmental
conditions, and iii) detect counterfeit polymers by density is demonstrated.
PMID- 25589231
TI - Training clinicians in how to use patient-reported outcome measures in routine
clinical practice.
AB - INTRODUCTION: Patient-reported outcome measures (PROs) were originally developed
for comparing groups of people in clinical trials and population studies, and the
results were used to support treatment recommendations or inform health policy,
but there was not direct benefit for the participants providing PROs data.
However, as the experience in using those measures increased, it became obvious
the clinical value in using individual patient PROs profiles in daily practice to
identify/monitor symptoms, evaluate treatment outcomes and support shared
decision-making. A key issue limiting successful implementation is clinicians'
lack of knowledge on how to effectively utilize PROs data in their clinical
encounters. METHODS: Using a change management theoretical framework, this paper
describes the development and implementation of three programs for training
clinicians to effectively use PRO data in routine practice. The training programs
are in three diverse clinical areas (adult oncology, lung transplant and
paediatrics), in three countries with different healthcare systems, thus
providing a rare opportunity to pull out common approaches whilst recognizing
specific settings. For each program, we describe the clinical and organizational
setting, the program planning and development, the content of the training
session with supporting material, subsequent monitoring of PROs use and evidence
of adoption. The common successful components and practical steps are identified,
leading to discussion and future recommendations. RESULTS: The results of the
three training programs are described as the implementation. In the oncology
program, PRO data have been developed and are currently evaluated; in the lung
transplant program, PRO data are used in daily practice and the integration with
electronic patient records is under development; and in the paediatric program,
PRO data are fully implemented with around 7,600 consultations since the start of
the implementation. CONCLUSION: Adult learning programs teaching clinicians how
to use and act on PROs in clinical practice are a key steps in supporting patient
engagement and participation in shared decision-making. Researchers and
clinicians from different clinical areas should collaborate to share ideas,
develop guidelines and promote good practice in patient-centred care.
PMID- 25589232
TI - The use of cognitive interviews to revise the Quality of Trauma Care Patient
Reported Experience Measure (QTAC-PREM).
AB - PURPOSE: The "Quality of Trauma Care Patient-Reported Experience Measure" is the
first measure of patient experiences with overall injury care. The objective of
this study was to use cognitive interviews to inform revision of the measure into
a parsimonious set of items that function as intended, in preparation for
multicenter testing. METHODS: Concurrent and retrospective cognitive interviews
with injured patients (n = 17) and family members (n = 13) using semi-structured
interview guides. Responses were analyzed using thematic analysis. RESULTS: Six
broad themes were identified and guided revisions: (1) participants did not have
the information to answer items (n = 9); (2) items were ambiguous or were
inconsistently interpreted (n = 13); (3) items did not measure the intended
constructs (n = 6); (4) items included assumptions about healthcare processes (n
= 4); (5) items measured non-priority aspects of injury care (n = 8); and (6)
items were redundant (n = 5). Two issues resulted in key conceptual and content
changes: participants' difficulty to evaluate pre-hospital, emergency department,
and intensive care unit services due to recall issues and the challenge to
evaluate the effectiveness and equity of care. In total, 39 items were deleted,
28 new items developed, and the final instrument included 63 items. CONCLUSIONS:
Our results informed changes to item content, format, and response options. This
study highlights key issues to consider when incorporating patient/family
perspectives into quality measurement, most notably, that few participants can
assess the quality of care in the pre-hospital and emergency department phases of
care and that novel methods are needed to evaluate the effectiveness and equity
of care.
PMID- 25589233
TI - Veteran, primary care provider, and specialist satisfaction with electronic
consultation.
AB - BACKGROUND: Access to specialty care is challenging for veterans in rural
locations. To address this challenge, in December 2009, the Veterans Affairs (VA)
Pittsburgh Healthcare System (VAPHS) implemented an electronic consultation (e
consult) program to provide primary care providers (PCPs) and patients with
enhanced specialty care access. OBJECTIVE: The aim of this quality improvement
(QI) project evaluation was to: (1) assess satisfaction with the e-consult
process, and (2) identify perceived facilitators and barriers to using the e
consult program. METHODS: We conducted semistructured telephone interviews with
veteran patients (N=15), Community Based Outpatient Clinic (CBOC) PCPs (N=15),
and VA Pittsburgh specialty physicians (N=4) who used the e-consult program
between December 2009 to August 2010. Participants answered questions regarding
satisfaction in eight domains and identified factors contributing to their
responses. RESULTS: Most participants were white (patients=87%; PCPs=80%;
specialists=75%) and male (patients=93%; PCPs=67%; specialists=75%). On average,
patients had one e-consult (SD 0), PCPs initiated 6 e-consults (SD 6), and VAPHS
specialists performed 17 e-consults (SD 11). Patients, PCPs, and specialty
physicians were satisfied with e-consults median (range) of 5.0 (4-5) on 1-5
Likert-scale, 4.0 (3-5), and 3.5 (3-5) respectively. The most common reason why
patients and specialists reported increased overall satisfaction with e-consults
was improved communication, whereas improved timeliness of care was the most
common reason for PCPs. Communication was the most reported perceived barrier and
facilitator to e-consult use. CONCLUSIONS: Veterans and VA health care providers
were satisfied with the e-consult process. Our findings suggest that while the
reasons for satisfaction with e-consult differ somewhat for patients and
physicians, e-consult may be a useful tool to improve VA health care system
access for rural patients.
PMID- 25589236
TI - Simultaneous ultrasound-assisted water extraction and beta-cyclodextrin
encapsulation of polyphenols from Mangifera indica stem bark in counteracting
TNFalpha-induced endothelial dysfunction.
AB - This study proposes an alternative technique to prevent heat degradation induced
by classic procedures of bioactive compound extraction, comparing classical
maceration/decoction in hot water of polyphenols from Mango (Mangifera indica L.)
(MI) with ultrasound-assisted extraction (UAE) in a water solution of beta
cyclodextrin (beta-CD) at room temperature and testing their biological activity
on TNFalpha-induced endothelial dysfunction. Both extracts counteracted TNFalpha
effects on EAhy926 cells, down-modulating interleukin-6, interleukin-8,
cyclooxygenase-2 and intracellular adhesion molecule-1, while increasing
endothelial nitric oxide synthase levels. beta-CD extract showed higher efficacy
in improving endothelial function. These effects were abolished after pre
treatment with the oestrogen receptor inhibitor ICI1182,780. Moreover, the beta
CD extract induced Akt activation and completely abolished the TNFalpha-induced
p38MAPK phosphorylation. UAE and beta-CD encapsulation provide an efficient
extraction protocol that increases polyphenol bioavailability. Polyphenols from
MI play a protective role on endothelial cells and may be further considered as
oestrogen-like molecules with vascular protective properties.
PMID- 25589237
TI - Long-term effects of continuous theta-burst stimulation in visuospatial neglect.
AB - OBJECTIVE: To investigate whether the efficacy of continuous theta-burst
stimulation (cTBS) for improving visuospatial neglect can be enhanced by
providing more days of stimulation and more stimulation trains per day. METHODS:
In a prospective study, right-handed patients with right hemisphere stroke and
visuospatial neglect were randomized to cTBS or sham cTBS treatment for 2 weeks
and were followed up for 4 weeks. The cTBS group received active cTBS over the
posterior parietal cortex of the unaffected hemisphere, combined with
conventional rehabilitation therapy. Changes in scores for two paper-pencil tests
for visuospatial neglect (star cancellation and line bisection) were evaluated.
RESULTS: In each group, 10 patients completed follow up. Compared with the sham
group, star cancellation test scores in the cTBS group were improved by 37.03% at
the end of treatment and by 47.21% after 4 weeks' follow up, and the line
bisection score improved by 21.37% at the end of treatment and by 35.99% after 4
weeks' follow up. CONCLUSIONS: These results suggest that the efficacy of cTBS in
visuospatial neglect can be enhanced and prolonged by increasing the days of
stimulation and the number of stimulation trains per day over the left posterior
parietal cortex.
PMID- 25589239
TI - Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) promotes EIAV
replication and infectivity.
AB - Adenosine deaminases that act on RNA (ADARs) have been reported to be functional
on various viruses. ADAR1 may exhibit antiviral or proviral activity depending on
the type of virus. Human immunodeficiency virus (HIV)-1 is the most well-studied
lentivirus with respect to its interaction with ADAR1, and variable results have
been reported. In this study, we demonstrated that equine ADAR1 (eADAR1) was a
positive regulator of equine infectious anemia virus (EIAV), another lentivirus
of the Retroviridae family. First, eADAR1 significantly promoted EIAV
replication, and the enhancement of viral protein expression was associated with
the long terminal repeat (LTR) and Rev response element (RRE) regions. Second,
the RNA binding domain 1 of eADAR1 was essential only for enhancing LTR-mediated
gene expression. Third, in contrast with APOBEC proteins, which have been shown
to reduce lentiviral infectivity, eADAR1 increased the EIAV infectivity. This
study indicated that eADAR1 was proviral rather than antiviral for EIAV.
PMID- 25589240
TI - Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency
virus type-1 infection in peripheral blood monocyte-derived macrophages.
AB - Transfusion of blood and blood products contaminated with the pathogenic form of
prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt
Jakob disease (vCJD), may result in serious consequences in recipients with a
compromised immune system, for example, as seen in HIV-1 infection. In the
present study, we demonstrate that treatment of peripheral blood monocyte-derived
macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has
intrinsic functional activities related to the full-length protein, markedly
increased their susceptibility to HIV-1 infection, induced cytokine secretion,
and enhanced their migratory behavior in response to N-formyl-l-methionyl-l
leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence
of PrP106-126 showed large cell clusters indicative of cellular activation.
Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin
dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM
functions. These findings delineate a previously undefined functional role of
PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis.
PMID- 25589238
TI - An expanded taxonomy of hepatitis C virus genotype 6: Characterization of 22 new
full-length viral genomes.
AB - We characterized the full-length genomes of 22 hepatitis C virus genotype 6 (HCV
6) isolates: 10 from Vietnam (classified into subtypes 6e, 6h, 6p, 6r, 6s, and
6u), one from China (confirmed as a new subtype 6xd), and 11 from the Lao PDR
(representing a new subtype 6xe plus eight novel variants). With these 22 new
genomes, HCV-6 now has a diverse and extended taxonomic structure, comprised of
28 assigned subtypes (denoted 6a-6xe) and 27 unassigned lineages, all of which
have been represented by full-length genomes. Our phylogenetic analyses also
included many partially-sequenced novel variants of HCV-6 from Lao PDR. This
revealed that Lao HCV isolates are genetically very diverse and are
phylogenetically distributed in multiple lineages within genotype 6. Our results
suggest that HCV-6 has been maintained in Laos, a landlocked country, since the
common ancestor of genotype 6 and indicates historical dispersal of HCV-6 across
Southeast Asia.
PMID- 25589241
TI - Polyomavirus T antigens activate an antiviral state.
AB - Ectopic expression of Simian Virus 40 (SV40) large T antigen (LT) in mouse
embryonic fibroblasts (MEFs) increased levels of mRNAs encoding interferon
stimulated genes (ISGs). The mechanism by which T antigen increases levels of
ISGs in MEFs remains unclear. We present evidence that expression of T antigen
from SV40, Human Polyomaviruses BK (BKV) or JC (JCV) upregulate production of
ISGs in MEFs, and subsequently result in an antiviral state, as determined by
inhibition of VSV or EMCV growth. The first 136 amino acids of LT are sufficient
for these activities. Furthermore, increased ISG expression and induction of the
antiviral state requires STAT1. Finally, the RB binding motif of LT is necessary
for activation of STAT1. We conclude that the induction of the STAT1 mediated
innate immune response in MEFs is a common feature shared by SV40, BKV and JCV.
PMID- 25589242
TI - Systematic assessment of the correlations of household income with infectious,
biochemical, physiological, and environmental factors in the United States, 1999
2006.
AB - A fuller understanding of the social epidemiology of disease requires an extended
description of the relationships between social factors and health indicators in
a systematic manner. In the present study, we investigated the correlations
between income and 330 indicators of physiological, biochemical, and
environmental health in participants in the US National Health and Nutrition
Examination Survey (NHANES) (1999-2006). We combined data from 3 survey waves (n
= 249-23,649 for various indicators) to search for linear and nonlinear
(quadratic) correlates of income, and we validated significant (P < 0.00015)
correlations in an independent testing data set (n = 255-7,855). We validated 66
out of 330 factors, including infectious (e.g., hepatitis A), biochemical (e.g.,
carotenoids, high-density lipoprotein cholesterol), physiological (e.g., upper
leg length), and environmental (e.g., lead, cotinine) measures. We found only a
modest amount of association modification by age, race/ethnicity, and gender, and
there was no association modification for blacks. The present study is
descriptive, not causal. We have shown in our systematic investigation the
crucial place income has in relation to health risk factors. Future research can
use these correlations to better inform theory and studies of pathways to
disease, as well as utilize these findings to understand when confounding by
income is most likely to introduce bias.
PMID- 25589243
TI - A cautionary note about estimating effects of secondary exposures in cohort
studies.
AB - Cohort studies are often enriched for a primary exposure of interest to improve
cost-effectiveness, which presents analytical challenges not commonly discussed
in epidemiology. In this paper, we use causal diagrams to represent exposure
enriched cohort studies, illustrate a scenario wherein the risk ratio for the
effect of a secondary exposure on an outcome is biased, and propose an analytical
method for correcting for such bias. In our motivating example, maternal smoking
(Z) is a cause of fetal growth restriction (X), which subsequently affects
preterm birth (Y) (i.e., Z -> X -> Y); strong positive associations exist between
both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to
50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in
the risk ratio for the total effect of Z on Y. After application of inverse
probability weights, the bias is corrected, with a small loss of efficiency in
comparison with a same-sized study without X-enrichment. With increasing interest
in conducting secondary analyses to reduce research costs, caution should be
employed when analyzing studies that have already been enriched, intentionally or
unintentionally, for a primary exposure of interest. Causal diagrams can help
identify scenarios in which secondary analyses may be biased. Inverse probability
weights can be used to remove the bias.
PMID- 25589244
TI - LIMS2 mutations are associated with a novel muscular dystrophy, severe
cardiomyopathy and triangular tongues.
AB - Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of genetic
disorders leading to progressive muscle degeneration and often associated with
cardiac complications. We present two adult siblings with childhood-onset of
weakness progressing to a severe quadriparesis with the additional features of
triangular tongues and biventricular cardiac dysfunction. Whole exome sequencing
identified compound heterozygous missense mutations that are predicted to be
pathogenic in LIMS2. Biopsy of skeletal muscle demonstrated disrupted
immunostaining of LIMS2. This is the first report of mutations in LIMS2 and
resulting disruption of the integrin linked kinase (ILK)-LIMS-parvin complex
associated with LGMD.
PMID- 25589245
TI - Recurrent white thrombi formation in hemodialysis tubing: a case report.
AB - BACKGROUND: While the appearance of red clots in the dialyzer is a common
phenomenon in every hemodialysis unit, the occurrence of white thrombi in the
tubing is relatively rare. CASE PRESENTATION: We describe an adolescent male with
recurrent white thrombi formation in the hemodialysis tubing. This patient had
chronic renal failure from focal segmental glomerulosclerosis, but was no longer
nephrotic at the time of the thrombi formation. He had a history of recurrent
thrombosis of his vascular access. However, no pro-thrombotic risk factors could
be identified. White particulate matter, measuring 1 to 3mm in size, and adherent
to the arterial and venous blood tubing lines was found during the rinse back of
a hemodialysis session. This was associated with a 60% decrease in his platelet
count. Light microscopic examination of the deposits revealed the presence of
platelet aggregates. He subsequently developed thrombosis of his arteriovenous
graft six hours later. The white thrombi recurred at the next dialysis session,
as well as six months later. These episodes occurred regardless of the type of
dialysis machine or tubing, and appeared to resolve with an increase in heparin
dose. CONCLUSION: Recurrent white thrombi formation can occur in the hemodialysis
tubing of a patient with no identifiable pro-thrombotic factors. The white
thrombi may be a harbinger of arteriovenous graft thrombosis and may be prevented
by an increase in heparin dose.
PMID- 25589246
TI - Patients are being discharged to die in care homes, conference hears.
PMID- 25589247
TI - Relationship between nucleosome positioning and progesterone-induced alternative
splicing in breast cancer cells.
AB - Splicing of mRNA precursors can occur cotranscriptionally and it has been
proposed that chromatin structure influences splice site recognition and
regulation. Here we have systematically explored potential links between
nucleosome positioning and alternative splicing regulation upon progesterone
stimulation of breast cancer cells. We confirm preferential nucleosome
positioning in exons and report four distinct profiles of nucleosome density
around alternatively spliced exons, with RNA polymerase II accumulation closely
following nucleosome positioning. Hormone stimulation induces switches between
profile classes, correlating with a subset of alternative splicing changes.
Hormone-induced exon inclusion often correlates with higher nucleosome occupancy
at the exon or the preceding intronic region and with higher RNA polymerase II
accumulation. In contrast, exons skipped upon hormone stimulation display low
nucleosome densities even before hormone treatment, suggesting that chromatin
structure primes alternative splicing regulation. Skipped exons frequently harbor
binding sites for hnRNP AB, a hormone-induced splicing regulator whose knock down
prevents some hormone-induced skipping events. Collectively, our results argue
that a variety of chromatin architecture mechanisms can influence alternative
splicing decisions.
PMID- 25589248
TI - Unexpected selection to retain high GC content and splicing enhancers within
exons of multiexonic lncRNA loci.
AB - If sequencing was possible only for genomes, and not for RNAs or proteins, then
functional protein-coding exons would be recognizable by their unusual patterns
of nucleotide composition, specifically a high GC content across the body of
exons, and an unusual nucleotide content near their edges. RNAs and proteins can,
of course, be sequenced but the extent of functionality of intergenic long
noncoding RNAs (lncRNAs) remains under question owing to their low nucleotide
conservation. Inspired by the nucleotide composition patterns of protein-coding
exons, we sought evidence for functionality across lncRNA loci from diverse
species. We found that such patterns across multiexonic lncRNA loci mirror those
of proteincoding genes, although to a lesser degree: Specifically, compared with
introns, lncRNA exons are GC rich. Additionally we report evidence for the action
of purifying selection to preserve exonic splicing enhancers within human
multiexonic lncRNAs and nucleotide composition in fruit fly lncRNAs. Our findings
provide evidence for selection for more efficient rates of transcription and
splicing within lncRNA loci. Despite only a minor proportion of their RNA bases
being constrained, multiexonic intergenic lncRNAs appear to require accurate
splicing of their exons to transact their function.
PMID- 25589249
TI - Is drug-eluting bead transcatheter arterial chemoembolization (TACE) associated
with better tumor response than conventional TACE in meta-analysis?
PMID- 25589251
TI - Role of disorder in finite-amplitude shear of a 2D jammed material.
AB - A material's response to small but finite deformations can reveal the roots of
its response to much larger deformations. Here, we identify commonalities in the
responses of 2D soft jammed solids with different amounts of disorder. We
cyclically shear the materials while tracking their constituent particles, in
experiments that feature a stable population of repeated structural relaxations.
Using bidisperse particle sizes creates a more amorphous material, while
monodisperse sizes yield a more polycrystalline one. We find that the materials'
responses are very similar, both at the macroscopic, mechanical level and in the
microscopic motions of individual particles. However, both locally and in bulk,
crystalline arrangements of particles are stiffer (greater elastic modulus) and
less likely to rearrange. Our work supports the idea of a common description for
the responses of a wide array of materials.
PMID- 25589252
TI - An UPLC-MS/MS method for the analysis of glimepiride and fluoxetine in human
plasma.
AB - A sensitive and rapid ultra performance liquid chromatography tandem mass
spectrometry (UPLC-MS/MS) method was developed to determine glimepiride (GPD) and
fluoxetine (FLU) in human plasma using diazepam as the internal standard (IS)
simultaneously. The presented method used an Acquity UPLC BEH C18 column for
chromatographic separation with tandem mass spectrometric detection on a
QTrap5500 mass spectrometer operated in positive ESI mode. The mobile phase is a
mixture of acetonitrile and 1% formic acid in water with gradient elution at a
flow rate of 0.40mL/min. The GPD, FLU and IS were eluted at 1.46, 1.27 and
1.39min, respectively. The MRM transitions of m/z 491.3->126.3 and m/z 310.5
>148.1 were used to quantify for GPD and FLU, respectively. The linearity of this
method was found to be within the concentration range of 2.5-300ng/mL and 0.1
20ng/mL for GPD and FLU in human plasma, respectively. The intra- and inter-day
precision (RSD%) were less than 10.3% and accuracy (RE%) was within +/-7.3%. The
matrix effect were 95.3-100.7% for GPD and FLU. GPD and FLU were sufficiently
stable under all relevant analytical conditions. The method was also successfully
applied to the clinical samples after a single oral dose of 2mg GLP and 40mg FLU
in patients.
PMID- 25589253
TI - Dynamic pH junction-sweeping technique for on-line concentration of acidic amino
acids in human serum by capillary electrophoresis with indirect UV detection.
AB - Glutamic acid (Glu) and aspartic acid (Asp), as two important neurotransmitters,
have been the focus of increasingly intense research over the past several years.
Glu and Asp are present in biological fluids such as serum at trace levels, but
complex components in biological matrices make it difficult to determine them in
biological samples. In this paper, a sensitive and simple method coupled with
indirect UV detection, using benzoic acid (BA) as the UV-absorbing probe, was
developed and validated for the quantitative determination of Glu and Asp in
human serum and Compound Amino Acid Injection-18 AA. The method combines a
dynamic pH junction with a sweeping technique using beta-cyclodextrin (beta-CD)
as the complexing agent for sweeping. Employing this proposed method, low
detection limits of 0.061MUg/mL for Glu and 0.032MUg/mL for Asp were obtained.
The sensitivity was improved 30- and 55-fold for Glu and Asp compared to
conventional CE method. Standard curves were linear (r>0.999) over the
concentration range of 0.1-8.0MUg/mL. To further improve the resolution of Asp
from interfering substances in human serum, 6% (v/v) methanol was added to the
sample matrix, and resulted in the detection limits of 0.125MUg/mL for Glu and
0.057MUg/mL for Asp. With a simple precipitation of protein, the method has been
successfully applied to the analysis of human serum, and the recoveries (82% for
Glu and 87% for Asp) were achieved with relative standard deviations of 1.9% and
2.0%, respectively.
PMID- 25589254
TI - Development and validation of a high-performance liquid chromatography
fluorescence detection method for the accurate quantification of colistin in
human plasma.
AB - Recently, colistin has become one of the most important drugs for treating
infections caused by multidrug-resistant Gram-negative bacteria. Therapeutic drug
monitoring is recommended to ensure the safety and efficacy of colistin and to
improve clinical outcomes. This study developed an accurate and sensitive high
performance liquid chromatography-fluorescence detection (HPLC-FLD) method for
the quantification of colistin in human plasma. The sample preparation included
protein precipitation using trichloroacetic acid (TCA) and methanol, followed by
in-solid phase extraction (In-SPE) derivatization with 9-fluorenylmethyl
chloroformate (FMOC-Cl). A Poroshell 120 EC-C18 2.1*100mm (2.7MUm) column was
used in the HPLC method with a mobile phase composed of acetonitrile (ACN),
tetrahydrofuran (THF), and deionized (DI) water (82%, 2%, 16% (v/v),
respectively). Polymyxin B1 was used as the internal standard. The total analysis
time was 22min under optimal separation conditions. The HPLC-FLD method was
validated over a therapeutic range of 0.3-6.0MUgmL(-1). The intra-day and inter
day precisions for colistin A and colistin B were below 9.9% and 4.5% relative
standard deviations, respectively. The accuracy test results were between 100.2
and 118.4%. The extraction recoveries were between 81.6 and 94.1%. The method was
linear over the test range, with a 0.9991 coefficient of determination. The limit
of detection was 0.1MUgmL(-1). The validated HPLC-FLD method was successfully
applied to quantify the colistin concentrations in 2 patient samples for
therapeutic drug monitoring.
PMID- 25589255
TI - [PMIM]Br@TiO2 nanocomposite reinforced hollow fiber solid/liquid phase
microextraction: an effective extraction technique for measurement of
benzodiazepines in hair, urine and wastewater samples combined with high
performance liquid chromatography.
AB - A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was
developed for the determination of benzodiazepines (BZPs) in hair, urine and
wastewater. The membrane extraction with 1-pentyl-3-methylimidazolium bromide
coated titanium dioxide ([PMIM]Br@TiO2) sorbent used in this research is a two
phase supported membrane extraction consisting of an aqueous (donor phase), and n
octanol/nano [PMIM]Br@TiO2 (acceptor phase) system operated in direct immersion
sampling mode. The 1-pentyl-3-methylimidazolium bromide (ionic liquid) coated
nano TiO2 dispersed in the organic solvent (n-octanol) is held into a porous
membrane supported by capillary forces and sonification. It is in contact with
the feed phase, which is the aqueous sample. The experimental setup is very
simple and highly affordable. The hollow fiber is disposable, so single use of
the fiber reduces the risk of cross-contamination and carry-over problems. The
proposed method allows the very effective and enriched recuperation of BZPs into
one single extract. In order to obtain high extraction efficiency of the analytes
using this novel sorbent, the main parameters were optimized. Under the optimized
extraction conditions, the method showed good linearity (0.05-6000ngmL(-1)), low
limits of detection (0.08-0.5ngmL(-1)) and good enrichment (533-1190).
PMID- 25589256
TI - Capillary electrophoresis-mass spectrometry determination of morphine and its
isobaric glucuronide metabolites.
AB - The determination of morphine and its isobaric metabolites morphine-3-beta-d
glucuronide (M3G) and morphine-6-beta-d-glucuronide (M6G) is useful for
therapeutic drug monitoring and forensic identification of drug use. In
particular, capillary electrophoresis with mass spectrometry (CE-MS) represents
an attractive tool for opioid analysis. Whereas volatile background electrolytes
in CE often improve electrospray ionization for coupled MS detection, such
electrolytes may reduce CE separation efficiency and resolution. To better
understand the effects of background electrolyte (BGE) composition on separation
efficiency and detection sensitivity, this work compares and contrasts method
development for both volatile (ammonium formate and acetate) and nonvolatile
(ammonium phosphate and borate) buffers. Peak efficiencies and migration times
for morphine and morphine metabolites were optimal with a 25mM ammonium borate
buffer (pH=9.5) although greater sensitivities were achieved in the ammonium
formate buffer. Optimized CE methods allowed for the resolution of the isobaric
morphine metabolites prior to high mass accuracy, electrospray ionization
quadrupole time-of-flight (ESI-QTOF) MS detection applicable to the analysis of
urine samples in under seven minutes. Urine sample preparation required only a 10
fold dilution with BGE prior to analysis. Limits of detection (LOD) in normal
human urine were found to be 1.0MUg/mL for morphine and 2.5MUg/mL for each of M3G
and M6G by CE-ESI-QTOF-MS. These LODs were comparable to those for CE-UV analysis
of opioid standards in buffer, whereas CE-ESI-QTOF-MS analysis of opioid
standards in buffer yielded LODs an order of magnitude lower. Patient urine
samples (N=12) were analyzed by this new CE-ESI-QTOF-MS method and no significant
difference in total morphine content relative to prior liquid chromatography-mass
spectrometry (LC-MS) results was found as per a paired-t test at the 99%
confidence level. Whereas the LC-MS method applied to these samples determined
only total morphine content, this new CE-ESI-QTOF-MS method allowed for species
differentiation in addition to total morphine determination. By this method, it
was found that M3G and M6G metabolites were present in a 5:1 concentration ratio,
on average, in patient samples. Therefore, the CE-ESI-QTOF-MS method not only
allows for total morphine concentration determination comparable to established
LC-MS methods, but also allows for differentiation between morphine and its trace
glucuronides, yielding additional biochemical information about drug metabolism.
PMID- 25589257
TI - An UPLC-MS/MS method for quantitative profiling of bile acids in sea lamprey
plasma and tissues.
AB - Bile acids (BAs) have recently gained more attention because of their diverse
roles from digestion to signaling. Simultaneous analyses of various BAs in
biological samples are challenging due to their structural similarity, relatively
low concentrations, and the presence of isomeric forms. In this study, we report
a simple and sensitive UPLC-MS/MS method for simultaneous quantifications of 13
BAs including four unique sea lamprey BAs in sea lamprey plasma, liver,
intestine, and gills. A straightforward protein precipitation (PPT) method was
used to extract BAs from the biological samples. Separation of all target
analytes was achieved on a reverse-phase UPLC column in 15min, and detection was
carried out on MS/MS with ESI in the negative ionization mode. This method was
validated regarding its linearity, limits of detection (LOD), recovery, matrix
effect, reproducibility, accuracy and precision. Significant improvements
compared to previous LC-MS/MS methods were observed as a result of the
application of UPLC and extensive optimization of experimental conditions. The
method showed excellent linearity with high regression coefficients (>0.99) over
a range of 0.5-1000ng/mL and LODs ranged from 0.009 to 0.11ng/mL. The
applications of the developed method demonstrated that it simultaneously
determined all target BAs in different biological sample matrices with excellent
sensitivity, selectivity and reproducibility.
PMID- 25589258
TI - Evaluation of a rapid method for the therapeutic drug monitoring of aliskiren,
enalapril and its active metabolite in plasma and urine by UHPLC-MS/MS.
AB - Given the increasing popularity of aliskiren, particularly in combination with
angiotensin converting enzyme inhibitor (e.g. enalapril), it is important to
determine whether its use in combination with these agents is associated with
potentially life threatening safety events. Analytical methods for the
simultaneous determination of both drugs in plasma and urine utilized in clinical
studies on efficacy and safety have not been fully described in the literature.
In this work, a new, fast and reliable method using a digitally controlled
microextraction by packed sorbent (eVol((r))-MEPS) followed by ultra-high
performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry
(MS/MS) was developed and validated to quantify an aliskiren, enalapril and its
active metabolite in both human plasma and urine. Chromatographic separation was
accomplished on a Poroshell 120 EC-C18 column with a gradient elution system
consisting of 0.1% formic acid in water and acetonitrile (1.5min of total
analysis). Detection was performed by multiple reaction monitoring (MRM) mode
using electrospray ionization in the positive ion mode. This assay method has
been fully validated in terms of selectivity, linearity, accuracy, precision,
stability, recovery and matrix effect. The developed method can be applied to the
routine determination of selected compounds in human plasma and urine and can be
useful to elucidate the mechanisms of the potential risks triggered by the
combination of aliskiren and enalapril as well as its active metabolite
enalaprilat.
PMID- 25589259
TI - NHS can perform well against the private sector without compromising its core
values.
PMID- 25589262
TI - Peripheral and central effects of circulating catecholamines.
AB - Physical challenges, emotional arousal, increased physical activity, or changes
in the environment can evoke stress, requiring altered activity of visceral
organs, glands, and smooth muscles. These alterations are necessary for the
organism to function appropriately under these abnormal conditions and to restore
homeostasis. These changes in activity comprise the "fight-or-flight" response
and must occur rapidly or the organism may not survive. The rapid responses are
mediated primarily via the catecholamines, epinephrine, and norepinephrine,
secreted from the adrenal medulla. The catecholamine neurohormones interact with
adrenergic receptors present on cell membranes of all visceral organs and smooth
muscles, leading to activation of signaling pathways and consequent alterations
in organ function and smooth muscle tone. During the "fight-or-flight response,"
the rise in circulating epinephrine and norepinephrine from the adrenal medulla
and norepinephrine secreted from sympathetic nerve terminals cause increased
blood pressure and cardiac output, relaxation of bronchial, intestinal and many
other smooth muscles, mydriasis, and metabolic changes that increase levels of
blood glucose and free fatty acids. Circulating catecholamines can also alter
memory via effects on afferent sensory nerves impacting central nervous system
function. While these rapid responses may be necessary for survival, sustained
elevation of circulating catecholamines for prolonged periods of time can also
produce pathological conditions, such as cardiac hypertrophy and heart failure,
hypertension, and posttraumatic stress disorder. In this review, we discuss the
present knowledge of the effects of circulating catecholamines on peripheral
organs and tissues, as well as on memory in the brain.
PMID- 25589261
TI - Simple phenotypic sweeps hide complex genetic changes in populations.
AB - Changes in allele frequencies and the fixation of beneficial mutations are
central to evolution. The precise relationship between mutational and phenotypic
sweeps is poorly described however, especially when multiple alleles are
involved. Here, we investigate these relationships in a bacterial population over
60 days in a glucose-limited chemostat in a large population. High coverage
metagenomic analysis revealed a disconnection between smooth phenotypic sweeps
and the complexity of genetic changes in the population. Phenotypic adaptation
was due to convergent evolution and involved soft sweeps by 7-26 highly
represented alleles of several genes in different combinations. Allele
combinations spread from undetectably low baselines, indicating that minor
subpopulations provide the basis of most innovations. A hard sweep was also
observed, involving a single combination of rpoS, mglD, malE, sdhC, and malT
mutations sweeping to greater than 95% of the population. Other mutant genes
persisted but at lower abundance, including hfq, consistent with its demonstrated
frequency-dependent fitness under glucose limitation. Other persistent, newly
identified low-frequency mutations were in the aceF, galF, ribD and asm genes, in
noncoding regulatory regions, three large indels and a tandem duplication; these
were less affected by fluctuations involving more dominant mutations indicating
separate evolutionary paths. Our results indicate a dynamic subpopulation
structure with a minimum of 42 detectable mutations maintained over 60 days. We
also conclude that the massive population-level mutation supply in combination
with clonal interference leads to the soft sweeps observed, but not to the
exclusion of an occasional hard sweep.
PMID- 25589265
TI - Human locomotion and heat loss: an evolutionary perspective.
AB - Humans are unique in many respects including being furless, striding bipeds that
excel at walking and running long distances in hot conditions. This review
summarizes what we do and do not know about the evolution of these
characteristics, and how they are related. Although many details remain poorly
known, the first hominins (species more closely related to humans than to
chimpanzees) apparently diverged from the chimpanzee lineage because of selection
for bipedal walking, probably because it improved their ability to forage
efficiently. However, because bipedal hominins are necessarily slow runners,
early hominins in open habitats likely benefited from improved abilities to dump
heat in order to forage safely during times of peak heat when predators were
unable to hunt them. Endurance running capabilities evolved later, probably as
adaptations for scavenging and then hunting. If so, then there would have been
strong selection for heat-loss mechanisms, especially sweating, to persistence
hunt, in which hunters combine endurance running and tracking to drive their prey
into hyperthermia. As modern humans dispersed into a wide range of habitats over
the last few hundred thousand years, recent selection has helped populations cope
better with a broader range of locomotor and thermoregulatory challenges, but all
humans remain essentially adapted for long distance locomotion rather than speed,
and to dump rather than retain heat.
PMID- 25589250
TI - Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite
reductases.
AB - Nitric oxide (NO) is a signalling molecule involved in several physiological
processes, in both prokaryotes and eukaryotes, and nitrite is being recognised as
an NO source particularly relevant to cell signalling and survival under
challenging conditions. The "non-respiratory" nitrite reduction to NO is carried
out by "non-dedicated" nitrite reductases, making use of metalloproteins present
in cells to carry out other functions, such as several molybdoenzymes (a new
class of nitric oxide-forming nitrite reductases). This minireview will highlight
the physiological relevance of molybdenum-dependent nitrite-derived NO formation
in mammalian, plant and bacterial signalling (and other) pathways. The mammalian
xanthine oxidase/xanthine dehydrogenase, aldehyde oxidase, mitochondrial
amidoxime-reducing component, plant nitrate reductase and bacterial aldehyde
oxidoreductase and nitrate reductases will be considered. The nitrite reductase
activity of each molybdoenzyme will be described and the review will be oriented
to discuss the feasibility of the reactions from a (bio)chemical point of view.
In addition, the molecular mechanism proposed for the molybdenum-dependent
nitrite reduction will be discussed in detail.
PMID- 25589263
TI - Human cardiovascular responses to passive heat stress.
AB - Heat stress increases human morbidity and mortality compared to normothermic
conditions. Many occupations, disease states, as well as stages of life are
especially vulnerable to the stress imposed on the cardiovascular system during
exposure to hot ambient conditions. This review focuses on the cardiovascular
responses to heat stress that are necessary for heat dissipation. To accomplish
this regulatory feat requires complex autonomic nervous system control of the
heart and various vascular beds. For example, during heat stress cardiac output
increases up to twofold, by increases in heart rate and an active maintenance of
stroke volume via increases in inotropy in the presence of decreases in cardiac
preload. Baroreflexes retain the ability to regulate blood pressure in many, but
not all, heat stress conditions. Central hypovolemia is another cardiovascular
challenge brought about by heat stress, which if added to a subsequent central
volumetric stress, such as hemorrhage, can be problematic and potentially
dangerous, as syncope and cardiovascular collapse may ensue. These combined
stresses can compromise blood flow and oxygenation to important tissues such as
the brain. It is notable that this compromised condition can occur at cardiac
outputs that are adequate during normothermic conditions but are inadequate in
heat because of the increased systemic vascular conductance associated with
cutaneous vasodilation. Understanding the mechanisms within this complex
regulatory system will allow for the development of treatment recommendations and
countermeasures to reduce risks during the ever-increasing frequency of severe
heat events that are predicted to occur.
PMID- 25589267
TI - Autonomic regulation of hepatic glucose production.
AB - Glucose produced by the liver is a major energy source for the brain. Considering
its critical dependence on glucose, it seems only natural that the brain is
capable of monitoring and controlling glucose homeostasis. In addition to
neuroendocrine pathways, the brain uses the autonomic nervous system to
communicate with peripheral organs. Within the brain, the hypothalamus is the key
region to integrate signals on energy status, including signals from lipid,
glucose, and hormone sensing cells, with afferent neural signals from the
internal and external milieu. In turn, the hypothalamus regulates metabolism in
peripheral organs, including the liver, not only via the anterior pituitary gland
but also via multiple neuropeptidergic pathways in the hypothalamus that have
been identified as regulators of hepatic glucose metabolism. These pathways
comprise preautonomic neurons projecting to nuclei in the brain stem and spinal
cord, which relay signals from the hypothalamus to the liver via the autonomic
nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are
not separate entities. They appear to act as a single integrated regulatory
system, far more subtle, and complex than when each is viewed in isolation.
Consequently, hypothalamic regulation should be viewed as a summation of both
neuroendocrine and neural influences. As a result, our endocrine-based
understanding of diseases such as diabetes and obesity should be expanded by
integration of neural inputs into our concept of the pathophysiological process.
PMID- 25589268
TI - Trans-system mechanisms against ischemic myocardial injury.
AB - A mammalian organism possesses a hierarchy of naturally evolved protective
mechanisms against ischemic myocardial injury at the molecular, cellular, and
organ levels. These mechanisms comprise regional protective processes, including
upregulation and secretion of paracrine cell-survival factors, inflammation,
angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration.
There are also interactive protective processes between the injured heart,
circulation, and selected remote organs, defined as trans-system protective
mechanisms, including upregulation and secretion of endocrine cell-survival
factors from the liver and adipose tissue as well as mobilization of bone marrow,
splenic, and hepatic cells to the injury site to mediate myocardial protection
and repair. The injured heart and activated remote organs exploit molecular and
cellular processes, including signal transduction, gene expression, cell
proliferation, differentiation, migration, mobilization, and/or extracellular
matrix production, to establish protective mechanisms. Both regional and trans
system cardioprotective mechanisms are mediated by paracrine and endocrine
messengers and act in coordination and synergy to maximize the protective effect,
minimize myocardial infarction, and improve myocardial function, ensuring the
survival and timely repair of the injured heart. The concept of the trans-system
protective mechanisms may be generalized to other organ systems-injury in one
organ may initiate regional as well as trans-system protective responses, thereby
minimizing injury and ensuring the survival of the entire organism. Selected
trans-system processes may serve as core protective mechanisms that can be
exploited by selected organs in injury. These naturally evolved protective
mechanisms are the foundation for developing protective strategies for myocardial
infarction and injury-induced disorders in other organ systems.
PMID- 25589270
TI - Hypothalamus as an endocrine organ.
AB - The endocrine hypothalamus constitutes those cells which project to the median
eminence and secrete neurohormones into the hypophysial portal blood to act on
cells of the anterior pituitary gland. The entire endocrine system is controlled
by these peptides. In turn, the hypothalamic neuroendocrine cells are regulated
by feedback signals from the endocrine glands and other circulating factors. The
neuroendocrine cells are found in specific regions of the hypothalamus and are
regulated by afferents from higher brain centers. Integrated function is clearly
complex and the networks between and amongst the neuroendocrine cells allows fine
control to achieve homeostasis. The entry of hormones and other factors into the
brain, either via the cerebrospinal fluid or through fenestrated capillaries (in
the basal hypothalamus) is important because it influences the extent to which
feedback regulation may be imposed. Recent evidence of the passage of factors
from the pars tuberalis and the median eminence casts a new layer in our
understanding of neuroendocrine regulation. The function of neuroendocrine cells
and the means by which pulsatile secretion is achieved is best understood for the
close relationship between gonadotropin releasing hormone and luteinizing
hormone, which is reviewed in detail. The secretion of other neurohormones is
less rigid, so the relationship between hypothalamic secretion and the relevant
pituitary hormones is more complex.
PMID- 25589271
TI - Neuroendocrine regulation of lactation and milk production.
AB - Prolactin (PRL) released from lactotrophs of the anterior pituitary gland in
response to the suckling by the offspring is the major hormonal signal
responsible for stimulation of milk synthesis in the mammary glands. PRL
secretion is under chronic inhibition exerted by dopamine (DA), which is released
from neurons of the arcuate nucleus of the hypothalamus into the hypophyseal
portal vasculature. Suckling by the young activates ascending systems that
decrease the release of DA from this system, resulting in enhanced responsiveness
to one or more PRL-releasing hormones, such as thyrotropin-releasing hormone. The
neuropeptide oxytocin (OT), synthesized in magnocellular neurons of the
hypothalamic supraoptic, paraventricular, and several accessory nuclei, is
responsible for contracting the myoepithelial cells of the mammary gland to
produce milk ejection. Electrophysiological recordings demonstrate that shortly
before each milk ejection, the entire neurosecretory OT population fires a
synchronized burst of action potentials (the milk ejection burst), resulting in
release of OT from nerve terminals in the neurohypophysis. Both of these
neuroendocrine systems undergo alterations in late gestation that prepare them
for the secretory demands of lactation, and that reduce their responsiveness to
stimuli other than suckling, especially physical stressors. The demands of milk
synthesis and release produce a condition of negative energy balance in the
suckled mother, and, in laboratory rodents, are accompanied by a dramatic
hyperphagia. The reduction in secretion of the adipocyte hormone, leptin, a
hallmark of negative energy balance, may be an important endocrine signal to
hypothalamic systems that integrate lactation-associated food intake with
neuroendocrine systems.
PMID- 25589266
TI - Sympathoneural and adrenomedullary responses to mental stress.
AB - This concept-based review provides historical perspectives and updates about
sympathetic noradrenergic and sympathetic adrenergic responses to mental stress.
The topic of this review has incited perennial debate, because of disagreements
over definitions, controversial inferences, and limited availability of relevant
measurement tools. The discussion begins appropriately with Cannon's
"homeostasis" and his pioneering work in the area. This is followed by mental
stress as a scientific idea and the relatively new notions of allostasis and
allostatic load. Experimental models of mental stress in rodents and humans are
discussed, with particular attention to ethical constraints in humans. Sections
follow on sympathoneural responses to mental stress, reactivity of catecholamine
systems, clinical pathophysiologic states, and the cardiovascular reactivity
hypothesis. Future advancement of the field will require integrative approaches
and coordinated efforts between physiologists and psychologists on this
interdisciplinary topic.
PMID- 25589272
TI - Adrenocortical growth and cancer.
AB - The adrenal gland consists of two distinct parts, the cortex and the medulla.
Molecular mechanisms controlling differentiation and growth of the adrenal gland
have been studied in detail using mouse models. Knowledge also came from
investigations of genetic disorders altering adrenal development and/or function.
During embryonic development, the adrenal cortex acquires a structural and
functional zonation in which the adrenal cortex is divided into three different
steroidogenic zones. Significant progress has been made in understanding adrenal
zonation. Recent lineage tracing experiments have accumulated evidence for a
centripetal differentiation of adrenocortical cells from the subcapsular area to
the inner part of the adrenal cortex. Understanding of the mechanism of
adrenocortical cancer (ACC) development was stimulated by knowledge of adrenal
gland development. ACC is a rare cancer with a very poor overall prognosis.
Abnormal activation of the Wnt/beta-catenin as well as the IGF2 signaling plays
an important role in ACC development. Studies examining rare genetic syndromes
responsible for familial ACT have played an important role in identifying genetic
alterations in these tumors (like TP53 or CTNNB1 mutations as well as IGF2
overexpression). Recently, genomic analyses of ACT have shown gene expression
profiles associated with malignancy as well as chromosomal and methylation
alterations in ACT and exome sequencing allowed to describe the mutational
landscape of these tumors. This progress leads to a new classification of these
tumors, opening new perspectives for the diagnosis and prognostication of ACT.
This review summarizes current knowledge of adrenocortical development, growth,
and tumorigenesis.
PMID- 25589269
TI - Neural control of the circulation: how sex and age differences interact in
humans.
AB - The autonomic nervous system is a key regulator of the cardiovascular system. In
this review, we focus on how sex and aging influence autonomic regulation of
blood pressure in humans in an effort to understand general issues related to the
cardiovascular system as a whole. Younger women generally have lower blood
pressure and sympathetic activity than younger men. However, both sexes show
marked interindividual variability across age groups with significant overlap
seen. Additionally, while men across the lifespan show a clear relationship
between markers of whole body sympathetic activity and vascular resistance, such
a relationship is not seen in young women. In this context, the ability of the
sympathetic nerves to evoke vasoconstriction is lower in young women likely as a
result of concurrent beta2-mediated vasodilation that offsets alpha-adrenergic
vasoconstriction. These differences reflect both central sympatho-inhibitory
effects of estrogen and also its influence on peripheral vasodilation at the
level of the vascular smooth muscle and endothelium. By contrast postmenopausal
women show a clear relationship between markers of whole body sympathetic traffic
and vascular resistance, and sympathetic activity rises progressively in both
sexes with aging. These major findings in humans are discussed in the context of
differences in population-based trends in blood pressure and orthostatic
intolerance. The many areas where there is little sex-specific data on how the
autonomic nervous system participates in the regulation of the human
cardiovascular system are highlighted.
PMID- 25589274
TI - Developmental conditioning of the vasculature.
AB - There is increasing evidence from epidemiological and experimental animal studies
that the early life environment, of which nutrition is a key component, acts
through developmental adaptive responses to set the capacity of cardiovascular
and metabolic pathways to respond to physiological and pathophysiological
challenges in later life. One finding that is consistent to both population
studies and animal models is the propensity for such effects to induce
endothelial dysfunction throughout the vascular tree, including the
microvasculature. Obesity, type 2 diabetes and hypertension are associated with
changes in microvascular function affecting multiple tissues and organs. These
changes may be detected early, often before the onset of macrovascular disease
and the development of end organ damage. Suboptimal maternal nutrition and fetal
growth result in reduced microvascular perfusion and functional dilator capacity
in the offspring, which together with microvascular rarefaction and remodeling
serve to limit capillary recruitment, reduce exchange capacity and increase
diffusion distances of metabolic substrates; they also increase local and overall
peripheral resistance. This article explores how a developmentally conditioned
disadvantageous microvascular phenotype may represent an important and additional
risk factor for increased susceptibility to the development of cardio-metabolic
disease in adult life and considers the cell signaling pathways associated with
microvascular dysfunction that may be "primed" by the maternal environment. As
the microvasculature has been shown to be a potential target for early
therapeutic and lifestyle intervention, this article also considers evidence for
the efficacy of such strategies in humans and in animal models of the
developmental origins of health and disease.
PMID- 25589276
TI - [Reference standards in diagnostic research: problems and solutions].
AB - The accuracy of diagnostic tests is of utmost importance as biased test results
may lead to wrong decisions in clinical practice. In diagnostic accuracy research
the results of a diagnostic test, model or strategy are compared to those of the
reference standard, i.e. the best available method to determine whether a certain
condition or disease is present or absent. Problems with the reference standard
lead to biased test results. The umbrella term for this is 'verification bias'.
Verification bias arises if the reference standard cannot be applied to all
patients, if investigators use different reference standards or simply because
there is no reference standard. Correction of these problems is often possible,
and, if it is applied in a transparent and reproducible fashion it will deliver
useful diagnostic information. Clinicians who use a diagnostic test should take
possible verification bias into account.
PMID- 25589277
TI - [Post-injection syndrome after depot injection of olanzapine].
AB - BACKGROUND: Olanzapine pamoate injection is an anti-psychotic depot to be
administered intramuscularly once every 2-4 weeks. A post-injection syndrome may
occur shortly after administration, resulting in an acute intoxication with
olanzapine. CASE DESCRIPTION: A 42-year-old patient with a schizophrenic disorder
lost consciousness 30 min after administration of olanzapine pamoate. He was
admitted to a nearby hospital with tachycardia, hypotension, pin-point pupils and
respiratory distress leading to reduced oxygen saturation. He was ventilated
during one night and recovered within 2 days. CONCLUSION: A post-injection
syndrome may develop after administration of olanzapine pamoate when the entire
dose olanzapine is released at once from the muscle. Therefore, the patient
should be observed for at least 3 hours after every injection. The risk of a post
injection syndrome and the necessary observation period should to be taken into
account when deciding to start treatment with olanzapine pamoate depot.
PMID- 25589264
TI - Distal convoluted tubule.
AB - The distal convoluted tubule (DCT) is a short nephron segment, interposed between
the macula densa and collecting duct. Even though it is short, it plays a key
role in regulating extracellular fluid volume and electrolyte homeostasis. DCT
cells are rich in mitochondria, and possess the highest density of Na+/K+-ATPase
along the nephron, where it is expressed on the highly amplified basolateral
membranes. DCT cells are largely water impermeable, and reabsorb sodium and
chloride across the apical membrane via electroneurtral pathways. Prominent among
this is the thiazide-sensitive sodium chloride cotransporter, target of widely
used diuretic drugs. These cells also play a key role in magnesium reabsorption,
which occurs predominantly, via a transient receptor potential channel (TRPM6).
Human genetic diseases in which DCT function is perturbed have provided critical
insights into the physiological role of the DCT, and how transport is regulated.
These include Familial Hyperkalemic Hypertension, the salt-wasting diseases
Gitelman syndrome and EAST syndrome, and hereditary hypomagnesemias. The DCT is
also established as an important target for the hormones angiotensin II and
aldosterone; it also appears to respond to sympathetic-nerve stimulation and
changes in plasma potassium. Here, we discuss what is currently known about DCT
physiology. Early studies that determined transport rates of ions by the DCT are
described, as are the channels and transporters expressed along the DCT with the
advent of molecular cloning. Regulation of expression and activity of these
channels and transporters is also described; particular emphasis is placed on the
contribution of genetic forms of DCT dysregulation to our understanding.
PMID- 25589278
TI - [Loin pain haematuria syndrome].
AB - BACKGROUND: Loin pain haematuria syndrome is characterised by episodes of loin
pain and microscopic or macroscopic haematuria, without a urological origin. CASE
DESCRIPTION: We describe a 39-year-old woman who was referred to us because of
microscopic haematuria and proteinuria without an apparent cause, which had been
present for 20 years. For 9 months she had also had continuous loin pain,
aggravated by exertion. Additional examination showed erythrocytes in the renal
tubules and a thin glomerular basement membrane. We made the diagnosis of "loin
pain haematuria syndrome based on thin basement membrane nephropathy".
CONCLUSION: Loin pain haematuria syndrome is a potentially debilitating disorder
that is often poorly recognized due to the unfamiliarity of physicians with this
condition. Treatment of patients with loin pain haematuria syndrome consists of
patient education, treatment with ACE inhibitors, pain medication and cognitive
behavioural therapy. Renal artery denervation can be considered in cases of
persistent, disabling pain.
PMID- 25589280
TI - [Targeted public funding for health research in the Netherlands].
AB - The Dutch government funds health research in several ways. One component of
public funding consists of funding programmes issued by the Netherlands
Organisation for Health Research and Development (ZonMw). The majority of ZonMw's
programmes provide funding for research in specific health research areas. Such
targeted funding plays an important role in addressing knowledge gaps and in
generating products for which there is a need. Good governance of the allocation
of targeted funding for health research requires three elements: a research
agenda, an overview of the health research currently being conducted, and a
transparent decision-making process regarding the distribution of funds. In this
article, we describe how public funding for health research is organized in the
Netherlands and how the allocation of targeted funds is governed. By describing
the questions that the current model of governance raises, we take a first step
towards a debate about the governance of targeted public funding for health
research in the Netherlands.
PMID- 25589279
TI - [Acute hamstring injuries in athletes].
AB - Acute hamstring injuries are the most common injuries in participants in popular
sports such as football and track and field athletics. The diagnosis is made if
there is a history of acute-onset pain in the posterior thigh, and presence of
the triad of pain on contraction, stretching and palpation. Additional
investigations and possible referral for surgical intervention are indicated if
there is a suspicion of a complete hamstring rupture or avulsion fracture, both
of which are rare. The basis of treatment of patients with acute hamstring
injuries without complete rupture is a progressive physiotherapeutic exercise
programme. Currently there is insufficient scientific evidence to support other
treatment methods. The mean recovery time for athletes with acute hamstring
injuries is 3-6 weeks. The individual recovery time is however hard to predict.
It is difficult to define exactly when the sport can be resumed, particularly
because of the high risk of recurrent hamstring injury. The most valuable
indications for the risk of recurrent hamstring injury are: a history of previous
injuries of the athlete; monitoring hamstring tenderness; flexibility; and
strength of the hamstring after resuming sporting activities.
PMID- 25589281
TI - [Chronic dizziness in older people: apply a multifactorial approach].
AB - It has been suggested that chronic dizziness in older people may constitute a
multifactorial geriatric syndrome. Considering dizziness to be a geriatric
syndrome with multiple contributory factors may provide additional leads for
treatment. A structured history, followed by physical examination and additional
tests if necessary, can yield clues to factors that may contribute to dizziness.
To illustrate such a multifactorial approach, we present two patients with
chronic dizziness. In both cases, the general practitioner considered
multifactorial dizziness with several treatable contributory factors. By treating
these contributory factors, the frequency of dizziness and dizziness-related
impairment decreased temporarily in one patient and permanently in the other.
PMID- 25589282
TI - [A woman with gingival hyperplasia].
AB - A woman visited her dentist with complaints of swollen gums. If there was a
serious infection of multiple teeth, the surgeon had to do a total extraction of
the upper jaw. The clinical picture was suspicious for a lymphoma, a fibromatosis
or a gingivitis. The biopsy showed a chronical infection. In this case the
gingival overgrowth and the subsequent infection of the teeth were caused by
nifedipine. Gingival enlargement can be a consequence of the administration of
calcium channel blockers and can occur if these are administered during a few
months or years. The incidence is 0,01-0,1% and the prevalence is 20%. Drug
substitution should be considered a valid treatment option and can be successful
within a few weeks.
PMID- 25589283
TI - [Optimizing hypertension drug treatment: can the patients do it better
themselves?].
AB - A recent study trial shows that in high-risk patients with hypertension, blood
pressure measurements and initiation of changes in blood pressure lowering drugs
by the patient him- or herself reduces the systolic blood pressure by on average
of 9 mmHg compared with usual care. Even though additional trials confirming
these findings are useful, self-management of high-risk patients with
hypertension could be considered in daily practice.
PMID- 25589284
TI - [Cognitive behavioural therapy for breast cancer: cost-effectiveness
demonstrated].
AB - Behavioural medicine research provides evidence for the positive effects of
cognitive behavioural approaches to psychosocial problems in patients with cancer
and other chronic somatic illnesses. In an extension of this research line, Mewes
et al. now provide evidence for the cost-effectiveness of cognitive behavioural
therapy and physical exercise for alleviating treatment-induced menopausal
symptoms in breast cancer patients [J Cancer Surviv, Sep 2 2014]. These important
findings are discussed and put into the context of future research and clinical
practice regarding quality of life, quality-adjusted life years and patient
reported outcomes. The benefits for the women concerned appear to be
considerable.
PMID- 25589285
TI - [The complexity of medical care of frail older patients].
AB - Medicine for frail elderly patients is complex because of the omnipresent
multimorbidity, multicausality, the high risk of adverse effects, lack of an
evidence base for guideline-based treatment options, and the predominance of
quality of life-related outcomes, rather than mortality and morbidity. This
complexity puts off most medical students, while there is a requirement for
physicians who like and are well trained to work with frail older persons.
Luckily, there are signs of increasing interest, for example in the excellent
introduction to geriatric medicine written by author/surgeon Atul Gawande in his
last book "Being mortal" (2014). With this commentary, this journal is starting a
series presenting new research findings, insights and case studies on frail older
patients in order to spread the expanding knowledge base of geriatrics, and
suggest tools for working effectively with this fast-growing, complex but
rewarding patient group.
PMID- 25589286
TI - Local and systemic metal ion release occurs intraoperatively during correction
and instrumented spinal fusion for scoliosis.
AB - STUDY DESIGN: Prospective pilot study. OBJECTIVES: The aim of this study was to
measure titanium, niobium and aluminium levels in various intraoperative and
postoperative samples to determine patterns of metal ion release that occur
within the first month following instrumented spinal fusion. Raised serum metal
ion levels are reported following instrumented spinal fusion in adolescent
idiopathic scoliosis. The exact topological origin and chronology of metal ion
release remains conjectural. Recent literature suggests an immediate rise in
serum metal levels within the first postoperative week. METHODS: Titanium,
niobium and aluminium levels were measured before, during and after surgery in
serum and local intraoperative fluid samples obtained from two pediatric patients
undergoing posterior correction and instrumentation for scoliosis. RESULTS:
Measurable metal ion levels were detected in all local samples obtained from
wound irrigation fluid, cell saver blood, and fluid that immersed metal universal
reduction screw tabs. Postoperative serum metal ion levels were elevated compared
to baseline preoperative levels. In general, metal ion levels were considerably
higher in the intraoperative fluid samples compared to those observed in the
serum levels. CONCLUSION: Our findings of contextually high metal ion
concentrations in intraoperative and early postoperative samples provide further
empirical support of a 'putting-in' phenomenon of metal ion release following
instrumented spinal fusion. This challenges existing beliefs that metal ion
release occurs during an intermediate 'wearing-in' phase. We recommend thorough
irrigation of the operative site prior to wound closure to dilute and remove
intraoperative metal ion debris. Possibilities of filtering trace metal ions from
cell saver content may be considered.
PMID- 25589287
TI - Splenic lipidosis in intensively cultured perch, Perca fluviatilis L.
AB - Macroscopically visible lipid deposition varying in size from pinpoint to 8-mm
diameter was found in spleens of a population of intensively farmed perch, Perca
fluviatilis L. over a 24-month rearing period. Large agglomerates of adipocytes
distinguishable from surrounding normal tissue occurred in all individuals with
spleen lipidosis. Several affected fish presented total dystrophy of large
clusters of hepatocytes. Prevalence of lipidosis was 5.0% at 12 months and 16.6%
at 24 months. There was no significant difference between fatty acid profiles of
liver or perivisceral fat of perch with and without lipidosis except for
linoleic, myristic, gamma-linoleic, cis-eicosatrienic, palmitooleic acid. Body
weight and hepatosomatic, perivisceral fat and splenosomatic indices were not
associated with lipidosis. There was no significant effect of lipidosis on
mortality or growth.
PMID- 25589288
TI - Cardioprotective properties of citicoline against hyperthyroidism-induced
reperfusion damage in rat hearts.
AB - Hyperthyroidism represents an increased risk factor for cardiovascular morbidity,
especially when the heart is subjected to an ischemia/reperfusion process. The
aim of this study was to explore the possible protective effect of the nucleotide
citicoline on the susceptibility of hyperthyroid rat hearts to undergo
reperfusion-induced damage, which is associated with mitochondrial dysfunction.
Hence, we analyzed the protective effect of citicoline on the electrical behavior
and on the mitochondrial function in rat hearts. Hyperthyroidism was established
after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight)
during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body
weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against
reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the
accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high
transmembrane electric gradient that protected against the release of cytochrome
c. It also preserved the activity of the enzyme aconitase that inhibited the
release of cytokines. The protection also included the inhibition of oxidative
stress-induced mDNA disruption. We conclude that citicoline protects against the
reperfusion damage that is found in the hyperthyroid myocardium. This effect
might be due to its inhibitory action on the permeability transition in
mitochondria.
PMID- 25589289
TI - Robustness screen in enantioselective catalysis enabled generation of
enantioenriched heterocyclic scaffolds in one pot.
AB - Enantioselective catalysis has emerged as a powerful synthetic paradigm and has
accelerated the development of new methods to make diverse chiral molecules.
Generally, these reactions are very sensitive to the steric and electronic
environment present in the catalyst as well as the substrates. With this
scenario, the presence of an additional component in the reaction mixture is
expected to add complexity in achieving the enantioselective variants. Herein, we
report that various enantioenriched molecules could be obtained from multiple
starting materials in one pot. The reaction of aminoaromatics A with alkynols B1,
B2, B3...?Bn with a Au(I)/chiral Bronsted acid catalyst afforded AB1*, AB2*,
AB3*...ABn*; while, the reaction of alkynols B with aminoaromatics A1, A2,
A3...An under the same reaction conditions gave A1B*, A2B*, A3B*...AnB*.
PMID- 25589275
TI - Autonomic control of the eye.
AB - The autonomic nervous system influences numerous ocular functions. It does this
by way of parasympathetic innervation from postganglionic fibers that originate
from neurons in the ciliary and pterygopalatine ganglia, and by way of
sympathetic innervation from postganglionic fibers that originate from neurons in
the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary
body and the sphincter pupillae muscle of the iris to control ocular
accommodation and pupil constriction, respectively. Superior cervical ganglion
neurons project to the dilator pupillae muscle of the iris to control pupil
dilation. Ocular blood flow is controlled both via direct autonomic influences on
the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as
via indirect influences on retinal blood flow. In mammals, this vasculature is
innervated by vasodilatory fibers from the pterygopalatine ganglion, and by
vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure
is regulated primarily through the balance of aqueous humor formation and
outflow. Autonomic regulation of ciliary body blood vessels and the ciliary
epithelium is an important determinant of aqueous humor formation; autonomic
regulation of the trabecular meshwork and episcleral blood vessels is an
important determinant of aqueous humor outflow. These tissues are all innervated
by fibers from the pterygopalatine and superior cervical ganglia. In addition to
these classical autonomic pathways, trigeminal sensory fibers exert local,
intrinsic influences on many of these regions of the eye, as well as on some
neurons within the ciliary and pterygopalatine ganglia.
PMID- 25589291
TI - Time dilates more with apparent than with physical speed.
AB - The perceived duration of a moving stimulus correlates positively with its speed.
It is not known whether such duration dilation depends on the physical or
apparent speed. Here we show the latter to be true. The perceived duration of a
shortly presented (500, 900, 1300 ms) Gabor patch whose carrier moved at 1
degrees /s in a direction opposite to a background of random black dots rigidly
moving at 3 degrees /s appeared to last 20% longer and to drift 240% faster than
the same Gabor carrier moving in the same direction as the random-dot background.
Assessment of the perceived speed of each of the two configurations relative to a
moving Gabor patch in the absence of the moving background allowed the comparison
of the observed duration dilation with that obtained as a function of the
corresponding physical speeds, which should have yielded a dilation of only 7%,
i.e., three times less. In line with the proposal that perceived duration
correlates with the strength of the neural response evoked by the stimuli to be
timed, the present data can be accounted for by the increased responsiveness of
antagonistic center-surround motion-receptive fields when stimulated with center
surround antagonist motions.
PMID- 25589290
TI - Broadband optical absorption by tunable Mie resonances in silicon nanocone
arrays.
AB - Nanostructure arrays such as nanowire, nanopillar, and nanocone arrays have been
proposed to be promising antireflection structures for photovoltaic applications
due to their great light trapping ability. In this paper, the optical properties
of Si nanopillar and nanocone arrays in visible and infrared region were studied
by both theoretical calculations and experiments. The results show that the Mie
resonance can be continuously tuned across a wide range of wavelength by varying
the diameter of the nanopillars. However, Si nanopillar array with uniform
diameter exhibits only discrete resonance mode, thus can't achieve a high
broadband absorption. On the other hand, the Mie resonance wavelength in a Si
nanocone array can vary continuously as the diameters of the cross sections
increase from the apex to the base. Therefore Si nanocone arrays can strongly
interact with the incident light in the broadband spectrum and the absorbance by
Si nanocone arrays is higher than 95% over the wavelength from 300 to 2000 nm. In
addition to the Mie resonance, the broadband optical absorption of Si nanocone
arrays is also affected by Wood-Rayleigh anomaly effect and metal impurities
introduced in the fabrication process.
PMID- 25589292
TI - How the visual aspects can be crucial in reading acquisition? The intriguing case
of crowding and developmental dyslexia.
AB - Developmental dyslexia (DD) is the most common neurodevelopmental disorder (about
10% of children across cultures) characterized by severe difficulties in learning
to read. According to the dominant view, DD is considered a phonological
processing impairment that might be linked to a cross-modal, letter-to-speech
sound integration deficit. However, new theories-supported by consistent data
suggest that mild deficits in low-level visual and auditory processing can lead
to DD. This evidence supports the probabilistic and multifactorial approach for
DD. Among others, an interesting visual deficit that is often associated with DD
is excessive visual crowding. Crowding is defined as difficulty in the ability to
recognize objects when surrounded by similar items. Crowding, typically observed
in peripheral vision, could be modulated by attentional processes. The direct
consequence of stronger crowding on reading is the inability to recognize letters
when they are surrounded by other letters. This problem directly translates to
reading at a slower speed and being more prone to making errors while reading.
Our aim is to review the literature supporting the important role of crowding in
DD. Moreover, we are interested in proposing new possible studies in order to
clarify whether the observed excessive crowding could be a cause rather than an
effect of DD. Finally, we also suggest possible remediation and even prevention
programs that could be based on reducing the crowding in children with or at risk
for DD without involving any phonological or orthographic training.
PMID- 25589293
TI - James Jurin (1684-1750): a pioneer of crowding research?
AB - James Jurin wrote an extended essay on distinct and indistinct vision in 1738. In
it, he distinguished between "perfect," "distinct," and "indistinct vision" as
perceptual categories, and his meticulous descriptions and analyses of perceptual
phenomena contained observations that are akin to crowding. Remaining with the
concepts of his day, however, he failed to recognize crowding as separate from
spatial resolution. We present quotations from Jurin's essay and place them in
the context of the contemporary concerns with visual resolution and crowding.
PMID- 25589295
TI - Reward modulates perception in binocular rivalry.
AB - Our perception does not provide us with an exact imprint of the outside world,
but is continuously adapted to our internal expectations, task sets, and
behavioral goals. Although effects of reward-or value in general-on perception
therefore seem likely, how valuation modulates perception and how such modulation
relates to attention is largely unknown. We probed effects of reward on
perception by using a binocular-rivalry paradigm. Distinct gratings drifting in
opposite directions were presented to each observer's eyes. To objectify their
subjective perceptual experience, the optokinetic nystagmus was used as measure
of current perceptual dominance. In a first experiment, one of the percepts was
either rewarded or attended. We found that reward and attention similarly biased
perception. In a second experiment, observers performed an attentionally
demanding task either on the rewarded stimulus, the other stimulus, or both. We
found that-on top of an attentional effect on perception-at each level of
attentional load, reward still modulated perception by increasing the dominance
of the rewarded percept. Similarly, penalizing one percept increased dominance of
the other at each level of attentional load. In turn, rewarding-and similarly
nonpunishing-a percept yielded performance benefits that are typically associated
with selective attention. In conclusion, our data show that value modulates
perception in a similar way as the volitional deployment of attention, even
though the relative effect of value is largely unaffected by an attention task.
PMID- 25589294
TI - Learning to integrate contradictory multisensory self-motion cue pairings.
AB - Humans integrate multisensory information to reduce perceptual uncertainty when
perceiving the world and self. Integration fails, however, if a common causality
is not attributed to the sensory signals, as would occur in conditions of
spatiotemporal discrepancies. In the case of passive self-motion, visual and
vestibular cues are integrated according to statistical optimality, yet the
extent of cue conflicts that do not compromise this optimality is currently
underexplored. Here, we investigate whether human subjects can learn to integrate
two arbitrary, but co-occurring, visual and vestibular cues of self-motion.
Participants made size comparisons between two successive whole-body rotations
using only visual, only vestibular, and both modalities together. The vestibular
stimulus provided a yaw self-rotation cue, the visual a roll (Experiment 1) or
pitch (Experiment 2) rotation cue. Experimentally measured thresholds in the
bimodal condition were compared with theoretical predictions derived from the
single-cue thresholds. Our results show that human subjects combine and optimally
integrate vestibular and visual information, each signaling self-motion around a
different rotation axis (yaw vs. roll and yaw vs. pitch). This finding suggests
that the experience of two temporally co-occurring but spatially unrelated self
motion cues leads to inferring a common cause for these two initially unrelated
sources of information about self-motion. We discuss our results in terms of
specific task demands, cross-modal adaptation, and spatial compatibility. The
importance of these results for the understanding of bodily illusions is also
discussed.
PMID- 25589296
TI - Area summation of first- and second-order modulations of luminance.
AB - To extend our understanding of the early visual hierarchy, we investigated the
long-range integration of first- and second-order signals in spatial vision. In
our first experiment we performed a conventional area summation experiment where
we varied the diameter of (a) luminance-modulated (LM) noise and (b) contrast
modulated (CM) noise. Results from the LM condition replicated previous findings
with sine-wave gratings in the absence of noise, consistent with long-range
integration of signal contrast over space. For CM, the summation function was
much shallower than for LM suggesting, at first glance, that the signal
integration process was spatially less extensive than for LM. However, an
alternative possibility was that the high spatial frequency noise carrier for the
CM signal was attenuated by peripheral retina (or cortex), thereby impeding our
ability to observe area summation of CM in the conventional way. To test this, we
developed the "Swiss cheese" stimulus of Meese and Summers (2007) in which signal
area can be varied without changing the stimulus diameter, providing some
protection against inhomogeneity of the retinal field. Using this technique and a
two-component subthreshold summation paradigm we found that (a) CM is spatially
integrated over at least five stimulus cycles (possibly more), (b) spatial
integration follows square-law signal transduction for both LM and CM and (c) the
summing device integrates over spatially-interdigitated LM and CM signals when
they are co-oriented, but not when cross-oriented. The spatial pooling mechanism
that we have identified would be a good candidate component for a module involved
in representing visual textures, including their spatial extent.
PMID- 25589297
TI - Contextual processing of brightness and color in Mongolian gerbils.
AB - Brightness and color cues are essential for visually guided behavior. However,
for rodents, little is known about how well they do use these cues. We used a
virtual reality setup that offers a controlled environment for sensory testing to
quantitatively investigate visually guided behavior for achromatic and chromatic
stimuli in Mongolian gerbils (Meriones unguiculatus). In two-alternative forced
choice tasks, animals had to select target stimuli based on relative intensity or
color with respect to a contextual reference. Behavioral performance was
characterized using psychometric analysis and probabilistic choice modeling. The
analyses revealed that the gerbils learned to make decisions that required
judging stimuli in relation to their visual context. Stimuli were successfully
recognized down to Weber contrasts as low as 0.1. These results suggest that
Mongolian gerbils have the perceptual capacity for brightness and color
constancy.
PMID- 25589298
TI - Spatial statistics and attentional dynamics in scene viewing.
AB - In humans and in foveated animals visual acuity is highly concentrated at the
center of gaze, so that choosing where to look next is an important example of
online, rapid decision-making. Computational neuroscientists have developed
biologically-inspired models of visual attention, termed saliency maps, which
successfully predict where people fixate on average. Using point process theory
for spatial statistics, we show that scanpaths contain, however, important
statistical structure, such as spatial clustering on top of distributions of gaze
positions. Here, we develop a dynamical model of saccadic selection that
accurately predicts the distribution of gaze positions as well as spatial
clustering along individual scanpaths. Our model relies on activation dynamics
via spatially-limited (foveated) access to saliency information, and, second, a
leaky memory process controlling the re-inspection of target regions. This
theoretical framework models a form of context-dependent decision-making, linking
neural dynamics of attention to behavioral gaze data.
PMID- 25589299
TI - Context affects lightness at the level of surfaces.
AB - Visual perception of object attributes such as surface lightness is crucial for
successful interaction with the environment. How the visual system assigns
lightness to image regions is not yet understood. It has been shown that the
context in which a surface is embedded influences its perceived lightness, but
whether that influence involves predominantly low-, mid-, or high-level visual
mechanisms has not been resolved. To answer this question, we measured whether
perceptual attributes of target image regions affected their perceived lightness
when they were placed in different contexts. We varied the sharpness of the edge
while keeping total target flux fixed. Targets with a sharp edge were consistent
with the perceptual interpretation of a surface, and in that case, observers
perceived significant brightening or darkening of the target. Targets with
blurred edges rather appeared to be spotlights instead of surfaces; for targets
with blurred edges, there was much less of a contextual effect on target
lightness. The results indicate that the effect of context on the lightness of an
image region is not fixed but is strongly affected by image manipulations that
modify the perceptual attributes of the target, implying that a mid-level scene
interpretation affects lightness perception.
PMID- 25589300
TI - The geometric structure of color.
AB - Color is commonly described in terms of the three perceptual attributes-hue,
saturation, and brightness-of which only hue has a qualitative nature, saturation
and brightness being of a quantitative nature. A possible reason for such a
phenomenological structure of the color manifold, and its geometric
representation, are discussed.
PMID- 25589301
TI - The effect of motion on crowding: zooming text.
AB - Crowding is the major sensory factor responsible for the slow reading speeds
exhibited in peripheral vision. Past attempts to improve peripheral reading via
crowding reduction have generally focused on applying spatial changes to the
stimulus and have been largely ineffective. Recent evidence indicates that
dynamic approaches have good potential for reducing crowding in peripheral
reading. We tested this hypothesis by introducing "zooming" motion (smooth letter
resizing across the presentation duration) to trigram stimuli (groups of three
randomly selected letters) presented at 10 degrees in the lower visual field and
evaluating recognition of the middle letter. Crowding was alleviated in the
presence of this motion, both when dynamic cues were introduced to all letters in
the trigram simultaneously and when they were applied to individual letters
alone. The magnitude and direction of crowding reduction depended on the
amplitude and direction of motion. These results suggest that dynamic
presentation may be a useful tool for improving peripheral reading through
reducing letter crowding. Zooming motion, in particular, has the additional
advantage of conserving text layout, making it a good candidate for such an
application.
PMID- 25589273
TI - Neural control of the lower urinary tract.
AB - This article summarizes anatomical, neurophysiological, pharmacological, and
brain imaging studies in humans and animals that have provided insights into the
neural circuitry and neurotransmitter mechanisms controlling the lower urinary
tract. The functions of the lower urinary tract to store and periodically
eliminate urine are regulated by a complex neural control system in the brain,
spinal cord, and peripheral autonomic ganglia that coordinates the activity of
smooth and striated muscles of the bladder and urethral outlet. The neural
control of micturition is organized as a hierarchical system in which spinal
storage mechanisms are in turn regulated by circuitry in the rostral brain stem
that initiates reflex voiding. Input from the forebrain triggers voluntary
voiding by modulating the brain stem circuitry. Many neural circuits controlling
the lower urinary tract exhibit switch-like patterns of activity that turn on and
off in an all-or-none manner. The major component of the micturition switching
circuit is a spinobulbospinal parasympathetic reflex pathway that has essential
connections in the periaqueductal gray and pontine micturition center. A computer
model of this circuit that mimics the switching functions of the bladder and
urethra at the onset of micturition is described. Micturition occurs
involuntarily in infants and young children until the age of 3 to 5 years, after
which it is regulated voluntarily. Diseases or injuries of the nervous system in
adults can cause the re-emergence of involuntary micturition, leading to urinary
incontinence. Neuroplasticity underlying these developmental and pathological
changes in voiding function is discussed.
PMID- 25589302
TI - Adrenal Insufficiency as a Result of Ritonavir and Exogenous Steroid Exposure:
Report of 6 Cases and Recommendation for Management.
AB - Numerous cases of Cushing syndrome have been reported as a result of the
interaction between ritonavir (RTV) and exogenous steroid medications. Another
complication that frequently occurs is secondary adrenal insufficiency, which can
be profound and has not been well described. Here, we report 6 cases of adrenal
suppression caused by RTV and exogenous steroids, all of which required
corticosteroid replacement therapy and 2 of which were severe enough to require
hospitalization. These cases add to the body of literature on the dangerous
interaction between RTV and corticosteroids and highlight the risk of secondary
adrenal suppression. We also review the literature on this complication and make
a recommendation for managing and monitoring such cases.
PMID- 25589303
TI - Perception of HIV Testing and Counseling among Integrated Counseling and Testing
Center Clients of Tertiary Level Hospitals.
AB - BACKGROUND: The purpose of establishing integrated counseling and testing center
(ICTC) is to detect HIV at the earliest time, providing information on modes of
transmission and prevention of HIV by promoting behavioral change and reducing
vulnerability, and informing individuals on HIV prevention, care, and treatment
services. OBJECTIVE: To know the awareness of the clients about ICTC before
pretest counseling. METHODS: This facility-based cross-sectional study was
conducted among 105 pretest counseling clients who visited ICTC for the first
time in 3 ICTCs of tertiary care hospitals attached to a medical college in
Mangalore. RESULT: Majority of the clients were pregnant women (n = 57, 54.30%),
and most of the clients were referred by the treating doctor (n = 91, 86.7%).
Most of the clients, being unaware of ICTC, are not aware of its functions and
activities. CONCLUSION: Although ICTCs have been functional for nearly a decade,
the awareness of ICTC and its functions among the people is poor.
PMID- 25589304
TI - Factors Associated with Late Engagement to HIV Care in Western Kenya: A Cross
Sectional Study.
AB - BACKGROUND: Late presentation of patients contributes significantly to the high
mortality reported in HIV -care and treatment programs in sub-Saharan Africa.
METHODS: A cross-sectional study was conducted to assess factors associated with
late engagement to HIV care at the Academic Model Providing Access to Healthcare
in western Kenya. Late engagement was defined as baseline CD4 <=100 cells/mm3.
RESULTS: Of the 10 533 participants included in the analysis, 67% were female and
mean age was 36.7 years. Overall, 23% of the participants presented late. Factors
associated with late engagement included male gender (adjusted odds ratio [AOR]:
1.54, 95% confidence interval [CI]: 1.35-1.75), older age (AOR: 1.62, 95% CI:
1.02-2.56), and longer travel time to clinic (AOR: 1.18, 95% CI: 1.04-1.34).
CONCLUSION: Nearly one-quarter of HIV-infected patients in our setting present
with advanced immune suppression at initial encounter. Being male, older age, and
living further away from clinic are associated with late engagement to care.
PMID- 25589305
TI - His-bundle bigeminy evidenced by short his-ventricular interval.
PMID- 25589307
TI - A new FRET ratiometric fluorescent chemosensor for Hg2+ and its application in
living EC 109 cells.
AB - On the basis of fluorescent resonance energy transfer, a new fluorophore dyad (L)
bearing rhodamine B and naphthalimide was developed as fluorescent ratiometric
chemosensor for Hg(2+) in aqueous solution. L exhibited high selectivity and
excellent sensitivity towards Hg(2+) with a broad pH span (1.0-8.0) and the
detection limit of L was 2.11*10(-8) M. Sensor L for the detection of Hg(2+) was
rapid and the recognizing event could complete in 2.5 min. A significant change
in the color could be used for naked-eye detection. The selective fluorescence
response of L to Hg(2+) is due to the Hg(2+)-promoted ring opening of spirolactam
of rhodamine moiety, leading to a cyclization reaction of thiourea moiety. In
addition, fluorescence imaging experiments of Hg(2+) in living EC 109 cells
demonstrated its value of practical applications in biological systems.
PMID- 25589306
TI - Effect of ischemic postconditioning on myocardial salvage in patients undergoing
primary percutaneous coronary intervention for ST-segment elevation myocardial
infarction: cardiac magnetic resonance substudy of the POST randomized trial.
AB - In the effects of postconditioning on myocardial reperfusion in patients with ST
segment elevation myocardial infarction (POST) trial, ischemic postconditioning
did not improve myocardial reperfusion in 700 patients with STEMI undergoing
primary PCI. However, the impact of postconditioning on myocardial salvage and
infarct size still needs to be addressed. The aim of this study was to
investigate the effect of ischemic postconditioning on myocardial salvage using
cardiac magnetic resonance (CMR) in patients with STEMI undergoing primary PCI.
For the CMR substudy, a total of 111 patients was analyzed, 56 in the
postconditioning group and 55 undergoing conventional primary PCI in the control
group. Postconditioning was performed immediately after restoration of coronary
flow by four cycles of 1-min balloon occlusion separated by 1 min of deflation.
The primary end point was myocardial salvage measured by CMR 3 days after the
index event. The myocardial salvage index was not improved by ischemic
postconditioning compared with conventional PCI (46.3 +/- 18.5 vs. 45.7 +/-
20.5%, p = 0.86). The infarct size was not significantly different between the
two groups (18.8 +/- 10.3 vs. 20.2 +/- 11.0%, p = 0.52). Moreover, there was no
significant difference in the rates of microvascular obstruction or hemorrhagic
infarction between the groups. CMR study demonstrated that ischemic
postconditioning during primary PCI in STEMI patients did not improve myocardial
salvage or reduce infarct size. These findings further support the results of the
POST trial which showed no benefit of ischemic postconditioning as an adjunctive
treatment of primary PCI.
PMID- 25589308
TI - Clinical validation of free breathing respiratory triggered retrospectively
cardiac gated cine balanced steady-state free precession cardiovascular magnetic
resonance in sedated children.
AB - BACKGROUND: Cine balanced steady-state free precession (SSFP), the preferred
sequence for ventricular function, demands uninterrupted radio frequency (RF)
excitation to maintain the steady-state during suspended respiration. This is
difficult to accomplish in sedated children. In this work, we validate a
respiratory triggered (RT) SSFP sequence that drives the magnetization to steady
state before commencing retrospectively cardiac gated cine acquisition in a
sedated pediatric population. METHODS: This prospective study was performed on 20
sedated children with congenital heart disease (8.6 +/- 4 yrs). Identical imaging
parameters were used for multiple number of signal averages (MN) and RT cine SSFP
sequences covering both the ventricles in short-axis (SA) orientation. Image
quality assessment and quantitative volumetric analysis was performed on the
datasets by two blinded observers. One-sided Wilcoxon signed rank test and Box
plot analysis were performed to compare the clinical scores. Bland-Altman (BA)
analysis was performed on LV and RV volumes. RESULTS: Scan duration for SA stack
using RT-SSFP (3.9 +/- 0.8 min) was slightly shorter than MN-SSFP (4.6 +/- 0.9
min) acquisitions. The endocardial edge definition was significantly better for
RT than MN, blood to myocardial contrast was better for RT than MN without
reaching statistical significance, and inter slice alignment was comparable. BA
analysis indicates that the variability of volumetric indices between RT and MN
is comparable to inter and intra-observer variability reported in the literature.
CONCLUSIONS: The free breathing RT-SSFP sequence allows diagnostic images in
sedated children with significantly better edge definition when compared to MN
SSFP, without any penalty for total scan time.
PMID- 25589309
TI - Pediatric Patient and Hospital Characteristics Associated With Treatment of
Peritonsillar Abscess and Peritonsillar Cellulitis.
AB - OBJECTIVE: To identify patient and hospital characteristics associated with the
choice of treatment for pediatric patients who present in the acute setting with
peritonsillar abscess/cellulitis (PTA/PTC). STUDY DESIGN: A retrospective cohort
study was performed using Healthcare Cost and Utilization Project emergency
department, ambulatory, and inpatient state databases for the years 2010 and
2011. Children aged 0 to 17 years were identified using International
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
diagnosis code for PTA/PTC. The main outcome of interest was treatment received,
which included medical therapy alone, incision and drainage (IND) or
tonsillectomy. Multiple logistic regression analyses were conducted to model non
clinical factors associated with treatment received after adjusting for age,
hospital state, race, primary expected payer, existing chronic condition(s), and
type of hospital. RESULTS: We identified 2994 patients who presented with
PTA/PTC. The most common treatment choice was medical therapy alone (30.8%),
followed by IND (30.5%) and tonsillectomy (9.4%). There were significant
associations between treatment choice and race, primary payer status, and type of
hospital (P < .05). We found that Hispanic patients, those with Medicaid as their
primary expected payer, and those treated at a designated children's hospital
were 3 nonclinical factors independently associated with an increase in
likelihood of receiving tonsillectomy as treatment. CONCLUSION: There are
important nonclinical factors associated with treatment of children who present
in the acute setting with PTA/PTC. Additional research is recommended to
understand these observed differences in care and how they may affect health
outcomes.
PMID- 25589310
TI - Phentermine plus topiramate for weight reduction: more tolerable and effective?
PMID- 25589311
TI - [Simulation technologies in anesthesiology, resuscitation and intensive care:
state of the problem].
AB - The foundation of simulation technologies application in educational process is
presented in the article. It is described difficulties during anesthesiologists
resuscitators training and education of physicians of not intensive care
specialty in intensive care methods. It was emphasized that new innovative
educational stage is formed at present time. It is simulation stage between
preclinical and clinical stages. Theoretical foundation and practical evidence of
efficiency of simulation training are expressed in detail.
PMID- 25589312
TI - [The results of carotid endarterectomy in patients with carotid arteries stenosis
and chronic ischemic optical neuropathy].
AB - It was estimated an efficiency of surgical and conservative treatment of patients
with atherosclerotic carotid arteries stenosis and chronic ischemic optical
neuropathy. The first group included 30 patients after carotid endarterectomy.
The second group included 20 patients who underwent conservative treatment. The
methods of investigation included determination of visual acuity,
autorefractometry, direct and inverse ophthalmoscopy under mydriasis, computer
static perimetry, assessment of functional status of optic nerve by using of
threshold of electric sensitivity and lability, ultrasonic scanning of eyes
arteries and carotid arteries. Follow-up terms were baseline, in one month and in
one year after surgery or conservative treatment. Improvement of visual acuity on
0.1 and more in 1st/2nd groups was 9/2 (p=0.1629), in one year - 12/1 (p=0.0075).
Improvement of field of vision: in 1 month in 1st/2nd groups it was 12/3
(p=0.0692), in 1 year - 17/1 (p=0.0002). The dynamics of neurological status:
there was equal ratio of asymptomatic/symptomatic patients at baseline in
subgroups. In the 1st group it was 19/11 vs. 16/4 in the 2nd group (p=0.3451). In
1 year after two kinds of treatment significant changes were revealed. There was
26/4 in the 1st group vs. 13/7 in the 2nd group (p=0.0902) with improvement only
after carotid endarterectomy - 19/11 at baseline vs. 26/4 in 1 year (p=0.0716).
Insignificant deterioration was diagnosed after conservative treatment - 16/4 vs.
13/7 (p=0.4801).
PMID- 25589313
TI - [Caprini score as individual risk assessment model of postoperative venous
thromboembolism in patients with high surgical risk].
AB - The aim of this study was to estimate the role of Caprini model in forecasting of
postoperative venous thromboembolism (VTE) in patients with high surgical risk
and to determine patients with extremely high risk of venous thrombosis by using
of this scale. It was performed prospective multicenter observational study
involving 140 high risk patients who underwent large abdominal (48%) or
neurosurgical (52%) intervention. All patients were assessed with the Caprini
model and had a mean score of 9.5+/-2.7 (range: 5-15). Complex postoperative
prevention of venous thromboembolic complications included elastic compression of
low extremities and standard prophylactic doses of direct anticoagulants. Duplex
ultrasonic scanning was performed during the first 12 hours after surgery and
then every 3-5 days until discharge to assess the lower limbs venous system. If
venous thrombosis was observed pulmonary embolism has been excluded by using of
echocardiography, planar perfusion scintigraphy of the lungs, SPECT-imaging with
computed tomography. Venous thrombosis was diagnosed in 39 (28%) patients. The
incidence of VTE was 1.9% in the lowest tertile of the Caprini score (5-8); it
was 26.1% in the middle tertile (score 9-11) and 65% in the upper tertile (score
12-15) (p<0.001). The area under ROC curve was 0.874 (95% CI 0.81 to 0.94) and
Caprini score 11 was a cut-off point that provided the highest sensitivity and
specificity. 2 (2.6%) of 77 patients with score less than 11 had venous
thrombosis. In contrast, 37 (58.7%) of 63 patients with Caprini score 11 and more
had venous thrombosis (p<0.001). There is significant correlation between Caprini
scores and frequency of postoperative venous thromboembolism in patients with
high surgical risk. Score 11 and more can identify patients with extremely high
risk. These patients need for more effective prevention.
PMID- 25589314
TI - [Experience of two-staged liver resection (ALPPS)].
AB - The aim was to estimate single center results of ALPPS. It was performed 5 ALPPS
procedures in our center during the period from February 2013 to March 2014.
There were 1 female and 4 males in the age of 58-64 years. The indications for
surgery were colorectal cancer metastases in 4 cases, bladder cancer metastases
in 1 observation. The operations included 3 right-sided hemihepatectomies, 2
extended right-sided hemihepatectomies. In 3 cases operations were accompanied by
additional atypical resection of residuary liver lobe. In 2 observations
unsuccessful embolization of the portal vein was done. The waiting time between
procedures consisted 18 days in the first case and 6 days in other cases. Final
hepatectomy was performed in all observations. Hypertrophy of left liver lobe was
more than 50% in all cases. Postoperative complications happened in 3 out of 5
cases. One patient died because of progressive thrombosis of inferior vena cava
and developed multiorgan failure. There were 1 complication of level 2 and 1
complication of level 4a according to Dindo-Clavien classification. One patient
had biliary fistula after final hepatectomy. It wasn't observed cases of severe
liver failure. ALPPS is appropriate method for fast residuary liver lobe
hypertrophy. It allows to perform R0-resection of liver but ALPPS has high
postoperative complication rate.
PMID- 25589315
TI - [Esophageal stenting complications].
AB - The aim of the study was to analyze esophageal stenting complications in case of
cancer and benign diseases. It was investigated complications in 8 patients in
terms from 7 days to 1 year after intervention. In 4 patients esophageal stenting
was performed for constrictive esophageal cancer and compression with pulmonary
cancer metastases into mediastinal lymphatic nodes. 2 patients had esophageal
stenting for post-tracheostomy tracheo-esophageal fistula, 1 patient - for
spontaneous esophageal rupture, 1 patient - for post-burn scar narrowing of
esophagus and output part of the stomach. Severe patients' condition with tumor
was determined by intensive esophageal bleeding in 2 cases, bilateral abscessed
aspiration pneumonia, tumor bleeding, blood aspiration (1 case), posterior
mediastinitis (1 case). Severe patients' condition with benign disease was
associated with decompensated esophageal narrowing about proximal part of stent
(1 case), increase of tracheo-esophageal fistula size complicated by aspiration
pneumonia (1 case), stent migration into stomach with recurrence of esophago
mediastino-pleural fistula and pleural empyema (1 case), decompensated narrowing
of esophagus and output part of the stomach (1 case). Patients with cancer died.
And patients with benign diseases underwent multi-stage surgical treatment and
recovered. Stenting is palliative method for patients with esophageal cancer.
Patients after stenting should be under outpatient observation for early
diagnosis of possible complications. Esophageal stenting in patients with benign
diseases should be performed only by life-saving indications, in case of
inability of other treatment and for the minimum necessary period.
PMID- 25589316
TI - [Rationale of application of the drug Cytoflavin in complex treatment of patients
with diabetic foot syndrome with mediacalcification arteries].
AB - The study involved 60 patients with diabetic foot syndrome (DFS) with severe
subcompensated diabetes type II. All patients were available mediacalcification
foot and lower leg arteries of different severity. Depending on the treatment,
all patients were divided into 2 groups by stratified randomization. The first
group received basic therapy that is indicated for DFS which included
antibiotics, vessels extending drugs neuroprotective and detoxification
facilities. The second group of patients in addition to basic therapy received
the drug cytoflavin 10 ml 0.9% NaCl 200 ml for 10 days, followed by transfer to
the tablet form cytoflavin 2 tablets 2 times a day orally for 1 month. We noted a
positive trend treat patients in addition to standard therapy received the drug
cytoflavin, resulting in a marked neuroprotective, antihypoxant and antioxidant
effects of the drug. Thus, the use of complex surgical treatment of patients with
mixed form DFS cytoflavin reduces the severity of distal polyneuropathy, improves
tissue oxygenation and restores the activity of antioxidant enzymes system,
manifested a marked neuroprotective, anti-hypoxic and antioxidant effects of
drugs and indications to justify its use in this condition.
PMID- 25589317
TI - [Blood loss during total knee-joint replacement: a combination of anticoagulant
and hemostatic techniques].
PMID- 25589318
TI - [Minimally-invasive treatment of upper urinary tract strictures].
PMID- 25589319
TI - [Removal of the posterior mediastinum chordoma with resection of aortic arch and
descending aorta, thoracic esophagus and the upper lobe of the left lung under
left atrial-aortic bypass].
PMID- 25589320
TI - [Postoperative small intestine intussusception in adults].
PMID- 25589321
TI - [Pancreatogenic ascites in chronic pancreatitis].
PMID- 25589322
TI - [Duodenal bleeding from heterotopic salivary gland].
PMID- 25589323
TI - [Intramuscular myxoma of iliopsoas muscle].
PMID- 25589324
TI - [Surgical treatment of patient with paraprosthetic infection complicated by
prosthetic-enteric bedsores and multiple abscesses of the right kidney after
aorto-femoral reconstruction and renal artery replacement].
PMID- 25589325
TI - [Traumatic rupture of giant multinodular goiter with mixed etiology].
PMID- 25589327
TI - Evidence to implementation continuum for universal health coverage.
PMID- 25589326
TI - Efficacy and safety of albendazole plus ivermectin, albendazole plus mebendazole,
albendazole plus oxantel pamoate, and mebendazole alone against Trichuris
trichiura and concomitant soil-transmitted helminth infections: a four-arm,
randomised controlled trial.
AB - BACKGROUND: Existing anthelmintic drugs (eg, albendazole and mebendazole) have
low efficacy against the intestinal nematode species Trichuris trichiura and the
drug pipeline is exhausted. We aimed to investigate the strategy of combination
chemotherapy with existing drugs to establish whether their efficacy could be
enhanced and broadened. METHODS: In this randomised controlled trial, we compared
three drug combinations and one standard drug alone in children aged 6-14 years
in two schools on Pemba Island, Tanzania infected with T trichiura and
concomitant intestinal nematodes. We assigned children, via a randomisation list
with block sizes of either four or eight, to orally receive albendazole (400 mg)
plus ivermectin (200 MUg/kg); albendazole (400 mg) plus mebendazole (500 mg);
albendazole (400 mg) plus oxantel pamoate (20 mg/kg); or mebendazole (500 mg)
alone. The primary endpoints were the proportion of children cured of T trichiura
infection and the reduction of T trichiura eggs in stool based on geometric
means, both analysed by available case. This study is registered with ISRCTN,
number ISRCTN80245406. FINDINGS: We randomly assigned 440 eligible children
infected with T trichiura between Sept 2, and Oct 18, 2013, to one of the four
treatment groups (110 children per group). Data for 431 children were included in
the analysis for the primary endpoints. Albendazole plus oxantel pamoate (74 of
108 children cured [68.5%, 95% CI 59.6-77.4]; egg reduction 99.2%, 98.7-99.6) and
albendazole plus ivermectin (30 of 109 cured [27.5%, 19.0-36.0]; egg reduction
94.5%, 91.7-96.3) were significantly more effective against T trichiura than
mebendazole alone (nine of 107 cured [8.4%, 3.1-13.8]; egg reduction 58.5%, 45.2
70.9). Albendazole plus mebendazole had similar low efficacy (nine of 107 cured
[8.4%, 3.1-13.8; egg reduction 51.6%, 35.0-65.3) to mebendazole alone. About a
fifth of the children reported adverse events, which were mainly mild. Abdominal
cramps and headache were the most common adverse events after treatment;
abdominal cramps were reported by 13 (12.0%) children for albendazole plus
ivermectin, 10 (9.3%) for albendazole plus mebendazole, 20 (18.2%) for
albendazole plus oxantel pamoate, and 16 (14.5%) for mebendazole; headaches were
reported by 5 (4.6%) children for albendazole plus ivermectin, 6 (5.6%) for
albendazole plus mebendazole, 12 (10.9%) for albendazole plus oxantel pamoate,
and 7 (6.4%) for mebendazole. INTERPRETATION: Our head-to-head comparison of
three combination chemotherapies showed the highest efficacy for albendazole plus
oxantel pamoate for the treatment of infection with T trichiura. Further studies
should investigate the combination of albendazole plus oxantel pamoate so that it
can be considered for soil-transmitted helminthiasis control programmes. FUNDING:
Medicor Foundation and Swiss National Science Foundation.
PMID- 25589328
TI - Going forward through the world: thinking theoretically about first person
perspective digital ethnography.
AB - Engaging first person perspective recording as a type of digital ethnography
invites the question of how we might understand the status of the knowledge it
produces. To examine this question I will focus on how first person perspective
camera recordings might be engaged and made analytically meaningful in
disciplines where naturalistic and observational visual recording is uncommon and
where the idea of producing naturalistic or optimally objective visual recordings
of people's lives is problematized. In doing so I explore the wider possibilities
of these technologies for ethnographic research both beyond their existing uses
and for interdisciplinary research where the images they produce might be
analysed from more than one perspective.
PMID- 25589329
TI - Corrigenda: Two new species of Mediomastus (Annelida, Capitellidae) from Tokyo
Bay, Japan. ZooKeys 422: 115-126.
AB - [This corrects the article DOI: 10.3897/zookeys.422.7501.].
PMID- 25589331
TI - Association of tumour necrosis factor-alpha polymorphism in patients with end
stage renal disease.
AB - AIM: Cytokines play a critical role in the pathophysiology of end stage renal
disease (ESRD). Tumour necrosis factor-a (TNF-alpha) is an important cytokine
involved in initiation and progression of renal diseases. The present study
evaluated the association of specific alleles/genotype of TNF-alpha with chronic
renal failure (CRF) and ESRD. METHODS: A total of 30 CRF patients who were not on
renal replacement therapy, 85 ESRD patients and 120 healthy controls were
included in the study. The ESRD patients belonged to two subgroups: patients on
peritoneal dialysis (PD) without peritonitis (n = 50) and with peritonitis (n =
35). TNF-alpha genotype (-308 G > A) was determined by polymerase chain reaction
restriction fragment length polymorphism. Level of TNF-alpha was detected in the
sera of patients and healthy controls by enzyme linked immunosorbent assay
(ELISA), and also in the dialysate of patients on PD. RESULTS: The genotypic
distributions of TNF-alpha (-308 G > A) were significantly different between
patients and controls. Homozygous A/A genotype had significant association with
CRF and ESRD (P < 0.001, odds ratio [OR] = 25.02). Frequency of homozygous A/A
genotype was significantly higher in all subgroups of patients than controls (CRF
40% vs control 2.5%, P = 0.001; PD 54% vs control 2.5%, P < 0.001 and PD with
peritonitis 62.8% vs control 2.5%, P < 0.001). Patients with homozygous A/A
genotype had significantly elevated levels of TNF-alpha in the sera of patients
and in the dialysate of PD patients. CONCLUSIONS: Individuals with homozygous TNF
alpha (-308 G > A) polymorphisms has significant association with CRF and ESRD,
and thus may be a predictor for development of the disease. Elevated TNF-alpha
may be a contributory factor.
PMID- 25589330
TI - E-health physical activity interventions and moderate-to-vigorous intensity
physical activity levels among working-age women: a systematic review protocol.
AB - BACKGROUND: The rapid pace of modern life requires working-age women to juggle
occupational, family, and social demands. Despite the large numbers of working
age women in developed countries and the proven benefits of regular moderate-to
vigorous intensity aerobic physical activity (MVPA) in chronic disease
prevention, few women meet current physical activity (PA) recommendations of 150
min of MVPA per week. It is important that appropriate and effective behavioral
interventions targeting PA are identified and developed to improve the MVPA
levels of working-age women. As women worldwide embrace modern technologies, e
health innovations may provide opportune and convenient methods of implementing
programs and strategies to target PA in an effort to improve MVPA levels and
cardiometabolic health. Previous reviews on this topic have been limited; none
have focused on working-age women from developed countries who exhibit
inappropriately low PA levels. It remains unknown as to which e-health
interventions are most effective at increasing MVPA levels in this population.
The purpose of this systematic review is to examine the effectiveness of e-health
interventions in raising MVPA levels among working-age women in developed
countries and to examine the effectiveness of these interventions in improving
the health of women. METHODS: Eight electronic databases will be searched to
identify all prospective cohort and experimental studies examining the impact of
e-health interventions for increasing MVPA levels among working-age women (mean
age 18-65 years) in developed countries. Gray literature including theses,
dissertations, and government reports will also be examined. Study quality will
be assessed using a modified Downs and Black checklist, and risk of bias will be
assessed within and across all included studies using the Cochrane's risk of bias
tool and Grades of Recommendation, Assessment, Development and Evaluation
approach. A quantitative synthesis in the form of meta-analyses for measures of
MVPA and health outcomes will be conducted where possible. DISCUSSION: This
review will determine the effectiveness of e-health interventions in raising MVPA
levels in working-age women in developed countries. It will form a contemporary,
rigorously developed, and reliable research base for policy makers and
stakeholders; and inform and influence the development and implementation of
effective e-health interventions designed to increase MVPA levels and improve
health outcomes in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42014009534.
PMID- 25589332
TI - Controlled release from drug microparticles via solventless dry-polymer coating.
AB - A novel solvent-less dry-polymer coating process employing high-intensity
vibrations avoiding the use of liquid plasticizers, solvents, binders, and heat
treatments is utilized for the purpose of controlled release. The main hypothesis
is that such process having highly controllable processing intensity and time may
be effective for coating particularly fine particles, 100 MUm and smaller via
exploiting particle interactions between polymers and substrates in the dry
state, while avoiding breakage yet achieving conformal coating. The method
utilizes vibratory mixing to first layer micronized polymer onto active
pharmaceutical ingredient (API) particles by virtue of van der Waals forces and
to subsequently mechanically deform the polymer into a continuous film. As a
practical example, ascorbic acid and ibuprofen microparticles, 50-500 MUm, are
coated with the polymers polyethylene wax or carnauba wax, a generally recognized
as safe material, resulting in controlled release on the order of seconds to
hours. As a novelty, models are utilized to describe the coating layer thickness
and the controlled-release behavior of the API, which occurs because of a
diffusion-based mechanism. Such modeling would allow the design and control of
the coating process with application for the controlled release of
microparticles, particularly those less than 100 MUm, which are difficult to coat
by conventional solvent coating methods.
PMID- 25589333
TI - Risk of Bacterial Vaginosis Among Women With Herpes Simplex Virus Type 2
Infection: A Systematic Review and Meta-analysis.
AB - BACKGROUND: Bacterial vaginosis (BV) is a perturbation of vaginal flora
characterized by reduced levels of lactobacilli and concomitant overgrowth of
anaerobic bacterial species. BV is highly prevalent and associated with multiple
adverse outcomes, including enhanced human immunodeficiency virus transmission.
Because recent reports reveal that herpes simplex virus type 2 (HSV-2) infection
may increase BV risk, we initiated a systematic review and meta-analysis of the
link between HSV-2 infection and BV. METHODS: We searched the MEDLINE, EMBASE,
and CENTRAL databases to identify articles posted before 1 December 2014. Two
screeners independently reviewed the titles and abstracts of all identified
articles, reviewed the full text of articles deemed potentially eligible, and
extracted data from 14 cross-sectional and 3 prospective studies. Using random
effects models, we computed separate pooled estimates for cross-sectional and
prospective studies. RESULTS: The pooled odds ratio for cross-sectional studies
was 1.60 (95% confidence interval, 1.32-1.94). Stronger support for the causal
effect of HSV-2 infection on BV risk was revealed by the summary relative risk
for the prospective studies, which was 1.55 (95% confidence interval, 1.30-1.84),
with minimal heterogeneity (I(2) = 0). CONCLUSIONS: These analyses imply that HSV
2 infection is an important BV risk factor. Pharmacologic HSV-2 suppression may
reduce BV incidence and BV-associated adverse events.
PMID- 25589334
TI - Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza
Vaccination.
AB - BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised
patients. However, there are limited data on the interplay of T- and B- cell
responses to vaccination with simultaneous immunosuppression. METHODS: We
collected peripheral blood mononuclear cells from transplant recipients before
and 1 month after seasonal influenza vaccination. Before and after vaccination,
H1N1-specific T- and B-cell activation were quantified with flow cytometry. We
also developed a mathematical model using T- and B-cell markers and mycophenolate
mofetil (MMF) dosage. RESULTS: In the 47 patients analyzed, seroconversion to
H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)
producing CD4(+) T-cell frequencies increased significantly after vaccination in
53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells
was high in patients who seroconverted. Seroconversion against H1N1 was strongly
associated with HLA-DR expression on B cells, which was dependent on the increase
between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) =
0.35). High doses of MMF (>= 2 g/d) led to lower seroconversion rates, smaller
increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on
B cells. The mathematical model incorporating a MMF-inhibited positive feedback
loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells
captured seroconversion with high specificity. CONCLUSIONS: Seroconversion is
associated with influenza-specific T-helper 2 and B-cell activation and seems to
be modulated by MMF.
PMID- 25589335
TI - Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir.
AB - Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for
HIV eradication. Administration of autologous, ex vivo expanded, virus-specific,
cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive
antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies.
Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated
improved control of autologous reservoir virus compared to bulk CD8(+) T cells in
viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear
latently infected autologous resting CD4(+) T cells following exposure to the
latency-reversing agent, vorinostat. HXTCs will be ideal reagents to administer
with precise control in future in vivo studies in combination with latency
reversing agents.
PMID- 25589336
TI - Listeria arpJ gene modifies T helper type 2 subset differentiation.
AB - BACKGROUND: Although the T-cell subset differentiation pathway has been
characterized extensively from the view of host gene regulation, the effects of
genes of the pathogen on T-cell subset differentiation during infection have yet
to be elucidated. Especially, the bacterial genes that are responsible for this
shift have not yet been determined. METHODS: Utilizing a single-gene-mutation
Listeria panel, we investigated genes involved in the host-pathogen interaction
that are required for the initiation of T-cell subset differentiation in the
early phase of pathogen infection. RESULTS: We demonstrate that the induction of
T helper types 1 and 2 (Th1 and Th2) subsets are separate phenomena and are
mediated by distinct Listeria genes. We identified several candidate Listeria
genes that appear to be involved in the host-Listeria interaction. Among them,
arpJ is the strongest candidate gene for inhibiting Th2 subset induction.
Furthermore, the analysis utilizing arpJ-deficient Listeria monocytogenes (Lm)
revealed that the tumor necrosis factor (TNF) superfamily (Tnfsf) 9-TNF receptor
superfamily (Tnfrsf) 9 interaction inhibits the Th2 response during Lm infection.
CONCLUSIONS: arpJ is the candidate gene for inhibiting Th2 T-cell subset
induction. The arpJ gene product influences the expression of Tnfsf/Tnfrsf on
antigen-presenting cells and inhibits the Th2 T-cell subset differentiation
during Listeria infection.
PMID- 25589337
TI - Matrix Metalloproteinase-13 as a Target for Suppressing Corneal Ulceration Caused
by Pseudomonas aeruginosa Infection.
AB - PURPOSE: Pseudomonas aeruginosa keratitis is characterized by severe corneal
ulceration. This study investigated whether matrix metalloproteinase-13 (MMP13)
is involved in P. aeruginosa-induced corneal ulceration and whether it therefore
can be targeted for preventing P. aeruginosa keratitis. METHODS: MMP13 expression
in P. aeruginosa-infected C57BL/6 mouse corneas was assessed by quantitative
polymerase chain reaction and immunohistochemistry analyses. An MMP13-inhibitor
(MMP13i) was either injected subconjunctivally prior to or coapplied topically
with gatifloxacin 16 hours after infection. Disease severity was assessed by
corneal imaging, clinical scoring, bacterial burden, neutrophil infiltration, and
CXCL2 expression. Corneal damage and infiltration were also determined by
immunohistochemistry analysis and whole-mount confocal microscopy. RESULTS: P.
aeruginosa infection induced an increased expression of MMP13 in mouse corneas
from 6 to 24 hours after infection in a Toll-liked receptor 5-dependent manner.
Subconjunctival injection of MMP13i prior to P. aeruginosa inoculation
significantly decreased keratitis severity, as evidenced by preserved epithelium
integrity and intact basement membrane, leading to reduced bacterial
dissemination to the stroma. Furthermore, topical coapplication of MMP13i with
gatifloxacin greatly improved disease outcomes, including accelerated opacity
dissolution; decreased inflammation, cellular infiltration, and collagen
disorganization; and basement membrane preservation. CONCLUSIONS: Elevated MMP13
activity may contribute to P. aeruginosa keratitis through basement membrane
degradation, and its inhibition could potentially be used as an adjunctive
therapy to treat microbial keratitis and other mucosal infections.
PMID- 25589340
TI - Effects of light quality and nutrient availability on accumulation of mycosporine
like amino acids in Gymnodinium catenatum (Dinophycea).
AB - A Portuguese Gymnodinium catenatum Graham strain was studied for its ultraviolet
(UV) photoprotective pigments. This strain presented high absorption in the UVA
region, in particular in the near UVA region around 370nm, followed by the far
UVA region around 340nm. Absorption in the near-UVA increased when grown under
fluorescent when compared to halogen light. This was even more relevant when
grown under nutrient-limiting conditions, which even surpassed absorption in the
blue region, closely resembling absorption in natural plankton assemblages
reported in the literature. HPLC analysis for mycosporine-like amino acids
(MAAs), revealed several UV photoprotective pigments common in other marine
microalgae from the northwest Atlantic. Amongst the compounds absorbing in the
far-UVA region, three were identified by spectra and retention time
characteristics: shinorine, porphyra-334, and mycosporine-glycine. In the near
UVA region, the unknown M-370 was usually the most abundant, followed by
palythene. The proportional and absolute cellular concentrations of MAAs
absorbing in the near-UVA region increased with fluorescent light when compared
to halogen light. Additional experiments with light filtration suggest the set of
MAAs absorbing in the near-UVA region seem to be regulated separately from the
other set of MAAs absorbing in the far-UVA region, and those from the near-UVA
region might be stimulated not only by UV but by blue light also. Nutrient
availability affected profile: a shift towards MAAs with low nitrogen:carbon
ratio (e.g.: mycosporine-glycine) was observed. As G. catenatum requires
extensive UV-photoprotection over the entire UVA range, nitrogen availability
might strongly restrict blooming, as MAAs are nitrogen-based. This UV sensitivity
might help explaining its pronounced autumnal seasonality, tied to a reduced
solar exposure.
PMID- 25589339
TI - Efficacy of ezetimibe is not related to NPC1L1 gene polymorphisms in a pilot
study of Chilean hypercholesterolemic subjects.
AB - BACKGROUND AND OBJECTIVE: Niemann-Pick C1 Like 1 (NPC1L1) is a multi
transmembrane transport protein highly expressed in the small intestine. It
mediates sterol transfer throughout the brush border membrane of enterocytes,
becoming essential for intestinal cholesterol absorption and ensuing whole-body
cholesterol homeostasis. This protein is targeted by ezetimibe, a potent
cholesterol absorption inhibitor. Single nucleotide polymorphisms (SNPs) in
NPC1L1 have been associated to variation in both plasma low-density lipoprotein
(LDL) cholesterol levels and lipid-lowering medication with ezetimibe. However,
there are no data evaluating the impact of NPC1L1 variants on Chilean subjects
medicated with ezetimibe monotherapy. Therefore, we assessed the contribution of
two unexplored NPC1L1 variants on plasma lipids and response to ezetimibe in
Chilean hypercholesterolemic individuals. METHODS: Using PCR-restriction fragment
length polymorphism (RFLP), we analyzed the SNP distribution of two common
variants; -133A>G (rs17655652) and 1679C>G (rs2072183), and their relation with
plasma lipids and lipid-lowering response to ezetimibe in 60 hypercholesterolemic
Chilean subjects. RESULTS: Genotype distribution for the rs17655652 variant was
AA 57 %, 40 % AG and 3 % GG, whereas for the rs2072183 SNP was 57 % CC, 35 % CG
and 8 % GG. Minor allele frequencies (MAFs) were 0.23 and 0.26, respectively. No
association was observed between NPC1L1 SNPs and baseline cholesterol. After
therapy, none of the polymorphisms affected ezetimibe response in the studied
cohort (P > 0.05). CONCLUSION: Data obtained indicates that polymorphisms
rs17655652 and rs2072183 were not related to cholesterol variability. Also, lipid
lowering response to ezetimibe is not impacted by the NPC1L1 polymorphisms
studied in Chilean hypercholesterolemic subjects.
PMID- 25589341
TI - Photochemical properties of gemifloxacin: a laser flash photolysis study.
AB - The photochemical properties of gemifloxacin (GEFX), a fluoroquinolone
antibacterial drug that exhibits phototoxicity toward biological substrates, were
studied in aqueous solutions by laser flash photolysis (LFP) and pulse
radiolysis. GEFX triplet state ((3)GEFX(*)) absorption spectra showed maximum
absorption at 510nm. (3)GEFX(*) was quenched by naproxen (NAP) via energy
transfer with a rate constant of 1.2*10(8)dm(3)mol(-1)s(-1). The energy of
(3)GEFX(*) was 266kJmol(-1) and the transient absorption spectra showed direct
evidence of electron transfer from 2'-deoxyguanosine-5'-monophosphate, N,N,N',N'
tetramethyl-p-phenylenediamine, and tryptophan to (3)GEFX(*) with bimolecular
reaction rate constants of 4.1*10(6), 2.0*10(7), and 2.2*10(7)dm(3)mol(-1)s(-1),
respectively. The rate constants for reactions of GEFX with OH, eaq(-) were found
to be 1.5*10(10) and 1.4*10(10)dm(3)mol(-1)s(-1), respectively. The mechanisms
and products of the photosensitive damage of lysozyme were related to the GEFX
concentration, irradiation time, and ambient conditions.
PMID- 25589342
TI - IgA deficiency and risk of cancer: a population-based matched cohort study.
AB - PURPOSE: To investigate the risk of cancer in individuals with IgA deficiency
compared with the general population. METHODS: Prospective nationwide population
based cohort study. We identified 2320 individuals with IgA deficiency (IgA
levels < 0.07 g/L) diagnosed between 1980 and 2010 in six Swedish university
hospitals. Individuals with IgA deficiency were then matched on age, sex, place
of residence, and year of diagnosis with up to 10 general population controls (n
= 23,130). Through linkage with the Swedish Cancer Register we calculated
conditional hazard ratios (HRs) for cancer diagnosed after IgA deficiency
diagnosis in patients without a previous cancer diagnosis. RESULTS: During follow
up, 125 individuals with IgA deficiency (61/10,000 person-years) and 984 controls
(47/10,000 person-years) developed cancer (HR 1.31; 95%CI = 1.09-1.58). In cause
specific analyses, we found an increased risk of any gastrointestinal cancer (HR
= 1.64; 95%CI = 1.07-2.50), but not for lymphoproliferative malignancy (HR 1.68;
95%CI = 0.89-3.19). Relative risk estimates for overall cancer were very high in
the first year of follow-up (overall: HR = 2.80; 95%CI = 1.74-4.49), but failed
to reach statistical significance thereafter. IgA deficiency diagnosed in
childhood (n = 487) was not associated with overall cancer (HR = 3.26; 0.88
12.03). CONCLUSIONS: Individuals with IgA deficiency are at a moderately
increased risk of cancer, with excess risks of gastrointestinal cancer. This
excess risk is highest just after diagnosis suggesting a degree of surveillance
bias. Children with IgA deficiency were at no increased risk of cancer but the
statistical power was limited in subanalyses.
PMID- 25589343
TI - Determination of partial molar volumes from free energy perturbation theory.
AB - Partial molar volume is an important thermodynamic property that gives insights
into molecular size and intermolecular interactions in solution. Theoretical
frameworks for determining the partial molar volume (V degrees ) of a solvated
molecule generally apply Scaled Particle Theory or Kirkwood-Buff theory. With the
current abilities to perform long molecular dynamics and Monte Carlo simulations,
more direct methods are gaining popularity, such as computing V degrees directly
as the difference in computed volume from two simulations, one with a solute
present and another without. Thermodynamically, V degrees can also be determined
as the pressure derivative of the free energy of solvation in the limit of
infinite dilution. Both approaches are considered herein with the use of free
energy perturbation (FEP) calculations to compute the necessary free energies of
solvation at elevated pressures. Absolute and relative partial molar volumes are
computed for benzene and benzene derivatives using the OPLS-AA force field. The
mean unsigned error for all molecules is 2.8 cm(3) mol(-1). The present
methodology should find use in many contexts such as the development and testing
of force fields for use in computer simulations of organic and biomolecular
systems, as a complement to related experimental studies, and to develop a deeper
understanding of solute-solvent interactions.
PMID- 25589344
TI - Regulation of monocyte/macrophage polarisation by extracellular RNA.
AB - Monocytes/macrophages respond to external stimuli with rapid changes in the
expression of numerous inflammation-related genes to undergo polarisation towards
the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. We have previously
shown that, independently of Toll-like receptor activation, extracellular RNA
(eRNA) could exert pro-thrombotic and pro-inflammatory properties in the
cardiovascular system to provoke cytokine mobilisation. Here, mouse bone marrow
derived-macrophages (BMDM) differentiated with mouse macrophage-colony
stimulating factor (M-CSF) were found to be skewed towards the M1 phenotype when
exposed to eRNA. This resulted in up-regulated expression of inflammatory markers
such as Tnf-alpha and Il-6, together with Il-12 and iNOS, whereas anti
inflammatory genes such as chitinase-like proteins (Ym1/2) and macrophage mannose
receptor-2 (Cd206) were significantly down-regulated. Human peripheral blood
monocytes were treated with eRNA and analysed by micro-array analysis of the
whole human genome, revealing an up-regulation of 79 genes by at least four-fold;
27 of which are related to signal transduction and 15 genes associated with
inflammatory response. In accordance with the proposed actions of eRNA as a pro
inflammatory "alarm signal", these data shed light on the role of eRNA in the
context of chronic inflammatory diseases such as atherosclerosis.
PMID- 25589345
TI - Lysophosphatidic acid receptor LPAR6 supports the tumorigenicity of
hepatocellular carcinoma.
AB - The aberrant processes driving hepatocellular carcinoma (HCC) are not fully
understood. Lysophosphatidic acid receptors (LPAR) are commonly overexpressed in
HCC, but their contributions to malignant development are not well established.
In this report, we show that aberrant expression of LPAR6 sustains tumorigenesis
and growth of HCC. Overexpression of LPAR6 in HCC specimens associated with poor
survival in a cohort of 128 patients with HCC. We took a genetic approach to
elucidate how LPAR6 sustains the HCC tumorigenic process, including through an
expression profiling analysis to identify genes under the control of LPAR6. RNAi
mediated attenuation of LPAR6 impaired HCC tumorigenicity in tumor xenograft
assays. Expression profiling and mechanistic analyses identified Pim-3 as a
pathophysiologically relevant LPAR6 target gene. In nonmalignant cells where
LPAR6 overexpression was sufficient to drive malignant character, Pim-3 was
upregulated at the level of transcription initiation through a STAT3-dependent
mechanism. A further analysis of HCC clinical specimens validated the connection
between overexpression of LPAR6 and Pim-3, high proliferation rates, and poorer
survival outcomes. Together, our findings establish LPAR6 as an important
theranostic target in HCC tumorigenesis.
PMID- 25589348
TI - Th9 cells: a novel CD4 T-cell subset in the immune war against cancer.
AB - CD4 T cells are key components of the immune system that shape the anticancer
immune response in animal models and in humans. The biology of CD4 T cells is
complex because naive T cells can differentiate into various subpopulations with
various functions. Recently, a new population called Th9 cells was described.
These cells are characterized by their ability to produce IL9 and IL21. They were
first described in the context of parasite infections and allergic processes.
However, some reports described their presence in the tumor bed in mice and
humans. Their high secretion of IL9 and IL21 in the tumor bed contributes to
their anticancer functions. Indeed, these cytokines trigger the activation of
dendritic cells, mast cells, natural killer cells, and CD8 T cells to mount an
antitumor immune response, thus explaining the remarkable ability of Th9 cells to
control tumor growth. This review summarizes the latest advances in the Th9 field
in cancer and focuses on their potential role as new tool for cell therapy.
PMID- 25589346
TI - Bruton tyrosine kinase is a therapeutic target in stem-like cells from multiple
myeloma.
AB - Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is
currently undergoing clinical testing in patients with multiple myeloma, yet
important questions on the role of BTK in myeloma biology and treatment are
outstanding. Using flow-sorted side population cells from human myeloma cell
lines and multiple myeloma primary samples as surrogate for the elusive multiple
myeloma stem cell, we found that elevated expression of BTK in myeloma cells
leads to AKT/WNT/beta-catenin-dependent upregulation of key stemness genes (OCT4,
SOX2, NANOG, and MYC) and enhanced self-renewal. Enforced transgenic expression
of BTK in myeloma cells increased features of cancer stemness, including
clonogenicity and resistance to widely used myeloma drugs, whereas inducible
knockdown of BTK abolished them. Furthermore, overexpression of BTK in myeloma
cells promoted tumor growth in laboratory mice and rendered side population
derived tumors that contained high levels of BTK more sensitive to the selective,
second-generation BTK inhibitor, CGI1746, than side population-derived tumors
that harbored low levels of BTK. Taken together, these findings implicate BTK as
a positive regulator of myeloma stemness and provide additional support for the
clinical testing of BTK-targeted therapies in patients with myeloma.
PMID- 25589349
TI - Novel insights into head and neck cancer using next-generation "omic"
technologies.
AB - Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease
that develops via one of the two primary carcinogenic routes: chemical
carcinogenesis through exposure to tobacco and alcohol or virally induced
tumorigenesis. Human papillomavirus (HPV)-positive (HPV(+)) and HPV-negative
(HPV(-)) HNSCCs represent distinct clinical entities, with the latter associated
with significantly inferior outcome. The biologic basis of these different
outcomes is an area of intense investigation; their therapeutic regimens are
currently also being reevaluated, which would be significantly facilitated by
reliable biomarkers for stratification. With the advent of the omics era and
accelerated development of targeted therapies, there are unprecedented
opportunities to address the challenges in the management of HNSCC. As summarized
herein, side-by-side molecular characterization of HPV(+) versus HPV(-) HNSCC has
revealed distinct molecular landscapes, novel prognostic signatures, and
potentially targetable biologic pathways. In particular, we focus on the evidence
acquired from genome-wide omics pertinent to our understanding of the clinical
behavior of HNSCC and on insights into personalized treatment opportunities.
Integrating, mining, and validating these data toward clinically meaningful
outcomes for patients with HNSCC in conjunction with systematic verification of
the functional relevance of these findings are critical steps toward the design
of personalized therapies.
PMID- 25589351
TI - Molecular dynamics of different polymer blends containing poly(2,6-dimethyl-1,4
phenylene ether).
AB - Detailed atomistic molecular dynamics simulations were performed to investigate
the behavior of two different binary blends, a miscible system poly(2,6-dimethyl
1,4-phenylene ether)-polystyrene (PPE-PS) and an immiscible system poly(2,6
dimethyl-1,4-phenylene ether)-poly(methyl methacrylate) (PPE-PMMA). We compared
these two blends to study how PPE behaves when blended with different polymers.
In both cases, the structure and phase behavior of polymer melts were studied by
means of radial distribution functions (RDFs). Radii of gyration illustrate the
static properties. Packing features of the benzene rings were observed in PPE and
PS, both PS and PPE were well dispersed over the whole time scale of simulation.
Furthermore, there was a tendency for aggregation of PMMA chains in PPE-PMMA
systems. The mean squared displacements of monomers and whole chains describe the
mobility of polymers in various systems.
PMID- 25589352
TI - Controlled release of encapsulated bioactive volatiles by rupture of the capsule
wall through the light-induced generation of a gas.
AB - The encapsulation of photolabile 2-oxoacetates in core-shell microcapsules allows
the light-induced, controlled release of bioactive compounds. On irradiation with
UVA light these compounds degrade to generate an overpressure of gas inside the
capsules, which expands or breaks the capsule wall. Headspace measurements
confirmed the light-induced formation of CO and CO2 and the successful release of
the bioactive compound, while optical microscopy demonstrated the formation of
gas bubbles, the cleavage of the capsule wall, and the leakage of the oil phase
out of the capsule. The efficiency of the delivery system depends on the
structure of the 2-oxoacetate, the quantity used with respect to the thickness of
the capsule wall, and the intensity of the irradiating UVA light.
PMID- 25589350
TI - Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres
and maintains telomere G-overhangs.
AB - Proliferating mammalian stem and cancer cells express telomerase [telomerase
reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and
maintain telomere ends. Telomerase-expressing cells also have higher levels of
the single-stranded DNA-binding protein SSB1, which has a critical role in DNA
double-strand break (DSB) repair. Here, we report that SSB1 binds specifically to
G-strand telomeric DNA in vitro and associates with telomeres in vivo. SSB1
interacts with the TERT catalytic subunit and regulates its interaction with
telomeres. Deletion of SSB1 reduces TERT interaction with telomeres and leads to
G-overhang loss. Although SSB1 is recruited to DSB sites, we found no
corresponding change in TERT levels at these sites, implying that SSB1-TERT
interaction relies upon a specific chromatin structure or context. Our findings
offer an explanation for how telomerase is recruited to telomeres to facilitate G
strand DNA extension, a critical step in maintaining telomere ends and cell
viability in all cancer cells. Cancer Res; 75(5); 858-69. (c)2015 AACR.
PMID- 25589353
TI - [Histological spectrum of malignant melanoma].
AB - The diagnosis of melanocytic tumors is one of the most problematic areas in
dermatology and diagnostic pathology. Melanoma is a malignant melanocytic tumor
and the risk for metastasis and associated mortality is mainly dependent on tumor
thickness and depth of invasion. Early recognition and correct diagnosis is
therefore important for successful and effective treatment. The correct diagnosis
of melanoma is, however, challenging due to the wide morphological spectrum.
Historically, the disease was subdivided into superficial spreading, nodular,
lentigo maligna and acral lentiginous melanoma but many more subtypes have
subsequently been added. Some of these melanoma variants also show differences
relating to the genetic background, clinical presentation, prognosis and
treatment and may be associated with a specific differential diagnosis. In this
article four of these melanoma variants, desmoplastic melanoma, nevoid melanoma,
malignant blue nevus and pigment synthesizing melanoma will be discussed in more
detail.
PMID- 25589354
TI - [Cutaneous angiosarcoma: new aspects].
AB - Cutaneous angiosarcoma is an aggressive endothelial cell neoplasm with a high
associated mortality. Reliable and confident diagnosis is necessary but
frequently challenging due to the wide morphological spectrum and broad
differential diagnosis of the disease. Furthermore, the final diagnosis often
relies on immunohistochemical evidence of endothelial cell differentiation which
is further complicated by the lack of sensitivity and specificity of conventional
endothelial cell markers. The following article outlines the clinical and
histological spectrum of cutaneous angiosarcoma with emphasis on novel findings
relating to immunohistochemistry and molecular genetics in the context of the
relevant differential diagnosis.
PMID- 25589355
TI - [Cutaneous lymphomas: new entities and rare variants].
AB - Primary cutaneous lymphomas are the second most common group of extranodal non
Hodgkin lymphomas. Recently several new variants and entities have been described
but have not yet become part of the World Health Organization (WHO)
classification. These forms include the granulomatous form of mycosis fungoides,
which is associated with a poorer prognosis, as well as indolent CD8+
lymphoproliferations on the head and at acral localizations. Within the group of
cutaneous CD30+ lymphoproliferative disorders, new histological types of
lymphomatoid papulosis have been identified, such as type D (CD8+ epidermotropic)
and type E (angioinvasive) which simulate aggressive lymphomas. Cutaneous
peripheral T-cell lymphomas are a prognostically heterogeneous group of cutaneous
lymphomas. The cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma
and cutaneous gamma/delta T-cell lymphoma are very aggressive neoplasms, whereas
cutaneous CD4+ small to medium-sized T-cell lymphoma in its solitary or localized
form represents an indolent lymphoproliferation: the terminology, histogenesis
and differentiation from nodular T-cell pseudolymphoma are still a matter of
debate. Among B-cell lymphomas, disorders associated with Epstein-Barr virus
(EBV) are discussed focusing on EBV diffuse large B-cell lymphoma of the elderly
and EBV-associated mucocutaneous ulcer. This review describes the clinical,
histological and immunophenotypic features of new and rare entities and variants
of cutaneous lymphomas and highlights the impact of the clinicopathological
correlation in the diagnostic process.
PMID- 25589357
TI - [Health-related quality of life: a pivotal endpoint in benefit assessment of
medical procedures].
AB - BACKGROUND: According to German law, health-related quality of life is a relevant
criterion in the early assessment of the benefits of drug treatment. In spite of
its regulatory importance, the role of quality of life assessment in quantifying
the additional benefits of novel vs standard treatments is not yet clear.
OBJECTIVES: The paper is aimed at analyzing the theoretical foundation, the
methodological foundation, and the empirical evaluation of the criterion "quality
of life" in recent benefit dossiers, as published by the Federal Joint Committee
(G-BA) and the German Institute for Quality and Efficiency in Health Care
(IQWiG). MATERIALS AND METHODS: Benefit dossiers assessed by the end of 2013 were
quantitatively analyzed regarding the choice, frequency of use, and consequences
of quality of life assessment. RESULTS: In 59 of the 66 dossiers quality of life
assessment was performed, frequently using the EQ-5D (n = 16 procedures) and the
SF-36 (n = 8 procedures). Of the 107 evaluations of the subpopulation within
these 59 dossiers, in only 2 cases was an additional benefit due to the quality
of life declared by the IQWiG and G-BA. CONCLUSIONS: In spite of the acceptance
of quality of life measures and their inclusion in the dossiers, they have rarely
been the basis for the declaration of additional benefits. This reluctance does
not stem from the availability of instruments, but results from problems in their
selection, the design and conduct of the study, data interpretation, together
with shortcomings regarding the statistical and clinical significance of quality
of life data.
PMID- 25589356
TI - [Fibrohistiocytic tumors of the skin: a heterogeneous group of superficially
located mesenchymal neoplasms].
AB - So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum
of superficially located neoplasms that often show fibroblastic and/or
myofibroblastic differentiation. In this review clinicopathologically important
variants of dermatofibroma and dermatofibrosarcoma protuberans and their
differential diagnoses are discussed in detail. In addition, the
clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous
histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma
are presented. Entities that have to be considered in the differential diagnosis
are also mentioned.
PMID- 25589358
TI - Elemental biochemical analysis of the polysaccharides in the extracellular matrix
of the yeast Saccharomyces cerevisiae.
AB - In yeast multicellular aggregates, such as biofilms and colonies, cells are
supported by a yeast extracellular matrix (yECM) of glycosidic nature, the
composition of which is mostly unknown. Saccharomyces cerevisiae ECM was
produced, extracted and partitioned. An analytical-grade pure glycoside fraction
was obtained, fractionated by anionic exchange liquid chromatography and analyzed
by gas chromatography-mass spectrometry and polyacrylamide gel electrophoresis.
Two different molecular weight polysaccharides were found, composed of glucose,
mannose and small relative amounts of galactose. One of the polysaccharides had a
low molecular weight, compatible with the association with glycoproteins
abundantly occurring in yECM. In addition, these polysaccharide species were
separated by diaminopropane agarose gel electrophoresis and induced metachromatic
shift, suggesting chemical substitution, which was corroborated by
anticoagulation activity. This was shown to be associated with the double
deletion of the yeast homologues of the mammalian Hedgehog modulators Hhatl and
Hhat, respectively yeast Gup1 and Gup2. These results pioneer the study of the
molecular biology of the ECM supporting S. cerevisiae multicellular aggregates
such as biofilms.
PMID- 25589359
TI - Longitudinal impact of sleep on overweight and obesity in children and
adolescents: a systematic review and bias-adjusted meta-analysis.
AB - Short sleep duration is considered a potential risk for overweight/obesity in
childhood and adolescence. However, most of the evidence on this topic is
obtained from cross-sectional studies; therefore, the nature and extent of the
longitudinal associations are unclear. This study explores the prospective
association between short sleep and overweight/obesity in young subjects. The
MEDLINE, EMBASE, Pubmed, and CINAHL databases were searched for English-language
articles, published until May 2014, reporting longitudinal association between
sleep and body mass index (BMI) in children and adolescents. Recommendations of
the Sleep Health Foundation were used to standardize reference sleep duration.
Sleep category, with sleep duration less than the reference sleep, was considered
as the short sleep category. Meta-analysis was conducted to explore the
association between short sleep and overweight/obesity. A review of 22
longitudinal studies, with subjects from diverse backgrounds, suggested an
inverse association between sleep duration and BMI. Meta-analysis of 11
longitudinal studies, comprising 24,821 participants, revealed that subjects
sleeping for short duration had twice the risk of being overweight/obese,
compared with subjects sleeping for long duration (odds ratio 2.15; 95%
confidence interval: 1.64-2.81). This study provides evidence that short sleep
duration in young subjects is significantly associated with future
overweight/obesity.
PMID- 25589360
TI - The Elsevier Trophoblast Research Award Lecture: Importance of metzincin
proteases in trophoblast biology and placental development: a focus on ADAM12.
AB - Placental development is a highly regulated process requiring signals from both
fetal and maternal uterine compartments. Within this complex system,
trophoblasts, placental cells of epithelial lineage, form the maternal-fetal
interface controlling nutrient, gas and waste exchange. The commitment of
progenitor villous cytotrophoblasts to differentiate into diverse trophoblast
subsets is a fundamental process in placental development. Differentiation of
trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential
for uterine arterial remodeling and placental function. Inadequate placentation,
characterized by defects in trophoblast differentiation, may underlie the
earliest cellular events driving pregnancy disorders such as preeclampsia and
fetal growth restriction. Molecularly, invasive trophoblasts acquire
characteristics defined by profound alterations in cell-cell and cell-matrix
adhesion, cytoskeletal reorganization and production of proteolytic factors. To
date, most studies have investigated the importance of the matrix
metalloproteinases (MMPs) and their ability to efficiently remodel components of
the extracellular matrix (ECM). However, it is now becoming clear that besides
MMPs, other related proteases regulate trophoblast invasion via mechanisms other
than ECM turnover. In this review, we will summarize the current knowledge on the
regulation of trophoblast invasion by members of the metzincin family of
metalloproteinases. Specifically, we will discuss the emerging roles that A
Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a
particular focus on the ADAM subtype, ADAM12.
PMID- 25589363
TI - Enhancing and suppressing effects of an inner droplet on deformation of a double
emulsion droplet under shear.
AB - We combine experimental investigation with numerical simulation to explore
fundamental hydrodynamic effects of an inner droplet on deformation of a double
emulsion droplet under shear. The transient deformation oscillation is found to
be intensified by the inner droplet. Especially, we demonstrate that the double
emulsion droplet can exhibit both larger and smaller steady deformation than the
single-phase droplet, which arises from the competition between the coexisting
enhancing and suppressing effects by the inner droplet on the deformation. We
further provide a regime diagram to quantitatively recognize the respective
dominant regime of these two effects, depending on the capillary number and
radius ratio of the inner droplet to the outer one.
PMID- 25589362
TI - In vitro characterization of the digestive stress response and immunomodulatory
properties of microorganisms isolated from smear-ripened cheese.
AB - Thirty-six microorganisms (twenty-one bacteria, twelve yeasts and three fungi)
were isolated from surface-ripened cheeses and subjected to in vitro digestive
stress. The approach mimicked gastric and/or duodenal digestion. Lactobacillus
rhamnosus GG, Escherichia coli Nissle 1917 and Saccharomyces boulardii were used
as reference strains. We studied the microorganisms grown separately in culture
medium and then included (or not) in a rennet gel. The microorganisms'
immunomodulatory abilities were also assessed by profiling cytokine induction in
human peripheral blood mononuclear cells (PBMCs). The loss of viability was less
than 1 log CFU/mL for yeasts under all conditions. In contrast, Gram-negative
bacteria survived gastric and/or duodenal stress well but most of the Gram
positive bacteria were more sensitive (especially to gastric stress). Inclusion
of sensitive Gram-positive bacteria in rennet gel dramatically improved gastric
survival, when compared with a non-included cultured (with a 4 log CFU/mL change
in survival). However, the rennet gel did not protect the bacteria against
duodenal stress. The PBMC cytokine assay tests showed that the response to yeasts
was usually anti-inflammatory, whereas the response to bacteria varied from one
strain to another.
PMID- 25589365
TI - Direct bandgap transition in many-layer MoS2 by plasma-induced layer decoupling.
AB - We report a robust method for engineering the optoelectronic properties of many
layer MoS2 using low-energy oxygen plasma treatment. Gas phase treatment of MoS2
with oxygen radicals generated in an upstream N2 -O2 plasma is shown to enhance
the photoluminescence (PL) of many-layer, mechanically exfoliated MoS2 flakes by
up to 20 times, without reducing the layer thickness of the material. A blueshift
in the PL spectra and narrowing of linewidth are consistent with a transition of
MoS2 from indirect to direct bandgap material. Atomic force microscopy and Raman
spectra reveal that the flake thickness actually increases as a result of the
plasma treatment, indicating an increase in the interlayer separation in MoS2 .
Ab initio calculations reveal that the increased interlayer separation is
sufficient to decouple the electronic states in individual layers, leading to a
transition from an indirect to direct gap semiconductor. With optimized plasma
treatment parameters, we observed enhanced PL signals for 32 out of 35 many-layer
MoS2 flakes (2-15 layers) tested, indicating that this method is robust and
scalable. Monolayer MoS2 , while direct bandgap, has a small optical density,
which limits its potential use in practical devices. The results presented here
provide a material with the direct bandgap of monolayer MoS2 , without reducing
sample thickness, and hence optical density.
PMID- 25589361
TI - Reduced expression of the epidermal growth factor signaling system in
preeclampsia.
AB - INTRODUCTION: The epidermal growth factor (EGF) signaling system regulates
trophoblast differentiation, and its disruption could contribute to perinatal
disease. We hypothesized that this pathway is altered in preeclampsia, a disorder
associated with trophoblast apoptosis and failure to invade and remodel the
uterine spiral arteries. METHODS: Six EGF family peptides and a truncated EGF
receptor splice variant (p110/EGFR) were examined using immunohistochemistry in
the trophoblast of placentas (N = 76) from women with preeclampsia, and compared
to placentas from women of similar gestational age (GA) with preterm labor (PTL)
or small for gestational age (SGA) fetuses, as well as normal term placentas.
EGF, transforming growth factor-alpha (TGFA), and heparin-binding EGF-like growth
factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20
pregnancies with or without preeclampsia. Cell death was evaluated in the HTR
8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective
effects of EGF peptides. RESULTS: Trophoblast HBEGF, TGFA, and EGF were
significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR
accumulated significantly on the surface of the chorionic villi (p < 0.05).
Plasma EGF levels were significantly decreased in preeclamptic patients, compared
to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and
betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05).
DISCUSSION: Three members of the EGF family are dysregulated in placentas with
preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is
overexpressed. These findings are consistent with the concept that disruption of
the EGF signaling system contributes to aberrant trophoblast development
associated with preeclampsia.
PMID- 25589364
TI - Reduced cerebrospinal fluid ethanolamine concentration in major depressive
disorder.
AB - Amino acids play key roles in the function of the central nervous system, and
their alterations are implicated in psychiatric disorders. In the search for a
biomarker for major depressive disorder (MDD), we used high-performance liquid
chromatography to measure amino acids and related molecules in the cerebrospinal
fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54
matched controls. Significant differences were found in four amino acid
concentrations between the depressed patients and controls. After Bonferroni
correction, only ethanolamine (EA) levels remained significantly reduced in
depressed patients (nominal P = 0.0000011). A substantial proportion of the
depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 MUM) (P =
0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with
high EA levels were compared, the former had higher scores for overall depression
severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In
unmedicated subjects, CSF EA levels showed a significant positive correlation
with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P =
0.019). To our knowledge, this is the first study showing that patients with MDD
have significantly lower CSF EA concentrations compared with control subjects.
CSF EA could be a state-dependent biomarker for a subtype of MDD.
PMID- 25589366
TI - Thrombophilic state in young patients with acute myocardial infarction.
AB - The prevalence of thrombophilia and dyslipidemia among young survivors of acute
coronary syndrome has not been clearly defined. The purpose of the current study
was to investigate the prevalence of multiple markers of thrombophilia and
dyslipidemia in a cohort of consecutive young survivors of acute coronary
syndrome. The study cohort included 156 consecutive young patients (men <45 and
women <50 years), admitted to the intensive cardiac care unit with newly
diagnosed acute coronary syndrome. Analysis included baseline, clinical and
epidemiological characteristics, angiographic coronary anatomy, echocardiographic
evaluation, extensive lipid and thrombophilia laboratory profiles, and in
hospital and 1-year clinical outcomes for all patients. Acute myocardial
infarction was diagnosed in 142 (92 %) patients, of whom 108 (72 %) had ST
segment elevation. Eighteen (12 %) patients had no traditional risk factors. Low
levels of high-density lipoprotein (<40 mg/dL) were found in 101 (65 %) patients,
and 49 (34 %) patients had elevated levels of lipoprotein(a) (Lp(a)) (>30 mg/dL).
Eighteen (12 %) patients were diagnosed with antiphospholipid antibody syndrome
(APS), and 73 (47 %) had at least one laboratory finding consistent with
thrombophilia. Patients with APS had significantly higher levels of Lp(a) (46 +/-
32 vs. 29 +/- 31 mg/dL, p = 0.005). APS is a common prothrombotic state found in
young survivors of acute coronary syndrome. Lp(a) levels are elevated among APS
patients who present with premature acute coronary syndrome.
PMID- 25589367
TI - Application of mobile technology for improving expanded program on immunization
among highland minority and stateless populations in northern Thailand border.
AB - BACKGROUND: Studies of undervaccinated children of minority/stateless populations
have highlighted significant barriers at individual, community, and state levels.
These include geography-related difficulties, poverty, and social norms/beliefs.
OBJECTIVE: The objective of this study was to assess project outcomes regarding
immunization coverage, as well as maternal attitudes and practices toward
immunization. METHODS: The "StatelessVac" project was conducted in Thailand
Myanmar-Laos border areas using cell phone-based mechanisms to increase
immunization coverage by incorporating phone-to-phone information sharing for
both identification and prevention. With limitation of the study among vulnerable
populations in low-resource settings, the pre/post assessments without comparison
group were conducted. Immunization coverage was collected from routine monthly
reports while behavior-change outcomes were from repeat surveys. RESULTS: This
study revealed potential benefits of the initiative for case identification;
immunization coverage showed an improved trend. Prevention strategies were
successfully integrated into the routine health care workflows of immunization
activities at point-of-care. A behavior-change-communication package contributes
significantly in raising both concern and awareness in relation to child care.
CONCLUSIONS: The mobile technology has proven to be an effective mechanism in
improving a children's immunization program among these hard-to-reach
populations. Part of the intervention has now been revised for use at health
centers across the country.
PMID- 25589368
TI - EPA's proposed Worker Protection Standard and the burdens of the past.
AB - BACKGROUND: An Environmental Protection Agency (EPA) recommendation for extensive
changes to the Agency's 40-year-old Worker Protection Standard is currently
stalled in the "proposed rule" stage. The proposal, which was available for
public comment until 18 August, would improve safety, training, and hazard
communication policies for agricultural pesticides. Exposure to hazards,
including high heat, heavy machinery, stoop labor, and pesticides, makes
occupational illness uncommonly common among the USA's estimated 2.5 million farm
workers. OBJECTIVES: To consider the proposed revisions' likelihood of addressing
historical gaps in farmworker protection. METHODS: The proposal was compared to
the existing Worker Protection Standard, and key aspects were analyzed in
relation to existing science on farm labor hazards, as well as historic
occupational health, labor and immigration policy. RESULTS: US law historically
has left farm workers largely unprotected. These exclusions and delays have been
tolerated in part thanks to the myth of the independent family farmer, but more
significant is the stingy nativism that presumes to benefit from immigrant labor
without assuming any responsibility to protect the humans who provide it. In the
first half of the 1970s, workers lobbied for robust protections, but rule making
was impeded by lack of data and by the disproportionate influence of agricultural
employers who sought minimal regulation. In 1974, the EPA passed the first Worker
Protection Standard for farm workers. Key aspects of the proposed revision
include stronger protections against drift and re-entry exposures, better
information provision and training, and increased protections for workers under
16 years. CONCLUSIONS: The proposed changes represent an improvement over
existing legislation, but do not go far enough. The revision should be
strengthened along lines suggested by farm workers themselves, and other labor
laws must also be amended to give the men, women, and children who work in the
fields of this country full rights and protections.
PMID- 25589369
TI - Quantifying the costs and benefits of occupational health and safety
interventions at a Bangladesh shipbuilding company.
AB - BACKGROUND: This study is the first cost-benefit analysis (CBA) of occupational
health and safety (OHS) in a low-income country. It focuses on one of the largest
shipbuilding companies in Bangladesh, where globally recognised Occupational
Health and Safety Advisory Services (OHSAS) 18001 certification was achieved in
2012. OBJECTIVES: The study examines the relative costs of implementing OHS
measures against qualitative and quantifiable benefits of implementation in order
to determine whether OHSAS measures are economically advantageous. METHODS:
Quantifying past costs and benefits and discounting future ones, this study looks
at the returns of OHS measures at Western Marine Shipbuilding Company Ltd.
RESULTS: Costs included investments in workplace and environmental safety, a new
clinic that also serves the community, and personal protective equipment (PPE)
and training. The results are impressive: previously high injury statistics
dropped to close to zero. CONCLUSIONS: OHS measures decrease injuries, increase
efficiency, and bring income security to workers' families. Certification has
proven a competitive edge for the shipyard, resulting in access to greater
markets. Intangible benefits such as trust, motivation and security are deemed
crucial in the CBA, and this study finds the high investments made are difficult
to offset with quantifiable benefits alone.
PMID- 25589371
TI - Maternal Functioning Differences Based on ADHD Subtype.
AB - OBJECTIVE: Maternal functioning differences in parenting stress, parental
efficacy, and parenting behaviors were examined for mothers of children with
ADHD. METHOD: Participants included 29 mothers of children with ADHD,
Predominantly Inattentive Type (ADHD-I) and 38 mothers of children with ADHD,
Predominantly Hyperactive-Impulsive or Combined Type (ADHD-HI/C). RESULTS:
Findings suggest that mothers of children with ADHD-HI/C reported significantly
greater parenting stress and engaged in more negative parenting behaviors than
mothers of children with ADHD-I. CONCLUSION: This study suggests that tailoring
behavioral parent training based on ADHD subtype may be particularly helpful for
parents of children with ADHD-HI/C.
PMID- 25589370
TI - Isoprenoid geranylgeraniol: the influence on cell characteristics of endothelial
progenitor cells after bisphosphonate therapy in vitro.
AB - OBJECTIVES: Geranylgeraniol (GGOH) has been reported as a potential treatment
option for bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ). The aim
of this study was to analyze the effects of GGOH on endothelial progenitor cells
(EPC) after bisphosphonate treatment in vitro. MATERIALS AND METHODS: EPC were
incubated with different nitrogen (N-BPs: ibandronate, pamidronate, zoledronate)
and a non-nitrogen-containing bisphosphonates (NN-BP: clodronate) with and
without GGOH. Cell viability was measured by MTT and PrestoBlue assay. Migration
ability was analyzed with a Boyden and Scratch assay. Apoptosis rates were
determined by colony-forming, Tunel and ToxiLight assays. RESULTS: Negative
effects of N-BPs on EPC were shown in all tests without GGOH. The substitution of
GGOH demonstrated significantly increased cell viability (MTT: p each N-BP
<=0.004; PrestoBlue: p each N-BP <0.001) and migration ability (Boyden: p each N
BP <0.001; Scratch: p each N-BP <0.001). Concerning the apoptosis rates,
increased EPC colony densities (p each N-BP <=0.009), decreased numbers of
apoptotic cells in the Tunel assay (p each N-BP <0.001), and a decreased
adenylate kinase release in the ToxiLight assay (p each N-BP <=0.03) were
observed. For the clodronate-treated cells, no significant differences could be
detected with or without GGOH in any assay (p each N-BP/NN-BP >0.05).
CONCLUSIONS: GGOH cell treatment reversed the negative effects of bisphosphonates
on EPC. CLINICAL RELEVANCE: These findings support the hypothesis that systemic
or local GGOH treatment might lead to new therapeutic strategies for BP-ONJ.
PMID- 25589372
TI - Evaluation of Cartilage Repair by Mesenchymal Stem Cells Seeded on a PEOT/PBT
Scaffold in an Osteochondral Defect.
AB - The main objective of this study was to evaluate the effectiveness of a
mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene
terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral
defect using a rabbit model. Material characterisation using scanning electron
microscopy indicated that the scaffold had a 3D architecture characteristic of
the additive manufacturing fabrication method, with a strut diameter of 296 +/-
52 MUm and a pore size of 512 +/- 22 MUm * 476 +/- 25 MUm * 180 +/- 30 MUm. In
vitro optimisation revealed that the scaffold did not generate an adverse cell
response, optimal cell loading conditions were achieved using 50 MUg/ml
fibronectin and a cell seeding density of 25 * 10(6) cells/ml and
glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of
TGFbeta3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted
in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects
employed as controls. On examination of toluidine blue staining for
chondrogenesis and GAG accumulation, both the empty defect and the cell-seeded
scaffold appeared to promote repair. However, the empty defect and the cell-free
scaffold stained positive for collagen type I or fibrocartilage, while the cell
seeded scaffold stained positive for collagen type II indicative of hyaline
cartilage and was statistically better than the cell-free scaffold in the blinded
histological evaluation. In summary, MSCs in combination with a 3D PEOT/PBT
scaffold created a reparative environment for cartilage repair.
PMID- 25589373
TI - The Changes of Trunk Motion Rhythm and Spinal Loading During Trunk Flexion and
Extension Motions Caused by Lumbar Muscle Fatigue.
AB - Previous studies indicated that lumbar extensor muscle fatigue could potentially
affect lumbar-pelvic rhythm and influence spinal loading during trunk motions. In
this study, the effects of lumbar extensor muscle fatigue on the normalized
lumbar-pelvic rotation rhythm and the associated L5/S1 joint loading during
weight lifting and lowering tasks were investigated. Thirteen volunteers
performed lifting and lowering of a 20-lbs box both before and after lumbar
extensor muscle fatigue, which was generated through a static weight holding
task. The normalized lumbar-pelvic motion ratio (L/P ratio) and the external
moment on the L5/S1 joint were calculated and compared. Results showed that
subjects demonstrated significantly larger normalized L/P ratios during both
weight lifting and lowering tasks with the influence of fatigue. In addition,
although the spinal loadings remain unchanged at the beginning and ending of both
lifting and lowering motions, significantly larger L5/S1 joint moments were
observed during both motions after fatigue. Such changes indicate potentially
elevated risk of back injury. In a clinical setting, the current results
demonstrated that lumbar muscle fatigue could cause transient changes in lumbar
pelvic motion rhythm. Therefore, lumbar muscle fatigue must be avoided when using
lumbar-pelvic motion rhythms for patient diagnosis or rehabilitation assessment.
PMID- 25589374
TI - An In Vitro Evaluation of Emboli Trajectories Within a Three-Dimensional Physical
Model of the Circle of Willis Under Cerebral Blood Flow Conditions.
AB - In vitro simulations of the trajectory and lodgement locations of emboli within
the circle of Willis (CoW) are crucial in understanding the associated
hemodynamic effects in stroke patients. A clot was fabricated from the hemolymph
of a crustacean species. Clots were injected into the internal carotid artery via
a cerebral flow facility housing a manufactured CoW human model. The trajectory
of the clot was tracked and its hemodynamic effects monitored. The clots traveled
with an average velocity of 88 mm/s along the ipsilateral side with momentary
pauses along high curvature regions before finally lodging within the distal
branches of the ipsilateral middle cerebral artery (MCA). These clots either
elongated along the branching vessels or compressed against a bifurcation point.
A blocked M1-segment of the MCA reduced the efferent blood pressure and flow
rates by (15-77%) and (20-100%) respectively with a re-distribution of the flow
towards the other efferent vessels. Mimicking blood clots with crustacean
hemolymph provides a much lower biohazard risk than using human or mammalian
blood clots and a superior alternative to synthetic materials. The geometry of
the distal MCA vasculature will determine the end morphology of the lodged clot.
Clotting severely reduces the distal flow rates and pressures.
PMID- 25589375
TI - Tap density equations of granular powders based on the rate process theory and
the free volume concept.
AB - The tap density of a granular powder is often linked to the flowability via the
Carr index that measures how tight a powder can be packed, under an assumption
that more easily packed powders usually flow poorly. Understanding how particles
are packed is important for revealing why a powder flows better than others.
There are two types of empirical equations that were proposed to fit the
experimental data of packing fractions vs. numbers of taps in the literature: the
inverse logarithmic and the stretched exponential. Using the rate process theory
and the free volume concept under the assumption that particles will obey similar
thermodynamic laws during the tapping process if the "granular temperature" is
defined in a different way, we obtain the tap density equations, and they are
reducible to the two empirical equations currently widely used in literature. Our
equations could potentially fit experimental data better with an additional
adjustable parameter. The tapping amplitude and frequency, the weight of the
granular materials, and the environmental temperature are grouped into this
parameter that weighs the pace of the packing process. The current results, in
conjunction with our previous findings, may imply that both "dry" (granular) and
"wet" (colloidal and polymeric) particle systems are governed by the same
physical mechanisms in term of the role of the free volume and how particles
behave (a rate controlled process).
PMID- 25589376
TI - Risk aversion, time preference and health production: theory and empirical
evidence from Cambodia.
AB - This paper quantifies the relationship between risk aversion and discount rates
on the one hand and height and weight on the other. It studies this link in the
context of poor households in Cambodia. Evidence is based on an original dataset
that contains both experimental measures of risk taking and impatience along with
anthropometric measurements of children and adults. The aim of the paper is to
(i) explore the importance of risk and time preferences in explaining
undernutrition and (ii) compare the evidence stemming from poor households to
strikingly similar findings from industrialized countries. It uses an inter
generational approach to explain observed correlations in adults and children
that is inspired by the height premium on labor markets. Parents can invest in
the health capital of their child to increase future earnings and their
consumption when old: better nutrition during infancy translates into better
human capital and better wages, and ultimately better financial means to take
care of elderly parents. However this investment is subject to considerable
uncertainty, since parents neither perfectly foresee economic conditions when the
child starts earning nor fully observe the ability to transform nutritional
investments into long-term health capital. As a result, risk taking households
have taller and heavier children. Conversely, impatience does not affect child
health. In the case of adults, only weight and the body mass index (BMI), but not
height, are positively and moderately correlated with risk taking and impatience.
PMID- 25589377
TI - Many cancer deaths could be eliminated by greater awareness and access to latest
treatments, report says.
PMID- 25589378
TI - Major depressive episodes over the course of 7 years and hippocampal subfield
volumes at 7 tesla MRI: the PREDICT-MR study.
AB - INTRODUCTION: Smaller hippocampal volumes have been associated with major
depressive disorder (MDD). The hippocampus consists of several subfields that may
be differentially related to MDD. We investigated the association of occurrence
of major depressive episodes (MDEs), assessed five times over seven years, with
hippocampal subfield and entorhinal cortex volumes at 7 tesla MRI. METHODS: In
this prospective study of randomly selected general practice attendees, MDEs
according to DSM-IV-R criteria were assessed at baseline and after 6, 12, 39 and
84 months follow-up. At the last follow-up, a T2 (0.7 mm(3)) 7 tesla MRI scan was
obtained in 47 participants (60+/-10 years). The subiculum, cornu ammonis (CA) 1
to 3, dentate gyrus&CA4 and entorhinal cortex volumes were manually segmented
according a published protocol. RESULTS: Of the 47 participants, 13 had one MDE
and 5 had multiple MDEs. ANCOVAs, adjusted for age, sex, education and
intracranial volume, revealed no significant differences in hippocampal subfield
or entorhinal cortex volumes between participants with and without an MDE in the
preceding 84 months. Multiple episodes were associated with smaller subiculum
volumes (B=-0.03 mL/episode; 95% CI -0.06; -0.003), but not with the other
hippocampal subfield volumes, entorhinal cortex, or total hippocampal volume.
LIMITATIONS: A limitation of this study is the small sample size which makes
replication necessary. CONCLUSIONS: In this exploratory study, we found that an
increasing number of major depressive episodes was associated with smaller
subiculum volumes in middle-aged and older persons, but not with smaller volumes
in other hippocampal subfields or the entorhinal cortex.
PMID- 25589379
TI - New BPD predicts lung function at school age: Follow-up study and meta-analysis.
AB - New treatment practices have improved survival of preterm infants and decreased
airway pathology in bronchopulmonary dysplasia (BPD). Our aim was to investigate
whether preterm birth, BPD, and the severity of BPD predict lung function in
school children that are born in surfactant era. We studied pulmonary function of
88 school-aged children born very preterm (gestational age <32 weeks) and paired
them with 88 age- and sex-matched controls born at term. Spirometry and diffusion
capacity were recorded. We also performed a meta-analysis covering the era of
antenatal corticosteroid and surfactant treatment. BPD was defined as oxygen
dependence for >= 28 days and it was severity-graded by oxygen requirement at 36
weeks postmenstrual age (mild, none; moderate, FiO2 = 0.22-0.29; severe, FiO2 >=
0.30). Preterm children had lower forced expiratory volume in 1 sec (FEV1 ) 86.4
+/- 11.8 versus 94.9 +/- 10.1 (mean % predicted +/- SD; P < 0.001), and lower
diffusion capacity (DLCO) 87.6 +/- 13.9 versus 93.7 +/- 12.0 (P = 0.005) compared
with term controls. BPD group differed in both FEV1 (P = 0.037) and DLCO (P =
0.018) from those without BPD. For meta-analysis, search identified 210 articles.
Together with present results, six articles met the inclusion criteria. FEV1 of
no BPD, all BPD, and moderate to severe BPD groups differed from that in term
controls by -7.4, -10.5, and -17.8%, respectively. According to meta-analysis and
follow-up study, the adverse effects of prematurity on pulmonary function are
still detectable in school-age. BPD was associated with reductions in both
diffusion capacity and spirometry. New interventions are required to document a
further decrease in the life-long consequences of prematurity.
PMID- 25589382
TI - Fullerene-ionic-liquid conjugates: a new class of hybrid materials with
unprecedented properties.
AB - A modular approach has been followed for the synthesis of a series of fullerene
ionic-liquid (IL) hybrids in which the number of IL moieties (two or twelve),
anion, and cation have been varied. The combination of C60 and IL give rise to
new unique properties in the conjugates such as solubility in water, which was
higher than 800 mg mL(-1) in several cases. In addition, one of the C60 -IL
hybrids has been employed for the immobilization of palladium nanoparticles
through ion exchange followed by reduction with sodium borohydride. Surprisingly,
during the reduction several carbon nanostructures were formed that comprised
nano-onions and nanocages with few-layer graphene sidewalls, which have been
characterized by means of thermogravimetric analysis (TGA), X-ray photoelectron
spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy/energy
dispersive X-ray analysis (SEM-EDAX), and high-resolution transmission electron
microscopy (HRTEM). Finally, the material thus obtained was successfully applied
as catalyst in Suzuki and Mizoroki-Heck reactions in a concentration of just 0.2
mol %. In the former process it was recyclable for five runs with no loss in
activity.
PMID- 25589381
TI - Supplanting ecosystem services provided by scavengers raises greenhouse gas
emissions.
AB - Global warming due to human-induced increments in atmospheric concentrations of
greenhouse gases (GHG) is one of the most debated topics among environmentalists
and politicians worldwide. In this paper we assess a novel source of GHG
emissions emerged following a controversial policy decision. After the outbreak
of bovine spongiform encephalopathy in Europe, the sanitary regulation required
that livestock carcasses were collected from farms and transformed or destroyed
in authorised plants, contradicting not only the obligations of member states to
conserve scavenger species but also generating unprecedented GHG emission.
However, how much of this emission could be prevented in the return to
traditional and natural scenario in which scavengers freely remove livestock
carcasses is largely unknown. Here we show that, in Spain (home of 95% of
European vultures), supplanting the natural removal of dead extensive livestock
by scavengers with carcass collection and transport to intermediate and
processing plants meant the emission of 77,344 metric tons of CO2 eq. to the
atmosphere per year, in addition to annual payments of ca. $50 million to
insurance companies. Thus, replacing the ecosystem services provided by
scavengers has not only conservation costs, but also important and unnecessary
environmental and economic costs.
PMID- 25589380
TI - Novel interventions to prevent HIV and HCV among persons who inject drugs.
AB - Persons who inject drugs (PWID) are at high risk for infection with and poor
outcomes from HIV and hepatitis C virus (HCV). Well-established interventions for
HIV/HCV prevention among PWID include syringe access, opioid agonist maintenance
treatment, and supervised injection facilities, yet these interventions remain
unavailable or inadequately resourced in much of the world. We review recent
literature on biomedical and behavioral interventions to reduce the burden of
HIV/HCV among PWID, with an emphasis on randomized controlled trials and quasi
experimental studies. Since 2013, there have been significant advancements in
utilizing antiviral therapy and behavioral interventions for prevention among
PWID, including approaches that address the unique needs of couples and sex
workers. In addition, there have been significant developments in
pharmacotherapies for substance use and the implementation of naloxone for opioid
overdose prevention. Notwithstanding multiple ongoing structural challenges in
delivering HIV/HCV prevention interventions to PWID, these emerging and
rigorously evaluated interventions expand possibilities for prevention among
PWID.
PMID- 25589384
TI - Immunotherapy of melanoma: present options and future promises.
AB - Metastatic melanoma is notorious for its immune evasion and resistance to
conventional chemotherapy. The recent success of ipilimumab, a human monoclonal
antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in
increasing the median survival time and stabilizing the disease progression
renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose
interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment
of patients with unresectable advanced melanoma, and pegylated interferon-alpha2b
(p-IFN-alpha2b) is approved as an adjuvant for the treatment of patients with
surgically resected high-risk melanoma. The present review describes the
currently approved immune-modulators and the promising immune-based interventions
that are currently in clinical trials. We present the four commonly used
strategies to boost immune responses against the tumors; monoclonal antibodies,
cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists
of ongoing clinical trials include details of the trial phase, target patients,
intervention details, status of the study, and expected date of completion.
Further, our review discusses the challenges faced by immunotherapy and the
various strategies adopted to overcome them.
PMID- 25589383
TI - Determination of N-acetylglucosamine in cosmetic formulations and skin test
samples by hydrophilic interaction liquid chromatography and UV detection.
AB - N-Acetylglucosamine is an ingredient in pharmaceuticals, nutritional supplements
and in cosmetics. N-Acetylglucosamine in cosmetics is expected to improve skin
hydration, reparation, and to contribute as anti-wrinkle agent. This study
reports on the validation and application of an HPLC method based on HILIC and UV
detection for determining N-acetylglucosamine in cosmetics and in samples
obtained after testing the skin exposed to cosmetics formulations. The
chromatographic column used is a ZIC((r))-pHILIC (150 mm * 4.6 mm, 5 MUm particle
size) on which a mobile phase containing acetonitrile-aqueous KH2PO4 (70:30, v/v)
15 mM was applied in isocratic elution mode injecting 20 MUl of sample at 0.5
ml/min constant flow-rate and 10+/-1 degrees C column temperature. Under these
conditions the total run time was 10 min and N-acetylglucosamine eluted baseline
separated from all other compounds in the samples. Calibration in the range from
40 to 80 MUg/ml allowed to assess the method linearity (R(2)>0.999) in a
concentration range corresponding to about 50% to 120% of the expected levels of
N-acetylglucosamine in the formulations. Precision expressed by RSD% was always
better than 2% in intra-day and inter-day assays of authentic samples. Accuracy
was in all cases within 95-105% of the expected concentration value in
formulations containing N-acetylglucosamine. The sensitivity of the method was at
the level of 10 MUg/ml as limit of detection, and at 40 MUg/ml as limit of
quantitation. The application of the method to formulations containing solid
lipid nanoparticles documents its usefulness in cosmetic quality control. The
results witness that the method is also suitable for the determination of N
acetylglucosamine in samples obtained from skin test strips.
PMID- 25589385
TI - Quantitative MRI T2 relaxation time evaluation of knee cartilage: comparison of
meniscus-intact and -injured knees after anterior cruciate ligament
reconstruction.
AB - BACKGROUND: Associated meniscal injury is well recognized at anterior cruciate
ligament (ACL) reconstruction, and it is a known risk factor for osteoarthritis.
PURPOSE: To evaluate and characterize the postoperative appearance of articular
cartilage after different meniscal treatment in ACL-reconstructed knees using T2
relaxation time evaluation on MRI. STUDY DESIGN: Cohort study; Level of evidence,
3. METHODS: A total of 62 consecutive patients who under ACL reconstruction were
recruited in this study, including 23 patients undergoing partial meniscectomy
(MS group), 21 patients undergoing meniscal repair (MR group), and 18 patients
with intact menisci (MI group) at time of surgery. Clinical evaluation, including
subjective functional scores and physical examination, was performed on the same
day as the MRI examination and at follow-up times ranging from 2 to 4.2 years.
The MRI multiecho sagittal images were segmented to determine the T2 relaxation
time value of each meniscus and articular cartilage plate. Differences in each
measurement were compared among groups. RESULTS: No patient had joint-line
tenderness or reported pain or clicking on McMurray test or instability. There
were also no statistically significant differences in functional scores or medial
or lateral meniscus T2 values among the 3 groups (P > .05 for both). There was a
significantly higher articular cartilage T2 value in the medial femorotibial
articular cartilage for the MS group (P < .01) and the MR group (P < .05)
compared with that of the MI group, while there was no significant difference in
articular cartilage T2 value between the MS and MR groups (P > .05) in each
articular cartilage plate. The medial tibial articular cartilage T2 value had a
significant positive correlation with medial meniscus T2 value (r = 0.287; P =
.024) CONCLUSION: This study demonstrates that knees with meniscectomy or
meniscal repair had articular cartilage degeneration at 2 to 4 years
postoperatively, with higher articular cartilage T2 relaxation time values
compared with the knees with an intact meniscus.
PMID- 25589386
TI - Effect of lateral meniscal root tear on the stability of the anterior cruciate
ligament-deficient knee.
AB - BACKGROUND: Meniscal root tears are an increasingly recognized subset of meniscal
injury. The menisci are critical secondary stabilizers of the anterior cruciate
ligament (ACL). The kinematic effect of lateral meniscus posterior root tear in
the setting of ACL injury is not known. PURPOSE/HYPOTHESIS: The purpose of this
study was to determine the effect of tear of the lateral meniscal root on
stability of the ACL-deficient knee. The hypothesis was that disruption of the
lateral meniscal root will further destabilize the ACL-deficient knee during a
simulated pivot shift. STUDY DESIGN: Controlled laboratory study. METHODS: Pivot
shift testing of 8 fresh-frozen cadaveric knees was performed after attachment of
photoreflective flags and preparation of CT scans. Each knee was mounted in a
custom activity simulator and dynamically loaded from 15 degrees to 90 degrees
of flexion with all the permutations of the following: iliotibial band force (50,
75, 100, 125, 150, and 175 N), internal rotation moments (1, 2, and 3 N.m), and
valgus moments (5 and 7 N.m). In addition, anterior stability tests were
performed by applying a 90-N anterior force to the tibia at flexion angles of 15
degrees , 30 degrees , 45 degrees , 60 degrees , and 90 degrees . During each
test, the anterior tibial translation and rotation of the tibia were measured
with a high-resolution multiple infrared camera motion analysis system for the
following 3 conditions: ACL-intact (ACL-I), ACL-deficient (ACL-D), and ACL
deficient/lateral meniscal posterior root avulsion (ACL-D/LMR-A). RESULTS: A
pivot-shift phenomenon was observed in the ACL-D and ACL-D/LMR-A conditions. The
mean tibial translation of the lateral tibial condyle during the pivot-shift
maneuver was 2.62 +/- 0.53 mm for the ACL-I knees, 6.01 +/- 0.51 mm for the ACL-D
knees (P value vs. intact: .0005), and 8.13 +/- 0.75 mm for the ACL-D/LMR-A knees
(P value vs intact: <.0001). During the pivot-shift maneuver, translation was
significantly increased in the ACL-D/LMR-A condition compared with the ACL-D
condition (P = .0146). Compared with the intact group, anterior tibial
translation during the Lachman maneuver also increased at 30 degrees and 90
degrees of flexion in the ACL-D group (P < .0001) and the ACL-D/LM group (P <
.0001). No statistically significant difference was found between the ACL-D and
ACL-D/LMR-A groups during the Lachman maneuver at 30 degrees and 90 degrees (P
= .16 and .72, respectively). CONCLUSION: A tear of the lateral meniscal
posterior root further reduces the stability of the ACL-deficient knee during
rotational loading. CLINICAL RELEVANCE: This study shows that lateral meniscal
root injury further destabilizes the ACL-deficient knee and thus advances the
concept that the lateral meniscus is a secondary stabilizer of the knee under
pivot-shift loading. In the absence of stronger evidence, the study data suggest
a rationale for surgical repair of lateral meniscal root tears encountered in the
setting of ACL tears.
PMID- 25589387
TI - Conformational preferences of 3,4-dihydroxyphenylacetic acid (DOPAC).
AB - The conformational space of 3,4-dihydroxyphenylacetic acid (DOPAC), an important
dopamine metabolite, has been investigated by quantum chemical methods (B3LYP and
MP2, with the 6-311++G(d,p) basis set) and matrix-isolation infrared
spectroscopy. Detailed analysis of the calculated potential energy surfaces of
the molecule led to identification of thirteen unique conformers, all of them
showing the acetic acid side chain out of the aromatic ring plane by 60-95
degrees . According to the calculated Gibbs energies, the five lowest energy
conformers make up 99.7% of the conformational mixture at 298.15K, exhibiting
individual populations falling between 16% and 24%. The main conformational
trends of this molecule were interpreted on the grounds of a thorough analysis of
the structural parameters and by the application of the Natural Bond Orbital
theory. The role of the intramolecular interactions on the relative stability and
structure of the conformers was also investigated. The infrared spectrum of DOPAC
was registered after isolation of its monomers in argon and xenon matrices. Only
one of DOPAC forms populated in the gas phase could be trapped in both matrix
gases. This result is in agreement with the predicted low energy barriers for
conformational isomerization and is also supported by annealing experiments. The
spectra of matrix-isolated model compounds, phenylacetic acid and catechol, were
studied under the same experimental conditions. These data were used as
references and assisted in the interpretation of the results obtained for DOPAC.
PMID- 25589388
TI - Spectroscopic studies and quantum chemical investigations of (3,4
dimethoxybenzylidene) propanedinitrile.
AB - The Fourier Transform Infrared (FTIR), Ultra-Violet Visible (UV-Vis) spectroscopy
and Thermogravimetric (TG) analysis of (3,4-dimethoxybenzylidene)
propanedinitrile have been carried out and investigated using quantum chemical
calculations. The molecular geometry, harmonic vibrational frequencies, Mulliken
charges, natural atomic charges and thermodynamic properties in the ground state
have been investigated by using Hartree Fock Theory (HF) and Density Functional
Theory (DFT) using B3LYP functional with 6-311G(d,p) basis set. Both HF and DFT
methods yield good agreement with the experimental data. Vibrational modes are
assigned with the help of Vibrational Energy Distribution Analysis (VEDA)
program. UV-Visible spectrum was recorded in the spectral range of 190-800nm and
the results are compared with the calculated values using TD-DFT approach.
Stability of the molecule arising from hyperconjugative interactions, charge
delocalization have been analyzed using natural bond orbital (NBO) analysis. The
results obtained from the studies of Highest Occupied Molecular Orbital (HOMO)
and Lowest Unoccupied Molecular Orbital (LUMO) are used to calculate molecular
parameters like ionization potential, electron affinity, global hardness,
electron chemical potential and global electrophilicity.
PMID- 25589389
TI - Reactivity and molecular modeling of new solvatochromic mixed-ligand copper(II)
chelates of 2-acetylbutyrolactone and dinitrogen bases.
AB - A new series of solvatochromic mononuclear mixed ligand chelates with the general
formula: Cu(AcBL)(L)X; where AcBL=2-acetylbutyrolactonate, L=N,N,N',N'
tetramethylethylenediamine (Me4en), N,N,N',N'-tetramethylpropylene diamine
(Me4pn), 1,10-phenanthroline (Phen) or 2,2'-bipyridyl (Bipy) and X=ClO4-, NO3- or
Br- have been synthesized and characterized by the analytical and spectral
methods, as well as magnetic and molar conductance measurements. The d-d
absorption bands of Me4en-chelates as Nujol mulls or weak donor solvents
solutions revealed square-planar, distorted octahedral and/or distorted trigonal
bipyramid geometries for the perchlorate, nitrate and bromide chelates,
respectively. However, an octahedral structure is identified for chelates in
strong donor solvents. Perchlorate chelates show a remarkable color change from
violet to green as the Lewis basicity of the donor solvent increases, whereas
bromide chelates are mainly affected by the Lewis acidity of solvent. Specific
and non-specific interactions of solvent molecules with the chelates were
investigated on the basis of unified solvation model. Structural parameters of
the free ligands and their Cu(II)-chelates have been calculated on the basis of
semiempirical PM3 level and correlated with the experimental data.
PMID- 25589390
TI - Quantum chemical calculation (electronic and topologic) and experimental (FT-IR,
FT-Raman and UV) analysis of isonicotinic acid N-oxide.
AB - In this work, the molecular conformation, vibrational and electronic analysis of
isonicotinic acid N-oxide (iso-NANO) were presented in the ground state using
experimental techniques (FT-IR, FT-Raman and UV) and density functional theory
(DFT) employing B3LYP exchange correlation with the 6-311++G(d,p) basis set. The
geometry optimization and energies associated possible two conformers (Rot-I and
Rot-II) were computed. The 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 and
PQS program. The obtained structures were analyzed with the Atoms in Molecules
(AIMs) methodology. The computational results diagnose the most stable conformer
of iso-NANO as the Rot-I form. Total density of state (TDOS) and partial density
of state (PDOS) and also overlap population density of state (OPDOS) diagrams
analysis for the most stable conformer (Rot-I) were calculated using the same
method. Thermodynamic properties (heat capacity, entropy and enthalpy) of the
title compound at different temperatures were calculated. As a result, the
optimized geometry and calculated spectroscopic data show a good agreement with
the experimental results.
PMID- 25589391
TI - Infra-red spectroscopic characteristics of naphthalocyanine in
bis(naphthalocyaninato) rare earth complexes peripherally substituted with
thiophenyl derivatives.
AB - The infra-red (IR) spectroscopic data for a series of eleven rare earth double
deckers MIII[Nc(SPh)8]2 (M=Y, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho and Er) have
been collected and systematically investigated. For MIII[Nc(SPh)8]2, typical IR
marker bands for the naphthalocyanine anion radical [Nc(SPh)8].- were observed at
1317-1325 cm(-1) as the most intense absorption bands, which can be attributed to
the pyrrole stretching. As for Ce[Nc(SPh)8]2, the typical IR marker band was also
observed at 1317 cm(-1), which shows that the cerium complex exists as the form
of CeIII[Nc(SPh)8]2-[Nc(SPh)8].-. In addition, both the Q-bands of electronic
absorption spectra and the typical IR absorption bands of naphthalocyanine
radical anion [Nc(SPh)8].- move to the high energy as the decrease of rare earth
metal ionic radius. These facts suggest that the pi-pi electron interaction in
these double-deckers becomes stronger along with the lanthanide contraction.
PMID- 25589392
TI - Temperature-related degradation and colour changes of historic paintings
containing vivianite.
AB - Temperature-related degradation of pure synthetic as well as partly oxidised
natural vivianite has been studied by high-temperature X-ray diffraction (HT-XRD)
covering the whole extent of the temperature-related stability of its structure.
While temperatures around 70 degrees C are already damaging to vivianite,
exposition to 160 degrees C results in complete amorphisation of both the
vivianite and its oxidation products. As indicated by Mossbauer spectroscopy,
temperature-induced oxidation of vivianite starts at 90 degrees C. To study the
occurring structural as well as accompanying colour changes in more detail, model
vivianite paint layer samples with different historic binders were prepared and
subjected to increased temperatures. Exposition to 80 degrees C caused pronounced
colour changes of all the samples: ground natural blue vivianite became grey--a
colour change which has been described in actual works of art. Regarding the
binders, the oil seemed to facilitate the transfer of heat to vivianite's grains.
To simulate conditions of conservation treatment under which the painting is
exposed to increased temperatures, oil-on-canvas mock-ups with vivianite were
prepared and relined in a traditional way using iron. The treatment affected
preferentially larger grains of vivianite; the micro-samples documented their
change to grey, and their Raman spectra showed the change from vivianite to
metavivianite.
PMID- 25589393
TI - Polymer complexes. LX. Supramolecular coordination and structures of N(4
(acrylamido)-2-hydroxybenzoic acid) polymer complexes.
AB - A number of novel polymer complexes of various anions of copper(II), cobalt(II),
nickel(II) and uranyl(II) with N(4-(acrylamido)-2-hydroxy benzoic acid) (ABH)
have been synthesized and characterized by elemental analysis, IR, 1H NMR,
magnetic susceptibility measurements, electronic spin resonance, vibrational
spectra and thermal analysis. The molecular structures of the ligand are
optimized theoretically and the quantum chemical parameters are calculated.
Tentative structures for the polymeric metal complexes due to their potential
application are also suggested. The IR data exhibit the coordination of
ONO2/OAc/SO4 with the metal ions in the polymeric metal complex. Vibrational
spectra indicate coordination of carboxylate oxygen and phenolic OH of the ligand
giving a MO4 square planar chromophore. Ligand field ESR spectra support square
planar geometry around Cu(II). The thermal decomposition of the polymer complexes
were discussed in relation to structure, and the thermodynamic parameters of the
decomposition stages were evaluated applying Coast-Redfern and Horowitz-Metzger
methods.
PMID- 25589394
TI - Application of spectroscopic methods for identification (FT-IR, Raman
spectroscopy) and determination (UV, EPR) of quercetin-3-O-rutinoside.
Experimental and DFT based approach.
AB - Vibrational (FT-IR, Raman) and electronic (UV, EPR) spectral measurements were
performed for an analysis of rutin (quercetin-3-O-rutinoside) obtained from
Rutaofficinalis. The identification of rutin was done with the use of FT-IR and
Raman spectra. Those experimental spectra were determined with the support of
theoretical calculations based on a DFT method with the B3LYP hybrid functional
and 6-31G(d,p) basis set. The application of UV and EPR spectra was found to be a
suitable analytical approach to the evaluation of changes in rutin exposed to
certain physicochemical factors. Differences in absorbance observed in direct UV
spectra were used to monitor changes in the concentration of rutin in degraded
samples. Spectra of electron paramagnetic resonance allowed studying the process
of free-radical quenching in rutin following its exposure to light. The molecular
electrostatic potential (MEP) and frontier molecular orbitals (LUMO-HOMO) were
also determined in order to predict structural changes and reactive sites in
rutin.
PMID- 25589395
TI - beta-Hydroxy-alpha-naphthaldehyde [2-(quinolin-8'-yloxy) acetyl] hydrazone as an
efficient fluorescent chemosensor for Mg2+.
AB - An efficient fluorescent sensor based on beta-hydroxy-alpha-naphthaldehyde [2
(quinolin-8'-yloxy) acetyl] hydrazone (HL) for Mg2+ has been designed and
synthesized. The receptor showed "off-on" fluorescent responses toward Mg2+ in
acetonitrile. The reasons for this phenomenon is that the addition of Mg2+ to the
solution of HL induce the formation of a 1:1 ligand-metal complex which inhibit
excited-state intramolecular proton transfer (ESIPT).
PMID- 25589396
TI - Investigation on growth, structure and characterization of succinate salt of 8
hydroxyquinoline: an organic NLO crystal.
AB - 8-Hydroxyquinolinium succinate (8-HQSU) has been synthesized and single crystals
were grown from ethanol solvent by employing the technique of slow evaporation at
room temperature. The structure of the grown crystal has been elucidated by
single crystal X-ray diffraction analysis. It reveals that 8-HQSU crystallizes in
monoclinic system with non-centro symmetric space group P2(1). FTIR, 1H and 13C
NMR spectral investigations have been carried out to identify the vibrational
modes of various functional groups and placement of proton and carbon in the 8
HQSU compound, respectively. UV-vis-NIR transmission spectrum shows the cutoff
wavelength around 357 nm. In addition, a photoluminescence spectral analysis was
carried out for 8-HQSU crystals. The thermal properties of crystals were
evaluated from TGA and DTA techniques and the crystal was found to be stable up
to 145 degrees C. The dielectric studies show that the dielectric constant and
dielectric loss decrease exponentially with frequency at different temperatures.
Photoconductivity studies were carried out on the grown crystals it reveals the
positive photo conducting nature. Powder second harmonic generation property of
the crystal was confirmed by Kurtz and Perry powder SHG technique and it is found
to be 1.3 times greater than that of KDP.
PMID- 25589398
TI - Recurrent pregnancy loss and obesity.
AB - Recurrent pregnancy loss (RPL) was defined as two or more miscarriages.
Antiphospholipid syndrome, uterine anomalies, and parental chromosomal
abnormalities, particularly translocation and abnormal embryonic karyotype, are
identifiable causes of RPL. Obesity may increase the risk of sporadic miscarriage
in pregnancies conceived spontaneously. Obesity with body mass index (BMI)>30
kg/m2 is an independent risk factor for further miscarriage with odds ratio 1.7
3.5 in patients with early RPL. Obesity is associated with euploid miscarriage.
Unexplained RPL with euploid embryo might be a common disease caused by both
polymorphisms of multiple susceptibility genes and lifestyle factors such as
women's age, obesity, and smoking. Patients with a history of RPL were found to
have a higher risk of cardiovascular disease, celiac disease, gastric ulcer,
gastritis, and atopic dermatitis. No study has examined the effect of weight loss
on the prevention of further miscarriage in patients with RPL.
PMID- 25589397
TI - Mutations in Bruton's tyrosine kinase impair IgA responses.
AB - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by
mutations in Bruton's tyrosine kinase (BTK), and is characterized by markedly
decreased numbers of blood B cells and an absence of all immunoglobulin isotypes.
We performed whole exome sequencing in a male pediatric patient with
dysgammaglobulinemia with IgA deficiency. Genetic analysis revealed a BTK
missense mutation (Thr316Ala). To investigate whether a BTK mutation underlay
this antibody deficiency with marked decrease of IgA in this patient, we
performed functional analyses of B cells and phagocytes, and molecular analyses
of somatic hypermutation and class switch recombination. The BTK missense
mutation resulted in B cells with reduced BTK and high IgM expression. Equal
proportions of CD19(low) and CD19(normal) fractions were observed, and both
included naive and memory B cells. Calcium influx and phospholipase Cgamma2
phosphorylation upon IgM stimulation were marginally impaired in CD19(low), but
not in CD19(+) B cells. Similar to XLA patients, IgA transcripts showed low SHM
levels, whereas IgG transcripts were hardly affected. Our analyses suggest that
the BTK mutation likely underlies the disease in this case, and that hypomorphic
BTK mutations can result in normal circulating B cell numbers, but specifically
impair IgA responses.
PMID- 25589399
TI - Reviews: Rapid! Rapid! Rapid! ...and systematic.
PMID- 25589401
TI - Erratum: Disease burden of pneumonia in Korean adults aged over 50 years
stratified by age and underlying diseases.
AB - [This corrects the article on p. 764 in vol. 29, PMID: 25378975.].
PMID- 25589403
TI - Increasing Epilepsy Awareness in Schools: A Seizure Smart Schools Project.
AB - A high prevalence of epilepsy diagnoses and seizure events among students was
identified at a large Midwestern school district. In partnership with the
Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was
conducted to provide education and resources to staff caring for school children
with seizures. School nurses (N = 26) were trained as seizure management
educators and instructed staff in 21 schools on seizure awareness and response.
School nurses utilized new seizure management resources, a procedural guideline,
and care plan updates. The majority of school nurses rated the resources and
training interventions as "very helpful." School nurse confidence in managing
students with seizures increased, seizure action plan use increased, and 88% of
children's records with new seizure diagnoses had completed documentation. School
nurses played vital roles in increasing seizure awareness as educators and care
managers. EFMN is using this project as an exemplar for expanding its Seizure
Smart Schools program.
PMID- 25589402
TI - Effect of silicone on the collagen fibrillogenesis and stability.
AB - Collagen, the most abundant protein in mammals, is able to form fibrils, which
have central role in tissue repair, fibrosis, and tumor invasion. As a component
of skin, tendons, and cartilages, this protein contacts with any implanted
materials. An inherent problem associated with implanted prostheses is their
propensity to be coated with host proteins shortly after implantation. Also,
silicone implants undergoing relatively long periods of contact with blood can
lead to formation of thrombi and emboli. In this paper, we demonstrate the
existence of interactions between siloxanes and collagen. Low-molecular-weight
cyclic siloxane (hexamethylcyclotrisiloxane-D3) and polydimethylsiloxanes (PDMS)
forming linear chains, ranging in viscosity from 20 to 12,000 cSt, were analyzed.
We show that D3 as well as short-chain PDMS interact with collagen, resulting in
a decrease in fibrillogenesis. However, loss of collagen native structure does
not occur because of these interactions. Rather, collagen seems to be sequestered
in its native form in an interlayer formed by collagen-siloxane complexes. On the
other hand, silicone molecules with longer chains (i.e., PDMS with viscosity of
1000 and 12,000 cSt, the highest viscosity analyzed here) demonstrate little
interaction with this protein and do not seem to affect collagen activity.
PMID- 25589405
TI - In reply to "impact of the psychiatry clerkship on medical student attitudes
towards psychiatry and to psychiatry as a career".
PMID- 25589404
TI - Remobilizing deleted piggyBac vector post-integration for transgene stability in
silkworm.
AB - Deletion of transposable elements post-genomic integration holds great promise
for stability of the transgene in the host genome and has an essential role for
the practical application of transgenic animals. In this study, a modified
piggyBac vector that mediated deletion of the transposon sequence post
integration for transgene stability in the economically important silkworm Bombyx
mori was constructed. The piggyBac vector architecture contains inversed terminal
repeat sequences L1, L2 and R1, which can form L1/R1 and L2/R1 types of
transposition cassettes. hsp70-PIG as the piggyBac transposase expression
cassette for initial transposition, further remobilization and transgene
stabilization test was transiently expressed in a helper vector or integrated
into the modified vector to produce a transgenic silkworm. Shortening L2
increased the transformation frequency of L1/R1 into the silkworm genome compared
to L2/R1. After the integration of L1/R1 into the genome, the remobilization of
L2/R1 impaired the transposon structure and the resulting transgene linked with
an impaired transposon was stable in the genome even in the presence of
exogenously introduced transposase, whereas those flanked by the intact
transposon were highly mobile in the genome. Our results demonstrated the
feasibility of post-integration deletion of transposable elements to guarantee
true transgene stabilization in silkworm. We suggest that the modified vector
will be a useful resource for studies of transgenic silkworms and other piggyBac
transformed organisms.
PMID- 25589406
TI - "I started to feel like a 'real doctor'": medical students' reflections on their
psychiatry clerkship.
AB - OBJECTIVE: Medical students' reflective journals can be a rich source for
understanding what students learn and think about during clinical rotations and
can offer educators and mentors insight into students' professional identity
formation. The aim of this paper is to ascertain, from reflective accounts,
students' development and reactions to psychiatry following their psychiatry
clerkship. METHOD: The patterns, recurrent categories, and themes in 100
psychiatry clerks' reflective journals were analyzed using grounded theory.
Constant comparative method was employed to identify and quantify emergent themes
and uncover relationships between these themes. RESULTS: The most common
"unprompted" themes that students reported were the recognition of the complexity
of the illness condition and the fact that the psychiatric patient does not exist
in a vacuum (52 %); an acknowledgement of one's respect for the struggle of
patients with mental illness (49 %); an expressed or demonstrated empathy for
patients (48 %); and a reduced skepticism of the biological basis of mental
illness and efficacy of treatments (46 %). CONCLUSION: Reflective exercises-along
with quality mentorship-can be used to understand students' experience with
clinical encounters, facilitate change, refine assumptions among students, and
promote critical self-assessment and personal growth.
PMID- 25589407
TI - Labour Market Status and Well-Being in the Context of Return to Work After
Vocational Rehabilitation in Germany.
AB - INTRODUCTION: Although there is much empirical evidence for a given relationship
between health and labour market status (LMS), the following study focuses on a
group for which little is known in the German context: people with disabilities
in vocational rehabilitation for the purpose of re-integration into the labour
market. In this specific context, the article analyses how a change in LMS
affects physical, mental and general health. METHODS: Using a panel survey, 857
people with disabilities in vocational rehabilitation and their subjective health
condition were observed between 2008 and 2010. To reduce bias due to unobserved
heterogeneity, fixed-effects panel regression is applied. RESULTS: Results show
that a move from non-employment to employment positively affects-particularly
general-subjective health. In addition to LMS, the level of occupational
limitation due to disability appears to be of particular relevance in estimating
health. Interacting both the level of occupational limitation and LMS reveals
that non-employed people reporting serious occupational limitation due to their
disability have the worst subjective health across all aspects. However, people
in employment experiencing similarly serious limitations due to their disability
do not differ much from this group. These may be regarded as having taken up
disability-inappropriate employment. CONCLUSION: The results suggest that re
integration into employment particularly improves several health aspects if
rehabilitants are integrated in an occupational environment where disability does
not present an occupational limitation. Thus, placement in disability-appropriate
employment needs to be particularly encouraged.
PMID- 25589409
TI - Novel ALD-assisted growth of ZnO nanorods on graphene and its Cu2ZnSn(S(x)Se(1
x))4 solar cell application.
AB - The hydrothermal growth of ZnO nanorods on graphene draws a specific interest for
the advantages of low-temperature processability over a large area and low cost,
but challenges still remain in directly growing uniform ZnO seed layers on
pristine graphene without impairing its beneficial properties. In this work, the
direct growth of ZnO seed layers on graphene via H2O-based atomic layer
deposition (ALD) has been investigated. It is found that uniform ZnO thin films
can be deposited on graphene via ALD using a combination of single-layer
graphene/Cu stacks as substrates and a facile pre-H2O treatment process. After
growing ZnO nanorods on graphene, its photovoltaic application in a Cu2ZnSn(SxSe1
x)4 (CZTSSe) solar cell is demonstrated. The performance of graphene-based cells
approaches that of ITO-based cells with similar architectures, highlighting that
graphene is a potential replacement for ITO in optoelectronic devices. The method
reported herein for fabricating ZnO nanorods on graphene using ALD-ZnO as seed
layers preserves its properties, and is thus applicable to a wide variety of
graphene-based nanoelectronic devices.
PMID- 25589410
TI - The impact of social deprivation on coronary revascularisation treatment outcomes
within the National Health Service in England and Wales.
AB - BACKGROUND: There is strong evidence to suggest that social deprivation is linked
to health inequalities. In the UK, concerns have been raised regarding
disparities in the outcomes of acute cardiac services within the National Health
Service (NHS). This study explored whether differences exist in (a) elective
hospital presentation time (b) indicators of severity and disease burden and (c)
treatment outcomes (hospital stay and mortality) on the basis of the index of
multiple deprivation (IMD) status. DESIGN: This study was a retrospective
analysis of data from NHS databases for 13,758 patients that had undergone
cardiac revascularisation interventions at the Liverpool Heart and Chest Hospital
between April 2007-March 2012. METHODS: The data was analysed by descriptive,
univariate and multivariate statistics to explore the association between the IMD
quintiles (Q1-Q5) and revascularisation type, elective presentation time,
hospital length of stay and mortality. RESULTS AND CONCLUSIONS: Univariate
analysis indicated that there were significant differences between patients from
the most deprived areas (Q5) compared with patients from the least deprived areas
(Q1), these included admission volumes, time before presentation to hospital and
proportion of non-elective cases. After risk-adjustments, percutaneous coronary
intervention patients from Q5 compared with Q1 had significantly greater length
of hospital stay and risk of in-hospital major acute cardiovascular events. After
multivariate adjustment for baseline risk factors, patients from Q5 were
associated with significantly worse five-year survival as compared with Q1
(hazard ratio (HR) 1.52, 95% confidence interval (CI): 1.36-1.71; p < 0.001). In
conclusion, there is evidence to suggest that inequalities in cardiac
revascularisation choices and outcomes in the UK may be associated with social
deprivation.
PMID- 25589408
TI - Methodological advances: the unsung heroes of the GPCR structural revolution.
AB - G protein-coupled receptors (GPCRs) are intricately involved in a diverse array
of physiological processes and pathophysiological conditions. They constitute the
largest class of drug target in the human genome, which highlights the importance
of understanding the molecular basis of their activation, downstream signalling
and regulation. In the past few years, considerable progress has been made in our
ability to visualize GPCRs and their signalling complexes at the structural
level. This is due to a series of methodological developments, improvements in
technology and the use of highly innovative approaches, such as protein
engineering, new detergents, lipidic cubic phase-based crystallization and
microfocus synchrotron beamlines. These advances suggest that an unprecedented
amount of structural information will become available in the field of GPCR
biology in the coming years.
PMID- 25589411
TI - Cofactor-independent antiphospholipid antibodies activate the NLRP3-inflammasome
via endosomal NADPH-oxidase: implications for the antiphospholipid syndrome.
AB - The antiphospholipid syndrome (APS) is an autoimmune disease characterised by
thromboembolic events and/or pregnancy morbidity in the presence of
antiphospholipid antibodies (aPL). Here we show that three cofactor independent
human monoclonal aPL can induce transcription of NLRP3 and caspase-1 resulting in
inflammasome activation specific for NLRP3. This depends fully on activation of
endosomal NADPH-oxidase-2 (NOX2) by aPL. Activation of NOX2 and subsequent
inflammasome activation by aPL are independent from TLR2 or TLR4. While endosomal
superoxide production induces caspase-1 and NLRP3 transcription, it does not
affect prae-IL-1beta transcription. Therefore, release of IL-1beta occurs only
after activation of additional pathways like TLR7/8 or TLR2. All effects exerted
by the monoclonal aPL can be reproduced with IgG fractions of APS patients
proving that the monoclonal aPL are representative for the APS. IgG fractions of
healthy controls or patients suffering from systemic lupus erythematosus have no
effect. In a mouse model of the APS we can show inflammasome activation in vivo.
Furthermore, mononuclear cells isolated from patients with the APS show an
increased expression of caspase-1 and NLRP3 which is accompanied by a three-fold
increased serum concentration of IL-1beta suggesting chronic inflammasome
activation in APS patients. In summary, we provide further evidence that
endosomal NOX2 can be activated by cofactor independent aPL. This leads to
induction of the NLRP3 inflammasome. Our data indicate that cofactor independent
aPL might contribute significantly to the pathogenesis of the APS.
PMID- 25589414
TI - Transient anions of cis- and trans-cyclooctene studied by electron-impact
spectroscopy.
AB - The effect which deformation of the double bond in trans-cyclooctene (TCO),
compared to cis-cyclooctene (CCO), has on its negative ion - and indirectly on
the pi* virtual orbital - was studied by electron-impact spectroscopy.
Differential elastic and vibrational excitation cross sections were measured at a
scattering angle of theta = 135 degrees . The vertical attachment energy (VAE)
derived from the vibrational excitation spectra is 1.87 eV in TCO, only 0.09 eV
lower than in the unstrained CCO, 1.96 eV. The substantial deformation of the
C[double bond, length as m-dash]C bond in TCO thus stabilizes its transient
negative ion by a surprisingly small amount and this effect is ascribed in part
to the Pauli (steric) destabilization of the TCO pi* orbital by the alkyl chain
facing the pi* lobes. An interesting effect is observed in the elastic cross
section which is about 45% larger for TCO at low energies (~0.4 eV), despite the
similar geometrical size of the two molecules. Ramsauer-Townsend minima are
observed in the elastic cross section at 0.13 and 0.12 eV for CCO and TCO,
respectively. Implications of the findings on enhancement of the dienophile
capacity of TCO are discussed.
PMID- 25589412
TI - Control of ethanol sensitivity of the glycine receptor alpha3 subunit by
transmembrane 2, the intracellular splice cassette and C-terminal domains.
AB - Previous studies have shown that the effect of ethanol onglycine receptors
(GlyRs) containing the a1 subunit is affected by interaction with heterotrimeric
G proteins (Gbetagamma). GlyRs containing the alpha3 subunit are involved in
inflammatory pain sensitization and rhythmic breathing and have received much
recent attention. For example, it is unknown whether ethanol affects the function
of this important GlyR subtype. Electrophysiologic experiments showed that GlyR
alpha3 subunits were not potentiated by pharmacologic concentrations of ethanol
or by Gbetagamma. Thus, we studied GlyR alpha1-alpha3 chimeras and mutants to
determine the molecular properties that confer ethanol insensitivity. Mutation of
corresponding glycine 254 in transmembrane domain 2 (TM2) found in a1 in the
alpha3(A254G) -alpha1 chimera induced a glycine-evoked current that displayed
potentiation during application of ethanol (46 +/- 5%, 100 mM) and Gbetagamma
activation (80 +/- 17%). Interestingly,insertion of the intracellular alpha3L
splice cassette into GlyR alpha1 abolished the enhancement of the glycine
activated current by ethanol (5 +/- 6%) and activation by Gbetagamma (21 6 7%).
In corporation of the GlyR alpha1 C terminus into the ethanol-resistant
alpha3S(A254G) mutant produced a construct that displayed potentiation of the
glycine-activated current with 100 mM ethanol (40 +/- 6%)together with a current
enhancement after G protein activation (68 +/- 25%). Taken together, these data
demonstrate that GlyRalpha3 subunits are not modulated by ethanol. Residue A254
in TM2, the alpha3L splice cassette, and the C-terminal domain of alpha3GlyRs are
determinants for low ethanol sensitivity and form the molecular basis of subtype
selective modulation of GlyRs by alcohol.
PMID- 25589415
TI - Retinal vessel extraction using Lattice Neural Networks with Dendritic
Processing.
AB - Retinal images can be used to detect and follow up several important chronic
diseases. The classification of retinal images requires an experienced
ophthalmologist. This has been a bottleneck to implement routine screenings
performed by general physicians. It has been proposed to create automated systems
that can perform such task with little intervention from humans, with partial
success. In this work, we report advances in such endeavor, by using a Lattice
Neural Network with Dendritic Processing (LNNDP). We report results using several
metrics, and compare against well known methods such as Support Vector Machines
(SVM) and Multilayer Perceptrons (MLP). Our proposal shows better performance
than other approaches reported in the literature. An additional advantage is that
unlike those other tools, LNNDP requires no parameters, and it automatically
constructs its structure to solve a particular problem. The proposed methodology
requires four steps: (1) Pre-processing, (2) Feature computation, (3)
Classification and (4) Post-processing. The Hotelling T(2) control chart was used
to reduce the dimensionality of the feature vector, from 7 that were used before
to 5 in this work. The experiments were run on images of DRIVE and STARE
databases. The results show that on average, F1-Score is better in LNNDP,
compared with SVM and MLP implementations. Same improvement is observed for MCC
and the accuracy.
PMID- 25589416
TI - Tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene: a potential tetraradicaloid
hydrocarbon.
AB - A tetramesityl derivative of hitherto unknown
tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene (TCPTP), which is a potential
tetraradicaloid hydrocarbon, was synthesized. Theoretical calculations based on
spin-flip time-dependent density functional theory predict that the closed-shell
D2h form of TCPTP is more stable than the open-shell D4h form with its slightly
tetraradical character. The tetramesityl derivative (Mes)4 -TCPTP exhibits
remarkable antiaromaticity as a result of the peripheral 20-pi-electron circuit,
which causes an absorption maximum at a long wavelength and a small HOMO-LUMO
gap. In solution, (Mes)4 -TCPTP most likely adopts rapidly equilibrating D2h
structures that interconvert via the D4h transition state. X-ray crystallographic
analysis showed (Mes)4 -TCPTP as an approximate D2h structure.
PMID- 25589413
TI - The evolving role of nonsteroidal anti-inflammatory drugs in colon cancer
prevention: a cause for optimism.
AB - Colorectal cancer (CRC) is a serious yet preventable disease. The low acceptance
and cost of colonoscopy as a screening method or CRC make chemoprevention an
important option. Nonsteroidal anti-inflammatory drugs (NSAIDs), not currently
recommended for CRC prevention, have the potential to evolve into the agents of
choice for this indication. Here, we discuss the promise and challenge of NSAIDs
for this chemopreventive application.Multiple epidemiologic studies, randomized
clinical trials (RCTs) of sporadic colorectal polyp recurrence, RCTs in patients
with hereditary colorectal cancer syndromes, and pooled analyses of
cardiovascular-prevention RCTs linked to cancer outcomes have firmly established
the ability of conventional NSAIDs to prevent CRC. NSAIDs, however, are seriously
limited by their toxicity,which can become cumulative with their long-term
administration for chemoprevention, whereas drug interactions in vulnerable
elderly patients compound their safety. Newer, chemically modified NSAIDs offer
the hope of enhanced efficacy and safety.Recent work also indicates that
targeting earlier stages of colorectal carcinogenesis, such as the lower
complexity aberrant crypt foci, is a promising approach that may only require
relatively short use of chemopreventive agents. Drug combination approaches
exemplified by sulindac plus difluoromethylornithine appear very efficacious.
Identification of those at risk or most likely to benefit from a given
intervention using predictive biomarkers may usher in personalized
chemoprevention. Agents that offer simultaneous chemoprevention of diseases in
addition to CRC, e.g., cardiovascular and/or neurodegenerative diseases,may have
a much greater potential for a broad clinical application.
PMID- 25589418
TI - Geographic variations in epidemiology of two autoimmune bullous diseases:
pemphigus and bullous pemphigoid.
AB - Autoimmune bullous diseases are rare, organ-specific, a group of blistering
disease of skin and mucous membranes. Recent studies suggest that the frequency
of the autoimmune bullous diseases has been increasing. Pemphigus vulgaris and
bullous pemphigoid are the most frequently reported autoimmune bullous diseases.
High incidence of autoimmune bullous diseases in some ethnic groups such as
pemphigus in Ashkenazi Jewish, or in some regions such as pemphigus foliaceus in
Brazil has been shown to be related to genetic and environmental factors,
respectively. Pemphigus has been reported more frequently in the female gender.
Although it is most frequently diagnosed between the ages 50 and 60 in European
countries, in the remaining countries in the world, it is seen between the ages
of 30 and 50. Bullous pemphigoid is generally seen above 70 years of age.
Although overall incidence is slightly higher in females, after the age of 80
years it is more frequent in males. Both pemphigus vulgaris and bullous
pemphigoid has a chronic course with recurrences. Mortality risk of the patients
with bullous pemphigoid was found at least 2 times higher and the mortality risk
of the patients with pemphigus was found approximately 3 times higher than that
of the general population. In this review, the results obtained from the
epidemiological studies were analyzed according to geographic regions, and
especially epidemiologic features of two prevalent autoimmune bullous diseases,
pemphigus and bullous pemphigoid have been discussed.
PMID- 25589417
TI - Molecular diversity of LysM carbohydrate-binding motifs in fungi.
AB - LysM motifs are carbohydrate-binding modules found in prokaryotes and eukaryotes.
They bind to N-acetylglucosamine-containing carbohydrates, such as chitin, chitio
oligosaccharides and peptidoglycan. In this review, we summarize the features of
the protein architecture of LysM-containing proteins in fungi and discuss their
so far known biochemical properties, transcriptional profiles and biological
functions. Further, based on data from evolutionary analyses and consensus
pattern profiling of fungal LysM motifs, we show that they can be classified into
a fungal-specific group and a fungal/bacterial group. This facilitates the
classification and selection of further LysM proteins for detailed analyses and
will contribute to widening our understanding of the functional spectrum of this
protein family in fungi. Fungal LysM motifs are predominantly found in subgroup C
chitinases and in LysM effector proteins, which are secreted proteins with LysM
motifs but no catalytic domains. In enzymes, LysM motifs mediate the attachment
to insoluble carbon sources. In plants, receptors containing LysM motifs are
responsible for the perception of chitin-oligosaccharides and are involved in
beneficial symbiotic interactions between plants and bacteria or fungi, as well
as plant defence responses. In plant pathogenic fungi, LysM effector proteins
have already been shown to have important functions in the dampening of host
defence responses as well as protective functions of fungal hyphae against
chitinases. However, the large number and diversity of proteins with LysM motifs
that are being unravelled in fungal genome sequencing projects suggest that the
functional repertoire of LysM effector proteins in fungi is only partially
discovered so far.
PMID- 25589419
TI - The activation of cultured keratinocytes by cholesterol depletion during
reconstruction of a human epidermis is reminiscent of monolayer cultures.
AB - Transient cholesterol depletion from plasma membranes of human keratinocytes has
been shown to reversibly activate signalling pathways in monolayer cultures.
Consecutive changes in gene expression have been characterized in such conditions
and were interestingly found to be similar to transcriptional changes observed in
keratinocytes of atopic dermatitis (AD) patients. As an inflammatory skin
disease, AD notably results in altered histology of the epidermis associated with
a defective epidermal barrier. To further investigate whether the activation of
keratinocytes obtained by cholesterol depletion could be responsible for some
epidermal alterations reported in AD, this study was undertaken to analyse
cholesterol depletion in stratified cultures of keratinocytes, i.e. a
reconstructed human epidermis (RHE). RHE contains heterogeneous populations of
keratinocytes, either proliferating or progressively differentiating and
stratifying towards the creation of a cornified barrier. Cholesterol depletion
induced in this model was found reversible and resulted in activation of
signalling pathways similar to those previously identified in monolayers. In
addition, selected changes in the expression of several genes suggested that
keratinocytes in RHE respond to cholesterol depletion as monolayers. However,
preserved histology and barrier function indicate that some additional
activation, likely from the immune system, is required to obtain epidermal
alterations such as the ones found in AD.
PMID- 25589420
TI - [Cerebral MR imaging of malignant melanoma].
AB - CLINICAL/METHODICAL ISSUE: Melanoma is the third leading cancer entity to
metastasize to the central nervous system (CNS) after lung and breast cancer.
This is often an early event in the disease course and limits survival.
Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and
the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases
are commonly found in the subcortical white matter. The signal characteristics
can vary substantially and may change over time due to hemorrhages or the
accumulation of melanin and paramagnetic ions. It is not yet clear whether novel
targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging
characteristics. Also immune-related side effects, such as hypophysitis (in
approximately 5 % of patients receiving ipilimumab therapy) or granulomatous
disease (neurosarcoid) can occur. STANDARD RADIOLOGICAL METHODS: Melanoma
metastases are usually hyperdense in computed tomography (CT). In magnetic
resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery
(FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained.
Coronal and axial imaging planes should be scanned to cross-correlate findings.
METHODICAL INNOVATIONS: Susceptibility-weighted imaging is a new sensitive method
to detect melanoma metastases. Approximately 66 % of melanoma metastases show
intratumoral susceptibility signals (ITSS). This sets them apart from other
metastases (e.g. lung and breast cancer show less ITSSs, specificity
approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain
imaging. PERFORMANCE: Susceptibility-weighted imaging increases the sensitivity
to detect metastases but lacks specificity. Differentiating metastases,
microbleeding or calcification can be impossible. It is controversial how to
interpret susceptibility signals without correlative signs on other sequences
(differential diagnosis: metastasis, microbleeding and calcification). PRACTICAL
RECOMMENDATIONS: CNS metastases are common in melanoma. MRI screening starting in
stage IIc should be considered even in asymptomatic patients. Stage IV requires
quarterly MRI examinations. Melanotic and amelanotic metastases show different
MRI characteristics. The differentiation between metastasis and microbleeding can
be impossible and might require a follow-up scan. Susceptibility-weighted imaging
increases the sensitivity of metastases detection but lacks specificity. It can
help to differentiate between different metastatic entities.
PMID- 25589421
TI - [Whole-body staging of malignant melanoma: advantages, limitations and current
importance of PET-CT, whole-body MRI and PET-MRI].
AB - Cross-sectional imaging methods are currently the standard methods for staging of
advanced melanoma. The former time-consuming and expensive multimodality approach
is increasingly being replaced by novel whole-body (WB) staging methods, such as
18F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F
FDG-PET-CT) and whole-body magnetic resonance imaging (WBMRI) because they offer
a complete head-to-toe coverage of the patient in a single examination with an
accurate and sensitive detection of tumor spread. Several studies in patients
with advanced melanoma revealed that PET-CT is more sensitive and specific than
conventional modalities, such as CT alone resulting in a change of management in
up to 30 % of cases. Due to the limited sensitivity of PET for lesions smaller
than 1 cm, PET-CT is not useful for the initial work-up of patients with stage I
and II melanoma but has proven to be superior for detection of distant
metastases, which is essential prior to surgical metastasectomy. If PET-CT is not
available WB-CT or WB-MRI can alternatively be used and WB-MRI including
diffusion-weighted imaging (DWI) has become a real alternative for staging of
melanoma patients. So far, however, only few reports suffering from small numbers
of cases and heterogeneous design have compared the diagnostic performance of WB
MRI and PET-CT. The preliminary results indicate a high overall diagnostic
accuracy of both methods; however, these methods differ in organ-based detection
rates: PET-CT was more accurate in N-staging and detection of lung and soft
tissue metastases whereas WB-MRI was superior in detecting liver, bone and brain
metastases. The value of PET-MRI for staging of advanced melanoma is the subject
of ongoing clinical studies.
PMID- 25589423
TI - Continuous-flow sorting of stem cells and differentiation products based on
dielectrophoresis.
AB - This paper presents a continuous-flow microfluidic device for sorting stem cells
and their differentiation progenies. The principle of the device is based on the
accumulation of multiple dielectrophoresis (DEP) forces to deflect cells
laterally in conjunction with the alternating on/off electric field to manipulate
the cell trajectories. The microfluidic device containing a large array of
oblique interdigitated electrodes was fabricated using a combination of standard
and soft lithography techniques to generate a PDMS-gold electrode construct.
Experimental testing with human mesenchymal stem cells (hMSC) and their
differentiation progenies (osteoblasts) was carried out at different flow rates,
and clear separation of the two populations was achieved. Most of the osteoblasts
experiencing stronger DEP forces were deflected laterally and continuously,
following zig-zag trajectories, and moved towards the desired collection outlet,
whereas most of the hMSCs remained on the original trajectory due to weaker DEP
forces. The experimental measurements were characterized and evaluated
quantitatively, and consistent performance was demonstrated. Collection
efficiency up to 92% and 67% for hMSCs and osteoblasts, respectively, along with
purity up to 84% and 87% was obtained. The experimental results established the
feasibility of our microfluidic DEP sorting device for continuous, label-free
sorting of stem cells and their differentiation progenies.
PMID- 25589422
TI - Mass spectrometry-based plant metabolomics: Metabolite responses to abiotic
stress.
AB - Metabolomics is one omics approach that can be used to acquire comprehensive
information on the composition of a metabolite pool to provide a functional
screen of the cellular state. Studies of the plant metabolome include analysis of
a wide range of chemical species with diverse physical properties, from ionic
inorganic compounds to biochemically derived hydrophilic carbohydrates, organic
and amino acids, and a range of hydrophobic lipid-related compounds. This
complexitiy brings huge challenges to the analytical technologies employed in
current plant metabolomics programs, and powerful analytical tools are required
for the separation and characterization of this extremely high compound diversity
present in biological sample matrices. The use of mass spectrometry (MS)-based
analytical platforms to profile stress-responsive metabolites that allow some
plants to adapt to adverse environmental conditions is fundamental in current
plant biotechnology research programs for the understanding and development of
stress-tolerant plants. In this review, we describe recent applications of
metabolomics and emphasize its increasing application to study plant responses to
environmental (stress-) factors, including drought, salt, low oxygen caused by
waterlogging or flooding of the soil, temperature, light and oxidative stress (or
a combination of them). Advances in understanding the global changes occurring in
plant metabolism under specific abiotic stress conditions are fundamental to
enhance plant fitness and increase stress tolerance. (c) 2015 Wiley Periodicals,
Inc. Mass Spec Rev 35:620-649, 2016.
PMID- 25589424
TI - Tension-free vaginal tape-obturator and tension-free vaginal tape-Secur for the
treatment of stress urinary incontinence: a 5-year follow-up randomized study.
AB - OBJECTIVE: Single-incision slings were developed to overcome the complications
related to retropubic and trans-obturator tapes. TVT-Secur was the first of this
kind of devices to be marketed and yielded contrasting results. Aim of this non
inferiority study is to report the 5-year follow-up of a randomized, single
blind, controlled trial comparing TVT-O to TVT-Secur. STUDY DESIGN: Randomized,
single blind, controlled study conducted in two tertiary urogynecological
centers. 154 patients were allocated to either TVT-O or TVT-Secur and were
contacted 5 years after the procedure to undergo urogynecological examination
(POP-Q staging, challenge stress test and post-void residual urine evaluation),
to complete I-QOL and PGI-I questionnaires, and to score their satisfaction on a
5-point Likert scale. Patients who were not objectively evaluated were
interviewed over the telephone. Primary outcome was subjective success defined as
being "very much improved" or "much improved" on the PGI-I. RESULTS: 120 patients
were evaluated only subjectively (TVT-O: 62; TVT-Secur: 58) and 84 objectively
and subjectively (TVT-O: 46; TVT-Secur: 38). Subjective success (79% vs. 63.8%)
and objective cure rates (82.6% vs. 68.4%) 5 years after the procedure were lower
for TVT-Secur, but not significantly. Recurrent UTIs were reported by 17.8% of
women (TVT-O 9, TVT-Secur 6) and two de novo urgency cases (one per group) were
observed. Re-operation rate for stress urinary incontinence (SUI) was 20%.
CONCLUSIONS: TVT-Secur did not show an inferior subjective success rate in
comparison with TVT-O five year after the original procedure, even though
displaying a clear trend toward a lower efficacy. Considering that the long-term
safety profile is similar between the two procedures, there are no advantages in
using TVT-Secur.
PMID- 25589425
TI - A secreted protein (Canopy 2, CNPY2) enhances angiogenesis and promotes smooth
muscle cell migration and proliferation.
AB - AIMS: Ischaemic heart disease is a leading cause of mortality. After ischaemic
injury, tissue hypoxia induces the activity of angiogenic factors that promote
revascularization. Increased understanding of hypoxia-responsive genes and their
role in angiogenesis will lead to new therapies for ischaemic injury. We
delineated the function of Canopy 2 (CNPY2), a newly discovered, hypoxia
regulated gene. METHODS AND RESULTS: We found CNPY2 in a screen for genes induced
by low oxygen in human smooth muscle cells (SMCs). CNPY2 protein co-localized
with the endoplasmic reticulum and the Golgi. Treatment with Brefeldin A, which
destroys Golgi stacks, resulted in CNPY2 accumulation in the endoplasmic
reticulum. Secreted CNPY2 was detected in the blood of healthy mice and humans,
and the medium of cultured SMCs. SMCs under hypoxia or treated with a prolyl-4
hydroxylase inhibitor stabilized HIF-1alpha protein and up-regulated CNPY2, while
CNPY2 induction was lost after HIF-1alpha silencing. Chromatin
immunoprecipitation demonstrated that HIF-1alpha binds to a hypoxia response
element (HRE-1157) upstream of the human CNPY2 promoter, which was verified by a
luciferase reporter driven by HRE-1157-containing constructs. CNPY2 stimulation
activated Cdc42, PAK1, and FAK in SMCs, resulting in enhanced proliferation and
migration in vitro, and dramatic aortic ring sprouting ex vivo. CNPY2
significantly increased revascularization of the mouse retina after reperfusion
injury. CONCLUSIONS: CNPY2 is a HIF-1alpha-regulated, secreted angiogenic growth
factor that promotes SMC migration, proliferation, and tissue revascularization.
This new target may have a broader profile than currently available proteins.
PMID- 25589428
TI - Piezo-phototronic UV/visible photosensing with optical-fiber-nanowire hybridized
structures.
AB - An optical-fiber-nanowire hybridized UV-visible photodetector (PD) is reported.
The PD is designed to allow direct integration in optical communication systems
without requiring the use of couplers via fiber-welding technology. The PD works
in two modes: axial and off-axial illumination mode. By using the piezo
phototronic effect, the performance of the PD is enhanced/optimized by up to 718%
in sensitivity and 2067% in photoresponsivity.
PMID- 25589427
TI - Evaluation of the effects of chromium supplementation on growth and nitrogen
balance of camel calves under summer conditions.
AB - One of the most important problems in the production of camels in arid and semi
arid zones is the reduced feed intake and consequent low growth rate during
summer. Under these stressful environmental conditions, chromium (Cr)
supplementation to the diet of growing camel calves may be beneficial. Therefore,
the objective of this study was to evaluate the effects of feeding a diet
supplemented with different levels of Cr on growth performance of camel calves
reared in a hot arid environment. A total of 15 male camel calves (4-5-month-old,
123 +/- 7 kg body weight) were used in this study. The animals were divided into
three equal groups (A, B, C), 5 animals each, and housed individually under
shelter. Camel calves were fed ad libitum on either total mixed ration (TMR)
without Cr supplementation (group A), TMR supplemented with 0.5 mg Cr/kg DM
(group B), or TMR supplemented with 1.0 mg Cr/kg DM (group C). Supplementation of
0.5 mg Cr/kg DM to the diet of camel calves did not alter feed intake, however,
increased not significantly (P = 0.086) average daily gain (ADG) and N retention.
Plasma cortisol level was reduced by 10%, and feed utilization efficiency was
improved by 12% in 0.5 mg Cr/kg DM-supplemented group compared to the control.
Thus, 0.5 mg Cr/kg DM dietary supplementation to camel calves reared under hot
summer condition increased weight gain by 17% and reduced feeding cost of
producing a unit of weight by 11%.
PMID- 25589426
TI - The CarO rhodopsin of the fungus Fusarium fujikuroi is a light-driven proton pump
that retards spore germination.
AB - Rhodopsins are membrane-embedded photoreceptors found in all major taxonomic
kingdoms using retinal as their chromophore. They play well-known functions in
different biological systems, but their roles in fungi remain unknown. The
filamentous fungus Fusarium fujikuroi contains two putative rhodopsins, CarO and
OpsA. The gene carO is light-regulated, and the predicted polypeptide contains
all conserved residues required for proton pumping. We aimed to elucidate the
expression and cellular location of the fungal rhodopsin CarO, its presumed
proton-pumping activity and the possible effect of such function on F. fujikuroi
growth. In electrophysiology experiments we confirmed that CarO is a green-light
driven proton pump. Visualization of fluorescent CarO-YFP expressed in F.
fujikuroi under control of its native promoter revealed higher accumulation in
spores (conidia) produced by light-exposed mycelia. Germination analyses of
conidia from carO(-) mutant and carO(+) control strains showed a faster
development of light-exposed carO(-) germlings. In conclusion, CarO is an active
proton pump, abundant in light-formed conidia, whose activity slows down early
hyphal development under light. Interestingly, CarO-related rhodopsins are
typically found in plant-associated fungi, where green light dominates the
phyllosphere. Our data provide the first reliable clue on a possible biological
role of a fungal rhodopsin.
PMID- 25589433
TI - Pre-filled syringes: a review of the history, manufacturing and challenges.
AB - Pre-filled syringes are convenient devices for the delivery of parenteral
medications. They are small which makes them easy to carry and are dependable for
delivering a precise dose of medication. These and many other reasons are leading
to their growth in the pharmaceutical market. There are a number of review
articles that describe the advantages and disadvantages of pre-filled syringes.
However, there are few journal articles that present information on their
manufacturing and challenges. The intent of this review article is to provide
information on the history of the pre-filled syringe, methods of their
manufacture, methods of filling syringes as a drug product and to examine the
types of syringes available. This type of knowledge can familiarize the
formulation scientist with the choices available and their possible challenges.
PMID- 25589434
TI - Potential for use of industrial waste materials as filter media for removal of
Al, Mo, As, V and Ga from alkaline drainage in constructed wetlands--adsorption
studies.
AB - The potential to remove Al, Mo, V, As and Ga from alkaline (pH 8.0-8.6) drainage
originating from seawater neutralized bauxite processing residue storage areas
using constructed wetland technology was studied in a laboratory study. Bauxite
processing residue sand, bauxite, alum water treatment sludge and blast furnace
slag were investigated as potential active filter materials. Al was shown to
precipitate as Al(OH)3 in the pH range 7.0-8.0 in aqueous solution and 6.0-8.5 in
the presence of silica sand particles that provided a surface for nucleation. For
V As Mo and Ga, adsorption to the surfaces of the adsorbents decreased greatly at
elevated pH values (>pH 6-9). Water treatment sludge and bauxite had a greater
ability to adsorb V, As and Mo at high pH (As and V at pH 7-9 and Mo at pH 5-7)
than processing sand and slag. Adsorption isotherm data for As and V onto all
four adsorbent than processing sand and slag. Adsorption isotherm data for As and
V onto all four adsorbent materials fitted equally well to the Langmuir and
Freundlich equations but for Ga, and to a lesser extent Mo, the Freundlich
equation gave higher R(2) values. For all four ions, the maximum adsorption
capacity (Langmuir value qmax) was greatest for water treatment sludge. Bauxite
adsorbed more Mo, Ga and V than residue sand or slag. The pseudo-second order
equation gave a better fit to the experimental kinetic data than the pseudo-first
order model suggesting that chemisorption rather than diffusion/exchange was the
rate limiting step to adsorption. It was concluded that water treatment sludge
and bauxite were the most effective adsorbents and that for effective removal of
the target ions the pH of the drainage water needs to be decreased to 6.0-7.0.
PMID- 25589435
TI - Modeling the anaerobic digestion of cane-molasses vinasse: extension of the
Anaerobic Digestion Model No. 1 (ADM1) with sulfate reduction for a very high
strength and sulfate rich wastewater.
AB - This research presents the modeling of the anaerobic digestion of cane-molasses
vinasse, hereby extending the Anaerobic Digestion Model No. 1 with sulfate
reduction for a very high strength and sulfate rich wastewater. Based on a
sensitivity analysis, four parameters of the original ADM1 and all sulfate
reduction parameters were calibrated. Although some deviations were observed
between model predictions and experimental values, it was shown that sulfates,
total aqueous sulfide, free sulfides, methane, carbon dioxide and sulfide in the
gas phase, gas flow, propionic and acetic acids, chemical oxygen demand (COD),
and pH were accurately predicted during model validation. The model showed high
(+/-10%) to medium (10%-30%) accuracy predictions with a mean absolute relative
error ranging from 1% to 26%, and was able to predict failure of methanogenesis
and sulfidogenesis when the sulfate loading rate increased. Therefore, the
kinetic parameters and the model structure proposed in this work can be
considered as valid for the sulfate reduction process in the anaerobic digestion
of cane-molasses vinasse when sulfate and organic loading rates range from 0.36
to 1.57 kg [Formula: see text] m(-3) d(-1) and from 7.66 to 12 kg COD m(-3) d(
1), respectively.
PMID- 25589437
TI - The multidisciplinary depression guideline for children and adolescents: an
implementation study.
AB - It is important that depressed patients receive adequate and safe care as
described in clinical guidelines. The aim of this study was to evaluate the
implementation of the Dutch depression guideline for children and adolescents,
and to identify factors that were associated with the uptake of the guideline
recommendations. The study took place in specialised child and adolescent mental
healthcare. An implementation project was initiated to enhance the implementation
of the guideline. An evaluation study was performed alongside the implementation
project, using structured registration forms and interviews with healthcare
professionals. Six multidisciplinary teams participated in the implementation
study. The records of 655 patients were analysed. After 1 year, 72% of all
eligible patients had been screened for depression and 38% were diagnosed with
the use of a diagnostic instrument. The severity of the depression was assessed
in 77% of the patients during the diagnostic process, and 41% of the patients
received the recommended intervention based on the depression severity. Of the
patients that received antidepressants, 25% received weekly checks for suicidal
thoughts in the first 6 weeks. Monitoring of the patients' response was recorded
in 32% of the patients. A wide range of factors were perceived to influence the
uptake of guideline recommendations, e.g. the availability of capable
professionals, available time, electronic tools and reminders, and the
professionals' skills and attitudes. With the involvement of the teams,
recommendations were provided for nationwide implementation of the guideline. In
conclusion, a systematic implementation programme using stepped care principles
for the allocation of depression interventions seems successful, but there
remains room for further improvement.
PMID- 25589439
TI - Using interactive theater to create socioculturally relevant community-based
intimate partner violence prevention.
AB - This article describes the use of interactive theater, audience response
assessment, and peer educators to create community-generated approaches for
bystander interventions (i.e., actions taken by people who become aware of
controlling, abusive and violent behavior of others) to prevent intimate partner
violence (IPV) and to foster change in community norms. We include a case example
of an ongoing university-community partnership, which mobilizes community members
to develop and implement socioculturally relevant IPV prevention programs in
multiple Asian communities. We used interactive theater at a community event--a
walk to raise awareness about IPV in South Asian communities--and examined how
the enacted bystander interventions reflect specific community contexts. We
detail the challenges and limitations we have encountered in our attempts to
implement this approach in collaboration with our community partners.
PMID- 25589436
TI - Gender effects on brain changes in early-onset psychosis.
AB - Progressive loss of cortical gray matter (GM) and increase of cerebrospinal fluid
(CSF) have been reported in early-onset psychosis (EOP). EOP typically begins
during adolescence, a time when developmental brain trajectories differ by
gender. This study aimed to determine gender differences in progression of brain
changes in this population. A sample of 61 (21 females) adolescents with a first
psychotic episode and a matched sample of 70 (23 females) controls underwent both
baseline and 2-year follow-up anatomical brain imaging assessments. Regional GM
and CSF volumes were obtained using automated methods based on the Talairach's
proportional grid system. At baseline, only male patients showed a clear pattern
of alterations in the frontal lobe relative to controls (smaller GM and larger
CSF volumes). However, parallel longitudinal changes for male and female patients
relative to controls were observed, resulting in a common pattern of brain
changes across both genders: rate of left frontal lobe GM volume loss was larger
in male (-3.8%) and female patients (-4.2%) than in controls (-0.7% males; -0.4%
females). The reverse was found for the CSF volume in the left frontal lobe.
While the GM and CSF volumes of females with EOP appear to be within the normal
range at initial illness onset, our results point to a similar trajectory of
increased/accelerated brain changes in both male and female patients with EOP.
The pattern of progression of brain changes in psychosis appears to be
independent of gender or structural alterations on appearance of psychotic
symptoms.
PMID- 25589438
TI - Online sexual behaviours among Swedish youth: associations to background factors,
behaviours and abuse.
AB - Sexual activity online may result in positive experiences for young people, or
lead them to engage in risky behaviours possibly resulting in sexual assault or
abuse. The aim of our study was to investigate associations between online sexual
behaviours among Swedish youth and background factors as well as aspects of well
being. The behaviours investigated were: having sex online with a contact met
online, having sex with an online contact offline, posting sexual pictures
online, and selling sex online. We used data from a representative sample of
3,432 Swedish youth who were asked about their lifetime experiences as well as
their experiences within the previous year. We hypothesized that more advanced
online sexual behaviours were associated with more problematic background
factors, worse psychosocial well-being and riskier behaviours in general.
Bivariate relationships were evaluated followed by a multiple logistic regression
model. Our data suggested that most Swedish youth do not perform any of the
assessed online sexual behaviours. Young people who reported online sexual
behaviour showed a more problematic background, rated their health as poorer, had
a more sexualized life and had experienced more sexual or physical abuse.
Professionals who work with young people need to help them better evaluate
potential risks online and offer support when needed. Youths who sell sex online
are especially at risk and need extra attention, as they might be in greater need
of protection and therapeutic support.
PMID- 25589441
TI - Self-organized assemblies of colloidal particles obtained from an aligned
chromonic liquid crystal dispersion.
AB - The behavior of mono-disperse colloidal particles in a chromonic liquid crystal
was investigated. Poly(methyl methacrylate) spherical particles with three
different functionalizations, with and without surface charges, were utilized in
the nematic and columnar phases of disodium cromoglycate solutions. The nematic
phase was completely aligned parallel to the glass substrates by a simple rubbing
technique, and the columnar phase showed regions of similar alignment. The
behavior of the colloidal particles in the chromonic liquid crystal depended
critically on the functionality, with bromine functionalized particles not
dispersing at all, and cationic trimethylammonium and epoxy functionalized
particles dispersing well in the isotropic phase of the liquid crystal. At the
transition to the nematic and especially the columnar phase, the colloidal
particles were expelled into the remaining isotropic phase. Since the columnar
phase grew in parallel ribbons, the colloidal particles ended up in chain-like
assemblies. Such behavior opens the possibility of producing patterned assemblies
of colloidal particles by taking advantage of the self-organized structure of
chromonic liquid crystals.
PMID- 25589443
TI - Editor's spotlight/take 5: Natural polyphenols enhance stability of crosslinked
UHMWPE for joint implants.
PMID- 25589442
TI - Interactive effects of neurocognitive impairment and substance use on
antiretroviral non-adherence in HIV disease.
AB - While numerous studies have established the adverse independent effects of
clinical conditions including neurocognitive dysfunction, psychiatric illness,
and substance abuse/dependence on medication adherence among HIV-infected adults,
fewer have studied their interactive effects. The current study examined this
issue among 204 HIV-infected participants based upon current neurocognitive
functioning and DSM-IV-diagnosed psychiatric illness and current substance abuse
or dependence. Results confirmed that participants with any of these risk factors
demonstrated poorer adherence than individuals with no risk factors. A
neurocognitive status * substance abuse/dependence interaction was also
identified such that participants with impaired neurocognition and a co-occurring
substance abuse/dependence diagnosis demonstrated the poorest adherence. Results
confirm the deleterious impact of these risk factors in isolation and also
identify a specific interactive effect for individuals with comorbid
neurocognitive impairment and a substance abuse/dependence disorder. Findings
highlight the need for interventions that simultaneously address these problems.
PMID- 25589440
TI - The Release 6 reference sequence of the Drosophila melanogaster genome.
AB - Drosophila melanogaster plays an important role in molecular, genetic, and
genomic studies of heredity, development, metabolism, behavior, and human
disease. The initial reference genome sequence reported more than a decade ago
had a profound impact on progress in Drosophila research, and improving the
accuracy and completeness of this sequence continues to be important to further
progress. We previously described improvement of the 117-Mb sequence in the
euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using
a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing.
Here, we report an improved reference sequence of the single-copy and middle
repetitive regions of the genome, produced using cytogenetic mapping to mitotic
and polytene chromosomes, clone-based finishing and BAC fingerprint verification,
ordering of scaffolds by alignment to cDNA sequences, incorporation of other map
and sequence data, and validation by whole-genome optical restriction mapping.
These data substantially improve the accuracy and completeness of the reference
sequence and the order and orientation of sequence scaffolds into chromosome arm
assemblies. Representation of the Y chromosome and other heterochromatic regions
is particularly improved. The new 143.9-Mb reference sequence, designated Release
6, effectively exhausts clone-based technologies for mapping and sequencing.
Highly repeat-rich regions, including large satellite blocks and functional
elements such as the ribosomal RNA genes and the centromeres, are largely
inaccessible to current sequencing and assembly methods and remain poorly
represented. Further significant improvements will require sequencing
technologies that do not depend on molecular cloning and that produce very long
reads.
PMID- 25589445
TI - On patient safety: surgical complications do not always produce poor outcomes
(just bad feelings).
PMID- 25589444
TI - The 50 Most-cited Articles in Orthopaedic Surgery From Mainland China.
AB - BACKGROUND: Citation analysis has been widely used to evaluate the impact of
articles in medical and surgical specialties. Although China is the most populous
country in the world, and although more than 50,000 orthopaedic surgeons practice
there, to our knowledge no formal citation analysis of Chinese orthopaedic
articles has been performed. QUESTIONS/PURPOSES: We identified the 50 most-cited
orthopaedic articles from mainland China and evaluated these articles in terms of
their language of publication, source journals, and topics. METHODS: Science
Citation Index Expanded was searched in July 31, 2014 for citations of articles
published in 70 selected journals since the inception of the database. The 50
most-cited orthopaedic articles originating in mainland China were identified.
Basic information, including title, authors, year of publication, article type,
journal in which the work was published, city, institution, number of citations,
decade published, and topic or subspecialty of the research were recorded.
RESULTS: The number of citations for the top 50 papers ranged from 181 to 31
(mean, 52). These articles were published between 1981 and 2010. The decade of
2000 to 2009 was the most prolific, with 36 of the top 50 articles published
during this time. All articles were written in English and they were published in
a total of 16 journals. The journal Spine published the largest number of
articles (12), followed by Clinical Orthopaedics and Related Research ((r))
(seven). The journal Lancet had the highest impact factor (39.207 for 2013) among
any of the journals that published articles we identified. The top 50 articles
originated mainly from Beijing (16) and Shanghai (12), with basic research being
the focus of the majority (27 of 50; 54%); the remaining were clinical studies.
Bone was the most-investigated topic in basic research; the spine was the most
common topic among the identified clinical studies. CONCLUSIONS: The 50 most
cited articles that we identified should be considered influential, although a
large gap remains between mainland China and the global orthopaedic community in
terms of citations per article. Nevertheless, insofar as the most-recent decade
of our survey generated the most articles in this top-50 list, we would
characterize mainland China's effect on musculoskeletal research as increasing,
and as funding increases to programs in mainland China, we anticipate this trend
will continue in the future.
PMID- 25589446
TI - LcBiP, a endoplasmic reticulum chaperone binding protein gene from Lycium
chinense, confers cadmium tolerance in transgenic tobacco.
AB - Cadmium (Cd) accumulation is very toxic to plants. The presence of Cd may lead to
excessive production of reactive oxygen species (ROS), and then cause inhibition
of plant growth. The endoplasmic reticulum chaperone binding protein (BiP) is an
important functional protein, which has been shown to function as a sensor of
alterations in the ER environment. BiP overexpression in plants was shown to
increase drought tolerance through inhibition of ROS accumulation. Due to the
above relationships, it is likely that there may be a link between Cd stress
tolerance, ROS accumulation and the BiP transcript expression in plants. In this
study, a BiP gene, LcBiP, from L. chinense was isolated and characterized.
Overexpression of LcBiP in tobacco conferred Cd tolerance. Under Cd stress
conditions, the transgenic tobacco lines exhibited better chlorophyll retention,
less accumulation of ROS, longer root length, more glutathione (GSH) content, and
less antioxidant enzyme activity than the wild type. These data demonstrated that
LcBiP act as a positive regulator in Cd stress tolerance. It is hypothesized that
the improved Cd tolerance of the transgenic tobacco plants may be due to the
enhanced ROS scavenging capacity. The enhancement of GSH content might contribute
to this ROS scavenging capacity in the transgenic plants. However, the underlying
mechanism for BiP-mediated increase in Cd stress tolerance need to be further
clarified.
PMID- 25589448
TI - Convenient and highly efficient routes to 2 H-chromene and 4-chromanone
derivatives: iodine-promoted and p-toluenesulfonic acid catalyzed cascade
cyclizations of propynols.
AB - A convenient strategy is presented for the easy preparation of a series of 2 H
chromenes under mild conditions through iodocyclization of readily accessible
propynols. In addition, various 4-chromanones can be synthesized through a p
toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields
up to 99 %). Our developed reaction systems are proven to have good functional
group applicability and can be scaled up to gram quantities in satisfactory
yields. These systems also provide a new synthetic strategy for two types of
important flavonoid skeleton without using costly and toxic metal catalysts.
Additionally, the resulting halides could be further exploited in subsequent
palladium-catalyzed coupling reactions, so these compounds could act as potential
intermediates for the construction of some valuable drug molecules.
PMID- 25589449
TI - Meniscal allograft sterilisation: effect on biomechanical and histological
properties.
AB - Sterilisation of allografts are a crucial step in ensuring safety and viability.
Current sterilisation standards such as 25 kGy gamma irradiation (gamma) can have
adverse effects on the ultrastructure and biomechanical properties of allograft
tissue. Supercritical CO2 (SCCO2) technology, represents an improved
sterilisation process that potentially preserves tissue properties. This study
aimed to test the effect of SCCO2 sterilisation on the biomechanical and
histological properties of the meniscus and compare this to the current standard
of gamma. Thirty-two 18-month old ovine menisci were randomly assigned into three
groups for sterilisation (SCCO2, gamma and control). After treatment,
biomechanical indentation testing (stiffness and stress relaxation) or
histological analysis [percentage of void, cells and extracellular matrix (ECM)
per slide] was undertaken. Both SCCO2 and gamma groups displayed an increase in
stiffness and stress relaxation as compared to control, however, this difference
was lesser in samples treated with SCCO2. No significant histological
quantitative differences were detected between SCCO2 and control specimens. Gamma
treated samples demonstrated a significant increase in void and decrease in ECM.
Interestingly, both treatment groups demonstrated a decreasing mean void and
increasing ECM percentage when analysed from outer to inner zones. No significant
differences were detected in all-endpoints when analysed by section. SCCO2
sterilisation represents a potential feasible alternative to existing
sterilization techniques such as gamma.
PMID- 25589447
TI - Attention modulates cortical processing of pitch feedback errors in voice
control.
AB - Considerable evidence has shown that unexpected alterations in auditory feedback
elicit fast compensatory adjustments in vocal production. Although generally
thought to be involuntary in nature, whether these adjustments can be influenced
by attention remains unknown. The present event-related potential (ERP) study
aimed to examine whether neurobehavioral processing of auditory-vocal integration
can be affected by attention. While sustaining a vowel phonation and hearing
pitch-shifted feedback, participants were required to either ignore the pitch
perturbations, or attend to them with low (counting the number of perturbations)
or high attentional load (counting the type of perturbations). Behavioral results
revealed no systematic change of vocal response to pitch perturbations
irrespective of whether they were attended or not. At the level of cortex, there
was an enhancement of P2 response to attended pitch perturbations in the low-load
condition as compared to when they were ignored. In the high-load condition,
however, P2 response did not differ from that in the ignored condition. These
findings provide the first neurophysiological evidence that auditory-motor
integration in voice control can be modulated as a function of attention at the
level of cortex. Furthermore, this modulatory effect does not lead to a general
enhancement but is subject to attentional load.
PMID- 25589450
TI - Potential of 5-azacytidine induction decidual stromal cells from maternal human
term placenta towards cardiomyocyte-like cells in serum-free medium.
AB - Decidual stromal cells (DSCs) from maternal term placenta represent a potential
source of cells for the treatment of cardiovascular and graft-versus-host
diseases. However, it is not clear whether DSCs could be induced towards
cardiomyocyte-like differentiation. We chose the placentas which should bred male
new-baby. We isolated DSCs from placenta by tissue adherence. The morphology,
immunophenotype, and multi-lineage potential were analyzed. Karyotype analysis (G
band) was performed to determine the source and karyotype stability of DSCs. DSCs
were induced by 5-azacytidine. Expression of Myf5, alpha-cardiac actin, Cardiac
troponin T (cTnT) and GAPDH was assessed by PCR, and cTnT expression was also
analyzed by immunofluorescence. Karyotype analyses indicated that cells were
derived from the maternal matrix. After induction with 5-azacytidine, DSCs
expressed the cardiac-specific markers Myf5, myogenin and cTnT, indicating
differentiation towards cardiomyocyte-like cells.
PMID- 25589451
TI - The relationship between maternal postpartum psychological state and breast milk
secretory immunoglobulin A level.
AB - BACKGROUND: Maternal psychological state may influence the passive transfer of
immune factors (e.g., immunoglobulin) via the mother's breast milk. OBJECTIVE:
The aim of this study was to determine whether a correlation exists between
mothers' postpartum psychological state and their breast milk secretory
immunoglobulin A (SIgA) levels. STUDY DESIGN: Eighty-one mothers who delivered at
an urban general hospital were included in our analysis. Two weeks after
delivery, we measured their breast milk SIgA levels and simultaneously documented
their psychological state using the Profile of Mood States (POMS), General Health
Questionnaire (GHQ), and State-Trait Anxiety Inventory (STAI) scales. RESULTS:
Breast milk SIgA levels were negatively correlated with negative POMS states
(tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion).
A negative correlation was also observed between SIgA levels and GHQ mental
health (r = -.625, P = .000), and a similar negative correlation was observed
with STAI trait and state anxieties. However, no correlation existed between
breast milk SIgA levels and the positive POMS state (vigor). CONCLUSIONS: These
results indicate that the maternal psychological state may affect the immune
properties of breast milk.
PMID- 25589452
TI - Parental involvement in youth anxiety treatment: conceptual bases, controversies,
and recommendations for intervention.
AB - Parents are often perceived as a contributing or maintaining source of youth
anxiety disorders, making them natural targets for either intervention or
involvement in treatment protocols. Efforts to increase the efficacy and
durability of standard treatments by incorporating parents have been successful,
yet they often do not outperform child-focused treatment. Breinholst et al.
(2012) review and discuss several overlooked parental research variables
(anxiety, overcontrol, beliefs and assumptions, global family dysfunction) found
to promote and maintain child anxiety. However, it remains unclear how these
proposed variables interfere with active therapeutic ingredients (e.g., exposure)
or how the identified problems might be addressed. We propose that insufficient
attention to exposure-based treatment and family behavioral responses explain the
comparatively low added value for parental involvement in child anxiety treatment
and outline directions for research to address them. With meaningful attention
being given to exposure and its accompanying variables in the treatment of
childhood anxiety, we believe that treatment outcomes and intervention
acceptability can be improved.
PMID- 25589453
TI - Effectiveness of cognitive-behavioral group therapy for patients with
hypochondriasis (health anxiety).
AB - Cognitive behavioral therapy (CBT) has been shown to be highly effective in the
treatment of health anxiety. However, little is known about the effectiveness of
group CBT in the treatment of health anxiety. The current study is the largest
study that has investigated the effectiveness of combined individual and group
CBT for patients with the diagnosis of hypochondriasis (N=80). Therapy outcomes
were evaluated by several questionnaires. Patients showed a large improvement on
these primary outcome measures both post-treatment (Cohen's d=0.82-1.08) and at a
12-month follow-up (Cohen's d=1.09-1.41). Measures of general psychopathology and
somatic symptoms showed significant improvements, with small to medium effect
sizes. Patients with more elevated hypochondriacal characteristics at therapy
intake showed a larger therapy improvement, accounting for 7-8% of the variance
in therapy outcome. CBT group therapy has therefore been shown to be an
appropriate and cost-effective treatment for health anxiety.
PMID- 25589455
TI - A case of pancreaticobiliary fistula associated with an intraductal papillary
mucinous neoplasm of the pancreas.
PMID- 25589454
TI - Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat
pancreatic cancer in patients with impaired renal function.
AB - OBJECTIVE: Although pre-operative chemoradiotherapy appears to be a promising
treatment for patients with pancreatic ductal adenocarcinoma, there have been no
reports of the feasibility of pre-operative chemoradiotherapy in pancreatic
ductal adenocarcinoma patients with renal impairment. The aim of this study was
to evaluate retrospectively the feasibility of pre-operative chemoradiotherapy in
pancreatic ductal adenocarcinoma patients with renal impairment. METHODS: Twelve
patients with resectable pancreatic ductal adenocarcinoma and a creatinine
clearance of <60 ml/min were enrolled in this study. Gemcitabine-based pre
operative chemoradiotherapy was performed, followed by surgery. The feasibility
of the treatment was evaluated in terms of clinical outcome and adverse events in
the patients. RESULTS: All 12 patients completed gemcitabine-based pre-operative
chemoradiotherapy without worsening of renal function. Restaging after the
therapy revealed radiologically unresectable disease in two patients. Among the
remaining 10 patients who underwent laparotomy, curative resection was performed
in eight patients. After curative resection, five patients out of the eight
completed post-operative adjuvant therapy. The 1- and 3-year survival rates after
the start of chemoradiotherapy in the 12 patients were 80.8 and 36.9%,
respectively. CONCLUSIONS: Our findings suggest that gemcitabine-based pre
operative chemoradiotherapy may be a safe and effective treatment for pancreatic
ductal adenocarcinoma in patients with renal impairment.
PMID- 25589456
TI - Methodological issues in observational studies and non-randomized controlled
trials in oncology in the era of big data.
AB - Non-randomized controlled trials, cohort studies and database studies are
appealing study designs when there are urgent needs for safety data, outcomes of
interest are rare, generalizability is a matter of concern, or randomization is
not feasible. This paper reviews four typical case studies from methodological
viewpoints and clarifies how to minimize bias in observational studies in
oncology. In summary, researchers planning observational studies should be
cautious of selection of appropriate databases, validity of algorithms for
identifying outcomes, comparison with incident users or self-control, rigorous
collection of information on potential confounders and reporting details of
subject selection. Further, a careful study protocol and statistical analysis
plan are also necessary.
PMID- 25589457
TI - Inhalation devices and patient interface: human factors.
AB - The development of any inhalation product that does not consider the patient
needs will fail. The needs of the patients must be identified and aligned with
engineering options and physical laws to achieve a robust and intuitive-to-use
inhaler. A close interaction between development disciplines and real-use
evaluations in clinical studies or in human factor studies is suggested. The same
holds true when a marketed product needs to be changed. Caution is warranted if
an inhaler change leads to a change in the way the patient handles the device.
Finally, the article points out potential problems if many inhaler designs are
available. Do they confuse the patients? Can patients recall the correct handling
of each inhaler they use? How large is the risk that different inhaler designs
pose to the public health? The presentations were given at the Orlando Inhalation
Conference: Approaches in International Regulation co-organised by the University
of Florida and the International Pharmaceutical Aerosol Consortium on Regulation
& Science (IPAC-RS) in March 2014.
PMID- 25589458
TI - Is there an ideal outcome scoring system for facial reanimation surgery? A review
of current methods and suggestions for future publications.
AB - Facial reanimation is the surgical process of attempting to restore dynamic,
spontaneous symmetry to the paralysed face. We undertook to review the most
frequently used scoring systems and discuss a universal set of assessments which
every facial palsy surgeon can use to standardize the outcome of surgical
intervention and allow a comparison to be drawn when comparing different
operative techniques. A literature review was performed using PubMed and Cochrane
databases to identify scoring systems for facial palsy, facial nerve regeneration
and facial reanimation. The scoring systems were broken down into the following
broad categories: observational, mathematical and computer-graphical
measurements. More than 20 scoring systems were identified and included in the
study. The scoring systems were analysed and assessed for reproducibility and
inter-observer reliability. The current trend in the literature is to use the
House-Brackmann Score due to its historical longevity, brevity and ease of
understanding. However, this was never designed to assess outcomes of facial
reanimation and there are clear limitations. Other more appropriate methods such
as 3-D facial analysis are prohibitively expensive to widely implement. The quest
continues to develop an ideal system. From this review it is clear that a quick,
simple to use system should be used which incorporates the patient's own views.
Therefore a combination of pre- and post-operative photographs of the patient
should be assessed by an independent panel as well as the patient. We propose a
universal set of photographs that can be used to standardize the outcome of
surgical intervention when publishing results in the literature. This will allow
a comparison to be drawn when comparing different operative techniques and help
surgeons work collectively towards the same goal while improving patient
outcomes.
PMID- 25589459
TI - A systematic review of post-surgical pyoderma gangrenosum: identification of risk
factors and proposed management strategy.
AB - BACKGROUND: Post-surgical pyoderma gangrenosum (PSPG) presents as a rapidly
expanding cutaneous ulcer at a site of surgery with potentially devastating
consequences. We systematically reviewed the English and foreign language
literature to identify risk factors for PSPG and propose a management strategy.
METHODS: A systematic review was completed in PubMed, Medline, Embase, and
Cochrane Database for all published reports of PSPG from January 1946 to June
2013. We manually examined bibliographies for relevant references and used Google
Translate for articles in foreign languages, including Italian, Japanese, German,
Dutch, Turkish, Spanish, Chinese, Dutch, Russian, Portuguese, and Czech. RESULTS:
We identified 220 cases of PSPG (mean age 52.8 years, range 5-85 years). Thirty
seven patients (16.8%) had a history of pyoderma gangrenosum, nineteen (8.6%) had
a hematologic disorder such as leukemia or lymphoma, thirteen (5.9%) had
inflammatory bowel disease, and eight (3.6%) had rheumatoid arthritis. PSPG
occurred most commonly after breast (25%), cardiothoracic (14%), abdominal (14%),
and obstetric (13%) surgeries. The most common breast procedures were bilateral
reduction mammoplasty (45%), breast reconstruction (25%), and lumpectomy or
mastectomy (11%). Signs of wound complication occurred on average 7.0 days after
surgery. Nineteen patients (8.6%) at risk for PSPG received perioperative
corticosteroids during skin grafting or later surgeries with a favorable outcome.
CONCLUSIONS: Patients with a history of pyoderma gangrenosum, rheumatoid
arthritis, inflammatory bowel disease, or hematologic malignancy who are
undergoing breast, cardiothoracic, or abdominal surgeries should be carefully
observed for post-operative ulceration at incision sites. Debridement should not
be performed before dermatologic consultation to assess for PSPG. Patients at
risk of PSPG undergoing breast surgery may benefit from perioperative prednisone
to prevent PSPG which can lead to destructive wound enlargement and significant
scarring.
PMID- 25589460
TI - A simple technique for orientation of neck dissection specimens.
PMID- 25589461
TI - RBPJ inhibition impairs the growth of lung cancer.
AB - The exact effects of the modulation of Notch signaling pathway on cell growth
have been shown to depend on tumor cell type. Recombination signal-binding
protein Jkappa (RBPJ) is a key transcription factor downstream of receptor
activation in Notch signaling pathway. Here, we evaluated the effects of RBPJ
inhibition on the growth of lung cancer cells. We found that a short hairpin
interfering RNA (shRNA) for RBPJ efficiently inhibited RBPJ expression in lung
cancer cells, resulting in a significant decrease in the cell growth. Further
analyses showed that RBPJ inhibition altered the levels of its downstream
targets, including p21, p27, CDK2, Hes1, Bcl-2, and SKP2, to prevent the cells
from growing. Our data thus suggest that shRNA intervention of RBPJ expression
could be a promising therapeutic approach for treating human lung cancer.
PMID- 25589462
TI - Indole-3-carbinol suppresses NF-kappaB activity and stimulates the p53 pathway in
pre-B acute lymphoblastic leukemia cells.
AB - B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common type
of cancer in children. Dramatic improvements in primary therapy for childhood ALL
have led to an overall cure rate of 80 %, providing opportunities for innovative
combined-modality strategies that would increase cure rates while reducing the
toxic side effects of current intensive regimens. In this study, we report that
indole-3-carbinol (I3C), a natural phytochemical found in cruciferous vegetables,
had anti-leukemic properties in BCP-ALL NALM-6 cells. I3C induced cell growth
inhibition by G1 cell cycle arrest and triggered apoptosis in a dose- and time
dependent manner. p53, p21, and Bax proteins showed increased expression after
I3C treatment. Real-time PCR analysis of pro-apoptotic p53 target genes revealed
up-regulation of PUMA, NOXA, and Apaf-1. I3C also suppressed constitutive nuclear
factor-kappaB (NF-kappaB) activation and inhibited the protein expression of NF
kappa B-regulated antiapoptotic (IAP1, Bcl-xL, Bcl-2, XIAP) and proliferative (c
Myc) gene products. Coadministration of I3C with the topoisomerase II inhibitor,
doxorubicin, potentiates cytotoxic effects compared with either agent alone.
Apoptosis induction by the drug combination was associated with enhanced caspase
9 activation and PARP cleavage. Furthermore, I3C abolished doxorubicin-induced NF
kappaB activity as evidenced by decreased nuclear accumulation of p65, inhibition
of IkappaBalpha phosphorylation and its degradation, and decreased NF-kappaB DNA
binding activity. Western blot analysis revealed that doxorubicin-induced Bcl-2
protein expression was inhibited by I3C. Overall, our results indicated that
using nontoxic agents, such as I3C, in combination with anthracyclines might
provide a new insight into the development of novel combination therapies in
childhood BCP-ALL.
PMID- 25589465
TI - Ordered mesoporous silica films with pores oriented perpendicular to a titanium
nitride substrate.
AB - The production of thin mesoporous silica films with small (~2-3 nm) pores
oriented perpendicular to a titanium nitride growth surface is demonstrated using
two methods. These are the growth from a Stober silica solution with surfactant
ordering at the surface of the electrode, and electrochemically assisted growth
from an acidic sol achieved by polarisation of the electrode surface. The
thickness, pore order and pore size that can be achieved with these two methods
is contrasted. A number of methods to vary the pore size by using different
surfactants and swelling agents are explored. The advantage of applying these
growth methods on titanium nitride surfaces is that it provides access to a wider
electrochemical window for nanowire growth and sensor applications with non
aqueous electrolytes whilst retaining good film growth and adhesion properties.
PMID- 25589463
TI - SREBP1 regulates tumorigenesis and prognosis of pancreatic cancer through
targeting lipid metabolism.
AB - Sterol regulatory element-binding protein 1 (SREBP1) is a known transcription
factor of lipogenic genes, which plays important roles in regulating de novo
lipogenesis. Accumulating evidences indicate SREBP1 is involved in tumorigenesis,
yet its role in pancreatic cancer remains unclear. Here, we explored the
expression characteristic and function of SREBP1 in pancreatic cancer. Analysis
of 60 patients with pancreatic ducat cancer showed that SREBP1 level was
significantly higher in pancreatic cancer than that in adjacent normal tissues.
High expression of SREBP1 predicted poor prognosis in patients with pancreatic
cancer. Multivariate analysis revealed that SREBP1 was an independent factor
affecting overall survival. SREBP1 silencing resulted in proliferation inhibition
and induction of apoptosis in pancreatic cancer cells. Mechanistically, lipogenic
genes (acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), and stearoyl-CoA
desaturase-1 (SCD1)) and de novo lipogenesis were promoted by SREBP1. Inhibition
of lipogenic genes through specific inhibitors ablated SREBP1-mediated growth
regulation. Furthermore, depletion of SREBP1 could suppress lipid metabolism and
tumor growth in vivo. Our results indicate that SREBP1 had important role in
tumor progression and appears to be a novel prognostic marker for pancreatic
cancer.
PMID- 25589464
TI - Stable knockdown of LRG1 by RNA interference inhibits growth and promotes
apoptosis of glioblastoma cells in vitro and in vivo.
AB - Leucine-rich alpha2 glycoprotein 1 (LRG1) has been shown to be aberrantly
expressed in multiple human malignancies. However, the biological functions of
LRG1 in human glioblastoma remain unknown. Here, we report for the first time the
role of LRG1 in glioblastoma development based on the preliminary in vitro and in
vivo data. We first confirmed the expression of LRG1 in human glioblastoma cell
lines. Next, to investigate the role of LRG1 in the tumorigenesis and development
of glioblastoma, a short hairpin RNA (shRNA) construct targeting LRG1 mRNA was
transfected into U251 glioblastoma cells to generate a cell line with stably
silenced LRG1 expression. The results showed that silencing of LRG1 significantly
inhibited cell proliferation, induced cell cycle arrest at G0/G1 phase, and
enhanced apoptosis in U251 cells in vitro. Consistently, LRG1 silencing resulted
in the downregulation of key cell cycle factors including cyclin D1, B, and E and
apoptotic gene Bcl-2 while elevated the levels of pro-apoptotic Bax and cleaved
caspase-3, as determined by Western blot analysis. We further demonstrate that
the silencing of LRG1 expression effectively reduced the tumorigenicity of U251
cells, delayed tumor formation, and promoted apoptosis in a xenograft tumor model
in vivo. In conclusion, silencing the expression of LRG1 suppresses the growth of
glioblastoma U251 cells in vitro and in vivo, suggesting that LRG1 may play a
critical role in glioblastoma development, and it may have potential clinical
implications in glioblastoma therapy.
PMID- 25589467
TI - Hole delocalization over adenine tracts in single stranded DNA oligonucleotides.
AB - Adiabatic ionization energies of single stranded DNA oligonucleotides containing
adenine tracts of different sizes have been computed at the DFT level and
compared with the oxidation potentials determined by differential pulse
voltammetry. Geometry optimizations have been performed at the full quantum
mechanical level, including the sugar phosphate backbone and solvent effects. The
observed progressive lowering of the ionization energy upon increasing the number
of consecutive adenines is well predicted, the computed ionization potential
shifts being in very good agreement with the experimental outcomes, both by using
pure and hybrid functionals. The spin density of the oligonucleotide radical
cations is distributed almost over the whole adenine tract, forming delocalized
polarons.
PMID- 25589466
TI - Factor VIII organisation on nanodiscs with different lipid composition.
AB - Nanodiscs (ND) are lipid bilayer membrane patches held by amphiphilic scaffolding
proteins (MSP) of ~10 nm in diameter. Nanodiscs have been developed as lipid
nanoplatforms for structural and functional studies of membrane and membrane
associated proteins. Their size and monodispersity have rendered them unique for
electron microscopy (EM) and single particle analysis studies of proteins and
complexes either spanning or associated to the ND membrane. Binding of blood
coagulation factors and complexes, such as the Factor VIII (FVIII) and the Factor
VIIIa - Factor IXa (intrinsic tenase) complex to the negatively charged activated
platelet membrane is required for normal haemostasis. In this study we present
our work on optimising ND, specifically designed to bind FVIII at close to
physiological conditions. The binding of FVIII to the negatively charged ND rich
in phosphatidylserine (PS) was followed by electron microscopy at three different
PS compositions and two different membrane scaffolding protein (MSP1D1) to lipid
ratios. Our results show that the ND with highest PS content (80 %) and lowest
MSP1D1 to lipid ratio (1:47) are the most suitable for structure determination of
the membrane-bound FVIII by single particle EM. Our preliminary FVIII 3D
reconstruction as bound to PS containing ND demonstrates the suitability of the
optimised ND for structural studies by EM. Further assembly of the activated
FVIII form (FVIIIa) and the whole FVIIIa-FIXa complex on ND, followed by EM and
single particle reconstruction will help to identify the protein-protein and
protein-membrane interfaces critical for the intrinsic tenase complex assembly
and function.
PMID- 25589468
TI - Tunable photoluminescence across the entire visible spectrum from carbon dots
excited by white light.
AB - Although reports have shown shifts in carbon dot emission wavelengths resulting
from varying the excitation wavelength, this excitation-dependent emission does
not constitute true tuning, as the shifted peaks have much weaker intensity than
their dominant emission, and this is often undesired in real world applications.
We report for the first time the synthesis and photoluminescence properties of
carbon dots whose peak fluorescence emission wavelengths are tunable across the
entire visible spectrum by simple adjustment of the reagents and synthesis
conditions, and these carbon dots are excited by white light. Detailed material
characterization has revealed that this tunable emission results from changes in
the carbon dots' chemical composition, dictated by dehydrogenation reactions
occurring during carbonization. These significantly alter the nucleation and
growth process, resulting in dots with either more oxygen-containing or nitrogen
containing groups that ultimately determine their photoluminescence properties,
which is in stark contrast to previous observations of carbon dot excitation
dependent fluorescence. This new ability to synthesize broadband excitable carbon
dots with tunable peak emissions opens up many new possibilities, particularly in
multimodal sensing, in which multiple analytes and processes could be monitored
simultaneously by associating a particular carbon dot emission wavelength to a
specific chemical process without the need for tuning the excitation source.
PMID- 25589469
TI - Effect of real-time teledermatology on diagnosis, treatment and clinical
improvement.
AB - We assessed the effect of real-time teledermatology consultations on diagnosis
and disease management, patients' quality of life and time- and cost-savings. All
consecutive patients with skin diseases attending teledermatology clinics at two
rural hospitals in Jordan were included in the study. Patients were interviewed
at their initial visit and again after eight weeks. Various questionnaires and
forms, including quality of life questionnaires, were used to collect the data.
Ninety teledermatology consultations were performed for 88 patients between
September 2013 and January 2014. A diagnosis was established as part of the
teledermatology consultation in 43% of patients and changed from that of the
referring provider in 19% of patients. The treatment plan was established for 67%
of patients and changed for 9% patients. The mean SF-8 score increased
significantly (P < 0.005). The mean DLQI score decreased significantly (P <
0.005) indicating that there had been an improvement in the patients' quality of
life since baseline. Most patients perceived that the visit to the
teledermatology clinic required less travel time (96%), shorter waiting time
(83%) and less cost (96%) than a visit to the specialist clinic at the main
hospital. The patients' mean satisfaction score was 90.5 (SD 8.5), indicating a
high level of satisfaction. Teledermatology resulted in changes in the patients'
diagnosis and treatment plan, and was associated with improved health state and
quality of life.
PMID- 25589470
TI - Spatially resolved chemical reaction monitoring using magnetic resonance imaging.
AB - Over the previous three decades, the use of MRI for studying dynamic physical and
chemical processes of materials systems has grown significantly. This mini-review
provides a brief introduction to relevant principles of MRI, including methods of
spatial localization, factors contributing to image contrast, and chemical shift
imaging. A few historical examples of (1) H MRI for reaction monitoring will be
presented, followed by a review of recent research including (1) H MRI studies of
gelation and biofilms, (1) H, (7) Li, and (11) B MRI studies of electrochemical
systems, in vivo glucose metabolism monitored with (19) F MRI, and in situ
temperature monitoring with (27) Al MRI. Copyright (c) 2015 John Wiley & Sons,
Ltd.
PMID- 25589471
TI - Fracture fabrication of a multi-scale channel device that efficiently captures
and linearizes DNA from dilute solutions.
AB - This paper describes a simple technique for patterning channels on elastomeric
substrates, at two distinct scales of depth, through the use of controlled
fracture. Control of channel depth is achieved by the careful use of different
layers of PDMS, where the thickness and material properties of each layer, as
well as the position of the layers relative to one another, dictate the depth of
the channels formed. The system created in this work consists of a single 'deep'
channel, whose width can be adjusted between the micron- and the nano-scale by
the controlled application or removal of a uniaxial strain, and an array of
'shallow' nano-scale channels oriented perpendicular to the 'deep' channel. The
utility of this system is demonstrated through the successful capture and
linearization of DNA from a dilute solution by executing a two-step 'concentrate
then-linearize' procedure. When the 'deep' channel is in its open state and a
voltage is applied across the channel network, an overlapping electric double
layer forms within the 'shallow' channel array. This overlapping electric double
layer was used to prevent passage of DNA into the 'shallow' channels when the DNA
molecules migrate into the junctional region by electrophoresis. Release of the
applied strain then allows the 'deep' channel to return to its closed state,
reducing the cross-sectional area of this channel from the micro- to the nano
scale. The resulting hydrodynamic flow and nano-confinement effects then combine
to efficiently uncoil and trap the DNA in its linearized form. By adopting this
strategy, we were able to overcome the entropic barriers associated with
capturing and linearizing DNA derived from a dilute solution.
PMID- 25589472
TI - Nanostructured Zr-Pd metallic glass thin film for biochemical applications.
AB - Zr-Pd metallic glassy thin films with a hierarchical nano-scale structure,
produced by magnetron sputtering of the Zr and Pd powder mixture, demonstrate a
unique combination of physical and biochemical properties. Thermal stability of
the nano-structured glassy samples, their resistance to oxidation in dry air and
phase transformation behavior are discussed in the present work. These binary
alloy samples also show exceptionally high corrosion resistance and spontaneous
passivation in a simulated body fluid. Experiments on the catalytic activity and
biocompatibility of this nanostructured metallic glass indicate that this is a
very suitable material for biochemical applications. Compared to the
multicomponent alloys studied earlier this binary alloy has much simpler chemical
composition, which makes preparation of the sample with defined stoichiometry
easier, especially when the elements have different sputtering rates.
PMID- 25589473
TI - An alkene-promoted borane-catalyzed highly stereoselective hydrogenation of
alkynes to give Z- and E-alkenes.
AB - The stereoselective hydrogenation of alkynes to alkenes is an extremely useful
transformation in synthetic chemistry. Despite numerous reports for the synthesis
of Z-alkenes, the hydrogenation of alkynes to give E-alkenes is still not well
resolved. In particular, selective preparation of both Z- and E-alkenes by the
same catalytic hydrogenation system using molecular H2 has rarely been reported.
In this paper, a novel strategy of using simple alkenes as promoters for the
HB(C6 F5 )2 -catalyzed metal-free hydrogenation of alkynes was adopted.
Significantly, both Z- and E-alkenes can be furnished by hydrogenation with
molecular H2 in high yields with excellent stereoselectivities. Further
experimental and theoretical mechanistic studies suggest that interactions
between H and F atoms of the alkene promoter, borane intermediate, and H2 play an
essential role in promoting the hydrogenolysis reaction.
PMID- 25589474
TI - qPMS9: an efficient algorithm for quorum Planted Motif Search.
AB - Discovering patterns in biological sequences is a crucial problem. For example,
the identification of patterns in DNA sequences has resulted in the determination
of open reading frames, identification of gene promoter elements, intron/exon
splicing sites, and SH RNAs, location of RNA degradation signals, identification
of alternative splicing sites, etc. In protein sequences, patterns have led to
domain identification, location of protease cleavage sites, identification of
signal peptides, protein interactions, determination of protein degradation
elements, identification of protein trafficking elements, discovery of short
functional motifs, etc. In this paper we focus on the identification of an
important class of patterns, namely, motifs. We study the (l, d) motif search
problem or Planted Motif Search (PMS). PMS receives as input n strings and two
integers l and d. It returns all sequences M of length l that occur in each input
string, where each occurrence differs from M in at most d positions. Another
formulation is quorum PMS (qPMS), where the motif appears in at least q% of the
strings. We introduce qPMS9, a parallel exact qPMS algorithm that offers
significant runtime improvements on DNA and protein datasets. qPMS9 solves the
challenging DNA (l, d)-instances (28, 12) and (30, 13). The source code is
available at https://code.google.com/p/qpms9/.
PMID- 25589475
TI - The potential drug-drug interactions of ginkgolide B mediated by renal
transporters.
AB - Ginkgolide B (GB) is a selective and strong antagonist of platelet-activating
factor with great benefits in CNS diseases treatment. The renal excretion
constitutes the predominant secretory pathway of GB. Here, we investigated the
potential role of renal drug transporters in GB urinary excretion. The
intravenous administration of GB was conducted at 10 min post-administration of
probenecid (potential inhibitor of organic anion transporters/organic anion
transporting polypeptides) or bromosulfophthalein (traditional inhibitor of multi
drug resistance proteins) in rats. Pretreated with probenecid, the systemic
exposure of GB was significantly elevated from 8.319 +/- 1.646 to 14.75 +/- 1.328
ug . mL(-1) ?h but with reduced total clearance from 1.17 +/- 0.331 to 0.596 +/-
0.0573 L . h(-1) ?kg(-1) accompanying no changes in plasma elimination half-lives
compared with control group. With no pronounced effect on metabolic elimination,
the decreased total clearance was closely pertained to the reduced renal
excretion, indicating the potential effect of organic anion transporters and/or
organic anion transporting polypeptides in renal secretory of GB from blood to
urine. However, the possible effect of bromosulfophthalein was restricted within
a minor extent, suggesting the mild role of multi-drug resistance protein in GB
renal excretion.
PMID- 25589476
TI - Impact of the number of Robertsonian chromosomes on germ cell death in wild male
house mice.
AB - Previous studies in the house mouse have shown that the presence of Robertsonian
(Rb) metacentric chromosomes in heterozygous condition affects the process of
spermatogenesis. This detrimental effect mainly depends on the number of
metacentrics involved and the complexity of the resulting meiotic figures. In
this study, we aimed at elucidating the relationship between the chromosomal
composition and spermatogenesis impairment in mice present in an area of
chromosomal polymorphism (the so-called Barcelona system BRbS) in which Rb mice
are surrounded by all acrocentric animals, no established metacentric races are
present and the level of structural heterozygosity is relatively low. Using the
terminal deoxinucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)
assay, we report higher frequency of apoptotic spermatogenetic cells in mice
carrying six pairs of metacentrics at the homozygous state than in those carrying
two or three fusions at the heterozygous state. Specifically, we detected a
higher frequency of TUNEL-positive (T+) tubules and of T+ cells per tubule cross
section and also a lower spermatid/spermatocyte ratio. These results indicate
that the number of metacentrics at the homozygous state is more influential in
determining apoptotic germ cell death than that of moderate chromosome
heterozygosity. The percentage of germ cell death lower than 50 % found in our
samples and the geographic distribution of the set of metacentrics within the
BRbS indicate that although the spermatogenic alterations detected in this area
could act as a partial barrier to gene flow, they are not sufficient to prevent
Rb chromosomes from spreading in nature.
PMID- 25589477
TI - Relationship between motor skills, participation in leisure activities and
quality of life of children with Developmental Coordination Disorder: temporal
aspects.
AB - The study examined the relationship between motor skills, participation in
leisure activities and quality of life (QOL), within a temporal context (school
year vs. summer vacation and school days vs. weekends). Parents of 22 children
with Developmental Coordination Disorder (DCD) and of 55 typically developing
children, aged 6-11, filled out two questionnaires relating to their children's
participation in leisure activities (vigorous, moderate and sedentary) and QOL.
The Movement Assessment Battery for Children-2 (MABC-2) was administered to their
children. Results showed that among the children with DCD, balance scores
positively correlated with participation in sedentary activities, and in both
groups both balance and aiming and catching were related to the physical and
school aspects of QOL. Furthermore, participation in vigorous activities in the
summer was positively correlated with social and school QOL. In contrast, among
typically developing children, participation in vigorous activities during the
school year was negatively correlated with school QOL. Finally, in both groups,
participation in sedentary activities during school days was negatively
correlated with school QOL. These results suggest that the parents' perceptions
of their children's QOL may be related to the level of activeness of the leisure
activities but also to temporal aspects. Therefore, it is important that
therapists and educators consider the temporal aspects, when consulting with
parents and their children regarding participation in leisure activities.
PMID- 25589478
TI - Reading comprehension in adolescents with ADHD: exploring the poor comprehender
profile and individual differences in vocabulary and executive functions.
AB - The overall objective of this study was to investigate reading comprehension in
youth with and without a prior diagnosis of attention-deficit hyperactivity
disorder (ADHD). The first goal was to determine whether youth with and without
ADHD matched in word reading ability exhibited differences in reading
comprehension proficiency. The next goal was to determine whether good and poor
comprehenders within the ADHD subgroup differed from each other on language and
academic achievement measures. The third objective was to examine whether word
recognition or oral vocabulary knowledge mediated the effect of ADHD symptoms on
reading comprehension performance. Youth with ADHD scored significantly lower
than the comparison youth on a standardized measure of reading comprehension.
Relative to good comprehenders with ADHD, poor comprehenders with ADHD exhibited
weaknesses in expressive vocabulary, mathematical reasoning, written expression,
and exhibited more executive function (EF) difficulties as reported by the
teacher. Expressive vocabulary and word reading, but not teacher EF ratings,
accounted for unique variance in reading comprehension performance and mediated
the relationship between ADHD symptoms and reading comprehension. Implications
for further research and educational practice are discussed.
PMID- 25589479
TI - Autofluorescence of Skin Advanced Glycation End Products: Marker of Metabolic
Memory in Elderly Population.
AB - BACKGROUND: Advanced glycation end products are involved in the vascular
complications of diabetes, in chronic kidney disease, and in the aging process.
Their accumulation in the elderly people, as reflected by skin autofluorescence
(sAF), may be a marker of metabolic memory. We aimed to examine the association
of sAF with glycemic and renal status 10 years earlier in older persons. METHODS:
In retrospective cohort study, 328 elderly community dwellers aged of 75 years
and over had sAF measurement 10 years after their inclusion in the Three-City
cohort. Fasting plasma glucose and serum creatinine were measured at baseline and
at 10-year follow-up. In 125 participants, HbA1c was available at these two
times. Associations between sAF and the glycemic and renal status 10 years before
were analyzed by multivariate linear regression adjusted for age, sex,
hypertension, body mass index, hypertriglyceridemia, and smoking. RESULTS:
Participants were 82.4 (standard deviation = 4.1) years on average, and their
mean sAF was 2.8 (standard deviation = 0.7) arbitrary units (AU). After
adjustment, sAF was higher in participants with long-standing diabetes (+0.38 AU,
p = .01) or chronic kidney disease (+0.29 AU, p = .02) compared with healthy
participants. sAF was related to fasting plasma glucose (+1 mmol/L associated
with +0.08 AU, p = .01) and HbA1c (+1% associated with +0.15 AU, p = .03) 10
years earlier, but not to the current fasting plasma glucose (p = .82) and HbA1c
(p = .32). sAF was also related to the distal and current estimated glomerular
filtration rates (p = .002 and .004, respectively). CONCLUSIONS: sAF reflects
glycemic and renal status 10 years before, supporting its value as a marker of
metabolic memory in the elderly people.
PMID- 25589480
TI - Predicting speed at traffic lights--the problem with static assessments of
frailty.
PMID- 25589481
TI - Guideline treatment results in regression of atherosclerosis in type 2 diabetes
mellitus.
AB - BACKGROUND: Efficacy of guideline cardiovascular disease prevention regimens may
differ between patients with or without type II diabetes mellitus. We therefore
compared change in carotid artery wall dimensions in type II diabetes mellitus
and non-type II diabetes mellitus patients with a history of a major
cardiovascular disease event, using magnetic resonance imaging. METHODS: Thirty
type II diabetes mellitus patients and 29 age- and sex-matched non-diabetes
mellitus patients with a history of stroke or myocardial infarction and a carotid
artery stenosis (15%-70%) were included. In all patients, treatment was according
to cardiovascular risk management guidelines. At baseline and follow-up, carotid
artery vessel wall dimensions were measured using 1.5 T magnetic resonance
imaging. RESULTS: After 2 years of follow-up, total wall volume of the carotid
artery in type II diabetes mellitus patients decreased by 9.6% (p = 0.016). In
contrast, stabilization rather than regression of carotid artery wall dimensions
was observed in non-diabetes mellitus patients over a 2-year period. Body mass
index was identified as a predictor of total wall volume decrease. CONCLUSIONS:
Guideline treatment arrests atherogenesis in non-diabetes mellitus patients and
even decreases vessel wall dimensions in type II diabetes mellitus patients.
Baseline body mass index predicts cardiovascular disease prevention efficacy
expressed as decrease in total wall volume. These data emphasize the importance
of optimal cardiovascular-prevention, particularly in diabetes patients with a
high body mass index.
PMID- 25589483
TI - Terrestrial basking sea turtles are responding to spatio-temporal sea surface
temperature patterns.
AB - Naturalists as early as Darwin observed terrestrial basking in green turtles
(Chelonia mydas), but the distribution and environmental influences of this
behaviour are poorly understood. Here, we examined 6 years of daily basking
surveys in Hawaii and compared them with the phenology of local sea surface
temperatures (SST). Data and models indicated basking peaks when SST is coolest,
and we found this timeline consistent with bone stress markings. Next, we
assessed the decadal SST profiles for the 11 global green turtle populations.
Basking generally occurs when winter SST falls below 23 degrees C. From 1990 to
2014, the SST for these populations warmed an average 0.04 degrees C yr(-1)
(range 0.01-0.09 degrees C yr(-1)); roughly three times the observed global
average over this period. Owing to projected future warming at basking sites, we
estimated terrestrial basking in green turtles may cease globally by 2100. To
predict and manage for future climate change, we encourage a more detailed
understanding for how climate influences organismal biology.
PMID- 25589484
TI - A new mid-Silurian aquatic scorpion-one step closer to land?
AB - One of the oldest known fossil scorpions, a new species from the mid-Silurian
Eramosa Formation (430 myr) of Ontario, Canada, exhibits several surprising
features. The depositional environment and associated biota indicate a marine
habitat; however, the leg morphology of this scorpion, which has a short tarsus
in common with all Recent scorpions, suggests that a key adaptation for
terrestrial locomotion, the ability to support its weight on a subterminal
'foot', appeared remarkably early in the scorpion fossil record. Specimens are
preserved intact and undisturbed in a splayed posture typical of moults rather
than carcasses. We postulate that these animals were aquatic, but occasionally
ventured into extremely shallow water, or onto a transient subaerially exposed
surface while moulting, before returning to deeper water. Shed exuviae were
preserved in situ by rapid overgrowth of bacterial biofilm.
PMID- 25589482
TI - SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of
ongoing outcome trials.
AB - Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes
mellitus (T2DM), it is likely that interventions to mitigate this risk must
address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose
cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with
apparent multiple effects. Inherent in their mode of action to decrease glucose
reabsorption by the kidneys by increasing urinary glucose excretion, these agents
improve glycaemic control independent of insulin secretion with a low risk of
hypoglycaemia. In this review, we outline those CV risk factors that this class
appears to influence and provide the design features and trial characteristics of
six ongoing outcome trials involving more than 41,000 individuals with T2DM.
Those risk factors beyond glucose that can potentially be modulated positively
with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity,
hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels
and oxidative stress. On the other hand, small increases in low-density
lipoprotein (LDL)-cholesterol levels have also been observed for the class, which
theoretically might offset some of these benefits. The potential translational
impact of these effects is being tested with outcome trials, also reviewed in
this article, powered to assess both macrovascular as well as certain
microvascular outcomes in T2DM. These are expected to begin to report in late
2015.
PMID- 25589485
TI - Ancestor-descendant relationships in evolution: origin of the extant pygmy right
whale, Caperea marginata.
AB - Ancestor-descendant relationships (ADRs), involving descent with modification,
are the fundamental concept in evolution, but are usually difficult to recognize.
We examined the cladistic relationship between the only reported fossil pygmy
right whale, ?Miocaperea pulchra, and its sole living relative, the enigmatic
pygmy right whale Caperea marginata, the latter represented by both adult and
juvenile specimens. ?Miocaperea is phylogenetically bracketed between juvenile
and adult Caperea marginata in morphologically based analyses, thus suggesting a
possible ADR-the first so far identified within baleen whales (Cetacea:
Mysticeti). The ?Miocaperea-Caperea lineage may show long-term morphological
stasis and, in turn, punctuated equilibrium.
PMID- 25589486
TI - New partial skeletons of Palaeocene Nyctitheriidae and evaluation of proposed
euarchontan affinities.
AB - Small-bodied, insectivorous Nyctitheriidae are known in the Palaeogene fossil
record almost exclusively from teeth and fragmentary jaws and have been referred
to Eulipotyphla (shrews, moles and hedgehogs) based on dental similarities. By
contrast, isolated postcrania attributed to the group suggest arboreality and a
relationship to Euarchonta (primates, treeshrews and colugos). Cretaceous
Palaeocene adapisoriculid insectivores have also been proposed as early
euarchontans based on postcranial similarities. We describe the first known
dentally associated nyctitheriid auditory regions and postcrania, and use them to
test the proposed relationship to Euarchonta with cladistic analyses of 415
dental, cranial and postcranial characteristics scored for 92 fossil and extant
mammalian taxa. Although nyctitheriid postcrania share similarities with
euarchontans likely related to arboreality, results of cladistic analyses suggest
that nyctitheriids are closely related to Eulipotyphla. Adapisoriculidae is found
to be outside of crown Placentalia. These results suggest that similarities in
postcranial morphology among nyctitheriids, adapisoriculids and euarchontans
represent separate instances of convergence or primitive retention of climbing
capabilities.
PMID- 25589487
TI - Evidence for the buffer effect operating in multiple species at a national scale.
AB - A long-standing aim of ecologists is to understand the processes involved in
regulating populations. One such mechanism is the buffer effect, where lower
quality habitats are increasingly used as a species reaches higher population
densities, with a resultant average reduction in fecundity and survival limiting
population growth. Although the buffer effect has been demonstrated in
populations of a number of species, a test of its importance in influencing
population growth rates of multiple species across large spatial scales is
lacking. Here, we use habitat-specific population trends for 85 bird species from
long-term national monitoring data (the UK Breeding Bird Survey) to examine its
generality. We find that both patterns of population change and changes in
habitat preference are consistent with the predictions of the buffer effect,
providing support for its widespread operation.
PMID- 25589488
TI - The contribution of post-copulatory mechanisms to incipient ecological speciation
in sticklebacks.
AB - Ecology can play a major role in species diversification. As individuals are
adapting to contrasting habitats, reproductive barriers may evolve at multiple
levels. While pre-mating barriers have been extensively studied, the evolution of
post-mating reproductive isolation during early stages of ecological speciation
remains poorly understood. In diverging three-spined stickleback ecotypes from
two lakes and two rivers, we observed differences in sperm traits between lake
and river males. Interestingly, these differences did not translate into ecotype
specific gamete precedence for sympatric males in competitive in vitro
fertilization experiments, potentially owing to antagonistic compensatory
effects. However, we observed indirect evidence for impeded development of inter
ecotype zygotes, possibly suggesting an early stage of genetic incompatibility
between ecotypes. Our results show that pre-zygotic post-copulatory mechanisms
play a minor role during this first stage of ecotype divergence, but suggest that
genetic incompatibilities may arise at early stages of ecological speciation.
PMID- 25589489
TI - The cost of migration: spoonbills suffer higher mortality during trans-Saharan
spring migrations only.
AB - Explanations for the wide variety of seasonal migration patterns of animals all
carry the assumption that migration is costly and that this cost increases with
migration distance. Although in some studies, the relationships between migration
distance and breeding success or annual survival are established, none has
investigated whether mortality during the actual migration increases with
migration distance. Here, we compared seasonal survival between Eurasian
spoonbills (Platalea leucorodia leucorodia) that breed in The Netherlands and
migrate different distances (ca 1000, 2000 and 4500 km) to winter in France,
Iberia and Mauritania, respectively. On the basis of resightings of individually
marked birds throughout the year between 2005 and 2012, we show that summer,
autumn and winter survival were very high and independent of migration distance,
whereas mortality during spring migration was much higher (18%) for the birds
that wintered in Mauritania, compared with those flying only as far as France
(5%) or Iberia (6%). As such, this study is the first to show empirical evidence
for increased mortality during some long migrations, likely driven by the
presence of a physical barrier (the Sahara desert) in combination with suboptimal
fuelling and unfavourable weather conditions en route.
PMID- 25589490
TI - Leaf P increase outpaces leaf N in an Inner Mongolia grassland over 27 years.
AB - The dynamics of leaf nitrogen (N) and phosphorus (P) have been intensively
explored in short-term experiments, but rarely at longer timescales. Here, we
investigated leaf N : P stoichiometry over a 27-year interval in an Inner
Mongolia grassland by comparing leaf N : P concentration of 2006 with that of
1979. Across 80 species, both leaf N and P increased, but the increase in leaf N
lagged behind that of leaf P, leading to a significant decrease in the N : P
ratio. These changes in leaf N : P stoichiometry varied among functional groups.
For leaf N, grasses increased, woody species tended to increase, whereas forbs
showed no change. Unlike leaf N, leaf P of grasses and forbs increased, whereas
woody species showed no change. Such changes may reflect N deposition and P
release induced by soil acidification over the past decades. The interannual
effect of precipitation may somewhat have reduced the soil available N, leading
to the more modest increase of leaf N than of leaf P. Thus, leaf N : P
stoichiometry significantly responded to long-term environmental changes in this
temperate steppe, but different functional groups responded differently. Our
results indicate that conclusions of plant stoichiometry under short-term N
fertilization should be treated with caution when extrapolating to longer
timescales.
PMID- 25589492
TI - Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase
Inhibitor Enhances Radiation Effect in Bladder Cancer Cells.
AB - Blockade of EGFR has been proved useful in enhancing the effect of radiotherapy,
but the advantages of new-generation EGFR tyrosine kinase inhibitors (TKI) in
radiosensitization are not well known. We used two human bladder cancer cells
with wild-type EGFR to study the synergism between irradiation and afatinib (an
EGFR/HER2 dual kinase inhibitor) or erlotinib (an EGFR kinase inhibitor). Here,
we showed that afatinib has better radiosensitizing effect than erlotinib in
increasing cancer cell killing, the percentage of apoptotic cells, and DNA
damage. Afatinib is also superior to erlotinib in combining radiation to decrease
tumor size, inhibit glucose metabolism, and enhance apoptotic proteins in vivo.
Finally, erlotinib suppressed cell growth and induced more DNA damage in bladder
cancer cells transfected with HER2 shRNA, but not in control vector-treated
cells. In conclusion, concomitant blockade of radiation-activated EGFR and HER2
signaling by a new-generation EGFR TKI better inhibits the growth of bladder
cancer cells both in vitro and in vivo. The absence of radiosensitization by EGFR
inhibition alone and the greater radiosensitizing effect of EGFR inhibitor in
HER2 knocked down cells suggest the synergism between HER2 and EGFR in
determining radiosensitivity. The regained radiosensitizing activity of erlotinib
implies that with proper HER2 inhibition, EGFR tyrosine kinase is still a
potential target to enhance radiotherapy effect in these seemingly unresponsive
bladder cancer cells.
PMID- 25589493
TI - The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985
Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers.
AB - SYD985 is a HER2-targeting antibody-drug conjugate (ADC) based on trastuzumab and
vc-seco-DUBA, a cleavable linker-duocarmycin payload. To evaluate the therapeutic
potential of this new ADC, mechanistic in vitro studies and in vivo patient
derived xenograft (PDX) studies were conducted to compare SYD985 head-to-head
with T-DM1 (Kadcyla), another trastuzumab-based ADC. SYD985 and T-DM1 had similar
binding affinities to HER2 and showed similar internalization. In vitro
cytotoxicity assays showed similar potencies and efficacies in HER2 3+ cell
lines, but in cell lines with low HER2 expression, SYD985 was 3- to 50-fold more
potent than T-DM1. In contrast with T-DM1, SYD985 efficiently induced bystander
killing in vitro in HER2-negative (HER2 0) cells mixed with HER2 3+, 2+, or 1+
cell lines. At pH conditions relevant for tumors, cathepsin-B cleavage studies
showed efficient release of the active toxin by SYD985 but not by T-DM1. These in
vitro data suggest that SYD985 might be a more potent ADC in HER2-expressing
tumors in vivo, especially in low HER2-expressing and/or in heterogeneous tumors.
In line with this, in vivo antitumor studies in breast cancer PDX models showed
that SYD985 is very active in HER2 3+, 2+, and 1+ models, whereas T-DM1 only
showed significant antitumor activity in HER2 3+ breast cancer PDX models. These
properties of SYD985 may enable expansion of the target population to patients
who have low HER2-expressing breast cancer, a patient population with still unmet
high medical need.
PMID- 25589494
TI - CD30 is a potential therapeutic target in malignant mesothelioma.
AB - CD30 is a cytokine receptor belonging to the TNF superfamily (TNFRSF8) that acts
as a regulator of apoptosis. The presence of CD30 antigen is important in the
diagnosis of Hodgkin disease and anaplastic large cell lymphoma. There have been
sporadic reports of CD30 expression in nonlymphoid tumors, including malignant
mesothelioma. Given the remarkable success of brentuximab vedotin, an antibody
drug conjugate directed against CD30 antigen, in lymphoid malignancies, we
undertook a study to examine the incidence of CD30 in mesothelioma and to
investigate the ability to target CD30 antigen in mesothelioma. Mesothelioma
tumor specimens (N = 83) were examined for CD30 expression by IHC. Positive CD30
expression was noted in 13 mesothelioma specimens, primarily those of epithelial
histology. There was no significant correlation of CD30 positivity with tumor
grade, stage, or survival. Examination of four mesothelioma cell lines (H28,
H2052, H2452, and 211H) for CD30 expression by both FACS analysis and confocal
microscopy showed that CD30 antigen localized to the cell membrane. Brentuximab
vedotin treatment of cultured mesothelioma cells produced a dose-dependent
decrease in cell growth and viability at clinically relevant concentrations. Our
studies validate the presence of CD30 antigen in a subgroup of epithelial-type
mesothelioma tumors and indicate that selected mesothelioma patients may derive
benefit from brentuximab vedotin treatment.
PMID- 25589491
TI - The circadian clock in skin: implications for adult stem cells, tissue
regeneration, cancer, aging, and immunity.
AB - Historically, work on peripheral circadian clocks has been focused on organs and
tissues that have prominent metabolic functions, such as the liver, fat, and
muscle. In recent years, skin has emerged as a model for studying circadian clock
regulation of cell proliferation, stem cell functions, tissue regeneration,
aging, and carcinogenesis. Morphologically, skin is complex, containing multiple
cell types and structures, and there is evidence for a functional circadian clock
in most, if not all, of its cell types. Despite the complexity, skin stem cell
populations are well defined, experimentally tractable, and exhibit prominent
daily cell proliferation cycles. Hair follicle stem cells also participate in
recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among
other advantages of skin is a broad repertoire of available genetic tools
enabling the creation of cell type-specific circadian mutants. Also, due to the
accessibility of skin, in vivo imaging techniques can be readily applied to study
the circadian clock and its outputs in real time, even at the single-cell level.
Skin provides the first line of defense against many environmental and stress
factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV)
radiation and temperature. Studies have already linked the circadian clock to the
control of UVB-induced DNA damage and skin cancers. Due to the important role
that skin plays in the defense against microorganisms, it also represents a
promising model system to further explore the role of the clock in the regulation
of the body's immune functions. To that end, recent studies have already linked
the circadian clock to psoriasis, one of the most common immune-mediated skin
disorders. Skin also provides opportunities to interrogate the clock regulation
of tissue metabolism in the context of stem cells and regeneration. Furthermore,
many animal species feature prominent seasonal hair molt cycles, offering an
attractive model for investigating the role of the clock in seasonal organismal
behaviors.
PMID- 25589495
TI - Syngeneic Murine Ovarian Cancer Model Reveals That Ascites Enriches for Ovarian
Cancer Stem-Like Cells Expressing Membrane GRP78.
AB - Patients with ovarian cancer are generally diagnosed at FIGO (International
Federation of Gynecology and Obstetrics) stage III/IV, when ascites is common.
The volume of ascites correlates positively with the extent of metastasis and
negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic
reticulum chaperone that is also expressed on the plasma membrane ((mem)GRP78) of
aggressive cancer cells, plays a crucial role in the embryonic stem cell
maintenance. We studied the effects of ascites on ovarian cancer stem-like cells
using a syngeneic mouse model. Our study demonstrates that ascites-derived tumor
cells from mice injected intraperitoneally with murine ovarian cancer cells (ID8)
express increased (mem)GRP78 levels compared with ID8 cells from normal culture.
We hypothesized that these ascites-associated (mem)GRP78(+) cells are cancer stem
like cells (CSC). Supporting this hypothesis, we show that (mem)GRP78(+) cells
isolated from murine ascites exhibit increased sphere forming and tumor
initiating abilities compared with (mem)GRP78(-) cells. When the tumor
microenvironment is recapitulated by adding ascites fluid to cell culture, ID8
cells express more (mem)GRP78 and increased self-renewing ability compared with
those cultured in medium alone. Moreover, compared with their counterparts
cultured in normal medium, ID8 cells cultured in ascites, or isolated from
ascites, show increased stem cell marker expression. Antibodies directed against
the carboxy-terminal domain of GRP78: (i) reduce self-renewing ability of murine
and human ovarian cancer cells preincubated with ascites and (ii) suppress a
GSK3alpha-AKT/SNAI1 signaling axis in these cells. Based on these data, we
suggest that (mem)GRP78 is a logical therapeutic target for late-stage ovarian
cancer.
PMID- 25589496
TI - Mechanism of Oncogenic Signal Activation by the Novel Fusion Kinase FGFR3
BAIAP2L1.
AB - Recent cancer genome profiling studies have identified many novel genetic
alterations, including rearrangements of genes encoding FGFR family members.
However, most fusion genes are not functionally characterized, and their
potentials in targeted therapy are unclear. We investigated a recently discovered
gene fusion between FGFR3 and BAI1-associated protein 2-like 1 (BAIAP2L1). We
identified 4 patients with bladder cancer and 2 patients with lung cancer
harboring the FGFR3-BAIAP2L1 fusion through PCR and FISH assay screens. To
investigate the oncogenic potential of the fusion gene, we established an FGFR3
BAIAP2L1 transfectant with Rat-2 fibroblast cells (Rat-2_F3-B). The FGFR3
BAIAP2L1 fusion had transforming activity in Rat2 cells, and Rat-2_F3-B cells
were highly tumorigenic in mice. Rat-2_F3-B cells showed in vitro and in vivo
sensitivity in the selective FGFR inhibitor CH5183284/Debio 1347, indicating that
FGFR3 kinase activity is critical for tumorigenesis. Gene signature analysis
revealed that FGFR3-BAIAP2L1 activates growth signals, such as the MAPK pathway,
and inhibits tumor-suppressive signals, such as the p53, RB1, and CDKN2A
pathways. We also established Rat-2_F3-B-DeltaBAR cells expressing an FGFR3
BAIAP2L1 variant lacking the Bin-Amphiphysin-Rvs (BAR) dimerization domain of
BAIAP2L1, which exhibited decreased tumorigenic activity, FGFR3 phosphorylation,
and F3-B-DeltaBAR dimerization, compared with Rat-2_F3-B cells. Collectively,
these data suggest that constitutive dimerization through the BAR domain promotes
constitutive FGFR3 kinase activation and is essential for its potent oncogenic
activity.
PMID- 25589498
TI - Synthesis of lysozyme-metallacarborane conjugates and the effect of boron cluster
modification on protein structure and function.
AB - Two complementary methods, "in solution" and "in solid state", for the synthesis
of lysozyme modified with metallacarborane (cobalt bis(dicarbollide), Co(C2 B9
H11 )2 (2-) ) were developed. As metallacarborane donors, oxonium adducts of
cobalt bis(dicarbollide) and 1,4-dioxane or tetrahydropyran were used. The
physicochemical and biochemical properties of the obtained lysozyme
metallacarborane conjugates were studied for changes in secondary and tertiary
structure, aggregation behavior, and biological activity. Only minor changes in
primary, secondary, and tertiary protein structure were observed, caused by the
single substitution of metallacarborane on lysozyme. However, the modification
produced significant changes in lysozyme enzymatic activity and a tendency toward
time- and temperature-dependent aggregation.
PMID- 25589497
TI - A Combinatory Strategy for Detection of Live CTCs Using Microfiltration and a New
Telomerase-Selective Adenovirus.
AB - Circulating tumor cells (CTC) have become an important biomarker for early cancer
diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent
recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was
shown to detect live CTCs in blood samples of patients with cancer. Here, we
report a new class of adenoviruses containing regulatory elements that repress
the hTERT gene in normal cells. Compared with the virus with only the hTERT core
promoter, the new viruses showed better selectivity for replication in cancer
cells than in normal cells. In particular, Ad5GTSe, containing three extra copies
of a repressor element, displayed a superior tropism for cancer cells among
leukocytes and was thus selected for CTC detection in blood samples. To further
improve the efficiency and specificity of CTC identification, we tested a
combinatory strategy of microfiltration enrichment using flexible micro spring
arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently
detected both cancer cells spiked into healthy blood and potential CTCs in blood
samples of patients with breast and pancreatic cancer, demonstrating its
potential as a highly sensitive and reliable system for detection and capture of
CTCs of different tumor types.
PMID- 25589499
TI - Two decades of the oncologist.
PMID- 25589500
TI - Adjuvant therapy-related shortening of survival (ATRESS): an underrated
phenomenon.
PMID- 25589501
TI - In reply.
PMID- 25589502
TI - Doubling sensitivity in solids NMR: a simple and economical procedure for
compressing samples.
PMID- 25589504
TI - Application of an ultraminiature thermal neutron monitor for irradiation field
study of accelerator-based neutron capture therapy.
AB - Phantom experiments to evaluate thermal neutron flux distribution were performed
using the Scintillator with Optical Fiber (SOF) detector, which was developed as
a thermal neutron monitor during boron neutron capture therapy (BNCT)
irradiation. Compared with the gold wire activation method and Monte Carlo N
particle (MCNP) calculations, it was confirmed that the SOF detector is capable
of measuring thermal neutron flux as low as 10(5) n/cm(2)/s with sufficient
accuracy. The SOF detector will be useful for phantom experiments with BNCT
neutron fields from low-current accelerator-based neutron sources.
PMID- 25589503
TI - Difference in distant failure site between locally advanced squamous cell
carcinoma and adenocarcinoma of the uterine cervix after C-ion RT.
AB - We investigated the first site of distant failure after carbon ion radiotherapy
(C-ion RT) for locally advanced cervical cancer in three clinical trials. A total
of 91 cases were enrolled in the three trials (Protocol 9702, 9704 and 9902).
Histologically, 36 cases had squamous cell carcinoma (SqCC) and 55 cases had
adenocarcinoma (AC), including 13 with adenosquamous cell carcinoma. The number
of cases with Stage IIB, IIIB and IVA disease was 21, 59 and 11, respectively. Of
the 91 cases, 42 had positive pelvic lymph nodes (PLNs). The median tumor size
was 6.0 cm (range, 3.0-12.0 cm). The median follow-up duration for all cases was
40 months (range, 7-181 months). A total of 40 cases developed distant failure as
the first site of failure: 13 of 36 (36.1%) SqCC cases had distant failure, with
9 of them with para-aortic lymph node (PALN) failure; 27 of 55 (44.0%) AC cases
had distant failure, and 23 of them had distant failure excluding PALN
metastasis. Distant failure rates of SqCC cases who had positive and negative
PLNs before C-ion RT were 61.1% and 11.1%, respectively (P = 0.0045). Those of AC
cases were 54.2% and 45.2%, respectively (P = 0.507). In conclusion, there were
high rates of distant failure after C-ion RT in AC cases regardless of PLN
status, and there were high rates of distant failure after C-ion RT, especially
PALN failure, in SqCC cases with positive PLNs.
PMID- 25589506
TI - Structural investigation of the high spin->low spin relaxation dynamics of the
porous coordination network [Fe(pz)Pt(CN)4]?2.6 H2O.
AB - The Hoffman-type coordination compound [Fe(pz)Pt(CN)4]?2.6 H2O (pz = pyrazine)
shows a cooperative thermal spin transition at around 270 K. Synchrotron powder X
Ray diffraction studies reveal that a quantitative photoinduced conversion from
the low-spin (LS) state into the high-spin (HS) state, based on the light-induced
excited spin-state trapping effect, can be achieved at 10 K in a microcrystalline
powder. Time-resolved measurements evidence that the HS->LS relaxation proceeds
by a two-step mechanism: a random HS->LS conversion at the beginning of the
relaxation is followed by a nucleation and growth process, which proceeds until a
quantitative HS->LS transformation has been reached.
PMID- 25589505
TI - Assessment of transposed ovarian movement: how much of a safety margin should be
added during pelvic radiotherapy?
AB - The purpose of this study was to analyze transposed ovarian movement. Data from
27 patients who underwent ovarian transposition after surgical treatment for
uterine cancer were retrospectively analyzed. Computed tomography (CT) images
including transposed ovaries were superimposed on other CT images acquired at
different times, and were matched on bony structures. Differences in ovarian
position between the CT images were measured. The planning organ at risk volume
(PRV) margins were calculated from the formula of the 90% reference intervals
(RIs) and the 95% RI, which were defined as mean +/- 1.65 standard deviation (SD)
and mean +/- 1.96 SD, respectively. The 90% RI in the cranial, caudal, anterior,
posterior, left and right directions were 1.5, 1.5, 1.4, 1.0, 1.7 and 0.9 cm,
respectively. The 95% RI in the corresponding directions were 1.5, 2.0, 1.7, 1.2,
1.9 and 1.2 cm, respectively. These data suggest that bilateral ovaries need a
PRV margin of ~2 cm in all directions. The present study suggests that a
transposed ovary needs the same PRV margin as a normal ovary (~2 cm). Even after
transposition, ovaries should be kept away from the radiation field to take into
consideration the degree of ovarian movement.
PMID- 25589507
TI - The tissue distribution of lipoprotein lipase determines where chylomicrons bind.
AB - To determine the role of LPL for binding of lipoproteins to the vascular
endothelium, and for the distribution of lipids from lipoproteins, four lines of
induced mutant mice were used. Rat chylomicrons labeled in vivo with [(14)C]oleic
acid (primarily in TGs, providing a tracer for lipolysis) and [(3)H]retinol
(primarily in ester form, providing a tracer for the core lipids) were injected.
TG label was cleared more rapidly than core label. There were no differences
between the mouse lines in the rate at which core label was cleared. Two minutes
after injection, about 5% of the core label, and hence chylomicron particles,
were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle,
and had much reduced levels of LPL in the heart, binding of chylomicrons was
reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding
was increased to over 10%. The same patterns of distribution were evident at 20
min when most of the label had been cleared. Thus, the amount of LPL expressed in
muscle and heart governed both the binding of chylomicron particles and the
assimilation of chylomicron lipids in the tissue.
PMID- 25589508
TI - A robust all-atom model for LCAT generated by homology modeling.
AB - LCAT is activated by apoA-I to form cholesteryl ester. We combined two
structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2
position of oxidized (short) acyl chains of phospholipid, and bacteriophage
tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel
homology model for human LCAT. The juxtaposition of multiple structural motifs
matching experimental data is compelling evidence for the general correctness of
many features of the model: i) The N-terminal 10 residues of the model, required
for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15-20
A relative to PLA2. ii) The topography of the trough places the ester bond of the
sn-2 chain less than 5 A from the hydroxyl of the catalytic nucleophile, S181.
iii) A beta-hairpin resembling a lipase lid separates S181 from solvent. iv) S181
interacts with three functionally critical residues: E149, that regulates sn-2
chain specificity, and K128 and R147, whose mutations cause LCAT deficiency.
Because the model provides a novel explanation for the complicated thermodynamic
problem of the transfer of hydrophobic substrates from HDL to the catalytic triad
of LCAT, it is an important step toward understanding the antiatherogenic role of
HDL in reverse cholesterol transport.
PMID- 25589510
TI - Abnormal differentiation of dental pulp cells in cleidocranial dysplasia.
AB - Cleidocranial dysplasia (CCD) is a skeletal dysplasia caused by heterozygous
mutations of RUNX2, a gene that is essential for the mineralization of bone and
tooth. We isolated primary dental pulp cells from a 10-y-old patient and tested
their proliferative capacity, alkaline phosphatase activity, and ability to form
mineralized nodules, in comparison with those from 7 healthy children. All these
measures were reduced in primary dental pulp cells from the CCD patient. The
expression of the osteoblast/odontoblast-associated genes RUNX2, ALP, OCN, and
DSPP was also found to be significantly decreased in the primary dental pulp
cells of the CCD patient. The osteoclast-related markers TRAP, CTSK, CTR, and
MMP9 were decreased in primary dental pulp cells cocultured with human peripheral
blood mononuclear cells. Moreover, the expression of RANKL and the ratio of
RANKL/OPG were both reduced in the cells from the CCD patient, indicating that
the RUNX2 mutation interfered with the bone-remodeling pathway and decreased the
capacity of primary dental pulp cells to support osteoclast differentiation.
These effects may be partly responsible for the defects in tooth development and
the retention of primary teeth that is typical of CCD.
PMID- 25589512
TI - PPARgamma/mTOR signalling: striking the right balance in cartilage homeostasis.
PMID- 25589511
TI - Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a
multicentre, randomised, double-blind, non-inferiority trial versus celecoxib.
AB - OBJECTIVES: To compare the efficacy and safety of chondroitin sulfate plus
glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee
osteoarthritis and severe pain. METHODS: Double-blind Multicentre Osteoarthritis
interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and
Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with
Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain
(Western Ontario and McMaster osteoarthritis index (WOMAC) score >=301; 0-500
scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times
a day or 200 mg celecoxib every day for 6 months. The primary outcome was the
mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes
included WOMAC function and stiffness, visual analogue scale for pain, presence
of joint swelling/effusion, rescue medication consumption, Outcome Measures in
Rheumatology Clinical Trials and Osteoarthritis Research Society International
(OMERACT-OARSI) criteria and EuroQoL-5D. RESULTS: The adjusted mean change (95%
CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and
186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non
inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity
analyses were consistent with that result. At 6 months, 79.7% of patients in the
combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI
criteria. Both groups elicited a reduction >50% in the presence of joint
swelling; a similar reduction was seen for effusion. No differences were observed
for the other secondary outcomes. Adverse events were low and similarly
distributed between groups. CONCLUSIONS: CS+GH has comparable efficacy to
celecoxib in reducing pain, stiffness, functional limitation and joint
swelling/effusion after 6 months in patients with painful knee osteoarthritis,
with a good safety profile. TRIAL REGISTRATION NUMBER: NCT01425853.
PMID- 25589514
TI - Lymphocytic focus score as a prognostic tool.
PMID- 25589513
TI - Suppression of monosodium urate crystal-induced cytokine production by butyrate
is mediated by the inhibition of class I histone deacetylases.
AB - OBJECTIVES: Acute gouty arthritis is caused by endogenously formed monosodium
urate (MSU) crystals, which are potent activators of the NLRP3 inflammasome.
However, to induce the release of active interleukin (IL)-1beta, an additional
stimulus is needed. Saturated long-chain free fatty acids (FFAs) can provide such
a signal and stimulate transcription of pro-IL-1beta. In contrast, the short
chain fatty acid butyrate possesses anti-inflammatory effects. One of the
mechanisms involved is inhibition of histone deacetylases (HDACs). Here, we
explored the effects of butyrate on MSU+FFA-induced cytokine production and its
inhibition of specific HDACs. METHODS: Freshly isolated peripheral blood
mononuclear cells (PBMCs) from healthy donors were stimulated with MSU and
palmitic acid (C16.0) in the presence or absence of butyrate or a synthetic HDAC
inhibitor. Cytokine responses were measured with ELISA and quantitative PCR. HDAC
activity was measured with fluorimetric assays. RESULTS: Butyrate decreased
C16.0+MSU-induced production of IL-1beta, IL-6, IL-8 and IL-1beta mRNA in PBMCs
from healthy donors. Similar results were obtained in PBMCs isolated from
patients with gout. Butyrate specifically inhibited class I HDACs. The HDAC
inhibitor, panobinostat and the potent HDAC inhibitor, ITF-B, also decreased ex
vivo C16.0+MSU-induced IL-1beta production. CONCLUSIONS: In agreement with the
reported low inhibitory potency of butyrate, a high concentration was needed for
cytokine suppression, whereas synthetic HDAC inhibitors showed potent anti
inflammatory effects at nanomolar concentrations. These novel HDAC inhibitors
could be effective in the treatment of acute gout. Moreover, the use of specific
HDAC inhibitors could even improve the efficacy and reduce any potential adverse
effects.
PMID- 25589515
TI - Activating transcription factor 3 regulates canonical TGFbeta signalling in
systemic sclerosis.
AB - BACKGROUND: Activating transcription factor 3 (ATF3), a member of the ATF/cAMP
responsive element binding (CREB) family of transcription factors, regulates
cellular response to stress including oxidative stress. The aim of this study was
to analyse the role of ATF3 in fibroblast activation in systemic sclerosis (SSc).
METHODS: ATF3 was analysed by reverse transcription quantitative PCR, western
blot and immunohistochemistry. ATF3 knockout fibroblasts and mice were used to
study the functional role of ATF3. Knockdown experiments, reporter assays and
coimmunoprecipitation were performed to study the effects of ATF3 on Smad and
activation protein 1 (AP-1) signalling. The role of c-Jun was analysed by
costaining, specific inactivation and coimmunoprecipitation. RESULTS:
Transforming growth factor-beta (TGFbeta) upregulates the expression of ATF3 in
SSc fibroblasts. ATF3-deficient fibroblasts were less sensitive to TGFbeta,
whereas ectopic expression of ATF3 enhanced the profibrotic effects of TGFbeta.
Mechanistically, ATF3 interacts with Smad3 directly on stimulation with TGFbeta
and regulates Smad activity in a c-Jun-dependent manner. Knockout of ATF3
protected mice from bleomycin-induced fibrosis and fibrosis induced by
overexpression of a constitutively active TGFbeta receptor I. Reporter assays and
analyses of the expression of Smad target genes demonstrated that binding of ATF3
regulates the transcriptional activity of Smad3. CONCLUSIONS: We demonstrate for
the first time a key role for ATF3 in fibrosis. Knockout of the ATF3 gene reduced
the stimulatory effect of TGFbeta on fibroblasts by interfering with canonical
Smad signalling and protected the mice from experimental fibrosis in two
different models. ATF3 might thus be a candidate for molecular targeted therapies
for SSc.
PMID- 25589518
TI - Electronic cigarettes: reasons to be cautious.
PMID- 25589516
TI - Immune cells and preterm labour: do invariant NKT cells hold the key?
PMID- 25589519
TI - Functional brain imaging in respiratory medicine.
AB - Discordance of clinical symptoms with markers of disease severity remains a
conundrum in a variety of respiratory conditions. The breathlessness of chronic
lung disease correlates poorly with spirometry, yet is a better predictor of
mortality. In chronic cough, symptoms are often evident without clear physical
cause. In asthma, the terms 'over perceivers' and 'under perceivers' are common
parlance. In all these examples, aberrant brain mechanisms may explain the
mismatch between symptoms and pathology. Functional MRI is a non-invasive method
of measuring brain function. It has recently become significantly advanced enough
to be useful in clinical research and to address these potential mechanisms. This
article explains how FMRI works, current understanding from FMRI in
breathlessness, cough and asthma and suggests possibilities for future research.
PMID- 25589517
TI - Activation of decidual invariant natural killer T cells promotes
lipopolysaccharide-induced preterm birth.
AB - Invariant natural killer T (iNKT) cells are crucial for host defense against a
variety of microbial pathogens, but the underlying mechanisms of iNKT cells
activation by microbes are not fully explained. In this study, we investigated
the molecular mechanisms of iNKT cell activation in lipopolysaccharide (LPS)
stimulated preterm birth using an adoptive transfer system and diverse
neutralizing antibodies (Abs) and inhibitors. We found that adoptive transfer of
decidual iNKT cells to LPS-stimulated iNKT cell deficient Jalpha18(-/-) mice that
lack invariant Valpha14Jalpha281T cell receptor (TCR) expression significantly
decreased the time to delivery and increased the percentage of decidual iNKT
cells. Neutralizing Abs against Toll-like receptor 4 (TLR-4), CD1d, interleukin
(IL)-12 and IL-18, and inhibitors blocking the activation of nuclear factor
kappaB (NF-kappaB), mitogen-activated protein kinase (MAPK) p38 and extracellular
signal-regulated kinase (ERK) significantly reduced in vivo percentages of
decidual iNKT cells, their intracellular interferon (IFN)-gamma production and
surface CD69 expression. In vitro, in the presence of the same Abs and inhibitors
used as in vivo, decidual iNKT cells co-cultured with LPS-pulsed dendritic cells
(DCs) showed significantly decreased extracellular and intracellular IFN-gamma
secretion and surface CD69 expression. Our data demonstrate that the activation
of decidual iNKT cells plays an important role in inflammation-induced preterm
birth. Activation of decidual iNKT cells also requires TLR4-mediated NF-kappaB,
MAPK p38 and ERK pathways, the proinflammatory cytokines IL-12 and IL-18, and
endogenous glycolipid antigens presented by CD1d.
PMID- 25589520
TI - An alternative framework to investigating and understanding intraindividual
processes in substance abuse recovery: an idiographic approach and demonstration.
AB - BACKGROUND: Sustained recovery from substance abuse is a dynamic intraindividual
level process. OBJECTIVES: We argue that research on recovery process will
benefit from a theoretical approach that captures both the dynamic and the
idiographic nature of substance abuse recovery. In addition to setting out why we
believe that research on recovery can benefit from such an approach, we provide a
demonstration of idiographic within-individual analyses of between- and within
day associations among negative affect, substance use craving, and positive
social experiences. DESIGN AND SUBJECTS: The data used were drawn from 39
abstinent young adults in 12-step recovery from substance abuse (mean age = 22.9,
females = 12). Participants provided an average of 26.7 days of daily diary data
by end-of-day collections. Unified first-order structural equation models were
fit individually to predict daily levels of craving and negative affect from the
previous day's same two variables as well as from both the previous day's and the
same day's positive social experiences. RESULTS: Model estimates demonstrated
substantial interindividual heterogeneity in their day-to-day associations in
both direction and magnitude, highlighting the importance of applying idiographic
approach to understanding recovery. Cluster analyses were subsequently applied to
individual model estimates to identify homogeneous subgroups that demonstrated
similar day-to-day association patterns, revealing two distinct subgroups that
appeared to manage daily abstinence through different mechanisms. CONCLUSIONS:
The idiographic approach presented provides the potential value of framing
recovery as an idiosyncratic dynamic process and provides targets for tailored
and adaptive treatment and recovery supporting intervention in future design and
evaluation.
PMID- 25589521
TI - Extrafloral-nectar-based partner manipulation in plant-ant relationships.
AB - Plant-ant interactions are generally considered as mutualisms, with both parties
gaining benefits from the association. It has recently emerged that some of these
mutualistic associations have, however, evolved towards other forms of
relationships and, in particular, that plants may manipulate their partner ants
to make reciprocation more beneficial, thereby stabilizing the mutualism.
Focusing on plants bearing extrafloral nectaries, we review recent studies and
address three key questions: (i) how can plants attract potential partners and
maintain their services; (ii) are there compounds in extrafloral nectar that
could mediate partner manipulation; and (iii) are ants susceptible to such
compounds? After reviewing the current knowledge on plant-ant associations, we
propose a possible scenario where plant-derived chemicals, such as secondary
metabolites, known to have an impact on animal brain, could have evolved in
plants to attract and manipulate ant behaviour. This new viewpoint would place
plant-animal interaction in a different ecological context, opening new
ecological and neurobiological perspectives of drug seeking and use.
PMID- 25589523
TI - Understanding Patients' Preferences for Referrals to Specialists for an
Asymptomatic Condition.
AB - BACKGROUND: A specialty referral is a common but complex decision that often
requires a primary care provider to balance his or her own interests with those
of the patient. OBJECTIVE: To examine the factors that influence a patient's
choice of a specialist for consultation for an asymptomatic condition and better
understand the tradeoffs that patients are and are not willing to make in this
decision. DESIGN: Stratified cross-sectional convenience sample of subjects
selected to parallel US population demographics. PARTICIPANTS: Members of an
Internet survey panel who reported seeing a physician in the past year whose
responses met objective quality metrics for attention. MAIN MEASURES: Respondents
completed an adaptive conjoint analysis survey comparing specialists regarding
eight attributes. The reliability of assessments and the predictive validity of
models were measured using holdout samples. The relative importance (RI) of
different attributes was computed using paired t tests. The implications of
utility values were studied using market simulation methods. KEY RESULTS: Five
hundred and thirty subjects completed the survey and had responses that met
quality criteria. The reliability of responses was high (86% agreement), and
models were predictive of patients' preferences (82.6% agreement with holdout
choices). The most important attribute for patients was out-of-pocket cost (RI of
19.5%, P < 0.0001 v. other factors). Among the nonfinancial factors,
"collaboration and communication" with the primary care provider was the most
important attribute (RI of 13.1% P < 0.001). Third in importance was whether the
specialist practiced shared decision making (RI of 12.2% P < 0.001 v. other
factors except delay in consultation). Cost did not dominate decision making. In
market simulations, patients frequently preferred more expensive providers. For
example, most patients (76.3%) were willing to pay more ($80) to see a specialist
who both collaborated well with their primary care provider and practiced shared
decision making. Most patients prefer to wait for a doctor who practices shared
decision making: Only one-third (32.3%) of patients preferred a paternalistic
doctor who was available in 2 weeks over a doctor who practiced decision making
but was available in 4 weeks. CONCLUSIONS: In the setting of a referral for an
asymptomatic but serious condition, out-of-pocket costs are important to
patients; however, they also value specialists who collaborate and communicate
well with their primary care providers and who practice shared decision making.
Patients have wide variability in preferences for specialists, and referral
decisions should be individualized.
PMID- 25589524
TI - Graphical representation of life paths to better convey results of decision
models to patients.
AB - The inclusion of patients' perspectives in clinical practice has become an
important matter for health professionals, in view of the increasing attention to
patient-centered care. In this regard, this report illustrates a method for
developing a visual aid that supports the physician in the process of informing
patients about a critical decisional problem. In particular, we focused on
interpretation of the results of decision trees embedding Markov models
implemented with the commercial tool TreeAge Pro. Starting from patient-level
simulations and exploiting some advanced functionalities of TreeAge Pro, we
combined results to produce a novel graphical output that represents the
distributions of outcomes over the lifetime for the different decision options,
thus becoming a more informative decision support in a context of shared decision
making. The training example used to illustrate the method is a decision tree for
thromboembolism risk prevention in patients with nonvalvular atrial fibrillation.
PMID- 25589525
TI - Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based
US Online Sample.
AB - BACKGROUND: . While choices about genetic testing are increasingly common for
patients and families, and public opinion surveys suggest public interest in
genomics, it is not known how adults from the general population value genetic
testing for heritable conditions. We sought to understand in a US sample the
relative value of the characteristics of genetic tests to identify risk of
hereditary colorectal cancer, among the first genomic applications with evidence
to support its translation to clinical settings. METHODS: . A Web-enabled choice
format conjoint survey was conducted with adults age 50 years and older from a
probability-based US panel. Participants were asked to make a series of choices
between 2 hypothetical blood tests that differed in risk of false-negative test,
privacy, and cost. Random parameters logit models were used to estimate
preferences, the dollar value of genetic information, and intent to have genetic
testing. RESULTS: . A total of 355 individuals completed choice-format questions.
Cost and privacy were more highly valued than reducing the chance of a false
negative result. Most (97% [95% confidence interval (CI)], 95%-99%) would have
genetic testing to reduce the risk of dying of colorectal cancer in the best
scenario (no false negatives, results disclosed to primary care physician). Only
41% (95% CI, 25%-57%) would have genetic testing in the worst case (20% false
negatives, results disclosed to insurance company). CONCLUSIONS: . Given the
characteristics and levels included in the choice, if false-negative test results
are unlikely and results are shared with a primary care physician, the majority
would have genetic testing. As genomic services become widely available, primary
care professionals will need to be increasingly knowledgeable about genetic
testing decisions.
PMID- 25589526
TI - Oral squamous cell carcinoma in a patient treated with long-term pegylated
liposomal doxorubicin for recurrent ovarian cancer.
AB - We present a case of a woman who developed an oral squamous cell carcinoma (SCC)
after being treated for a recurrent ovarian carcinoma with subtotal gastric
resection and adjuvant pegylated liposomal doxorubicin (PLD). She received six
cycles of PLD induction and maintenance therapy, which was continued for 5 years.
She was free from disease at the following visits but 3 years later she developed
SCC of her left inferior edentulous gums. The patient was negative for human
papillomavirus and had never smoked in her life or had a history of alcohol use
or any other environmental risk factors. PLD is known to accumulate in eccrine
glands of the hands and the feet and in the oral mucosa, therefore causing skin
toxicity and mucositis. It is conceivable that this specific biodistribution to
the oral mucosa may be responsible for the onset of SCC.
PMID- 25589528
TI - Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?
AB - Rabies remains a serious public health problem in many developing countries. The
diagnosis is easy when a non-immunised patient presents with hydrophobia and
hypersalivation after a bite by a known rabid animal but more difficult when a
patient presents atypical symptoms after having received rabies postexposure
prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of
a 6-year-old boy who presented febrile seizure with agitation and cerebellar
signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite
four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation
of rabies encephalitis was made in post mortem on brain biopsies by fluorescent
antibody technique.
PMID- 25589527
TI - Airway compromise due to adenoid cystic carcinoma obstructing the distal trachea:
a review of current management and clinical trials.
AB - An 84-year-old man presented with a 2-month history of intermittent stridor and
worsening difficulty in breathing. Chest X-ray and flexible nasendoscopy were
unremarkable but following further deterioration a CT scan revealed an
obstructing lesion in the distal trachea. Bronchoscopy revealed an infiltrative
tumour arising 3 cm above the carina causing 90% obstruction. The mass was
biopsied and surgically debrided to leave a patent airway. Histological analysis
revealed a diagnosis of adenoid cystic carcinoma. Transthoracic surgical
resection was unsuccessful and the patient continues to be effectively managed
with periodic bronchoscopic debulking and radiotherapy. This case highlights the
diagnostic and therapeutic dilemmas posed by distal tracheal lesions and the need
for specialist input for effective management.
PMID- 25589529
TI - An unusual parotid mass.
AB - A 70-year-old Caucasian man with multiple comorbidities presented with a painless
lump over the right parotid gland which was gradually increasing in size over the
preceding 12 months. There were no systemic symptoms or facial weakness. Imaging
indicated a benign tumour of the right parotid. Superficial parotidectomy was
performed and the histology revealed a sialolipoma.
PMID- 25589530
TI - Langerhans cell histiocytosis (LCH) of the mandible in an adult: a rare case.
PMID- 25589531
TI - Enterobiasis: threadworm infection presenting as acute appendicitis in a 13-year
old girl.
PMID- 25589532
TI - Relationship between expression and methylation of obesity-related genes in
children.
AB - Epigenetic control of gene expression in children remains poorly understood, but
new technologies can help elucidate the relationship between expression and DNA
methylation. Here, we utilized the nCounter Analysis System to characterise the
expression of 60 genes in 69 9-year-old children from a cohort with a high
prevalence of obesity. nCounter expression levels ranged broadly (from 3 to over
10000 messenger RNA counts) and were divided into four categories: high (>2000
counts), moderate (200-1000 counts), low (100-200 counts) and marginal (<100
counts). For a subset of five genes (ADIPOR1, PPARG1, GSTM1, PON1 and ACACA) from
different expression level categories, we validated nCounter data using reverse
transcription-polymerase chain reaction (RT-PCR), and expanded RT-PCR analysis of
ADIPOR1 to include 180 children. Expression data from the two methodologies were
correlated for all five genes included in the validation experiment, with
estimates ranging from r s = 0.26 (P = 0.02) to r s = 0.88 (P < 5*10(-6)).
ADIPOR1 and PPARG1 nCounter expression levels were negatively correlated (r =
0.60, P < 5*10(-5)), and this relationship was stronger in overweight children (r
= -0.73, P < 5*10(-5)) than in normal weight children (r = -0.42, P = 0.016).
Using methylation data from the Infinium HumanMethylation450 BeadChip (n = 180),
we found eight CpG sites in ADIPOR1 and PPARG where methylation level was
associated with expression by RT-PCR (P < 0.05). Hypomethylation of PPARG gene
body site cg10499651 was associated with increased expression as measured by both
RT-PCR and nCounter (P < 0.05). We found no statistically significant
relationships between either expression or methylation of ADIPOR1 and PPARG and
body mass index or waist circumference. In addition to demonstrating the validity
of expression data derived from nCounter, our results illustrate the use of new
technologies in assessing epigenetic effects on expression in children.
PMID- 25589534
TI - Abnormal stress-related measures of arterial stiffness in middle-aged and elderly
men and women with impaired fasting glucose at risk for a first episode of
symptomatic heart failure.
AB - BACKGROUND: Abnormal resting arterial stiffness is present in middle-aged and
elderly persons with abnormalities of fasting glucose (diabetes or impaired
fasting glucose) and is associated with exercise intolerance. We sought to
determine whether these same persons exhibited stress-related abnormalities of
arterial stiffness. METHODS AND RESULTS: We analyzed dobutamine magnetic
resonance stress imaging results from 373 consecutively recruited persons aged 55
to 85 years with normal fasting glucose, impaired fasting glucose, or diabetes
who were at risk for but without symptomatic heart failure. Personnel blinded to
participant identifiers measured arterial stiffness (brachial pulse pressure/left
ventricular stroke volume indexed to body surface area, the aortic elastance
index [brachial end-systolic pressure/left ventricular stroke volume indexed to
body surface area], and thoracic aortic distensibility) at 80% of the maximum
predicted heart rate response for age. Participants averaged 69+/-8 years of age;
79% were white, 92% were hypertensive, and 66% were women. After accounting for
hypertension, sex, coronary artery disease, smoking, medications,
hypercholesterolemia, and visceral fat, we observed an effect of glycemic status
for stress measures of arterial stiffness in those with diabetes and impaired
fasting glucose relative to those with normal fasting glucose (P=0.002, P=0.02,
and P=0.003, respectively). CONCLUSION: Middle- and older-aged individuals with
diabetes or impaired fasting glucose have higher stress measures of arterial
stiffness than those with normal fasting glucose. These data emphasize the need
for future studies with larger sample sizes to determine whether stress-related
elevations in arterial stiffness are related to exercise intolerance and future
episodes of heart failure experienced by those with abnormalities of fasting
glucose. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/. Unique
identifier: NCT00542503.
PMID- 25589537
TI - Supratentorial ependymoma presenting as a cortical cyst with a mural nodule in an
adult.
AB - Supratentorial ependymoma is a rare tumour in the adult central nervous system.
We present an unusual case of supratentorial ependymoma in a young adult that
presented as a pure cortical cyst with a mural nodule and discuss the
differential diagnosis of such lesions in the brain.
PMID- 25589535
TI - Resting heart rate and risk of incident heart failure: three prospective cohort
studies and a systematic meta-analysis.
AB - BACKGROUND: The relationship between resting heart rate (RHR) and incident heart
failure (HF) has been questioned. METHODS AND RESULTS: RHR was assessed at
baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health
Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded
1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of
participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR
correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose
(r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine
(r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF
risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm)
versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence
interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to
1.53) with further adjustment for body mass index, history of diabetes,
hypertension, smoking status, serum creatinine, and left ventricular hypertrophy.
These findings remained consistent in analyses accounting for incident coronary
heart disease, excluding individuals with prior cardiovascular events, or those
taking beta-blockers; and in subgroups defined by several individual participant
characteristics. In a pooled random effects meta-analysis of 7 population-based
studies (43 051 participants and 3476 HF events), the overall hazard ratio
comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64).
CONCLUSIONS: There is a non-linear association between RHR and incident HF.
Further research is needed to understand the physiologic foundations of this
association.
PMID- 25589536
TI - Comparison of heritability of Cystatin C- and creatinine-based estimates of
kidney function and their relation to heritability of cardiovascular disease.
AB - BACKGROUND: Decreased renal function is an established risk factor for
cardiovascular disease (CVD). Causal mechanisms between estimates of renal
function and CVD are intricate and investigation of the relative importance of
genetic and environmental factors for the variability of these phenotypes could
provide new knowledge. METHODS AND RESULTS: Cystatin C and creatinine levels in
12 313 twins were analyzed. Uni- and bivariate heritability for these traits and
CVD was estimated through structured equation modelling and genome-wide complex
trait analysis (GCTA) in order to independently confirm additive genetic effects.
Twin model-estimated heritability of Cystatin C was 0.55 (95% confidence interval
[CI], 0.49 to 0.60) in men, 0.63 (0.59 to 0.66) in women, and 0.60 (0.56 to 0.63)
in both sexes combined. For creatinine, heritability estimates were in the same
range. Heritability of CVD was 0.39 (0.02 to 0.67) in men and 0.20 (0.00 to 0.61)
in women. The phenotypic correlation between Cystatin C and CVD correlation was
0.16 (0.12 to 0.20) in men and 0.17 (0.13 to 0.21) in women, whereas the genetic
correlation in males was 0.41 (0.21 to 0.62) while it was non-significant in
females. Trough GCTA, the heritability of Cystatin C and creatinine in both sexes
combined was estimated to 0.40 (SE 0.07, P=8E(-9)) and 0.19 (SE 0.07, P=0.003),
respectively. CONCLUSIONS: Twin model-based heritability of Cystatin C was higher
compared to previous studies. Co-variation between Cystatin C and CVD in males
was partly explained by additive genetic components, indicating that Cystatin C
and CVD share genetic influences. The GCTA provided independent evidence for
significant contribution of additive genetics to trait variance of Cystatin C.
PMID- 25589538
TI - An 18-year-old woman with a 34-cm metaplastic breast carcinoma.
AB - Metaplastic breast carcinomas (MBCs) are rare malignancies usually with poor
prognosis. We report a case of an 18-year-old African female patient who
presented with a 34-cm tumor on the right breast. Biopsy showed an extensively
necrotic MBC negative for estrogen receptor, progesterone receptor and human
epidermal growth factor receptor 2 (triple negative). A modified right radical
mastectomy was performed, followed by adjuvant chemotherapy. Histology confirmed
a widely necrotic undifferentiated malignant tumor, with strong and diffuse
expression of vimentin and B-cell lymphoma 2, focal high-molecular-weight
keratins and focal CD34 expression; Ki67 was >90%. There was no skin, deep margin
or lymph node involvement. Six months after surgery, the patient showed a 9 * 7
cm nodule adjacent to the suture and adherent to the anterior chest wall. The
tumor was considered unresectable and the patient evolved with rapid systemic
deterioration. The patient had a progression-free survival of 6 months and
overall survival of 9 months.
PMID- 25589539
TI - A simple case of gallstone ileus?
AB - A 68-year-old gentleman presented with abdominal distension and faeculent
vomiting. He had a background of cerebral palsy with learning difficulties making
history taking problematic. A CT scan suggested small bowel obstruction secondary
to gallstone ileus. The most likely differential diagnosis was an inguinal hernia
which was noted adjacent to the transition point. Laparotomy revealed grossly
dilated small bowel with a 3-cm intraluminal gallstone. The gallstone was freely
mobile within the lumen on the ileum and thus could not be causing obstruction. A
caecal mass was also found, which was determined to be the cause of the
obstruction. Limited ileocaecectomy was performed, which revealed a Duke's A
adenocarcinoma. Gallstone ileus and caecal tumour can commonly be confused prior
to surgery. There are however no previous reports of concurrent gallstone ileus
and caecal tumour. Communication issues with the patient are likely to have
contributed to the difficulty in diagnosis.
PMID- 25589540
TI - Perforation of the splenic flexure of the colon by an ingested wooden toothpick.
AB - We present the case of a 23-year-old man who consulted in the emergency
department 6 days after ingesting a wooden toothpick with features of a localized
peritonitis in the left upper quadrant of the abdomen. Surgical exploration
revealed a perforation of the splenic flexure of the colon by the toothpick
during its migration. This rare case is analysed in the light of the current
literature. There is need for a greater awareness about the dangers of a
swallowed toothpick. It is advisable to always trace the toothpick until it is
found or expelled.
PMID- 25589541
TI - Effect of Delay to Definitive Surgical Fixation on Wound Complications in the
Treatment of Closed, Intra-articular Calcaneus Fractures.
AB - BACKGROUND: There are conflicting data regarding the benefits of delaying
operative fixation of calcaneus fractures to decrease wound complication rates.
The purpose of this study was to examine the effect of delaying fixation on wound
complication rates as well as to identify other risk factors. METHODS: A
retrospective review at 4 institutions, including 24 surgeons, identified 405
closed, operatively treated, intra-articular calcaneus fractures. We compared
fractures with and without wound complications with regards to patient
demographics, medical risk factors, fracture severity, time to fixation,
operative approach, primary subtalar arthrodesis, and surgeon experience.
RESULTS: Wound complications were observed in 21% (87/405) of fractures, of which
33% (29/87) required operative intervention. Male sex (P = .032), smoking (P =
.028), and the extensile lateral approach (P < .001) were associated with higher
complication rates. Fractures treated with an extensile lateral approach had an
overall wound complication rate of 32.1%, while those treated with a sinus tarsi
or percutaneous approach had an overall wound complication rate of 8.3% (odds
ratio [OR], 5.3; 95% confidence interval [CI], 2.9-9.5; P < .001). Among patients
treated with an extensile lateral approach, delayed operative fixation did not
decrease wound complication rates despite comparable fracture severity across
time points. In contrast, among fractures treated with less invasive approaches,
delayed fixation beyond 2 weeks resulted in a significantly increased wound
complication rate of 15.2% as compared to a wound complication rate of only 2.1%
among fractures treated within a week of injury (OR, 3.2; 95% CI, 1.3-9.5; P =
.01). This was observed despite similar fracture severity across time points.
Primary subtalar arthrodesis did not impact complication rates. A higher wound
complication rate among senior surgeons was likely secondary to their
predilection for the extensile lateral approach. CONCLUSION: Delaying definitive
fixation of closed, intra-articular calcaneus fractures did not decrease wound
complication rates when using the extensile lateral approach, and we found an
increased wound complication rate when using less invasive approaches. LEVEL OF
EVIDENCE: Level III, observational study.
PMID- 25589542
TI - Correlation of postoperative midfoot position with outcome following
reconstruction of the stage II adult acquired flatfoot deformity.
AB - BACKGROUND: No studies investigating the effect of the midfoot (talonavicular
joint) position on clinical outcomes following flatfoot reconstruction have been
performed. The purpose of our study was to determine whether a postoperative
abducted or adducted forefoot alignment, as determined from anteroposterior (AP)
radiographs, was associated with a difference in outcomes using the Foot and
Ankle Outcome Score (FAOS). METHODS: Midfoot abduction was defined on
postoperative AP radiographs, evaluated at a mean of 1.9 years in 55 patients
from the authors' institution who underwent flatfoot reconstruction for a stage
II adult acquired flatfoot deformity (AAFD), as a lateral incongruency angle
greater than 5 degrees, a talonavicular uncoverage angle greater than 8 degrees,
and a talo-first metatarsal angle greater than 8 degrees based on previously
reported measurements. Patients with 2 or more measurements in the abduction
category were classified as the abduction group (n = 30); those with 1 or fewer
measurements in the abduction category were placed in the adduction group (n =
25). The preoperative and postoperative FAOS values with a mean follow-up of 3.1
years were compared using Wilcoxon rank-sum tests. RESULTS: Patients corrected to
a position of adduction showed significantly lower improvement in the FAOS daily
activities (P = .012) and quality of life subscales (P = .046). The mean
improvement in subscale scores for the adducted group was lower for pain (P =
.052) and sports activities (P = .085) but did not reach statistical
significance. No significant difference in the FAOS symptoms subscale (P = .372)
between groups was found. CONCLUSION: Correction of the talonavicular joint to a
position of adduction following a stage II AAFD was associated with decreased
patient outcomes in daily activities and quality of life compared with an
abducted position. These results suggest that overcorrection to a position of
midfoot adduction leads to a lesser amount of individual patient improvement in
reconstruction of a stage II AAFD.
PMID- 25589543
TI - DNA lesion identity drives choice of damage tolerance pathway in murine cell
chromosomes.
AB - DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology
dependent repair (HDR) functions to bypass DNA lesions encountered during
replication, and is critical for maintaining genome stability. Here, we present
piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA
containing a known lesion, measures the division of labor between the two DDT
pathways. We show that in the absence of DNA damage response, tolerance of the
most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse
embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is
bypassed primarily by HDR, providing the first evidence for this mechanism being
the main tolerance pathway for a biologically important lesion in a mammalian
genome. We also show that, far from being a last-resort strategy as it is
sometimes portrayed, TLS operates alongside nucleotide excision repair, handling
40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic
stem cells, exhibiting the same pattern-mutagenic TLS included-despite the risk
of propagating mutations along all cell lineages. The new method highlights the
importance of HDR, and provides an effective tool for studying DDT in mammalian
cells.
PMID- 25589544
TI - Opposing roles of H3- and H4-acetylation in the regulation of nucleosome
structure--a FRET study.
AB - Using FRET in bulk and on single molecules, we assessed the structural role of
histone acetylation in nucleosomes reconstituted on the 170 bp long Widom 601
sequence. We followed salt-induced nucleosome disassembly, using donor-acceptor
pairs on the ends or in the internal part of the nucleosomal DNA, and on H2B
histone for measuring H2A/H2B dimer exchange. This allowed us to distinguish the
influence of acetylation on salt-induced DNA unwrapping at the entry-exit site
from its effect on nucleosome core dissociation. The effect of lysine acetylation
is not simply cumulative, but showed distinct histone-specificity. Both H3- and
H4-acetylation enhance DNA unwrapping above physiological ionic strength;
however, while H3-acetylation renders the nucleosome core more sensitive to salt
induced dissociation and to dimer exchange, H4-acetylation counteracts these
effects. Thus, our data suggest, that H3- and H4-acetylation have partially
opposing roles in regulating nucleosome architecture and that distinct aspects of
nucleosome dynamics might be independently controlled by individual histones.
PMID- 25589545
TI - Amplification of small molecule-inducible gene expression via tuning of
intracellular receptor densities.
AB - Ligand-responsive transcription factors in prokaryotes found simple small
molecule-inducible gene expression systems. These have been extensively used for
regulated protein production and associated biosynthesis of fine chemicals.
However, the promoter and protein engineering approaches traditionally used often
pose significant restrictions to predictably and rapidly tune the expression
profiles of inducible expression systems. Here, we present a new unified and
rational tuning method to amplify the sensitivity and dynamic ranges of versatile
small molecule-inducible expression systems. We employ a systematic variation of
the concentration of intracellular receptors for transcriptional control. We show
that a low density of the repressor receptor (e.g. TetR and ArsR) in the cell can
significantly increase the sensitivity and dynamic range, whereas a high
activator receptor (e.g. LuxR) density achieves the same outcome. The
intracellular concentration of receptors can be tuned in both discrete and
continuous modes by adjusting the strength of their cognate driving promoters. We
exemplified this approach in several synthetic receptor-mediated sensing
circuits, including a tunable cell-based arsenic sensor. The approach offers a
new paradigm to predictably tune and amplify ligand-responsive gene expression
with potential applications in synthetic biology and industrial biotechnology.
PMID- 25589546
TI - Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of
the TRAMP complex is mediated by short peptides and important for snoRNA
processing.
AB - The RNA exosome is one of the main 3' to 5' exoribonucleases in eukaryotic cells.
Although it is responsible for degradation or processing of a wide variety of
substrate RNAs, it is very specific and distinguishes between substrate and non
substrate RNAs as well as between substrates that need to be 3' processed and
those that need to be completely degraded. This specificity does not appear to be
determined by the exosome itself but rather by about a dozen other proteins. Four
of these exosome cofactors have enzymatic activity, namely, the nuclear RNA
dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical
poly(A) polymerases, Trf4 and Trf5. Mtr4 and either Trf4 or Trf5 assemble into a
TRAMP complex. However, how these enzymes assemble into a TRAMP complex and the
functional consequences of TRAMP complex assembly remain unknown. Here, we
identify an important interaction site between Mtr4 and Trf5, and show that
disrupting the Mtr4/Trf interaction disrupts specific TRAMP and exosome
functions, including snoRNA processing.
PMID- 25589548
TI - Advanced digital subtraction angiography and MR fusion imaging protocol applied
to accurate placement of flow diverter device.
AB - In recent years there has been a progressive increase in interventional
neuroradiology procedures, partially due to improvements in devices, but also to
the simultaneous development of technologies and radiological images. Cone beam
CT (Dyna-CT; Siemens) is a method recently used to obtain pseudo CT images from
digital subtraction angiography (DSA) with a flat panel detector. Using dedicated
software, it is then possible to merge Dyna-CT images with images from a
different source. We report here the usefulness of advanced DSA techniques (Syngo
Dyna CT, three-dimensional DSA iPilot) for the treatment of an intracranial
aneurysm with a flow diverter device. Merging MR and Dyna-CT images at the end of
the procedure proved to be a simple and rapid additional method of verifying the
success of the intervention.
PMID- 25589547
TI - Sequences spanning the leader-repeat junction mediate CRISPR adaptation to phage
in Streptococcus thermophilus.
AB - CRISPR-Cas systems are RNA-based immune systems that protect prokaryotes from
invaders such as phages and plasmids. In adaptation, the initial phase of the
immune response, short foreign DNA fragments are captured and integrated into
host CRISPR loci to provide heritable defense against encountered foreign nucleic
acids. Each CRISPR contains a ~100-500 bp leader element that typically includes
a transcription promoter, followed by an array of captured ~35 bp sequences
(spacers) sandwiched between copies of an identical ~35 bp direct repeat
sequence. New spacers are added immediately downstream of the leader. Here, we
have analyzed adaptation to phage infection in Streptococcus thermophilus at the
CRISPR1 locus to identify cis-acting elements essential for the process. We show
that the leader and a single repeat of the CRISPR locus are sufficient for
adaptation in this system. Moreover, we identified a leader sequence element
capable of stimulating adaptation at a dormant repeat. We found that sequences
within 10 bp of the site of integration, in both the leader and repeat of the
CRISPR, are required for the process. Our results indicate that information at
the CRISPR leader-repeat junction is critical for adaptation in this Type II-A
system and likely other CRISPR-Cas systems.
PMID- 25589550
TI - Genetic, biochemical, and serological characterization of a new pneumococcal
serotype, 6H, and generation of a pneumococcal strain producing three different
capsular repeat units.
AB - Streptococcus pneumoniae clinical isolates were recently described that produced
capsular polysaccharide with properties of both serotypes 6A and 6B. Their hybrid
serological property correlated with mutations affecting the glycosyltransferase
WciP, which links rhamnose to ribitol by an alpha(1-3) linkage for serotypes 6A
and 6C and an alpha(1-4) linkage for serotypes 6B and 6D. The isolates had
mutations in the triad residues of WciP that have been correlated with enzyme
specificity. The canonical triad residues of WciP are Ala192-Ser195-Arg254 for
serotypes 6A and 6C and Ser192-Asn195-Gly254 for serotypes 6B and 6D. To prove
that the mutations in the triad residues are responsible for the hybrid serotype,
we introduced the previously described Ala192-Cys195-Arg254 triad into a 6A
strain and found that the change made WciP bispecific, resulting in 6A and 6B
repeat unit expression, although 6B repeat unit production was favored over
production of 6A repeat units. Likewise, this triad permitted a 6C strain to
express 6C and 6D repeat units. With reported bispecificity in WciN, which adds
either glucose or galactose as the second sugar in the serogroup 6 repeat unit,
the possibility exists for a strain to simultaneously produce all four serogroup
6 repeat units; however, when genes encoding both bispecific enzymes were
introduced into a 6A strain, only 6A, 6B, and 6D repeat units were detected
serologically. Nonetheless, this may be the first example of a bacterial
polysaccharide with three different repeat units. This strategy of expressing
multiple repeat units in a single polymer is a novel approach to broadening
vaccine coverage by eliminating the need for multiple polysaccharide sources to
cover multiple serogroup members.
PMID- 25589549
TI - Quest for correlates of protection against tuberculosis.
AB - A major impediment to tuberculosis (TB) vaccine development is the lack of
reliable correlates of immune protection or biomarkers that would predict vaccine
efficacy. Gamma interferon (IFN-gamma) produced by CD4(+) T cells and, recently,
multifunctional CD4(+) T cells secreting IFN-gamma, tumor necrosis factor (TNF),
and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune
parameter, reflecting activity of a vaccine and potentially predicting
protection. However, accumulating experimental evidence suggests that host
resistance against Mycobacterium tuberculosis infection is independent of IFN
gamma and TNF secretion from CD4(+) T cells. Furthermore, the booster vaccine
MVA85A, despite generating a high level of multifunctional CD4(+) T cell response
in the host, failed to confer enhanced protection in vaccinated subjects. These
findings suggest the need for identifying reliable correlates of protection to
determine the efficacy of TB vaccine candidates. This article focuses on
alternative pathways that mediate M. tuberculosis control and their potential for
serving as markers of protection. The review also discusses the significance of
investigating the natural human immune response to M. tuberculosis to identify
the correlates of protection in vaccination.
PMID- 25589551
TI - Mapping antigenic motifs in the trypomastigote small surface antigen from
Trypanosoma cruzi.
AB - The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from
Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino
acid polymorphisms in parasite isolates. TSSA expression is restricted to the
surface of infective cell-derived trypomastigotes, where it functions as an
adhesin and engages surface receptors on the host cell as a prerequisite for
parasite internalization. Previous results have established TSSA-CL, the isoform
encoded by the CL Brener clone, as an appealing candidate for use in serology
based diagnostics for Chagas disease. Here, we used a combination of peptide- and
recombinant protein-based tools to map the antigenic structure of TSSA-CL at
maximal resolution. Our results indicate the presence of different partially
overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which
contains most of the polymorphisms found in parasite isolates. Based on these
results, we assessed the serodiagnostic performance of a 21-amino-acid-long
peptide that spans TSSA-CL major antigenic determinants, which was similar to the
performance of the previously validated glutathione S-transferase (GST)-TSSA-CL
fusion molecule. Furthermore, the tools developed for the antigenic
characterization of the TSSA antigen were also used to explore other potential
diagnostic applications of the anti-TSSA humoral response in Chagasic patients.
Overall, our present results provide additional insights into the antigenic
structure of TSSA-CL and support this molecule as an excellent target for
molecular intervention in Chagas disease.
PMID- 25589552
TI - Long-term immunogenicity of an inactivated split-virion 2009 pandemic influenza A
H1N1 virus vaccine with or without aluminum adjuvant in mice.
AB - In 2009, a global epidemic of influenza A(H1N1) virus caused the death of tens of
thousands of people. Vaccination is the most effective means of controlling an
epidemic of influenza and reducing the mortality rate. In this study, the long
term immunogenicity of influenza A/California/7/2009 (H1N1) split vaccine was
observed as long as 15 months (450 days) after immunization in a mouse model.
Female BALB/c mice were immunized intraperitoneally with different doses of
aluminum-adjuvanted vaccine. The mice were challenged with a lethal dose (10* 50%
lethal dose [LD(50)]) of homologous virus 450 days after immunization. The
results showed that the supplemented aluminum adjuvant not only effectively
enhanced the protective effect of the vaccine but also reduced the immunizing
dose of the vaccine. In addition, the aluminum adjuvant enhanced the IgG antibody
level of mice immunized with the H1N1 split vaccine. The IgG level was correlated
to the survival rate of the mice. Aluminum-adjuvanted inactivated split-virion
2009 pandemic influenza A H1N1 vaccine has good immunogenicity and provided long
term protection against lethal influenza virus challenge in mice.
PMID- 25589553
TI - Antibody-mediated complement C3b/iC3b binding to group B Streptococcus in paired
mother and baby serum samples in a refugee population on the Thailand-Myanmar
border.
AB - Streptococcus agalactiae (group B streptococcus [GBS]) is the leading cause of
neonatal sepsis and meningitis. In this study, we determined antibody-mediated
deposition of complement C3b/iC3b onto the bacterial cell surface of GBS
serotypes Ia, Ib, II, III, and V. This was determined for 520 mother and
umbilical cord serum sample pairs obtained at the time of birth from a population
on the Thailand-Myanmar border. Antibody-mediated deposition of complement
C3b/iC3b was detected to at least one serotype in 91% of mothers, despite a known
carriage rate in this population of only 12%. Antibody-mediated C3b/iC3b
deposition corresponded to known carriage rates, with the highest levels of
complement deposition observed onto the most prevalent serotype (serotype II)
followed by serotypes Ia, III, V, and Ib. Finally, neonates born to mothers
carrying serotype II GBS at the time of birth showed higher antibody-mediated
C3b/iC3b deposition against serotype II GBS than neonates born to mothers with no
serotype II carriage. Assessment of antibody-mediated C3b/iC3b deposition against
GBS may provide insights into the seroepidemiology of anti-GBS antibodies in
mothers and infants in different populations.
PMID- 25589554
TI - Next-generation sequencing reveals a controlled immune response to Zaire Ebola
virus challenge in cynomolgus macaques immunized with vesicular stomatitis virus
expressing Zaire Ebola virus glycoprotein (VSVDeltaG/EBOVgp).
AB - Vesicular stomatitis virus expressing Zaire Ebola virus (EBOV) glycoprotein
(VSVDeltaG/EBOVgp) could be used as a vaccine to meet the 2014 Ebola virus
outbreak. To characterize the host response to this vaccine, we used mRNA
sequencing to analyze peripheral blood mononuclear cells (PBMCs) from cynomolgus
macaques after VSVDeltaG/EBOVgp immunization and subsequent EBOV challenge. We
found a controlled transcriptional response that transitioned to immune
regulation as the EBOV was cleared. This observation supports the safety of the
vaccine.
PMID- 25589555
TI - Evaluation of a multiplex bead immunoassay for determination of immune status to
varicella-zoster virus in medical center students and employees.
AB - This study evaluated an enzyme immunoassay, a multiplex bead immunoassay (MBIA),
and the anticomplement immunofluorescence (ACIF) test for detecting varicella
zoster virus IgG antibodies in sera from medical center students and employees.
The agreement between methods was >=95%. The MBIA was less sensitive than was the
ACIF test, with a negative predictive value of 66.7%.
PMID- 25589556
TI - HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular
cholesterol export.
AB - RATIONALE: High-density lipoprotein (HDL) is a heterogeneous population of
particles. Differences in the capacities of HDL subfractions to remove cellular
cholesterol may explain variable correlations between HDL-cholesterol and
cardiovascular risk and inform future targets for HDL-related therapies. The ATP
binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux to lipid
free apolipoprotein A-I, but the majority of apolipoprotein A-I in the
circulation is transported in a lipidated state and ABCA1-dependent efflux to
individual HDL subfractions has not been systematically studied. OBJECTIVE: Our
aims were to determine which HDL particle subfractions are most efficient in
mediating cellular cholesterol efflux from foam cell macrophages and to identify
the cellular cholesterol transporters involved in this process. METHODS AND
RESULTS: We used reconstituted HDL particles of defined size and composition,
isolated subfractions of human plasma HDL, cell lines stably expressing ABCA1 or
ABCG1, and both mouse and human macrophages in which ABCA1 or ABCG1 expression
was deleted. We show that ABCA1 is the major mediator of macrophage cholesterol
efflux to HDL, demonstrating most marked efficiency with small, dense HDL
subfractions (HDL3b and HDL3c). ABCG1 has a lesser role in cholesterol efflux and
a negligible role in efflux to HDL3b and HDL3c subfractions. CONCLUSIONS: Small,
dense HDL subfractions are the most efficient mediators of cholesterol efflux,
and ABCA1 mediates cholesterol efflux to small dense HDL and to lipid-free
apolipoprotein A-I. HDL-directed therapies should target increasing the
concentrations or the cholesterol efflux capacity of small, dense HDL species in
vivo.
PMID- 25589558
TI - Parsing the role of NADPH oxidase enzymes and reactive oxygen species in heart
failure.
PMID- 25589559
TI - Normal saline flushes performed once daily maintain peripheral intravenous
catheter patency: a randomised controlled trial.
AB - OBJECTIVE: Recent evidence supports the use of normal saline flushes in place of
heparin to maintain the patency of peripheral intravenous locks (IVLs); however,
there are no data regarding the recommended flush frequency. STUDY DESIGN: This
was an open, non-inferiority, randomised controlled trial. Children with IVLs,
aged 1-17 years, were randomly assigned to receive saline flushing every 12 h
(group A) or every 24 h (group B). The main outcome was the maintenance of
catheter patency. RESULTS: Four hundred patients were randomised; 198 subjects
were analysed in the 12 h group and 199 in the 24 h group (three patients were
lost at follow-up). Occlusion occurred in 15 children (7.6%) in group A versus 9
(4.5%) in group B (p=0.21). The difference in catheter patency was +3.1% in
favour of the 24 h group (95% CI -1.6% to 7.7%), showing the non-inferiority of
the 24 h procedure (the non-inferiority margin was set at -4%). Catheter-related
complications were not different between the two groups (12.1% in group A vs 9.5%
in group B; p=0.42). CONCLUSIONS: A flushing procedure with one flush per day
allows maintenance of catheter patency without an increase in catheter-related
complications. We propose a simplification of the flushing procedure with only
one flush per day, thereby reducing costs (materials use and nursing time),
labour and unnecessary manipulation of the catheters which can cause distress in
younger children and their parents. TRIAL REGISTRATION NUMBER: The study is
registered in the international database ClinicalTrial.gov under registration
number NCT02221024.
PMID- 25589557
TI - NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating
Akt/mTOR and NFkappaB signaling pathways.
AB - BACKGROUND: NADPH oxidase 4 (Nox4) has been implicated in cardiac remodeling, but
its precise role in cardiac injury remains controversial. Furthermore, little is
known about the downstream effector signaling pathways activated by Nox4-derived
reactive oxygen species in the myocardium. We investigated the role of Nox4 and
Nox4-associated signaling pathways in the development of cardiac remodeling.
METHODS AND RESULTS: Cardiac-specific human Nox4 transgenic mice (c-hNox4Tg) were
generated. Four groups of mice were studied: (1) control mice, littermates that
are negative for hNox4 transgene but Cre positive; (2) c-hNox4 Tg mice; (3)
angiotensin II (AngII)-infused control mice; and (4) c-hNox4Tg mice infused with
AngII. The c-hNox4Tg mice exhibited an ~10-fold increase in Nox4 protein
expression and an 8-fold increase in the production of reactive oxygen species,
and manifested cardiac interstitial fibrosis. AngII infusion to control mice
increased cardiac Nox4 expression and induced fibrosis and hypertrophy. The Tg
mice receiving AngII exhibited more advanced cardiac remodeling and robust
elevation in Nox4 expression, indicating that AngII worsens cardiac injury, at
least in part by enhancing Nox4 expression. Moreover, hNox4 transgene and AngII
infusion induced the expression of cardiac fetal genes and activated the Akt-mTOR
and NFkappaB signaling pathways. Treatment of AngII-infused c-hNox4Tg mice with
GKT137831, a Nox4/Nox1 inhibitor, abolished the increase in oxidative stress,
suppressed the Akt-mTOR and NFkappaB signaling pathways, and attenuated cardiac
remodeling. CONCLUSIONS: Upregulation of Nox4 in the myocardium causes cardiac
remodeling through activating Akt-mTOR and NFkappaB signaling pathways.
Inhibition of Nox4 has therapeutic potential to treat cardiac remodeling.
PMID- 25589560
TI - Behaviour and development in 24-month-old moderately preterm toddlers.
AB - OBJECTIVE: Moderately preterm children (gestational age 32-36+6 weeks) are at
risk of cognitive and behaviour problems at school age. The aim of this study was
to investigate if these problems are already present at the age of 2 years. STUDY
DESIGN: Developmental outcome was assessed at 24-months (corrected age) with the
Bayley-III-NL in 116 moderately preterm (M=34.66 +/- 1.35 weeks gestation) and 99
term born children (M=39.45 +/- 0.98 weeks gestation). Behaviour problems were
assessed with the Child Behaviour Checklist. RESULTS: With age corrected for
prematurity, moderately preterm children scored below term peers on Receptive
Communication skills (11.05 +/- 2.58 vs 12.02 +/- 2.74, p=0.02). Without
correcting age for prematurity, moderately preterm children scored below term
born peers on Cognition (8.97 +/- 2.11 vs 10.68 +/- 2.35, p<0.001), Fine Motor
(10.33 +/- 2.15 vs 11.96 +/- 2.15, p<0.001), Gross Motor (8.47 +/- 2.55 vs 9.39+/
2.80, p=0.05), Receptive Communication (10.09 +/- 2.48 vs 12.02 +/- 2.74,
p<0.001) and Expressive Communication (10.33 +/- 2.43 vs 11.49 +/- 2.51, p=0.005)
skills. Compared with term peers, more moderately preterm children showed a
(mild) delay (ie, scaled score <7) in gross motor skills with age uncorrected for
prematurity (20.7% vs 11.2%, p=0.04). Moderately preterm children had more
internalising behaviour problems than term children (44.76 +/- 8.94 vs 41.54 +/-
8.56, p=0.03). No group differences were found in percentages of (sub)clinical
scores. CONCLUSIONS: At the age of 2 years, uncorrected for prematurity,
differences in cognition, communication, and motor development were present in
moderately preterm children compared with term born peers. After correcting age
for prematurity, a difference was only found for receptive communication skills.
In addition, moderately preterm children show more internalising behaviour
problems.
PMID- 25589561
TI - Patterns of bruising in preschool children--a longitudinal study.
AB - INTRODUCTION: This study aims to identify the prevalence and pattern of bruises
in preschool children over time, and explore influential variables METHODS:
Prospective longitudinal study of children (<6 years) where bruises were recorded
on a body chart, weekly for up to 12 weeks. The number and location of bruises
were analysed according to development. Longitudinal analysis was performed using
multilevel modelling. RESULTS: 3523 bruises recorded from 2570 data collections
from 328 children (mean age 19 months); 6.7% of 1010 collections from premobile
children had at least one bruise (2.2% of babies who could not roll over and 9.8%
in those who could), compared with 45.6% of 478 early mobile and 78.8% of 1082
walking child collections. The most common site affected in all groups was below
the knees, followed by 'facial T' and head in premobile and early mobile. The
ears, neck, buttocks, genitalia and hands were rarely bruised (<1% of all
collections). None of gender, season or the level of social deprivation
significantly influenced bruising patterns, although having a sibling increased
the mean number of bruises. There was considerable variation in the number of
bruises recorded between different children which increased with developmental
stage and was greater than the variation between numbers of bruises in
collections from the same child over time. CONCLUSIONS: These data should help
clinicians understand the patterns of 'everyday bruising' and recognise children
who have an unusual numbers or distribution of bruises who may need assessment
for physical abuse or bleeding disorders.
PMID- 25589562
TI - Child mortality in the developed world: the UK and the rest.
PMID- 25589565
TI - In vivo recording of aerodynamic force with an aerodynamic force platform: from
drones to birds.
AB - Flapping wings enable flying animals and biomimetic robots to generate elevated
aerodynamic forces. Measurements that demonstrate this capability are based on
experiments with tethered robots and animals, and indirect force calculations
based on measured kinematics or airflow during free flight. Remarkably, there
exists no method to measure these forces directly during free flight. Such in
vivo recordings in freely behaving animals are essential to better understand the
precise aerodynamic function of their flapping wings, in particular during the
downstroke versus upstroke. Here, we demonstrate a new aerodynamic force platform
(AFP) for non-intrusive aerodynamic force measurement in freely flying animals
and robots. The platform encloses the animal or object that generates fluid force
with a physical control surface, which mechanically integrates the net
aerodynamic force that is transferred to the earth. Using a straightforward
analytical solution of the Navier-Stokes equation, we verified that the method is
accurate. We subsequently validated the method with a quadcopter that is
suspended in the AFP and generates unsteady thrust profiles. These independent
measurements confirm that the AFP is indeed accurate. We demonstrate the
effectiveness of the AFP by studying aerodynamic weight support of a freely
flying bird in vivo. These measurements confirm earlier findings based on
kinematics and flow measurements, which suggest that the avian downstroke, not
the upstroke, is primarily responsible for body weight support during take-off
and landing.
PMID- 25589566
TI - Constructor theory of life.
AB - Neo-Darwinian evolutionary theory explains how the appearance of purposive design
in the adaptations of living organisms can have come about without their
intentionally being designed. The explanation relies crucially on the possibility
of certain physical processes: mainly, gene replication and natural selection. In
this paper, I show that for those processes to be possible without the design of
biological adaptations being encoded in the laws of physics, those laws must have
certain other properties. The theory of what these properties are is not part of
evolution theory proper, yet without it the neo-Darwinian theory does not fully
achieve its purpose of explaining the appearance of design. To this end, I apply
constructor theory's new mode of explanation to express exactly within physics
the appearance of design, no-design laws, and the logic of self-reproduction and
natural selection. I conclude that self-reproduction, replication and natural
selection are possible under no-design laws, the only non-trivial condition being
that they allow digital information to be physically instantiated. This has an
exact characterization in the constructor theory of information. I also show that
under no-design laws an accurate replicator requires the existence of a 'vehicle'
constituting, together with the replicator, a self-reproducer.
PMID- 25589564
TI - Many hepatitis C reinfections that spontaneously clear may be undetected: Markov
chain Monte Carlo analysis of observational study data.
AB - Hepatitis C virus (HCV) reinfection rates are probably underestimated due to
reinfection episodes occurring between study visits. A Markov model of HCV
reinfection and spontaneous clearance was fitted to empirical data. Bayesian post
estimation was used to project reinfection rates, reinfection spontaneous
clearance probability and duration of reinfection. Uniform prior probability
distributions were assumed for reinfection rate (more than 0), spontaneous
clearance probability (0-1) and duration (0.25-6.00 months). Model estimates were
104 per 100 person-years (95% CrI: 21-344), 0.84 (95% CrI: 0.59-0.98) and 1.3
months (95% CrI: 0.3-4.1) for reinfection rate, spontaneous clearance probability
and duration, respectively. Simulation studies were used to assess model
validity, demonstrating that the Bayesian model estimates provided useful
information about the possible sources and magnitude of bias in epidemiological
estimates of reinfection rates, probability of reinfection clearance and duration
or reinfection. The quality of the Bayesian estimates improved for larger samples
and shorter test intervals. Uncertainty in model estimates notwithstanding,
findings suggest that HCV reinfections frequently and quickly result in
spontaneous clearance, with many reinfection events going unobserved.
PMID- 25589563
TI - Investigating cell mechanics with atomic force microscopy.
AB - Transmission of mechanical force is crucial for normal cell development and
functioning. However, the process of mechanotransduction cannot be studied in
isolation from cell mechanics. Thus, in order to understand how cells 'feel', we
must first understand how they deform and recover from physical perturbations.
Owing to its versatility, atomic force microscopy (AFM) has become a popular tool
to study intrinsic cellular mechanical properties. Used to directly manipulate
and examine whole and subcellular reactions, AFM allows for top-down and
reconstitutive approaches to mechanical characterization. These studies show that
the responses of cells and their components are complex, and largely depend on
the magnitude and time scale of loading. In this review, we generally describe
the mechanotransductive process through discussion of well-known mechanosensors.
We then focus on discussion of recent examples where AFM is used to specifically
probe the elastic and inelastic responses of single cells undergoing deformation.
We present a brief overview of classical and current models often used to
characterize observed cellular phenomena in response to force. Both simple
mechanistic models and complex nonlinear models have been used to describe the
observed cellular behaviours, however a unifying description of cell mechanics
has not yet been resolved.
PMID- 25589567
TI - Demographic buffering: titrating the effects of birth rate and imperfect immunity
on epidemic dynamics.
AB - Host demography can alter the dynamics of infectious disease. In the case of
perfectly immunizing infections, observations of strong sensitivity to
demographic variation have been mechanistically explained through analysis of the
susceptible-infected-recovered (SIR) model that assumes lifelong immunity
following recovery from infection. When imperfect immunity is incorporated into
this framework via the susceptible-infected-recovered-susceptible (SIRS) model,
with individuals regaining full susceptibility following recovery, we show that
rapid loss of immunity is predicted to buffer populations against the effects of
demographic change. However, this buffering is contrary to the dependence on
demography recently observed for partially immunizing infections such as
rotavirus and respiratory syncytial virus. We show that this discrepancy arises
from a key simplification embedded in the SIR(S) framework, namely that the
potential for differential immune responses to repeat exposures is ignored. We
explore the minimum additional immunological information that must be included to
reflect the range of observed dependencies on demography. We show that including
partial protection and lower transmission following primary infection is
sufficient to capture more realistic reduced levels of buffering, in addition to
changes in epidemic timing, across a range of partially and fully immunizing
infections. Furthermore, our results identify key variables in this relationship,
including R0.
PMID- 25589568
TI - Creating the brain and interacting with the brain: an integrated approach to
understanding the brain.
AB - In the past two decades, brain science and robotics have made gigantic advances
in their own fields, and their interactions have generated several
interdisciplinary research fields. First, in the 'understanding the brain by
creating the brain' approach, computational neuroscience models have been applied
to many robotics problems. Second, such brain-motivated fields as cognitive
robotics and developmental robotics have emerged as interdisciplinary areas among
robotics, neuroscience and cognitive science with special emphasis on humanoid
robots. Third, in brain-machine interface research, a brain and a robot are
mutually connected within a closed loop. In this paper, we review the theoretical
backgrounds of these three interdisciplinary fields and their recent progress.
Then, we introduce recent efforts to reintegrate these research fields into a
coherent perspective and propose a new direction that integrates brain science
and robotics where the decoding of information from the brain, robot control
based on the decoded information and multimodal feedback to the brain from the
robot are carried out in real time and in a closed loop.
PMID- 25589569
TI - Stick-slip friction of gecko-mimetic flaps on smooth and rough surfaces.
AB - The discovery and understanding of gecko 'frictional-adhesion' adhering and
climbing mechanism has allowed researchers to mimic and create gecko-inspired
adhesives. A few experimental and theoretical approaches have been taken to
understand the effect of surface roughness on synthetic adhesive performance, and
the implications of stick-slip friction during shearing. This work extends
previous studies by using a modified surface forces apparatus to quantitatively
measure and model frictional forces between arrays of polydimethylsiloxane gecko
footpad-mimetic tilted microflaps against smooth and rough glass surfaces.
Constant attachments and detachments occur between the surfaces during shearing,
as described by an avalanche model. These detachments ultimately result in
failure of the adhesion interface and have been characterized in this study.
Stick-slip friction disappears with increasing velocity when the flaps are
sheared against a smooth silica surface; however, stick-slip was always present
at all velocities and loads tested when shearing the flaps against rough glass
surfaces. These results demonstrate the significance of pre-load, shearing
velocity, shearing distances, commensurability and shearing direction of gecko
mimetic adhesives and provide us a simple model for analysing and/or designing
such systems.
PMID- 25589570
TI - Fluid-flow-induced mesenchymal stem cell migration: role of focal adhesion kinase
and RhoA kinase sensors.
AB - The study of mesenchymal stem cell (MSC) migration under flow conditions with
investigation of the underlying molecular mechanism could lead to a better
understanding and outcome in stem-cell-based cell therapy and regenerative
medicine. We used peer-reviewed open source software to develop methods for
efficiently and accurately tracking, measuring and processing cell migration as
well as morphology. Using these tools, we investigated MSC migration under flow
induced shear and tested the molecular mechanism with stable knockdown of focal
adhesion kinase (FAK) and RhoA kinase (ROCK). Under steady flow, MSCs migrated
following the flow direction in a shear stress magnitude-dependent manner, as
assessed by root mean square displacement and mean square displacement, motility
coefficient and confinement ratio. Silencing FAK in MSCs suppressed morphology
adaptation capability and reduced cellular motility for both static and flow
conditions. Interestingly, ROCK silencing significantly increased migration
tendency especially under flow. Blocking ROCK, which is known to reduce
cytoskeletal tension, may lower the resistance to skeletal remodelling during the
flow-induced migration. Our data thus propose a potentially differential role of
focal adhesion and cytoskeletal tension signalling elements in MSC migration
under flow shear.
PMID- 25589571
TI - C60 fullerene promotes lung monolayer collapse.
AB - Airborne nanometre-sized pollutants are responsible for various respiratory
diseases. Such pollutants can reach the gas-exchange surface in the alveoli,
which is lined with a monolayer of lung surfactant. The relationship between
physiological effects of pollutants and molecular-level interactions is largely
unknown. Here, we determine the effects of carbon nanoparticles on the properties
of a model of lung monolayer using molecular simulations. We simulate phase
separated lipid monolayers in the presence of a model pollutant nanoparticle, C60
fullerene. In the absence of nanoparticles, the monolayers collapse only at very
low surface tensions (around 0 mN m(-1)). In the presence of nanoparticles,
instead, monolayer collapse is observed at significantly higher surface tensions
(up to ca 10 mN m(-1)). Collapse at higher tensions is related to lower
mechanical rigidity of the monolayer. It is possible that similar mechanisms
operate on lung surfactant in vivo, which suggests that health effects of
airborne carbon nanoparticles may be mediated by alterations of the mechanical
properties of lung surfactant.
PMID- 25589572
TI - Automated segmentation of the lamina cribrosa using Frangi's filter: a novel
approach for rapid identification of tissue volume fraction and beam orientation
in a trabeculated structure in the eye.
AB - The lamina cribrosa (LC) is a tissue in the posterior eye with a complex
trabecular microstructure. This tissue is of great research interest, as it is
likely the initial site of retinal ganglion cell axonal damage in glaucoma.
Unfortunately, the LC is difficult to access experimentally, and thus imaging
techniques in tandem with image processing have emerged as powerful tools to
study the microstructure and biomechanics of this tissue. Here, we present a
staining approach to enhance the contrast of the microstructure in micro-computed
tomography (micro-CT) imaging as well as a comparison between tissues imaged with
micro-CT and second harmonic generation (SHG) microscopy. We then apply a
modified version of Frangi's vesselness filter to automatically segment the
connective tissue beams of the LC and determine the orientation of each beam.
This approach successfully segmented the beams of a porcine optic nerve head from
micro-CT in three dimensions and SHG microscopy in two dimensions. As an
application of this filter, we present finite-element modelling of the posterior
eye that suggests that connective tissue volume fraction is the major driving
factor of LC biomechanics. We conclude that segmentation with Frangi's filter is
a powerful tool for future image-driven studies of LC biomechanics.
PMID- 25589573
TI - Lateral assembly of N-cadherin drives tissue integrity by stabilizing adherens
junctions.
AB - Cadherin interactions ensure the correct registry and anchorage of cells during
tissue formation. Along the plasma membrane, cadherins form inter-junctional
lattices via cis- and trans-dimerization. While structural studies have provided
models for cadherin interactions, the molecular nature of cadherin binding in
vivo remains unexplored. We undertook a multi-disciplinary approach combining
live cell imaging of three-dimensional cell assemblies (spheroids) with a
computational model to study the dynamics of N-cadherin interactions. Using a
loss-of-function strategy, we demonstrate that each N-cadherin interface plays a
distinct role in spheroid formation. We found that cis-dimerization is not a
prerequisite for trans-interactions, but rather modulates trans-interfaces to
ensure tissue stability. Using a model of N-cadherin junction dynamics, we show
that the absence of cis-interactions results in low junction stability and loss
of tissue integrity. By quantifying the binding and unbinding dynamics of the N
cadherin binding interfaces, we determined that mutating either interface results
in a 10-fold increase in the dissociation constant. These findings provide new
quantitative information on the steps driving cadherin intercellular adhesion and
demonstrate the role of cis-interactions in junction stability.
PMID- 25589574
TI - Using argument notation to engineer biological simulations with increased
confidence.
AB - The application of computational and mathematical modelling to explore the
mechanics of biological systems is becoming prevalent. To significantly impact
biological research, notably in developing novel therapeutics, it is critical
that the model adequately represents the captured system. Confidence in adopting
in silico approaches can be improved by applying a structured argumentation
approach, alongside model development and results analysis. We propose an
approach based on argumentation from safety-critical systems engineering, where a
system is subjected to a stringent analysis of compliance against identified
criteria. We show its use in examining the biological information upon which a
model is based, identifying model strengths, highlighting areas requiring
additional biological experimentation and providing documentation to support
model publication. We demonstrate our use of structured argumentation in the
development of a model of lymphoid tissue formation, specifically Peyer's
Patches. The argumentation structure is captured using Artoo
(www.york.ac.uk/ycil/software/artoo), our Web-based tool for constructing fitness
for-purpose arguments, using a notation based on the safety-critical goal
structuring notation. We show how argumentation helps in making the design and
structured analysis of a model transparent, capturing the reasoning behind the
inclusion or exclusion of each biological feature and recording assumptions, as
well as pointing to evidence supporting model-derived conclusions.
PMID- 25589575
TI - Modelling the propagation of social response during a disease outbreak.
AB - Epidemic trajectories and associated social responses vary widely between
populations, with severe reactions sometimes observed. When confronted with fatal
or novel pathogens, people exhibit a variety of behaviours from anxiety to
hoarding of medical supplies, overwhelming medical infrastructure and rioting. We
developed a coupled network approach to understanding and predicting social
response. We couple the disease spread and panic spread processes and model them
through local interactions between agents. The social contagion process depends
on the prevalence of the disease, its perceived risk and a global media signal.
We verify the model by analysing the spread of disease and social response during
the 2009 H1N1 outbreak in Mexico City and 2003 severe acute respiratory syndrome
and 2009 H1N1 outbreaks in Hong Kong, accurately predicting population-level
behaviour. This kind of empirically validated model is critical to exploring
strategies for public health intervention, increasing our ability to anticipate
the response to infectious disease outbreaks.
PMID- 25589576
TI - A steering mechanism for phototaxis in Chlamydomonas.
AB - Chlamydomonas shows both positive and negative phototaxis. It has a single
eyespot near its equator, and as the cell rotates during the forward motion, the
light signal received by the eyespot varies. We use a simple mechanical model of
Chlamydomonas that couples the flagellar beat pattern to the light intensity at
the eyespot to demonstrate a mechanism for phototactic steering that is
consistent with observations. The direction of phototaxis is controlled by a
parameter in our model, and the steering mechanism is robust to noise. Our model
shows switching between directed phototaxis when the light is on and run-and
tumble behaviour in the dark.
PMID- 25589577
TI - Bacterial genospecies that are not ecologically coherent: population genomics of
Rhizobium leguminosarum.
AB - Biological species may remain distinct because of genetic isolation or ecological
adaptation, but these two aspects do not always coincide. To establish the nature
of the species boundary within a local bacterial population, we characterized a
sympatric population of the bacterium Rhizobium leguminosarum by genomic
sequencing of 72 isolates. Although all strains have 16S rRNA typical of R.
leguminosarum, they fall into five genospecies by the criterion of average
nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome,
support this division: recombination of core genes has been largely within
genospecies. Nevertheless, variation in ecological properties, including
symbiotic host range and carbon-source utilization, cuts across these
genospecies, so that none of these phenotypes is diagnostic of genospecies. This
phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr
criteria for biological species in respect of their core genes, but do not
correspond to coherent ecological groups, so periodic selection may not be
effective in purging variation within them. The population structure is
incompatible with traditional 'polyphasic taxonomy' that requires bacterial
species to have both phylogenetic coherence and distinctive phenotypes. More
generally, genomics has revealed that many bacterial species share adaptive
modules by horizontal gene transfer, and we envisage a more consistent taxonomic
framework that explicitly recognizes this. Significant phenotypes should be
recognized as 'biovars' within species that are defined by core gene phylogeny.
PMID- 25589578
TI - Drosophila gene tao-1 encodes proteins with and without a Ste20 kinase domain
that affect cytoskeletal architecture and cell migration differently.
AB - Tao-1, the single representative of the Sterile 20 kinase subfamily in
Drosophila, is best known for destabilizing microtubules at the actin-rich
cortex, regulating the cytoskeletal architecture of cells. More recently, Tao-1
was shown to act in the Salvador-Warts-Hippo pathway by phosphorylating Hippo,
regulating cell growth as well as cell polarity. Here, we show that tao-1 encodes
two proteins, one with the Sterile 20 kinase domain (Tao-L) and one without it
(Tao-S), and that they act in an antagonistic manner. Tao-L expression causes
lamellipodia-like cell protrusions, whereas Tao-S expression results in filopodia
like structures that make cells stick to the surface they attach to. Ectopic Tao
1 expression in the anterior region of Drosophila embryos results in pole cell
formation as normally observed at the posterior end. Tao-S expression causes
primordial germ cells (PGCs) to adhere to the inner wall of the gut primordia and
prevents proper transepithelial migration to the gonads. Conversely, RNAi
knockdowns of Tao-1 cause disordered migration of PGCs out of the gut epithelium,
their dispersal within the embryo and cell death. The results reveal a novel
function of Tao-1 in cell migration, which is based on antagonistic activities of
two proteins encoded by a single gene.
PMID- 25589579
TI - MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma
hyopneumoniae.
AB - Aminopeptidases are part of the arsenal of virulence factors produced by
bacterial pathogens that inactivate host immune peptides. Mycoplasma
hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic
repertoire to synthesize amino acids and relies on the host for availability of
amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell
surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125.
Plasmin plays an important role in regulating the inflammatory response in the
lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461
(rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate
specificity for leucine, alanine, phenylalanine, methionine and arginine and that
MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds
heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily
converted to plasmin in the presence of tPA. Computational modelling identified
putative DNA and heparin-binding motifs on solvent-exposed sites around a large
pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a
multifunctional adhesin on the cell surface of M. hyopneumoniae.
PMID- 25589580
TI - Spatial and Temporal Control Contribute to Step Length Asymmetry During Split
Belt Adaptation and Hemiparetic Gait.
AB - BACKGROUND: Step length asymmetry (SLA) is a common hallmark of gait poststroke.
Though conventionally viewed as a spatial deficit, SLA can result from
differences in where the feet are placed relative to the body (step position
strategy), the timing between foot strikes (step time strategy), or the velocity
of the body relative to the feet (step velocity strategy). OBJECTIVE: The goal of
this study was to characterize the relative contributions of each of these
strategies to SLA. METHODS: We developed an analytical model that parses SLA into
independent step position, step time, and step velocity contributions. This model
was validated by reproducing SLA values for 25 healthy participants when their
natural symmetric gait was perturbed on a split-belt treadmill moving at either a
2:1 or 3:1 belt-speed ratio. We then applied the validated model to quantify step
position, step time, and step velocity contributions to SLA in 15 stroke
survivors while walking at their self-selected speed. RESULTS: SLA was predicted
precisely by summing the derived contributions, regardless of the belt-speed
ratio. Although the contributions to SLA varied considerably across our sample of
stroke survivors, the step position contribution tended to oppose the other 2
possibly as an attempt to minimize overall SLA. CONCLUSIONS: Our results suggest
that changes in where the feet are placed or changes in interlimb timing could be
used as compensatory strategies to reduce overall SLA in stroke survivors. These
results may allow clinicians and researchers to identify patient-specific gait
abnormalities and personalize their therapeutic approaches accordingly.
PMID- 25589586
TI - Navigational path integration by cortical neurons: origins in higher-order
direction selectivity.
AB - Navigation relies on the neural processing of sensory cues about observer self
movement and spatial location. Neurons in macaque dorsal medial superior temporal
cortex (MSTd) respond to visual and vestibular self-movement cues, potentially
contributing to navigation and orientation. We moved monkeys on circular paths
around a room while recording the activity of MSTd neurons. MSTd neurons show a
variety of sensitivities to the monkey's heading direction, circular path through
the room, and place in the room. Changing visual cues alters the relative
prevalence of those response properties. Disrupting the continuity of self
movement paths through the environment disrupts path selectivity in a manner
linked to the time course of single neuron responses. We hypothesize that sensory
cues interact with the spatial and temporal integrative properties of MSTd
neurons to derive path selectivity for navigational path integration supporting
spatial orientation.
PMID- 25589585
TI - The effect of age on postural and cognitive task performance while using
vibrotactile feedback.
AB - Vibrotactile feedback (VTF) has been shown to improve balance performance in
healthy people and people with vestibular disorders in a single-task experimental
condition. It is unclear how age-related changes in balance affect the ability to
use VTF and if there are different attentional requirements for old and young
adults when using VTF. Twenty younger and 20 older subjects participated in this
two-visit study to examine the effect of age, VTF, sensory condition, cognitive
task, duration of time, and visit on postural and cognitive performance. Postural
performance outcome measures included root mean square of center of pressure
(COP) and trunk tilt, and cognitive performance was assessed using the reaction
time (RT) from an auditory choice RT task. The results showed that compared with
younger adults, older adults had an increase in COP in fixed platform conditions
when using VTF, although they were able to reduce COP during sway-referenced
platform conditions. Older adults also did not benefit fully from using VTF in
their first session. The RTs for the secondary cognitive tasks increased
significantly while using the VTF in both younger and older adults. Older adults
had a larger increase compared with younger adults, suggesting that greater
attentional demands were required in older adults when using VTF information.
Future training protocols for VTF should take into consideration the effect of
aging.
PMID- 25589587
TI - Nasotemporal ERP differences: evidence for increased inhibition of temporal
distractors.
AB - Previous research has demonstrated behavioral advantages for stimuli in the
temporal relative to the nasal visual hemifield. To investigate whether this
nasotemporal asymmetry reflects a genuinely attentional bias, we recorded event
related potentials in a task where participants identified a color-defined target
digit in one visual hemifield that was accompanied by an irrelevant distractor in
the opposite hemifield (experiment 1). To dissociate the processing of stimuli in
nasal and temporal visual hemifields, an eye-patching procedure was used. Targets
triggered N2pc components that marked their attentional selection. Unexpectedly,
these N2pc components were larger and emerged earlier for nasal relative to
temporal targets. Experiment 2 provided evidence that this nasotemporal asymmetry
for the N2pc is linked to an increased attentional inhibition of temporal
distractors. Relative to nasal distractors, temporal distractors elicited an
increased inhibition-related contralateral positivity, resulting in more
pronounced differences between contralateral and ipsilateral event-related
potentials on trials with temporal distractors and nasal targets. These results
provide novel evidence for a genuinely attentional contribution to nasotemporal
asymmetries and suggest that such asymmetries are associated with top-down
controlled distractor inhibition.
PMID- 25589589
TI - Comparative diffusion tractography of corticostriatal motor pathways reveals
differences between humans and macaques.
AB - The primate corticobasal ganglia circuits are understood to be segregated into
parallel anatomically and functionally distinct loops. Anatomical and
physiological studies in macaque monkeys are summarized as showing that an
oculomotor loop begins with projections from the frontal eye fields (FEF) to the
caudate nucleus, and a motor loop begins with projections from the primary motor
cortex (M1) to the putamen. However, recent functional and structural
neuroimaging studies of the human corticostriatal system report evidence
inconsistent with this organization. To obtain conclusive evidence, we directly
compared the pattern of connectivity between cortical motor areas and the
striatum in humans and macaques in vivo using probabilistic diffusion
tractography. In macaques we found that FEF is connected with the head of the
caudate and anterior putamen, and M1 is connected with more posterior sections of
the caudate and putamen, corroborating neuroanatomical tract tracing findings.
However, in humans FEF and M1 are connected to largely overlapping portions of
posterior putamen and only a small portion of the caudate. These results
demonstrate that the corticobasal connectivity for the oculomotor and primary
motor loop is not entirely segregated for primates at a macroscopic level and
that the description of the anatomical connectivity of corticostriatal motor
systems in humans does not parallel that of macaques, perhaps because of an
expansion of prefrontal projections to striatum in humans.
PMID- 25589588
TI - Electrogenic properties of the Na+/K+ ATPase control transitions between normal
and pathological brain states.
AB - Ionic concentrations fluctuate significantly during epileptic seizures. In this
study, using a combination of in vitro electrophysiology, computer modeling, and
dynamical systems analysis, we demonstrate that changes in the potassium and
sodium intra- and extracellular ion concentrations ([K(+)] and [Na(+)],
respectively) during seizure affect the neuron dynamics by modulating the outward
Na(+)/K(+) pump current. First, we show that an increase of the outward
Na(+)/K(+) pump current mediates termination of seizures when there is a
progressive increase in the intracellular [Na(+)]. Second, we show that the
Na(+)/K(+) pump current is crucial in maintaining the stability of the
physiological network state; a reduction of this current leads to the onset of
seizures via a positive-feedback loop. We then present a novel dynamical
mechanism for bursting in neurons with a reduced Na(+)/K(+) pump. Overall, our
study demonstrates the profound role of the current mediated by Na(+)/K(+) ATPase
on the stability of neuronal dynamics that was previously unknown.
PMID- 25589591
TI - Consequences of biomechanically constrained tasks in the design and
interpretation of synergy analyses.
AB - Matrix factorization algorithms are commonly used to analyze muscle activity and
provide insight into neuromuscular control. These algorithms identify low
dimensional subspaces, commonly referred to as synergies, which can describe
variation in muscle activity during a task. Synergies are often interpreted as
reflecting underlying neural control; however, it is unclear how these analyses
are influenced by biomechanical and task constraints, which can also lead to low
dimensional patterns of muscle activation. The aim of this study was to evaluate
whether commonly used algorithms and experimental methods can accurately identify
synergy-based control strategies. This was accomplished by evaluating synergies
from five common matrix factorization algorithms using muscle activations
calculated from 1) a biomechanically constrained task using a musculoskeletal
model and 2) without task constraints using random synergy activations. Algorithm
performance was assessed by calculating the similarity between estimated
synergies and those imposed during the simulations; similarities ranged from 0
(random chance) to 1 (perfect similarity). Although some of the algorithms could
accurately estimate specified synergies without biomechanical or task constraints
(similarity >0.7), with these constraints the similarity of estimated synergies
decreased significantly (0.3-0.4). The ability of these algorithms to accurately
identify synergies was negatively impacted by correlation of synergy activations,
which are increased when substantial biomechanical or task constraints are
present. Increased variability in synergy activations, which can be captured
using robust experimental paradigms that include natural variability in motor
activation patterns, improved identification accuracy but did not completely
overcome effects of biomechanical and task constraints. These results demonstrate
that a biomechanically constrained task can reduce the accuracy of estimated
synergies and highlight the importance of using experimental protocols with
physiological variability to improve synergy analyses.
PMID- 25589590
TI - Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors.
AB - The neuromodulator acetylcholine (ACh) shapes neocortical function during sensory
perception, motor control, arousal, attention, learning, and memory. Here we
investigate the mechanisms by which ACh affects neocortical pyramidal neurons in
adult mice. Stimulation of cholinergic axons activated muscarinic and nicotinic
ACh receptors on pyramidal neurons in all cortical layers and in multiple
cortical areas. Nicotinic receptor activation evoked short-latency, depolarizing
postsynaptic potentials (PSPs) in many pyramidal neurons. Nicotinic receptor
mediated PSPs promoted spiking of pyramidal neurons. The duration of the increase
in spiking was membrane potential dependent, with nicotinic receptor activation
triggering persistent spiking lasting many seconds in neurons close to threshold.
Persistent spiking was blocked by intracellular BAPTA, indicating that nicotinic
ACh receptor activation evoked persistent spiking via a long-lasting calcium
activated depolarizing current. We compared nicotinic PSPs in primary motor
cortex (M1), prefrontal cortex (PFC), and visual cortex. The laminar pattern of
nicotinic excitation was not uniform but was broadly similar across areas, with
stronger modulation in deep than superficial layers. Superimposed on this broad
pattern were local differences, with nicotinic PSPs being particularly large and
common in layer 5 of M1 but not layer 5 of PFC or primary visual cortex (V1).
Hence, in addition to modulating the excitability of pyramidal neurons in all
layers via muscarinic receptors, synaptically released ACh preferentially
increases the activity of deep-layer neocortical pyramidal neurons via nicotinic
receptors, thereby adding laminar selectivity to the widespread enhancement of
excitability mediated by muscarinic ACh receptors.
PMID- 25589592
TI - The lateral septum as a regulator of hippocampal theta oscillations and defensive
behavior in rats.
AB - Hippocampal theta oscillations are linked to various processes, including
locomotion, learning and memory, and defense and affect. The lateral septum (LS)
has been implicated in the generation of the hippocampal theta rhythm, but its
precise role in this process is not well understood. Here, we investigated the
effects of direct pharmacological inhibition or disinhibition of the dorsal LS
(dLS) on the frequency of hippocampal theta activity elicited by stimulation of
the reticular formation in urethane-anesthetized rats. We found that bilateral
infusions of the GABAA receptor agonist muscimol into the dLS significantly
increased theta frequency. Strikingly, intra-dLS infusions of the GABAA receptor
antagonist GABAzine largely abolished reticularly elicited theta activity. We
also locally injected these same compounds into the medial septum (MS) to test
for neuroanatomical specificity. In contrast to the effects seen in the dLS,
intra-MS infusions of muscimol had no effect on theta frequency, whereas intra-MS
infusions of GABAzine increased theta frequency. Given the hypothesized role of
hippocampal theta in behavioral defense, we also examined the effects of intra
dLS application of muscimol in two models of anxiety, the elevated plus maze and
the novelty-induced suppression of feeding paradigm; both tests revealed clear,
anxiolytic-like effects following muscimol infusions. The fact that dLS-muscimol
increased theta frequency while also reducing anxiety-like behaviors challenges
the influential theta suppression model of anxiolysis, which predicts a slowing
of theta with anxiolytic compounds. More importantly, the experiments reveal a
novel role of the LS, especially its dorsal aspects, as an important gating
mechanism for the expression of theta oscillations in the rodent hippocampus.
PMID- 25589594
TI - The human motor system alters its reaching movement plan for task-irrelevant,
positional forces.
AB - The minimum intervention principle and the uncontrolled manifold hypothesis state
that our nervous system only responds to force perturbations and sensorimotor
noise if they affect task success. This idea has been tested in muscle and joint
coordinate frames and more recently using workspace redundancy (e.g., reaching to
large targets). However, reaching studies typically involve spatial and or
temporal constraints. Constrained reaches represent a small proportion of
movements we perform daily and may limit the emergence of natural behavior. Using
more relaxed constraints, we conducted two reaching experiments to test the
hypothesis that humans respond to task-relevant forces and ignore task-irrelevant
forces. We found that participants responded to both task-relevant and
irrelevant forces. Interestingly, participants experiencing a task-irrelevant
force, which simply pushed them into a different area of a large target and had
no bearing on task success, changed their movement trajectory prior to being
perturbed. These movement trajectory changes did not counteract the task
irrelevant perturbations, as shown in previous research, but rather were made
into new areas of the workspace. A possible explanation for this behavior change
is that participants were engaging in active exploration. Our data have
implications for current models and theories on the control of biological motion.
PMID- 25589595
TI - Coding of relative size in monkey inferotemporal cortex.
AB - We seldom mistake a closer object as being larger, even though its retinal image
is bigger. One underlying mechanism could be to calculate the size of the retinal
image relative to that of another nearby object. Here we set out to investigate
whether single neurons in the monkey inferotemporal cortex (IT) are sensitive to
the relative size of parts in a display. Each neuron was tested on shapes
containing two parts that could be conjoined or spatially separated. Each shape
was presented in four versions created by combining the two parts at each of two
possible sizes. In this design, neurons sensitive to the absolute size of parts
would show the greatest response modulation when both parts are scaled up,
whereas neurons encoding relative size would show similar responses. Our main
findings are that 1) IT neurons responded similarly to all four versions of a
shape, but tuning tended to be more consistent between versions with
proportionately scaled parts; 2) in a subpopulation of cells, we observed
interactions that resulted in similar responses to proportionately scaled parts;
3) these interactions developed together with sensitivity to absolute size for
objects with conjoined parts but developed slightly later for objects with
spatially separate parts. Taken together, our results demonstrate for the first
time that there is a subpopulation of neurons in IT that encodes the relative
size of parts in a display, forming a potential neural substrate for size
constancy.
PMID- 25589596
TI - Explaining attention-related changes in behavior and electroencephalography data
through computational modeling.
AB - In a recent article, Itthipuripat and colleagues combined psychophysics,
neurophysiology, and mathematical modeling to investigate the neural mechanism
underlying behavioral benefits of spatial attention (Itthipuripat S, Ester EF,
Deering S, Serences JT. J Neurosci 34: 13384-13398, 2014). They found that
attention-related effects on behavior as well as neural signals could be better
explained by a response gain model than by a noise reduction model or an
efficient read-out model. In this Neuro Forum we discuss these results and raise
several interesting questions and potential interpretations.
PMID- 25589597
TI - Compression regimes after endovenous ablation for superficial venous
insufficiency--A survey of members of the Vascular Society of Great Britain and
Ireland.
AB - INTRODUCTION: The optimal compression regime following ultrasound guided foam
sclerotherapy (UGFS), radiofrequency ablation (RFA) and endovenous laser ablation
(EVLA) for varicose veins is not known. The aim of this study was to document
current practice. METHODS: Postal questionnaire sent to 348 consultant members of
the Vascular Society of Great Britain and Ireland. RESULTS: Valid replies were
received from 41% (n = 141) surgeons representing at least 68 (61%) vascular
units. UGFS was used by 74% surgeons, RFA by 70% and EVLA by 32%, but fewer
patients received UGFS (median 30) annually, than endothermal treatment (median
50)--P = 0.019. All surgeons prescribed compression: following UGFS for median
seven days (range two days to three months) and after endothermal ablation for 10
days (range two days to six weeks)--P = 0.298. Seven different combinations of
bandages, pads and compression stockings were reported following UGFS and four
after endothermal ablation. Some surgeons advised changing from bandages to
stockings from five days (range 1-14) after UGFS. Following endothermal ablation,
71% used bandages only, followed by compression stockings after two days (range 1
14). The majority of surgeons (87%) also treated varicose tributaries: 65% used
phlebectomy, the majority (65%) synchronously with endothermal ablation.
Concordance of compression regimes between surgeons within vascular units was
uncommon. Only seven units using UGFS and six units using endothermal ablation
had consistent compression regimes. CONCLUSION: Compression regimes after
treatments for varicose veins vary significantly: more evidence is needed to
guide practice.
PMID- 25589593
TI - Magnetic resonance imaging demonstrates compartmental muscle mechanisms of human
vertical fusional vergence.
AB - Vertical fusional vergence (VFV) normally compensates for slight vertical
heterophorias. We employed magnetic resonance imaging to clarify extraocular
muscle contributions to VFV induced by monocular two-prism diopter (1.15 degrees
) base-up prism in 14 normal adults. Fusion during prism viewing requires
monocular infraduction. Scans were repeated without prism, and with prism shifted
contralaterally. Contractility indicated by morphometric indexes was separately
analyzed in medial and lateral vertical rectus and superior oblique (SO) putative
compartments, and superior and inferior horizontal rectus extraocular muscle
putative compartments, but in the whole inferior oblique (IO). Images confirmed
appropriate VFV that was implemented by the inferior rectus (IR) medial
compartment contracting ipsilateral and relaxing contralateral to prism. There
was no significant contractility in the IR lateral compartment. The superior but
not inferior lateral rectus (LR) compartment contracted significantly in the
prism viewing eye, but not contralateral to prism. The IO contracted ipsilateral
but not contralateral to the prism. In the infraducting eye, the SO medial
compartment relaxed significantly, while the lateral compartment was unchanged;
contralateral to prism, the SO lateral compartment contracted, while the medial
compartment was unchanged. There was no contractility in the superior or medial
rectus muscles in either eye. There was no globe retraction. We conclude that the
vertical component of VFV is primarily implemented by IR medial compartment
contraction. Since appropriate vertical rotation is not directly implemented, or
is opposed, by associated differential LR and SO compartmental activity, and IO
contraction, these actions probably implement a torsional component of VFV.
PMID- 25589598
TI - Gendered Facial Cues Influence Race Categorizations.
AB - Race and gender categories, although long presumed to be perceived independently,
are inextricably tethered in social perception due in part to natural confounding
of phenotypic cues. We predicted that target gender would affect race
categorizations. Consistent with this hypothesis, feminine faces compelled White
categorizations, and masculine faces compelled Asian or Black categorizations of
racially ambiguous targets (Study 1), monoracial targets (Study 2), and real
facial photographs (Study 3). The efficiency of judgments varied concomitantly.
White categorizations were rendered more rapidly for feminine, relative to
masculine faces, but the opposite was true for Asian and Black categorizations
(Studies 1-3). Moreover, the effect of gender on categorization efficiency was
compelled by racial phenotypicality for Black targets (Study 3). Finally, when
targets' race prototypicality was held constant, gender still influenced race
categorizations (Study 4). These findings indicate that race categorizations are
biased by presumably unrelated gender cues.
PMID- 25589599
TI - Constructing rich false memories of committing crime.
AB - Memory researchers long have speculated that certain tactics may lead people to
recall crimes that never occurred, and thus could potentially lead to false
confessions. This is the first study to provide evidence suggesting that full
episodic false memories of committing crime can be generated in a controlled
experimental setting. With suggestive memory-retrieval techniques, participants
were induced to generate criminal and noncriminal emotional false memories, and
we compared these false memories with true memories of emotional events. After
three interviews, 70% of participants were classified as having false memories of
committing a crime (theft, assault, or assault with a weapon) that led to police
contact in early adolescence and volunteered a detailed false account. These
reported false memories of crime were similar to false memories of noncriminal
events and to true memory accounts, having the same kinds of complex descriptive
and multisensory components. It appears that in the context of a highly
suggestive interview, people can quite readily generate rich false memories of
committing crime.
PMID- 25589600
TI - Loss of migratory behaviour increases infection risk for a butterfly host.
AB - Long-distance animal migrations have important consequences for infectious
disease dynamics. In some cases, migration lowers pathogen transmission by
removing infected individuals during strenuous journeys and allowing animals to
periodically escape contaminated habitats. Human activities are now causing some
migratory animals to travel shorter distances or form sedentary (non-migratory)
populations. We focused on North American monarch butterflies and a specialist
protozoan parasite to investigate how the loss of migratory behaviours affects
pathogen spread and evolution. Each autumn, monarchs migrate from breeding
grounds in the eastern US and Canada to wintering sites in central Mexico.
However, some monarchs have become non-migratory and breed year-round on exotic
milkweed in the southern US. We used field sampling, citizen science data and
experimental inoculations to quantify infection prevalence and parasite virulence
among migratory and sedentary populations. Infection prevalence was markedly
higher among sedentary monarchs compared with migratory monarchs, indicating that
diminished migration increases infection risk. Virulence differed among parasite
strains but was similar between migratory and sedentary populations, potentially
owing to high gene flow or insufficient time for evolutionary divergence. More
broadly, our findings suggest that human activities that alter animal migrations
can influence pathogen dynamics, with implications for wildlife conservation and
future disease risks.
PMID- 25589601
TI - The oldest parareptile and the early diversification of reptiles.
AB - Amniotes, tetrapods that evolved the cleidoic egg and thus independence from
aquatic larval stages, appeared ca 314 Ma during the Coal Age. The rapid
diversification of amniotes and other tetrapods over the course of the Late
Carboniferous period was recently attributed to the fragmentation of coal-swamp
rainforests ca 307 Ma. However, the amniote fossil record during the
Carboniferous is relatively sparse, with ca 33% of the diversity represented by
single specimens for each species. We describe here a new species of reptilian
amniote that was collected from uppermost Carboniferous rocks of Prince Edward
Island, Canada. Erpetonyx arsenaultorum gen. et sp. nov. is a new parareptile
distinguished by 29 presacral vertebrae and autapomorphies of the carpus.
Phylogenetic analyses of parareptiles reveal E. arsenaultorum as the closest
relative of bolosaurids. Stratigraphic calibration of our results indicates that
parareptiles began their evolutionary radiation before the close of the
Carboniferous Period, and that the diversity of end-Carboniferous reptiles is 80%
greater than suggested by previous work. Latest Carboniferous reptiles were still
half as diverse as synapsid amniotes, a disparity that may be attributable to
preservational biases, to collecting biases, to the origin of herbivory in
tetrapods or any combination of these factors.
PMID- 25589602
TI - Space race functional responses.
AB - We derive functional responses under the assumption that predators and prey are
engaged in a space race in which prey avoid patches with many predators and
predators avoid patches with few or no prey. The resulting functional response
models have a simple structure and include functions describing how the
emigration of prey and predators depend on interspecific densities. As such, they
provide a link between dispersal behaviours and community dynamics. The derived
functional response is general but is here modelled in accordance with
empirically documented emigration responses. We find that the prey emigration
response to predators has stabilizing effects similar to that of the DeAngelis
Beddington functional response, and that the predator emigration response to prey
has destabilizing effects similar to that of the Holling type II response. A
stability criterion describing the net effect of the two emigration responses on
a Lotka-Volterra predator-prey system is presented. The winner of the space race
(i.e. whether predators or prey are favoured) is determined by the relationship
between the slopes of the species' emigration responses. It is predicted that
predators win the space race in poor habitats, where predator and prey densities
are low, and that prey are more successful in richer habitats.
PMID- 25589603
TI - Ecology of information: social transmission dynamics within groups of non-social
insects.
AB - While many studies focus on how animals use public information, the dynamics of
information spread and maintenance within groups, i.e. the 'ecology of
information', have received little attention. Here we use fruitflies trained to
lay eggs on specific substrates to implement information into groups containing
both trained and untrained individuals. We quantify inter-individual interactions
and then measure the spread of oviposition preference with behavioural tests.
Untrained individuals increase their interactive approaches in the presence of
trained individuals, and the oviposition preference transmission is directly
proportional to how much trained and untrained individuals interact.
Unexpectedly, the preference of trained individuals to their trained oviposition
substrate decreases after interactions with untrained individuals, leading to an
overall informational loss. This shows that social learning alone is not enough
to support informational stability.
PMID- 25589604
TI - How to catch more prey with less effective traps: explaining the evolution of
temporarily inactive traps in carnivorous pitcher plants.
AB - Carnivorous Nepenthes pitcher plants capture arthropods with specialized slippery
surfaces. The key trapping surface, the pitcher rim (peristome), is highly
slippery when wetted by rain, nectar or condensation, but not when dry. As
natural selection should favour adaptations that maximize prey intake, the
evolution of temporarily inactive traps seems paradoxical. Here, we show that
intermittent trap deactivation promotes 'batch captures' of ants. Prey surveys
revealed that N. rafflesiana pitchers sporadically capture large numbers of ants
from the same species. Continuous experimental wetting of the peristome increased
the number of non-recruiting prey, but decreased the number of captured ants and
shifted their trapping mode from batch to individual capture events. Ant
recruitment was also lower to continuously wetted pitchers. Our experimental data
fit a simple model that predicts that intermittent, wetness-based trap activation
should allow safe access for 'scout' ants under dry conditions, thereby promoting
recruitment and ultimately higher prey numbers. The peristome trapping mechanism
may therefore represent an adaptation for capturing ants. The relatively rare
batch capture events may particularly benefit larger plants with many pitchers.
This explains why young plants of many Nepenthes species additionally employ
wetness-independent, waxy trapping surfaces.
PMID- 25589605
TI - Why inclusive fitness can make it adaptive to produce less fit extra-pair
offspring.
AB - Social monogamy predominates in avian breeding systems, but most socially
monogamous species engage in promiscuous extra-pair copulations (EPCs). The
reasons behind this remain debated, and recent empirical work has uncovered
patterns that do not seem to fit existing hypotheses. In particular, some results
seem to contradict the inbreeding avoidance hypothesis: females can prefer extra
pair partners that are more closely related to them than their social partners,
and extra-pair young can have lower fitness than within-pair young. Motivated by
these studies, we show that such results can become explicable when an asymmetry
in inbreeding tolerance between monogamy and polygamy is extended to species that
combine both strategies within a single reproductive season. Under fairly general
conditions, it can be adaptive for a female to choose an unrelated social
partner, but inbreed with an extra-pair partner. Inbreeding depression is
compensated for by inclusive fitness benefits, which are only fully realized in
EPCs. We also show that if a female has already formed a suboptimal social bond,
there are scenarios where it is beneficial to engage in EPCs with less related
males, and others where EPCs with more related males increase her inclusive
fitness. This has implications for detecting general relatedness or fitness
trends when averaged over several species.
PMID- 25589606
TI - Chimpanzees trust conspecifics to engage in low-cost reciprocity.
AB - Many of humans' most important social interactions rely on trust, including most
notably among strangers. But little is known about the evolutionary roots of
human trust. We presented chimpanzees (Pan troglodytes) with a modified version
of the human trust game--trust in reciprocity--in which subjects could opt either
to obtain a small but safe reward on their own or else to send a larger reward to
a partner and trust her to reciprocate a part of the reward that she could not
access herself. In a series of three studies, we found strong evidence that in
interacting with a conspecific, chimpanzees show spontaneous trust in a novel
context; flexibly adjust their level of trust to the trustworthiness of their
partner and develop patterns of trusting reciprocity over time. At least in some
contexts then, trust in reciprocity is not unique to humans, but rather has its
evolutionary roots in the social interactions of humans' closest primate
relatives.
PMID- 25589607
TI - Symbiodinium identity alters the temperature-dependent settlement behaviour of
Acropora millepora coral larvae before the onset of symbiosis.
AB - The global distribution of marine species, many of which disperse during the
larval stages, is influenced by ocean temperature regimes. Here, we test how
temperature and the coral symbionts (Symbiodinium) affect survival, symbiont
uptake, settlement success and habitat choice of Acropora millepora larvae.
Experiments were conducted at Heron Island (Australia), where larvae were exposed
to 22.5, 24.5, 26.5 and 28.5 degrees C. Within each temperature treatment, larvae
were offered symbionts with distinct characteristics: (i) homologous Symbiodinium
type C3, (ii) regionally homologous thermo-tolerant type D1, and (iii)
heterologous thermo-tolerant type C15, as well as controls of (iv) un-filtered
and (v) filtered seawater. Results show that lower instead of higher temperatures
adversely affected recruitment by reducing larval survival and settlement. Low
temperatures also reduced recruit habitat choice and initial symbiont densities,
both of which impact on post-settlement survival. At lower temperatures, larvae
increasingly settle away from preferred vertical surfaces and not on crustose
coralline algae (CCA). Surprisingly, substrate preference to CCA was modified by
the presence of specific symbiont genotypes that were present ex-hospite (outside
the coral larvae). When different symbionts were mixed, the outcomes were non
additive, indicating that symbiont interactions modify the response. We propose
that the observed influence of ex-hospite symbionts on settlement behaviour may
have evolved through ecological facilitation and the study highlights the
importance of biological processes during coral settlement.
PMID- 25589608
TI - A phylogenetic backbone for Bivalvia: an RNA-seq approach.
AB - Bivalves are an ancient and ubiquitous group of aquatic invertebrates with an
estimated 10 000-20 000 living species. They are economically significant as a
human food source, and ecologically important given their biomass and effects on
communities. Their phylogenetic relationships have been studied for decades, and
their unparalleled fossil record extends from the Cambrian to the Recent.
Nevertheless, a robustly supported phylogeny of the deepest nodes, needed to
fully exploit the bivalves as a model for testing macroevolutionary theories, is
lacking. Here, we present the first phylogenomic approach for this important
group of molluscs, including novel transcriptomic data for 31 bivalves obtained
through an RNA-seq approach, and analyse these data with published genomes and
transcriptomes of other bivalves plus outgroups. Our results provide a well
resolved, robust phylogenetic backbone for Bivalvia with all major lineages
delineated, addressing long-standing questions about the monophyly of
Protobranchia and Heterodonta, and resolving the position of particular groups
such as Palaeoheterodonta, Archiheterodonta and Anomalodesmata. This now fully
resolved backbone demonstrates that genomic approaches using hundreds of genes
are feasible for resolving phylogenetic questions in bivalves and other animals.
PMID- 25589609
TI - Payoff-based learning explains the decline in cooperation in public goods games.
AB - Economic games such as the public goods game are increasingly being used to
measure social behaviours in humans and non-human primates. The results of such
games have been used to argue that people are pro-social, and that humans are
uniquely altruistic, willingly sacrificing their own welfare in order to benefit
others. However, an alternative explanation for the empirical observations is
that individuals are mistaken, but learn, during the game, how to improve their
personal payoff. We test between these competing hypotheses, by comparing the
explanatory power of different behavioural rules, in public goods games, where
individuals are given different amounts of information. We find: (i) that
individual behaviour is best explained by a learning rule that is trying to
maximize personal income; (ii) that conditional cooperation disappears when the
consequences of cooperation are made clearer; and (iii) that social preferences,
if they exist, are more anti-social than pro-social.
PMID- 25589611
TI - Gut Feeling in AKI: The Long Arm of Short-Chain Fatty Acids.
PMID- 25589610
TI - Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.
AB - Progressive CKD is generally detected at a late stage by a sustained decline in
eGFR and/or the presence of significant albuminuria. With the aim of early and
improved risk stratification of patients with CKD, we studied urinary peptides in
a large cross-sectional multicenter cohort of 1990 individuals, including 522
with follow-up data, using proteome analysis. We validated that a previously
established multipeptide urinary biomarker classifier performed significantly
better in detecting and predicting progression of CKD than the current clinical
standard, urinary albumin. The classifier was also more sensitive for identifying
patients with rapidly progressing CKD. Compared with the combination of baseline
eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the
multipeptide biomarker classifier significantly improved CKD risk prediction
(AUC=0.831) as assessed by the net reclassification index (0.303+/--0.065;
P<0.001) and integrated discrimination improvement (0.058+/-0.014; P<0.001).
Correlation of individual urinary peptides with CKD stage and progression showed
that the peptides that associated with CKD, irrespective of CKD stage or CKD
progression, were either fragments of the major circulating proteins, suggesting
failure of the glomerular filtration barrier sieving properties, or different
collagen fragments, suggesting accumulation of intrarenal extracellular matrix.
Furthermore, protein fragments associated with progression of CKD originated
mostly from proteins related to inflammation and tissue repair. Results of this
study suggest that urinary proteome analysis might significantly improve the
current state of the art of CKD detection and outcome prediction and that
identification of the urinary peptides allows insight into various ongoing
pathophysiologic processes in CKD.
PMID- 25589613
TI - Can the Urinary Peptidome Outperform Creatinine and Albumin to Predict Renal
Function Decline?
PMID- 25589612
TI - Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion.
AB - Short-chain fatty acids (SCFAs) are fermentation end products produced by the
intestinal microbiota and have anti-inflammatory and histone deacetylase
inhibiting properties. Recently, a dual relationship between the intestine and
kidneys has been unraveled. Therefore, we evaluated the role of SCFA in an AKI
model in which the inflammatory process has a detrimental role. We observed that
therapy with the three main SCFAs (acetate, propionate, and butyrate) improved
renal dysfunction caused by injury. This protection was associated with low
levels of local and systemic inflammation, oxidative cellular stress, cell
infiltration/activation, and apoptosis. However, it was also associated with an
increase in autophagy. Moreover, SCFAs inhibited histone deacetylase activity and
modulated the expression levels of enzymes involved in chromatin modification. In
vitro analyses showed that SCFAs modulated the inflammatory process, decreasing
the maturation of dendritic cells and inhibiting the capacity of these cells to
induce CD4(+) and CD8(+) T cell proliferation. Furthermore, SCFAs ameliorated the
effects of hypoxia in kidney epithelial cells by improving mitochondrial
biogenesis. Notably, mice treated with acetate-producing bacteria also had better
outcomes after AKI. Thus, we demonstrate that SCFAs improve organ function and
viability after an injury through modulation of the inflammatory process, most
likely via epigenetic modification.
PMID- 25589615
TI - Potential role of pNF-H, a biomarker of axonal damage in the central nervous
system, as a predictive marker of chemotherapy-induced cognitive impairment.
AB - PURPOSE: Chemotherapy-induced cognitive impairment (CICI) is a clinically
significant problem. Previous studies using magnetic resonance imaging indicated
structural changes in the cerebral white matter of patients with CICI.
Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in
axons, was recently reported to be elevated in the serum of patients with some
central nervous system disorders. We performed a cross-sectional analysis of
neuropsychological test results and serum pNF-H levels in patients undergoing
adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is
accompanied by axonal damage that can be detected by elevated serum pNF-H levels.
EXPERIMENTAL DESIGN: Seventy-six patients with early breast cancer in various
phases of treatment (naive to chemotherapy; after one, three, or seven cycles of
chemotherapy; or with a history of chemotherapy) were assessed by self
administered neuropsychological tests and a single pNF-H measurement. The chi(2)
and Mann-Whitney tests were used for statistical analysis. RESULTS: Increased pNF
H levels were observed in 28.8% of the patients who underwent chemotherapy, but
in none of the chemotherapy-naive patients or patients with a history of
chemotherapy. The pNF-H-positive rate increased significantly in proportion to
the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven
cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test
results were observed among the groups. CONCLUSIONS: The serum pNF-H level in
patients undergoing chemotherapy for breast cancer increased in a cumulative dose
dependent manner, suggesting its potential application as a biomarker of neural
damage after chemotherapy.
PMID- 25589616
TI - Interleukin-6 as a therapeutic target.
AB - Human IL6 is a cytokine produced by many cell types that has pleiotropic effects.
In agreement, anti-IL6 therapy reduces inflammation, hepatic acute phase
proteins, and anemia and has antiangiogenic effects. Blocking IL6 has
demonstrated therapeutic efficacy with drug registration in Castleman disease and
inflammatory diseases (rheumatoid arthritis) without major toxicity.
Interestingly, the inhibition of C-reactive protein (CRP) production is a
trustworthy surrogate marker of anti-IL6 therapy efficacy. Clinically registered
IL6 inhibitors include siltuximab, an anti-IL6 mAb, and tocilizumab, an anti-IL6R
mAb. In various cancers, in particular plasma cell cancers, large randomized
trials showed no efficacy of IL6 inhibitors, despite a full inhibition of CRP
production in treated patients in vivo, the numerous data showing an involvement
of IL6 in these diseases, and initial short-term treatments demonstrating a
dramatic inhibition of cancer cell proliferation in vivo. A likely explanation is
the plasticity of cancer cells, with the presence of various subclones, making
the outgrowth of cancer subclones possible using growth factors other than IL6.
In addition, current therapeutic strategies used in these cancers already target
IL6 activity. Thus, anti-IL6 therapeutics are able to neutralize IL6 production
in vivo and are safe and useful in inflammatory diseases and Castleman disease.
PMID- 25589614
TI - Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal
Cancer.
AB - PURPOSE: VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach
for patients with metastatic renal cell carcinoma (RCC). However, resistance to
treatment is inevitable. Identification of novel targets could lead to better
treatment for patients with TKI-naive or -resistant RCC. EXPERIMENTAL DESIGN: In
this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in
a murine model and discovered that the SPHK-S1P pathway is upregulated at the
time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition
using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and
assessed tumor SPHK expression and S1P plasma levels in patients with metastatic
RCC. RESULTS: Resistant tumors expressed several hypoxia-regulated genes. The
SPHK1 pathway was among the most highly upregulated pathways that accompanied
resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the
product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC,
suggesting that human RCC behavior could, in part, be due to overproduction of
S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both
mouse models. Mice bearing tumors that had developed resistance to sunitinib
treatment also exhibited tumor growth suppression with sphingomab. Sphingomab
treatment led to a reduction in tumor blood flow as measured by MRI. CONCLUSIONS:
Our findings suggest that S1P inhibition may be a novel therapeutic strategy in
patients with treatment-naive RCC and also in the setting of resistance to VEGFR
TKI therapy.
PMID- 25589617
TI - A comparative study of molecular characteristics of diffuse large B-cell lymphoma
from patients with and without human immunodeficiency virus infection.
AB - PURPOSE: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically
different from DLBCL in the general population. We compared, by HIV status, the
expression and prognostic significance of selected oncogenic markers in DLBCL
diagnosed at Kaiser Permanente in California, between 1996 and 2007. EXPERIMENTAL
DESIGN: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected
DLBCL patients by age, gender, and race. Twenty-three markers in the following
categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell
activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor
marker expression was compared across HIV infection status by Fisher exact test.
For markers differentially expressed in HIV-related DLBCL, logistic regression
was used to evaluate the association between tumor marker expression and 2-year
overall mortality, adjusting for International Prognostic Index, cell-of-origin
phenotype, and DLBCL morphologic variants. RESULTS: Expression of cMYC (%
positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%),
PKC-beta2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was
significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs.
75%) was significantly reduced. Of these, cMYC expression was independently
associated with increased 2-year mortality in HIV-infected patients [relative
risk = 3.09 (0.90-10.55)] in multivariable logistic regression. CONCLUSIONS:
These results suggest that HIV-related DLBCL pathogenesis more frequently
involves cMYC and BCL6 among other factors. In particular, cMYC-mediated
pathogenesis may partly explain the more aggressive clinical course of DLBCL in
HIV-infected patients.
PMID- 25589618
TI - Genomic analysis of metastatic cutaneous squamous cell carcinoma.
AB - PURPOSE: A rare 5% of cutaneous squamous cell carcinomas (cSCC) metastasize, lack
FDA-approved therapies, and carry a poor prognosis. Our aim was to identify
recurrent genomic alterations in this little-studied population of metastatic
cSCCs. EXPERIMENTAL DESIGN: We performed targeted sequencing of 504 cancer
associated genes on lymph node metastases in 29 patients with cSCC and identified
mutations and somatic copy-number alterations associated with metastatic cSCC. We
determined significantly mutated, deleted, and amplified genes and associated
genomic alterations with clinical variables. RESULTS: The cSCC genome is
heterogeneous with widely varying numbers of genomic alterations and does not
appear to be associated with human papillomavirus. We found previously identified
recurrently altered genes (TP53, CDKN2A, NOTCH1/2) but also a wide spectrum of
oncogenic mutations affecting RAS/RTK/PI3K, squamous differentiation, cell cycle,
and chromatin remodeling pathway genes. Specific mutations in known oncogenic
drivers and pathways were correlated with inferior patient outcomes. Our results
suggest potential therapeutic targets in metastatic cSCC, including PIK3CA,
FGFR3, BRAF, and EGFR, similar to those reported in SCCs of the lung and head and
neck, suggesting that clinical trials could be developed to accrue patients with
SCCs from multiple sites of origin. CONCLUSIONS: We have genomically
characterized a rare cohort of 29 metastatic cSCCs and identified a diverse array
of oncogenic alterations that can guide future studies of this disease.
PMID- 25589619
TI - The BRAF and MEK Inhibitors Dabrafenib and Trametinib: Effects on Immune Function
and in Combination with Immunomodulatory Antibodies Targeting PD-1, PD-L1, and
CTLA-4.
AB - PURPOSE: To assess the immunologic effects of dabrafenib and trametinib in vitro
and to test whether trametinib potentiates or antagonizes the activity of
immunomodulatory antibodies in vivo. EXPERIMENTAL DESIGN: Immune effects of
dabrafenib and trametinib were evaluated in human CD4(+) and CD8(+) T cells from
healthy volunteers, a panel of human tumor cell lines, and in vivo using a CT26
mouse model. RESULTS: Dabrafenib enhanced pERK expression levels and did not
suppress human CD4(+) or CD8(+) T-cell function. Trametinib reduced pERK levels,
and resulted in partial/transient inhibition of T-cell proliferation/expression
of a cytokine and immunomodulatory gene subset, which is context dependent.
Trametinib effects were partially offset by adding dabrafenib. Dabrafenib and
trametinib in BRAF V600E/K, and trametinib in BRAF wild-type tumor cells induced
apoptosis markers, upregulated HLA molecule expression, and downregulated certain
immunosuppressive factors such as PD-L1, IL1, IL8, NT5E, and VEGFA. PD-L1
expression in tumor cells was upregulated after acquiring resistance to BRAF
inhibition in vitro. Combinations of trametinib with immunomodulators targeting
PD-1, PD-L1, or CTLA-4 in a CT26 model were more efficacious than any single
agent. The combination of trametinib with anti-PD-1 increased tumor-infiltrating
CD8(+) T cells in CT26 tumors. Concurrent or phased sequential treatment, defined
as trametinib lead-in followed by trametinib plus anti-PD-1 antibody,
demonstrated superior efficacy compared with anti-PD-1 antibody followed by anti
PD-1 plus trametinib. CONCLUSION: These findings support the potential for
synergy between targeted therapies dabrafenib and trametinib and immunomodulatory
antibodies. Clinical exploration of such combination regimens is under way.
PMID- 25589620
TI - Pharmacogenetic Analysis of INT 0144 Trial: Association of Polymorphisms with
Survival and Toxicity in Rectal Cancer Patients Treated with 5-FU and Radiation.
AB - PURPOSE: We tested whether 18 polymorphisms in 16 genes (GSTP1, COX2, IL10, EGFR,
EGF, FGFR4, CCDN1, VEGFR2, VEGF, CXCR2, IL8, MMP3, ICAM1, ERCC1, RAD51, and
XRCC3) would predict disease-free survival (DFS), overall survival (OS), and
toxicity in the INT0144 trial, which was designed to investigate different
postoperative regimens of 5-fluorouracil (5-FU)-based chemoradiation (CRT) in
locally advanced rectal cancers: Arm 1 consisted of bolus 5-FU followed by 5-FU
protracted venous infusion (PVI) with radiotherapy; arm 2 was induction and
concomitant PVI 5-FU with radiotherapy and arm 3 was induction and concomitant
bolus 5-FU with radiotherapy. EXPERIMENTAL DESIGN: DNA from 746 stage II/III
rectal patients enrolled in the Southwest Oncology Group (SWOG) S9304 phase III
trial was analyzed. Genomic DNA was extracted from formalin-fixed, paraffin
embedded (FFPE) tumor tissue. The polymorphisms were analyzed using direct DNA
sequencing or polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP). RESULTS: GSTP1-Ile105Val (rs1695) was significantly associated with
DFS and OS and its effect did not vary by treatment arm. The five-year DFS and OS
were 53% and 58%, respectively, for G/G, 66% and 72% for G/A, and 57% and 66% for
A/A patients. In arm 2, IL8-251A/A genotype (rs4073) was associated with a lower
risk of toxicities (P = 0.04). The VEGFR2 H472Q Q/Q genotype (rs1870377) was
associated with a higher risk of grade 3-5 proximal upper gastrointestinal tract
(PUGIT) mucositis (P = 0.04) in arm 2. However, in arm 1, this genotype was
associated with a lower risk of PUGIT mucositis (P = 0.004). CONCLUSION: rs1695
may be prognostic in patients with rectal cancer treated with adjuvant CRT.
rs4073 and rs1870377 may exhibit different associations with toxicity, according
to the 5-FU schedule.
PMID- 25589621
TI - Pilot trial of combined BRAF and EGFR inhibition in BRAF-mutant metastatic
colorectal cancer patients.
AB - PURPOSE: BRAF-mutant metastatic colorectal cancer (mCRC) forms an aggressive
subset of colorectal cancer with minimal response to selective RAF inhibitors.
Preclinical data show that reactivation of EGFR signaling occurs in colorectal
tumor cells treated with RAF inhibitors and that the addition of an EGFR
inhibitor enhances antitumor activity. These data suggest that combined therapy
with RAF and EGFR inhibitors could be an effective strategy for treating BRAF
V600E mCRC. EXPERIMENTAL DESIGN: We undertook a pilot trial to assess the
response rate and safety of the BRAF inhibitor vemurafenib combined with anti
EGFR antibody panitumumab in patients with BRAF-mutant mCRC. Patients received
standard approved doses of panitumumab and vemurafenib. RESULTS: Fifteen patients
were treated. Performance status was Eastern Cooperative Oncology Group (ECOG) 0
in 4 patients (27%) and ECOG 1 in 11 patients (73%). All patients had progressed
through at least one standard treatment regimen, and 8 (53%) had received
previous fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy. Treatment
was well tolerated, with less cutaneous toxicity than would be expected with
either agent, and no cases of keratoacanthomas/squamous cell carcinomas. Tumor
regressions were seen in 10 of 12 evaluable patients with partial responses in 2
patients (100% and 64% regression lasting 40 and 24 weeks, respectively), and
stable disease lasting over 6 months in 2 patients. CONCLUSIONS: Combined RAF and
EGFR inhibition is well tolerated, with less cutaneous toxicity than would be
expected with either agent, and results in modest clinical activity in this
highly aggressive and chemoresistant subset of CRC.
PMID- 25589622
TI - Gain of HIF-1alpha under normoxia in cancer mediates immune adaptation through
the AKT/ERK and VEGFA axes.
AB - PURPOSE: Adaptation to host immune surveillance is now recognized as a hallmark
of cancer onset and progression, and represents an early, indispensable event in
cancer evolution. This process of evolution is first instigated by an immune
selection pressure imposed by natural host surveillance mechanisms and may then
be propagated by vaccination or other types of immunotherapy. EXPERIMENTAL
DESIGN: We developed a system to simulate cancer evolution in a live host and to
dissect the mechanisms responsible for adaptation to immune selection. Here, we
show that the oxygen-sensitive alpha subunit of hypoxia-inducible factor 1 (HIF
1alpha) plays a central role in cancer immune adaptation under conditions of
normal oxygen tension. RESULTS: We found that tumor cells gain HIF-1alpha in the
course of immune selection under normoxia and that HIF-1alpha renders tumor cells
resistant to lysis by tumor-specific cytotoxic T lymphocytes (CTL) in culture and
in mice. The effects of HIF-1alpha on immune adaptation were mediated through
VEGFA-dependent activation of the AKT and ERK signaling pathways, which induced
an antiapoptotic gene expression network in tumor cells. CONCLUSIONS: Our study
therefore establishes a link between immune selection, overexpression of HIF
1alpha, and cancer immune adaptation under normoxia, providing new opportunities
for molecular intervention in patients with cancer.
PMID- 25589623
TI - KEAP1 Genetic Polymorphisms Associate with Breast Cancer Risk and Survival
Outcomes.
AB - PURPOSE: Defective oxidative stress response may increase cancer susceptibility.
In tumors, these rescue mechanisms may cause chemo- and radioresistance impacting
patient outcome. We previously showed that genetic variation in the nuclear
factor erythroid 2-related factor 2 (NFE2L2) is associated with breast cancer
risk and prognosis. Here we further studied this pathway by investigating Kelch
like ECH-associated protein 1 (KEAP1). EXPERIMENTAL DESIGN: Five tagging SNPs in
the KEAP1 gene were genotyped in 996 breast cancer cases and 880 controls from
two Finnish case-control sets. KEAP1 protein expression was studied in 373
invasive breast cancer tumors. RESULTS: rs34197572 genotype TT was associated
with increased risk of breast cancer in the KBCP samples [P = 1.8*10(-4); OR,
7.314; confidence interval (CI), 2.185-24.478]. rs11085735 allele A was
associated with lower KEAP1 protein expression (P = 0.040; OR,= 3.545) and high
nuclear NRF2 expression (P = 0.009; OR, 2.445) and worse survival in all invasive
cases (P = 0.023; HR, 1.634). When including treatment data, rs11085735 was
associated with recurrence-free survival (RFS; P = 0.020; HR, 1.545) and breast
cancer-specific survival (P = 0.016; HR, 1.683) and rs34197572 with overall
survival (P = 0.045; HR, 1.304). rs11085735 associated with RFS also among
tamoxifen-treated cases (P = 0.003; HR, 3.517). Among radiotherapy-treated cases,
overall survival was associated with rs34197572 (P = 0.018; HR, 1.486) and
rs8113472 (P = 0.025; HR, 1.455). RFS was associated with rs9676881 (P = 0.024;
HR, 1.452) and rs1048290 (P = 0.020; HR, 1.468) among all invasive cases and
among estrogen receptor (ER)-positive tamoxifen-treated cases (P = 0.018; HR,
2.407 and P = 0.015; HR, 2.476, respectively). CONCLUSIONS: The present findings
suggest that the investigated SNPs have effects related to oxidative stress
induced by cancer treatment, supporting involvement of the NRF2/KEAP1 pathway in
breast cancer susceptibility and patient outcome.
PMID- 25589625
TI - Antibody-mediated delivery of anti-KRAS-siRNA in vivo overcomes therapy
resistance in colon cancer.
AB - PURPOSE: KRAS mutations are frequent driver mutations in multiple cancers. KRAS
mutations also induce anti-EGFR antibody resistance in adenocarcinoma such as
colon cancer. The aim of this study was to overcome anti-EGFR antibody resistance
by coupling the antibody to KRAS-specific siRNA. EXPERIMENTAL DESIGN: The anti
EGFR antibody was chemically coupled to siRNA. The resulting complex was tested
for antibody binding efficiency, serum stability and ability to deliver siRNA to
EGFR-expressing cells. Western blotting, viability, apoptosis, and colony
formation assays were performed for efficacy evaluation in vitro. Furthermore,
therapeutic activity of the antibody-KRAS-siRNA complexes was examined in in vivo
xenograft mouse tumor models. RESULTS: Antibody-siRNA complexes were targeted and
internalized via the EGFR receptor. Upon internalization, target gene expression
was strongly and specifically repressed, followed by a reduced proliferation and
viability, and induced apoptosis of the cells in vitro. Clonogenic growth of
mutant KRAS-bearing cells was suppressed by KRAS-siRNA-anti-EGFR antibody
complexes. In xenograft mouse models, anti-EGFR antibody-KRAS-siRNA complexes
significantly slowed tumor growth in anti-EGFR-resistant cells. CONCLUSIONS: The
coupling of siRNA against KRAS to anti-EGFR antibodies provides a novel therapy
approach for KRAS-mutated EGFR-positive cancer cells in vitro and in vivo. These
findings provide an innovative approach for cancer-specific siRNA application and
for enhanced therapeutic potential of monoclonal antibody therapy and
personalized treatment of cancer entities.
PMID- 25589624
TI - Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous
Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian
Cancer.
AB - PURPOSE: Veliparib, a PARP inhibitor, demonstrated clinical activity in
combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors
in a phase I trial. To define the relative contribution of PARP inhibition to the
observed clinical activity, we conducted a randomized phase II trial to determine
the response rate of veliparib in combination with cyclophosphamide compared with
cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or
in patients with pretreated primary peritoneal, fallopian tube, or high-grade
serous ovarian cancers (HGSOC). EXPERIMENTAL DESIGN: Adult patients were
randomized to receive cyclophosphamide alone (50 mg orally once daily) or with
veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the
combination was allowed at disease progression. RESULTS: Seventy-five patients
were enrolled and 72 were evaluable for response; 38 received cyclophosphamide
alone and 37 the combination as their initial treatment regimen. Treatment was
well tolerated. One complete response was observed in each arm, with three
partial responses (PR) in the combination arm and six PRs in the cyclophosphamide
alone arm. Genetic sequence and expression analyses were performed for 211 genes
involved in DNA repair; none of the detected genetic alterations were
significantly associated with treatment benefit. CONCLUSION: This is the first
trial that evaluated single-agent, low-dose cyclophosphamide in HGSOC,
peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well
tolerated and clinical activity was observed; the addition of veliparib at 60 mg
daily did not improve either the response rate or the median progression-free
survival.
PMID- 25589626
TI - Clinical and biological effects of an agonist anti-CD40 antibody: a Cancer
Research UK phase I study.
AB - PURPOSE: This phase I study aimed to establish the biologic effects and MTD of
the agonistic IgG1 chimeric anti-CD40 antibody ChiLob7/4 in patients (pts) with a
range of CD40-expressing solid tumors and diffuse large B-cell lymphoma,
resistant to conventional therapy. Potential mechanisms of action for agonistic
anti-CD40 include direct cytotoxic effects on tumor cells and conditioning of
antigen-presenting cells. EXPERIMENTAL DESIGN: ChiLob7/4 was given by IV infusion
weekly for 4 doses at a range from 0.5 to 240 mg/dose. Validated ELISAs were used
to quantify ChiLob7/4 in serum and test for anti-chimeric MAb (HACA) responses.
Pharmacodynamic assessments included quantitation of T-cell, natural killer-cell,
and B-cell numbers and activation in blood by flow cytometry and a panel of
cytokines in plasma by Luminex technology. Planned dose escalation was in cohorts
of 3 patients until MTD or biologic effect, defined as reduction of peripheral
blood CD19(+) B cells to 10% or less of baseline. RESULTS: Twenty-nine courses of
treatment were given to 28 subjects. The MTD was 200 mg * 4, with dose-limiting
toxicity of liver transaminase elevations at 240 mg. At 200 mg (range between 2.1
mg/kg and 3.3 mg/kg based on patient body weight), the trough level pretreatment
was above 25 MUg/mL. Grade 1-2 infusion reactions were seen above the dose of 16
mg, but could be prevented with single-dose corticosteroid premedication. HACA
responses were seen after doses between 1.6 mg and 50 mg, but not above this.
There were dose-dependent falls in blood B-cell numbers accompanied by reduced
expression of CD21, and transient reductions in NK cell numbers with increased
CD54 expression from 50 mg upward. MIP-1beta and IL12 plasma concentrations rose
after doses above 16 mg. Fifteen of 29 treatments were accompanied by disease
stabilization for a median 6 months, the longest for 37 months. CONCLUSIONS:
ChiLob7/4 can activate B and NK cells at doses that can be administered safely,
and should be tested in combination with other antibodies and chemotherapy
agents.
PMID- 25589627
TI - Identification of Biological Relevant Minor Histocompatibility Antigens within
the B-lymphocyte-Derived HLA-Ligandome Using a Reverse Immunology Approach.
AB - PURPOSE: T-cell recognition of minor histocompatibility antigens (MiHA) not only
plays an important role in the beneficial graft-versus-leukemia (GVL) effect of
allogeneic stem cell transplantation (allo-SCT) but also mediates serious GVH
complications associated with allo-SCT. Using a reverse immunology approach, we
aim to develop a method enabling the identification of T-cell responses directed
against predefined antigens, with the goal to select those MiHAs that can be used
clinically in combination with allo-SCT. EXPERIMENTAL DESIGN: In this study, we
used a recently developed MiHA selection algorithm to select candidate MiHAs
within the HLA-presented ligandome of transformed B cells. From the HLA-presented
ligandome that predominantly consisted of monomorphic peptides, 25 polymorphic
peptides with a clinically relevant allele frequency were selected. By high
throughput screening, the availability of high-avidity T cells specific for these
MiHA candidates in different healthy donors was analyzed. RESULTS: With the use
of MHC multimer enrichment, analyses of expanded T cells by combinatorial coding
MHC multimer flow cytometry, and subsequent single-cell cloning, positive T-cell
clones directed to two new MiHA: LB-CLYBL-1Y and LB-TEP1-1S could be
demonstrated, indicating the immunogenicity of these two MiHAs. CONCLUSIONS: The
biologic relevance of MiHA LB-CLYBL-1Y was demonstrated by the detection of LB
CLYBL-1Y-specific T cells in a patient suffering from acute myeloid leukemia
(AML) that experienced an anti-leukemic response after treatment with allo-SCT.
PMID- 25589629
TI - Tackling the achilles' heel of genetic testing.
AB - Assigning pathogenicity to rare genetic variants is at its hardest with the
enormous titin gene, but comprehensive genomic analysis makes the task more
tractable (Roberts et al., this issue).
PMID- 25589628
TI - Cross-species antibody microarray interrogation identifies a 3-protein panel of
plasma biomarkers for early diagnosis of pancreas cancer.
AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of
cancer-related death in the United States, and its incidence is on the rise.
Advanced disease is nearly uniformly lethal, emphasizing the need to identify PDA
at its earliest stages. To discover early biomarkers of PDA, we evaluated the
circulating proteome in murine preinvasive and invasive plasma samples and human
prediagnostic and diagnostic samples. EXPERIMENTAL DESIGN: Using a customized
antibody microarray platform containing >4,000 features, we interrogated plasma
samples spanning preinvasive and invasive disease from a highly faithful mouse
model of PDA. In parallel, we mined prediagnostic plasma from women in the
Women's Health Initiative (WHI) who would later succumb to PDA together with
matched, cancer-free control samples. Samples collected after an establishing
diagnosis of PDA were also interrogated to further validate markers. RESULTS: We
identified ERBB2 and TNC in our cross-species analyses, and multiple antibodies
identified ESR1 in prediagnostic plasma from people that succumb to PDA. This 3
marker panel had an AUC of 0.86 (95% confidence interval [CI], 0.76-0.96) for the
diagnostic cohort that increased to 0.97 (95% CI, 0.92-1.0) with CA19-9 included.
The 3-marker panel also had an AUC of 0.68 (95% CI, 0.58-0.77) for the
prediagnostic cohort. CONCLUSIONS: We identified potential disease detection
markers in plasma up to 4 years before death from PDA with superior performance
to CA19-9. These markers might be especially useful in high-risk cohorts to
diagnose early, resectable disease, particularly in patients that do not produce
CA19-9.
PMID- 25589631
TI - The long-acting integrase inhibitor GSK744 protects macaques from repeated
intravaginal SHIV challenge.
AB - Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention
strategy; however, its effectiveness is limited by low adherence. Antiretroviral
drug formulations that require infrequent dosing may increase adherence and thus
PrEP effectiveness. We investigated whether monthly injections of a long-acting
formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented
simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in
macaques. Female pigtail macaques (n = 12) were exposed to intravaginal
inoculations of SHIV twice a week for up to 11 weeks. Half of the animals
received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744
LA, at plasma concentrations achievable with quarterly injections in humans,
protected all six macaques from infection. Placebo controls were all infected
after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was
related to high and sustained vaginal and plasma drug concentrations that
remained above the protein-adjusted 90% inhibitory concentration during the
dosing cycles. These data support advancement of GSK744 LA as a potential PrEP
candidate for women.
PMID- 25589630
TI - A long-acting integrase inhibitor protects female macaques from repeated high
dose intravaginal SHIV challenge.
AB - Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV
(simian immunodeficiency virus) integrase and was shown to be an effective
preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human
immunodeficiency virus) rhesus macaque challenge model. We examined the
pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose
intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera
(depot medroxyprogesterone acetate), which promotes viral transmission vaginally.
When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50
mg/kg) monthly, systemic and tissue drug concentrations were lower than
previously observed in male rhesus macaques. GSK744 concentrations were fivefold
lower on average in cervical tissues than in rectal tissues. Eight female rhesus
macaques were treated with GSK744 LA at week 0, and four female rhesus macaques
served as controls. All animals received a high-dose challenge of SHIV162P3 at
week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas
viremia was detected 1 to 2 weeks after SHIV challenge in all control animals.
The GSK744 LA-treated rhesus macaques were given a second administration of drug
at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected
six of eight female rhesus macaques against three high-dose SHIV challenges,
whereas all control animals became infected after the first challenge (P =
0.0003, log-rank test). These results support further clinical development of
GSK744 LA for PrEP.
PMID- 25589633
TI - Atypical risk factor profile and excellent long-term outcomes of young patients
treated with primary percutaneous coronary intervention for ST-elevation
myocardial infarction.
AB - INTRODUCTION: Several studies have examined the relationship between age and
clinical outcomes in patients with ST-elevation myocardial infarction (STEMI)
treated by primary percutaneous coronary intervention (PPCI). The majority of
studies have concentrated on describing elderly patients and there has been less
focus on the profile and outcome of young patients suffering from STEMI. The aim
of this study was to describe the clinical profile and outcomes of young patients
compared with an older cohort and to establish what risk factors were associated
with young patients having PPCI for STEMI. METHODS: This was an observational
cohort study of 3618 patients with STEMI treated by PPCI at a regional heart
attack centre in London between January 2004 and September 2012. Clinical
characteristics and outcomes in (young) patients aged <= 45 years were compared
with those in (older) patients aged >45 years. The primary and main secondary
outcomes were all-cause mortality and major adverse cardiovascular event rates,
respectively, at a median follow-up of 3.0 (interquartile range 1.2-4.6) years.
RESULTS: Of the 3618 patients, 367 (10.1%) were aged <= 45 years and 3251 (89.9%)
were aged >45 years. The proportion of patients aged <= 45 years increased from
8.5% to 11.5% (p=0.04) during the study period. Compared with older patients,
those aged <= 45 years were more likely to be male, smokers, of South Asian
ethnicity and to have a family history of premature coronary artery disease.
Young patients were less likely to have a history of hypertension,
hypercholesterolaemia, diabetes mellitus, previous myocardial infarction,
myocardial revascularisation, or to have left ventricular systolic impairment or
renal impairment. Over the follow-up period, mortality (2.7% vs. 7.6%; p<0.0001)
and major adverse cardiovascular event rates (7.0% vs. 13.5%; p<0.0001) were
significantly lower in patients aged <= 45 years compared with older patients.
After adjustment for potential confounding factors, young age remained a
predictor of reduced all cause mortality when compared with older patients
(hazard ratio 0.12 (95% confidence interval 0.04-0.38)), including after
incorporation of a propensity score (hazard ratio: 0.14 (95% confidence interval
0.04-0.36)). CONCLUSIONS: In this cohort of patients with STEMI treated by PPCI
there was an increasing incidence of young patients aged <= 45 years throughout
the study period. These patients were more often male, smokers and of South Asian
ethnicity. Outcomes in younger patients was good. Focusing preventative
strategies on smokers and high risk ethnic groups may help reduce the incidence
of premature coronary artery disease.
PMID- 25589634
TI - A simple risk chart for initial risk assessment of 30-day mortality in patients
with cardiogenic shock from ST-elevation myocardial infarction.
AB - AIMS: Early risk stratification is important in patients with cardiogenic shock
from ST-elevation myocardial infarction (STEMI). We aimed to develop a simple
risk chart that includes clinical parameters that are readily available at time
of hospital admission to assess risk of 30-day mortality. METHODS AND RESULTS: A
series of 544 STEMI patients admitted to undergo primary percutaneous coronary
intervention and presenting with cardiogenic shock were included between 2000 and
2012. Overall 30-day mortality was 38.4% and did not change over the years (p
trend=0.64). Baseline variables that were available at time of hospital admission
were entered into a logistic regression model in a forward stepwise manner. Only
age (odds ratio (OR) per year 1.05, 95% confidence interval (CI) 1.04-1.07,
p<0.001), initial serum lactate level (OR per mmol/l 1.17, 95% CI 1.11-1.24,
p<0.001) and initial creatinine level above the upper limit of normal (OR 2.89,
95% CI 1.90-4.37, p<0.001) remained independent predictors, and were subsequently
used to develop a risk chart that stratifies risk of 30-day mortality into
categories ranging from 0-20% to 80-100%. The calibration plot showed a close
relationship between expected and observed mortality. The risk chart had a higher
discriminative accuracy than the GRACE score (c-index 0.75 vs. 0.66, p=0.009).
Adding variables that were obtained from coronary angiography and during clinical
course did not significantly improve discriminative accuracy of risk chart (c
index 0.77, p=0.48). CONCLUSION: Mortality of patients with cardiogenic shock
from STEMI undergoing primary percutaneous coronary intervention can be well
predicted already at time of hospital admission by a risk chart that uses only
three variables, namely, age, initial serum lactate and creatinine level.
PMID- 25589635
TI - Antigenic relationships among porcine epidemic diarrhea virus and transmissible
gastroenteritis virus strains.
AB - Porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus
(TGEV) are economically important swine enteropathogenic coronaviruses. These two
viruses belong to two distinct species of the Alphacoronavirus genus within
Coronaviridae and induce similar clinical signs and pathological lesions in
newborn piglets, but they are presumed to be antigenically distinct. In the
present study, two-way antigenic cross-reactivity examinations between the
prototype PEDV CV777 strain, three distinct U.S. PEDV strains (the original
highly virulent PC22A, S indel Iowa106, and S 197del PC177), and two
representative U.S. TGEV strains (Miller and Purdue) were conducted by cell
culture immunofluorescent (CCIF) and viral neutralization (VN) assays. None of
the pig TGEV antisera neutralized PEDV and vice versa. One-way cross-reactions
were observed by CCIF between TGEV Miller hyperimmune pig antisera and all PEDV
strains. Enzyme-linked immunosorbent assays, immunoblotting using monoclonal
antibodies and Escherichia coli-expressed recombinant PEDV and TGEV nucleocapsid
(N) proteins, and sequence analysis suggested at least one epitope on the N
terminal region of PEDV/TGEV N protein that contributed to this cross-reactivity.
Biologically, PEDV strain CV777 induced greater cell fusion in Vero cells than
did U.S. PEDV strains. Consistent with the reported genetic differences, the
results of CCIF and VN assays also revealed higher antigenic variation between
PEDV CV777 and U.S. strains. IMPORTANCE: Evidence of antigenic cross-reactivity
between porcine enteric coronaviruses, PEDV and TGEV, in CCIF assays supports the
idea that these two species are evolutionarily related, but they are distinct
species defined by VN assays. Identification of PEDV- or TGEV-specific antigenic
regions allows the development of more specific immunoassays for each virus.
Antigenic and biologic variations between the prototype and current PEDV strains
could explain, at least partially, the recurrence of PEDV epidemics. Information
on the conserved antigenicity among PEDV strains is important for the development
of PEDV vaccines to protect swine from current highly virulent PEDV infections.
PMID- 25589636
TI - Mapping the Interactions between the NS4B and NS3 proteins of dengue virus.
AB - Flavivirus RNA synthesis is mediated by a multiprotein complex associated with
the endoplasmic reticulum membrane, named the replication complex (RC). Within
the flavivirus RC, NS4B, an integral membrane protein with a role in virulence
and regulation of the innate immune response, binds to the NS3 protease-helicase.
NS4B modulates the RNA helicase activity of NS3, but the molecular details of
their interaction remain elusive. Here, we used dengue virus (DENV) to map the
determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ
proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV
infected cells and cells coexpressing both proteins. Surface plasmon resonance
demonstrated that subdomains 2 and 3 of the NS3 helicase region and the
cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic
resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible,
with a tendency to form a three-turn alpha-helix and two short beta-strands. Upon
binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B
exhibited line broadening, suggesting a participation in the interaction.
Sequence alignment showed that 4 of these 12 residues are strictly conserved
across different flaviviruses. Mutagenesis analysis showed that three (Q134,
G140, and N144) of the four evolutionarily conserved NS4B residues are essential
for DENV replication. The mapping of the NS3/NS4B-interacting regions described
here can assist the design of inhibitors that disrupt their interface for
antiviral therapy. IMPORTANCE: NS3 and NS4B are essential components of the
flavivirus RC. Using DENV as a model, we mapped the interaction between the viral
NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the
cytoplasmic loop of NS4B are critical for the interaction. Functional analysis
delineated residues within the NS4B cytoplasmic loop that are crucial for DENV
replication. Our findings reveal molecular details of how flavivirus NS3 protein
cooperates with NS4B within the RC. In addition, this study has established the
rationale and assays to search for inhibitors disrupting the NS3-NS4B interaction
for antiviral drug discovery.
PMID- 25589632
TI - Integrated allelic, transcriptional, and phenomic dissection of the cardiac
effects of titin truncations in health and disease.
AB - The recent discovery of heterozygous human mutations that truncate full-length
titin (TTN, an abundant structural, sensory, and signaling filament in muscle) as
a common cause of end-stage dilated cardiomyopathy (DCM) promises new prospects
for improving heart failure management. However, realization of this opportunity
has been hindered by the burden of TTN-truncating variants (TTNtv) in the general
population and uncertainty about their consequences in health or disease. To
elucidate the effects of TTNtv, we coupled TTN gene sequencing with cardiac
phenotyping in 5267 individuals across the spectrum of cardiac physiology and
integrated these data with RNA and protein analyses of human heart tissues. We
report diversity of TTN isoform expression in the heart, define the relative
inclusion of TTN exons in different isoforms (using the TTN transcript
annotations available at http://cardiodb.org/titin), and demonstrate that these
data, coupled with the position of the TTNtv, provide a robust strategy to
discriminate pathogenic from benign TTNtv. We show that TTNtv is the most common
genetic cause of DCM in ambulant patients in the community, identify clinically
important manifestations of TTNtv-positive DCM, and define the penetrance and
outcomes of TTNtv in the general population. By integrating genetic,
transcriptome, and protein analyses, we provide evidence for a length-dependent
mechanism of disease. These data inform diagnostic criteria and management
strategies for TTNtv-positive DCM patients and for TTNtv that are identified as
incidental findings.
PMID- 25589638
TI - On the stability of parainfluenza virus 5 F proteins.
AB - The crystal structure of the F protein (prefusion form) of the paramyxovirus
parainfluenza virus 5 (PIV5) WR isolate was determined. We investigated the basis
by which point mutations affect fusion in PIV5 isolates W3A and WR, which differ
by two residues in the F ectodomain. The P22 stabilizing site acts through a
local conformational change and a hydrophobic pocket interaction, whereas the
S443 destabilizing site appears sensitive to both conformational effects and
amino acid charge/polarity changes.
PMID- 25589637
TI - A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene.
AB - Recombinant trimeric mimics of the human immunodeficiency virus type 1 (HIV-1)
envelope glycoprotein (Env) spike should expose as many epitopes as possible for
broadly neutralizing antibodies (bNAbs) but few, if any, for nonneutralizing
antibodies (non-NAbs). Soluble, cleaved SOSIP.664 gp140 trimers based on the
subtype A strain BG505 approach this ideal and are therefore plausible vaccine
candidates. Here, we report on the production and in vitro properties of a new
SOSIP.664 trimer derived from a subtype B env gene, B41, including how to make
this protein in low-serum media without proteolytic damage (clipping) to the V3
region. We also show that nonclipped trimers can be purified successfully via a
positive-selection affinity column using the bNAb PGT145, which recognizes a
quaternary structure-dependent epitope at the trimer apex. Negative-stain
electron microscopy imaging shows that the purified, nonclipped, native-like B41
SOSIP.664 trimers contain two subpopulations, which we propose represent an
equilibrium between the fully closed and a more open conformation. The latter is
different from the fully open, CD4 receptor-bound conformation and may represent
an intermediate state of the trimer. This new subtype B trimer adds to the
repertoire of native-like Env proteins that are suitable for immunogenicity and
structural studies. IMPORTANCE: The cleaved, trimeric envelope protein complex is
the only neutralizing antibody target on the HIV-1 surface. Many vaccine
strategies are based on inducing neutralizing antibodies. For HIV-1, one approach
involves using recombinant, soluble protein mimics of the native trimer. At
present, the only reliable way to make native-like, soluble trimers in practical
amounts is via the introduction of specific sequence changes that confer
stability on the cleaved form of Env. The resulting proteins are known as
SOSIP.664 gp140 trimers, and the current paradigm is based on the BG505 subtype A
env gene. Here, we describe the production and characterization of a SOSIP.664
protein derived from a subtype B gene (B41), together with a simple, one-step
method to purify native-like trimers by affinity chromatography with a trimer
specific bNAb, PGT145. The resulting trimers will be useful for structural and
immunogenicity experiments aimed at devising ways to make an effective HIV-1
vaccine.
PMID- 25589639
TI - High preexisting serological antibody levels correlate with diversification of
the influenza vaccine response.
AB - Reactivation of memory B cells allows for a rapid and robust immune response upon
challenge with the same antigen. Variant influenza virus strains generated
through antigenic shift or drift are encountered multiple times over the lifetime
of an individual. One might predict, then, that upon vaccination with the
trivalent influenza vaccine across multiple years, the antibody response would
become more and more dominant toward strains consistently present in the vaccine
at the expense of more divergent strains. However, when we analyzed the vaccine
induced plasmablast, memory, and serological responses to the trivalent influenza
vaccine between 2006 and 2013, we found that the B cell response was most robust
against more divergent strains. Overall, the antibody response was highest when
one or more strains contained in the vaccine varied from year to year. This
suggests that in the broader immunological context of viral antigen exposure, the
B cell response to variant influenza virus strains is not dictated by the
composition of the memory B cell precursor pool. The outcome is instead a
diversified B cell response. IMPORTANCE: Vaccine strategies are being designed to
boost broadly reactive B cells present in the memory repertoire to provide
universal protection to the influenza virus. It is important to understand how
past exposure to influenza virus strains affects the response to subsequent
immunizations. The viral epitopes targeted by B cells responding to the vaccine
may be a direct reflection of the B cell memory specificities abundant in the
preexisting immune repertoire, or other factors may influence the vaccine
response. Here, we demonstrate that high preexisting serological antibody levels
to a given influenza virus strain correlate with low production of antibody
secreting cells and memory B cells recognizing that strain upon revaccination. In
contrast, introduction of antigenically novel strains generates a robust B cell
response. Thus, both the preexisting memory B cell repertoire and serological
antibody levels must be taken into consideration in predicting the quality of the
B cell response to new prime-boost vaccine strategies.
PMID- 25589640
TI - Absence of the uracil DNA glycosylase of murine gammaherpesvirus 68 impairs
replication and delays the establishment of latency in vivo.
AB - Uracil DNA glycosylases (UNG) are highly conserved proteins that preserve DNA
fidelity by catalyzing the removal of mutagenic uracils. All herpesviruses encode
a viral UNG (vUNG), and yet the role of the vUNG in a pathogenic course of
gammaherpesvirus infection is not known. First, we demonstrated that the vUNG of
murine gammaherpesvirus 68 (MHV68) retains the enzymatic function of host UNG in
an in vitro class switch recombination assay. Next, we generated a recombinant
MHV68 with a stop codon in ORF46/UNG (DeltaUNG) that led to loss of UNG activity
in infected cells and a replication defect in primary fibroblasts. Acute
replication of MHV68DeltaUNG in the lungs of infected mice was reduced 100-fold
and was accompanied by a substantial delay in the establishment of splenic
latency. Latency was largely, yet not fully, restored by an increase in virus
inoculum or by altering the route of infection. MHV68 reactivation from latent
splenocytes was not altered in the absence of the vUNG. A survey of host UNG
activity in cells and tissues targeted by MHV68 indicated that the lung tissue
has a lower level of enzymatic UNG activity than the spleen. Taken together,
these results indicate that the vUNG plays a critical role in the replication of
MHV68 in tissues with limited host UNG activity and this vUNG-dependent
expansion, in turn, influences the kinetics of latency establishment in distal
reservoirs. IMPORTANCE: Herpesviruses establish chronic lifelong infections using
a strategy of replicative expansion, dissemination to latent reservoirs, and
subsequent reactivation for transmission and spread. We examined the role of the
viral uracil DNA glycosylase, a protein conserved among all herpesviruses, in
replication and latency of murine gammaherpesvirus 68. We report that the viral
UNG of this murine pathogen retains catalytic activity and influences replication
in culture. The viral UNG was impaired for productive replication in the lung.
This defect in expansion at the initial site of acute replication was associated
with a substantial delay of latency establishment in the spleen. The levels of
host UNG were substantially lower in the lung compared to the spleen, suggesting
that herpesviruses encode a viral UNG to compensate for reduced host enzyme
levels in some cell types and tissues. These data suggest that intervention at
the site of initial replicative expansion can delay the establishment of latency,
a hallmark of chronic herpesvirus infection.
PMID- 25589641
TI - Constitutive but not inducible attenuation of transforming growth factor beta
signaling increases natural killer cell responses without directly affecting
dendritic cells early after persistent viral infection.
AB - Rapid innate responses to viral encounters are crucial to shaping the outcome of
infection, from viral clearance to persistence. Transforming growth factor beta
(TGF-beta) is a potent immune suppressor that is upregulated early upon viral
infection and maintained during chronic infections in both mice and humans.
However, the role of TGF-beta signaling in regulating individual cell types in
vivo is still unclear. Using infections with two different persistent viruses,
murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV;
Cl13), in their natural rodent host, we observed that TGF-beta signaling on
dendritic cells (DCs) did not dampen DC maturation or cytokine production in the
early stages of chronic infection with either virus in vivo. In contrast, TGF
beta signaling prior to (but not during) chronic viral infection directly
restricted the natural killer (NK) cell number and effector function. This
restriction likely compromised both the early control of and host survival upon
MCMV infection but not the long-term control of LCMV infection. These data
highlight the context and timing of TGF-beta signaling on different innate cells
that contribute to the early host response, which ultimately influences the
outcome of chronic viral infection in vivo. IMPORTANCE: In vivo host responses to
pathogens are complex processes involving the cooperation of many different
immune cells migrating to specific tissues over time, but these events cannot be
replicated in vitro. Viruses causing chronic infections are able to subvert this
immune response and represent a human health burden. Here we used two well
characterized viruses that are able to persist in their natural mouse host to
dissect the role of the suppressive molecule TGF-beta in dampening host responses
to infection in vivo. This report presents information that allows an increased
understanding of long-studied TGF-beta signaling by examining its direct effect
on different immune cells that are activated very early after in vivo viral
infection and may aid with the development of new antiviral therapeutic
strategies.
PMID- 25589642
TI - Overlapping local and long-range RNA-RNA interactions modulate dengue virus
genome cyclization and replication.
AB - The dengue virus genome is a dynamic molecule that adopts different conformations
in the infected cell. Here, using RNA folding predictions, chemical probing
analysis, RNA binding assays, and functional studies, we identified new cis
acting elements present in the capsid coding sequence that facilitate cyclization
of the viral RNA by hybridization with a sequence involved in a local dumbbell
structure at the viral 3' untranslated region (UTR). The identified interaction
differentially enhances viral replication in mosquito and mammalian cells.
PMID- 25589643
TI - The aberrant gene-end transcription signal of the matrix M gene of human
parainfluenza virus type 3 downregulates fusion F protein expression and the F
specific antibody response in vivo.
AB - Human parainfluenza virus type 3 (HPIV3), a paramyxovirus, is a major viral cause
of severe lower respiratory tract disease in infants and children. The gene-end
(GE) transcription signal of the HPIV3 matrix (M) protein gene is identical to
those of the nucleoprotein and phosphoprotein genes except that it contains an
apparent 8-nucleotide insert. This was associated with an increased synthesis of
a readthrough transcript of the M gene and the downstream fusion (F) protein
gene. We hypothesized that this insert may function to downregulate the
expression of F protein by interfering with termination/reinitiation at the M-F
gene junction, thus promoting the production of M-F readthrough mRNA at the
expense of monocistronic F mRNA. To test this hypothesis, two similar recombinant
HPIV3 viruses from which this insert in the M-GE signal was removed were
generated. The M-GE mutants exhibited a reduction in M-F readthrough mRNA and an
increase in monocistronic F mRNA. This resulted in a substantial increase in F
protein synthesis in infected cells as well as enhanced incorporation of F
protein into virions. The efficiency of mutant virus replication was similar to
that of wild-type (wt) HPIV3 both in vitro and in vivo. However, the F-protein
specific serum antibody response in hamsters was increased for the mutants
compared to wt HPIV3. This study identifies a previously undescribed viral
mechanism for attenuating the host adaptive immune response. Repairing the M-GE
signal should provide a means to increase the antibody response to a live
attenuated HPIV3 vaccine without affecting viral replication and attenuation.
IMPORTANCE: The HPIV3 M-GE signal was previously shown to contain an apparent 8
nucleotide insert that was associated with increased synthesis of a readthrough
mRNA of the M gene and the downstream F gene. However, whether this had any
significant effect on the synthesis of monocistronic F mRNA or F protein, virus
replication, virion morphogenesis, and immunogenicity was unknown. Here, we show
that the removal of this insert shifts F gene transcription from readthrough M-F
mRNA to monocistronic F mRNA. This resulted in a substantial increase in the
amount of F protein expressed in the cell and packaged in the virus particle.
This did not affect virus replication but increased the F-specific antibody
response in hamsters. Thus, in wild-type HPIV3, the aberrant M-GE signal operates
a previously undescribed mechanism that reduces the expression of a major
neutralization and protective antigen, resulting in reduced immunogenicity. This
has implications for the design of live attenuated HPIV3 vaccines; specifically,
the antibody response against F can be elevated by "repairing" the M-GE signal to
achieve higher-level F antigen expression, with no effect on attenuation.
PMID- 25589644
TI - Hepatitis C virus-mediated enhancement of microRNA miR-373 impairs the JAK/STAT
signaling pathway.
AB - Hepatitis C virus (HCV) is a serious global health problem and establishes
chronic infection in a significant number of infected humans worldwide.
Interferon (IFN) and IFN-stimulated genes (ISGs) are amplified during HCV
infection but fail to eliminate virus from the liver in a large number of
infected patients, and the mechanism is not fully understood. MicroRNAs (miRNAs)
have been implicated in the control of many biological processes, including IFN
signaling. To gain more insights into the role of cellular miRNAs in possible
countermeasures of HCV for suppression of the host antiviral response, a miRNA
array was performed by using primary human hepatocytes infected with in vitro
cell culture-grown HCV. A group of miRNAs were modulated in HCV-infected primary
human hepatocytes. We focused on miR-373, as this miRNA was significantly
upregulated in HCV-infected primary human hepatocytes. Here, we analyzed the
function of miR-373 in the context of HCV infection. HCV infection upregulates
miR-373 expression in hepatocytes and HCV-infected liver biopsy specimens.
Furthermore, we discovered that miR-373 directly targets Janus kinase 1 (JAK1)
and IFN-regulating factor 9 (IRF9), important factors in the IFN signaling
pathway. The upregulation of miR-373 by HCV also inhibited STAT1 phosphorylation,
which is involved in ISG factor 3 (ISGF3) complex formation and ISG expression.
The knockdown of miR-373 in hepatocytes enhanced JAK1 and IRF9 expression and
reduced HCV RNA replication. Taken together, our results demonstrated that miR
373 is upregulated during HCV infection and negatively regulated the type I IFN
signaling pathway by suppressing JAK1 and IRF9. Our results offer a potential
therapeutic approach for antiviral intervention. IMPORTANCE: Chronic HCV
infection is one of the major causes of end-stage liver disease worldwide.
Although the recent introduction of direct-acting antiviral (DAA) therapy is
extremely encouraging, some infected individuals do not respond to this therapy.
Furthermore, these drugs target HCV nonstructural proteins, and with selective
pressure, the virus may develop a resistant strain. Therefore, understanding the
impairment of IFN signals will help in designing additional therapeutic
modalities. In this study, we provide evidence of HCV-mediated upregulation of
miR-373 and show that miR-373 impairs IFN signaling by targeting JAK1/IRF9
molecules. The knockdown of miR-373 inhibited HCV replication by upregulating
interferon-stimulating gene expression. Together, these results provided new
mechanistic insights into the role of miR-373 in HCV infection and suggest a new
potential target against HCV infection.
PMID- 25589645
TI - Long-term control of simian immunodeficiency virus (SIV) in cynomolgus macaques
not associated with efficient SIV-specific CD8+ T-cell responses.
AB - The spontaneous control of human and simian immunodeficiency viruses (HIV/SIV) is
typically associated with specific major histocompatibility complex (MHC) class I
alleles and efficient CD8(+) T-cell responses, but many controllers maintain
viral control despite a nonprotective MHC background and weak CD8(+) T-cell
responses. Therefore, the contribution of this response to maintaining long-term
viral control remains unclear. To address this question, we transiently depleted
CD8(+) T cells from five SIV-infected cynomolgus macaques with long-term viral
control and weak CD8(+) T-cell responses. Among them, only one carried the
protective MHC allele H6. After depletion, four of five controllers experienced a
transient rebound of viremia. The return to undetectable viremia was accompanied
by only modest expansion of SIV-specific CD8(+) T cells that lacked efficient SIV
suppression capacity ex vivo. In contrast, the depletion was associated with
homeostatic activation/expansion of CD4(+) T cells that correlated with viral
rebound. In one macaque, viremia remained undetectable despite efficient CD8(+)
cell depletion and inducible SIV replication from its CD4(+) T cells in vitro.
Altogether, our results suggest that CD8(+) T cells are not unique contributors
to the long-term maintenance of low viremia in this SIV controller model and that
other mechanisms, such as weak viral reservoirs or control of activation, may be
important players in control. IMPORTANCE: Spontaneous control of HIV-1 to
undetectable levels is associated with efficient anti-HIV CD8(+) T-cell
responses. However, in some cases, this response fades over time, although viral
control is maintained, and many HIV controllers (weak responders) have very low
frequencies of HIV-specific CD8(+) T cells. In these cases, the importance of CD8
T cells in the maintenance of HIV-1 control is questionable. We developed a
nonhuman primate model of durable SIV control with an immune profile resembling
that of weak responders. Transient depletion of CD8(+) cells induced a rise in
the viral load. However, viremia was correlated with CD4(+) T-cell activation
subsequent to CD8(+) cell depletion. Regain of viral control to predepletion
levels was not associated with restoration of the anti-SIV capacities of CD8(+) T
cells. Our results suggest that CD8(+) T cells may not be involved in maintenance
of viral control in weak responders and highlight the fact that additional
mechanisms should not be underestimated.
PMID- 25589646
TI - Sp1 sites in the noncoding control region of BK polyomavirus are key regulators
of bidirectional viral early and late gene expression.
AB - In kidney transplant patients with BK polyomavirus (BKPyV) nephropathy, viral
variants arise bearing rearranged noncoding control regions (rr-NCCRs) that
increase viral early gene expression, replicative fitness, and cytopathology. rr
NCCRs result from various deletions and duplications of archetype NCCR (ww-NCCR)
sequences, which alter transcription factor binding sites (TFBS). However, the
role of specific TFBS is unclear. We inactivated 28 TFBS in the archetype NCCR by
selective point mutations and examined viral gene expression in bidirectional
reporter constructs. Compared to the archetype, group 1 mutations increased viral
early gene expression similar to rr-NCCR and resulted from inactivating one Sp1
or one Ets1 TFBS near the late transcription start site (TSS). Group 2 mutations
conferred intermediate early gene activation and affected NF1, YY1, and p53 sites
between early and late TSS. Group 3 mutations decreased early and late gene
expression and included two other Sp1 sites near the early TSS. Recombinant
viruses bearing group 1 NCCRs showed increased replication in human renal
epithelial cells similar to clinical rr-NCCR variants. Group 2 and 3 viruses
showed intermediate or no replication, respectively. A literature search revealed
unnoticed group 1 mutations in BKPyV nephropathy, hemorrhagic cystitis, and
disseminated disease. IMPORTANCE: The NCCRs of polyomaviruses mediate silent
persistence of the viral genome as well as the appropriately timed (re)activation
of the viral life cycle. This study indicates that the basal BKPyV NCCR is
critically controlled by a hierarchy of single TFBS in the archetype NCCR that
direct, modulate, and execute the bidirectional early and late viral gene
expression. The results provide new insights into how BKPyV NCCR functions as a
viral sensor of host cell signals and shed new light on how transcription factors
like Sp1 control bidirectional viral gene expression and contribute to
replication and pathology.
PMID- 25589647
TI - Requirement for Fc effector mechanisms in the APOBEC3/Rfv3-dependent neutralizing
antibody response.
AB - Antiretroviral neutralizing antibody (NAb) responses are often evaluated in the
absence of Fc-dependent immune effectors. In murine Friend retrovirus infection,
Apobec3/Rfv3 promotes a potent polyclonal NAb response. Here, we show that the
Apobec3/Rfv3-dependent NAb response correlated with virus-specific IgG2 titers
and that the in vivo neutralization potency of Apobec3/Rfv3-resistant antisera
was dependent on activating Fcgamma receptors but not complement. The data
strengthen retroviral vaccine strategies aimed at eliciting NAbs that activate
specific Fcgamma receptors.
PMID- 25589648
TI - Postchallenge administration of brincidofovir protects healthy and immune
deficient mice reconstituted with limited numbers of T cells from lethal
challenge with IHD-J-Luc vaccinia virus.
AB - Protection from lethality by postchallenge administration of brincidofovir (BCV,
CMX001) was studied in normal and immune-deficient (nude, nu/nu) BALB/c mice
infected with vaccinia virus (VACV). Whole-body bioluminescence imaging was used
to record total fluxes in the nasal cavity, lungs, spleen, and liver and to
enumerate pox lesions on tails of mice infected via the intranasal route with
10(5) PFU of recombinant IHD-J-Luc VACV expressing luciferase. Areas under the
flux curve (AUCs) were calculated for individual mice to assess viral loads. A
three-dose regimen of 20 mg/kg BCV administered every 48 h starting either on day
1 or day 2 postchallenge protected 100% of mice. Initiating BCV treatment earlier
was more efficient in reducing viral loads and in providing protection from pox
lesion development. All BCV-treated mice that survived challenge were also
protected from rechallenge with IHD-J-Luc or WRvFire VACV without additional
treatment. In immune-deficient mice, BCV protected animals from lethality and
reduced viral loads while animals were on the drug. Viral recrudescence occurred
within 4 to 9 days, and mice succumbed ~10 to 20 days after treatment
termination. Nude mice reconstituted with 10(5) T cells prior to challenge with
10(4) PFU of IHD-J-Luc and treated with BCV postchallenge survived the infection,
cleared the virus from all organs, and survived rechallenge with 10(5) PFU of IHD
J-Luc VACV without additional BCV treatment. Together, these data suggest that
BCV protects immunocompetent and partially T cell-reconstituted immune-deficient
mice from lethality, reduces viral dissemination in organs, prevents pox lesion
development, and permits generation of VACV-specific memory. IMPORTANCE: Mass
vaccination is the primary element of the public health response to a smallpox
outbreak. In addition to vaccination, however, antiviral drugs are required for
individuals with uncertain exposure status to smallpox or for whom vaccination is
contraindicated. Whole-body bioluminescence imaging was used to study the effect
of brincidofovir (BCV) in normal and immune-deficient (nu/nu) mice infected with
vaccinia virus, a model of smallpox. Postchallenge administration of 20 mg/kg BCV
rescued normal and immune-deficient mice partially reconstituted with T cells
from lethality and significantly reduced viral loads in organs. All BCV-treated
mice that survived infection were protected from rechallenge without additional
treatment. In immune-deficient mice, BCV extended survival. The data show that
BCV controls viral replication at the site of challenge and reduces viral
dissemination to internal organs, thus providing a shield for the developing
adaptive immunity that clears the host of virus and builds virus-specific
immunological memory.
PMID- 25589649
TI - Relationships among dissemination of primary parainfluenza virus infection in the
respiratory tract, mucosal and peripheral immune responses, and protection from
reinfection: a noninvasive bioluminescence-imaging study.
AB - Respiratory paramyxoviruses such as respiratory syncytial virus (RSV) and human
parainfluenza virus type 1 (HPIV1) to HPIV4 infect virtually all children by the
age of 2 to 5 years, leading to partial but incomplete protection from
reinfection. Here, we used luciferase-expressing reporter Sendai viruses (the
murine counterpart of HPIV1) to noninvasively measure primary infection, immune
responses, and protection from reinfection by either a lethal challenge or
natural transmission in living mice. Both nonattenuated and attenuated reporter
Sendai viruses were used, and three inoculation strategies were employed:
intramuscular (i.m.), intranasal (i.n.) at a low dose and low volume, and i.n. at
a high dose and high volume. High-dose, high-volume i.n. inoculation resulted in
the highest levels of antibody responses and protection from reinfection. Low
dose, low-volume i.n. inoculation afforded complete protection from contact
transmission and protection from morbidity, mortality, and viral growth during
lethal challenge. i.m. inoculation was inferior to i.n. inoculation at inducing
antibody responses and protection from challenge. For individual mice and across
groups, the levels of serum binding and neutralizing antibody responses
correlated with primary infection and protection from reinfection in the lungs.
Contact transmission, the predominant mode of parainfluenza virus transmission,
was modeled accurately by direct i.n. inoculation of Sendai virus at a low dose
and low volume and was completely preventable by i.n. vaccination of an
attenuated virus at a low dose and low volume. The data highlight differences in
infection and protection from challenge in the upper versus lower respiratory
tract and bear upon live attenuated vaccine development. IMPORTANCE: There are
currently no licensed vaccines against HPIVs and human RSV (HRSV), important
respiratory pathogens of infants and children. Natural infection leads to partial
but incomplete protective immunity, resulting in subsequent reinfections even in
the absence of antigenic drift. Here, we used noninvasive bioluminescence imaging
in a mouse model to dissect relationships among (i) the mode of inoculation, (ii)
the dynamics of primary infection, (iii) consequent immune responses, and (iv)
protection from high-dose, high-volume lethal challenge and contact transmission,
which we find here to be similar to that of a mild low-dose, low-volume upper
respiratory tract (URT)-biased infection. Our studies demonstrate the superiority
of i.n. versus i.m. vaccination in protection against both lethal challenge and
contact transmission. In addition to providing correlates of protection that will
assist respiratory virus vaccine development, these studies extend the
development of an increasingly used technique for the study of viral infection
and immunity, noninvasive bioluminescence imaging.
PMID- 25589651
TI - Immune screening identifies novel T cell targets encoded by antisense reading
frames of HIV-1.
AB - Cytotoxic-T lymphocyte (CTL) responses to epitopes in alternative HIV reading
frames have been reported. However, the extent of CTL responses to putative
proteins encoded in antisense reading frames is unknown. Using sequence
alignments and computational approaches, we here predict five potential antisense
HIV proteins and characterize common CTL responses against them. Results suggest
that antisense-derived sequences are commonly transcribed and translated and
could encode functional proteins that contain important targets of anti-HIV
cellular immunity.
PMID- 25589650
TI - Effective lethal mutagenesis of influenza virus by three nucleoside analogs.
AB - Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high
mutation rate and low mutational tolerance of many RNA viruses. This approach
uses mutagenic drugs to increase viral mutation rates and burden viral
populations with mutations that reduce the number of infectious progeny. We
investigated the effectiveness of lethal mutagenesis as a strategy against
influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5
fluorouracil. All three drugs were active against a panel of seasonal H3N2 and
laboratory-adapted H1N1 strains. We found that each drug increased the frequency
of mutations in influenza virus populations and decreased the virus' specific
infectivity, indicating a mutagenic mode of action. We were able to drive viral
populations to extinction by passaging influenza virus in the presence of each
drug, indicating that complete lethal mutagenesis of influenza virus populations
can be achieved when a sufficient mutational burden is applied. Population-wide
resistance to these mutagenic agents did not arise after serial passage of
influenza virus populations in sublethal concentrations of drug. Sequencing of
these drug-passaged viral populations revealed genome-wide accumulation of
mutations at low frequency. The replicative capacity of drug-passaged populations
was reduced at higher multiplicities of infection, suggesting the presence of
defective interfering particles and a possible barrier to the evolution of
resistance. Together, our data suggest that lethal mutagenesis may be a
particularly effective therapeutic approach with a high genetic barrier to
resistance for influenza virus. IMPORTANCE: Influenza virus is an RNA virus that
causes significant morbidity and mortality during annual epidemics. Novel
therapies for RNA viruses are needed due to the ease with which these viruses
evolve resistance to existing therapeutics. Lethal mutagenesis is a broad
spectrum strategy that exploits the high mutation rate and the low mutational
tolerance of most RNA viruses. It is thought to possess a higher barrier to
resistance than conventional antiviral strategies. We investigated the
effectiveness of lethal mutagenesis against influenza virus using three different
drugs. We showed that influenza virus was sensitive to lethal mutagenesis by
demonstrating that all three drugs induced mutations and led to an increase in
the generation of defective viral particles. We also found that it may be
difficult for resistance to these drugs to arise at a population-wide level. Our
data suggest that lethal mutagenesis may be an attractive anti-influenza strategy
that warrants further investigation.
PMID- 25589652
TI - Development of live-attenuated arenavirus vaccines based on codon deoptimization.
AB - Arenaviruses have a significant impact on public health and pose a credible
biodefense threat, but the development of safe and effective arenavirus vaccines
has remained elusive, and currently, no Food and Drug Administration (FDA)
licensed arenavirus vaccines are available. Here, we explored the use of a codon
deoptimization (CD)-based approach as a novel strategy to develop live-attenuated
arenavirus vaccines. We recoded the nucleoprotein (NP) of the prototypic
arenavirus lymphocytic choriomeningitis virus (LCMV) with the least frequently
used codons in mammalian cells, which caused lower LCMV NP expression levels in
transfected cells that correlated with decreased NP activity in cell-based
functional assays. We used reverse-genetics approaches to rescue a battery of
recombinant LCMVs (rLCMVs) encoding CD NPs (rLCMV/NP(CD)) that showed attenuated
growth kinetics in vitro. Moreover, experiments using the well-characterized
mouse model of LCMV infection revealed that rLCMV/NP(CD1) and rLCMV/NP(CD2) were
highly attenuated in vivo but, upon a single immunization, conferred complete
protection against a subsequent lethal challenge with wild-type (WT) recombinant
LCMV (rLCMV/WT). Both rLCMV/NP(CD1) and rLCMV/NP(CD2) were genetically and
phenotypically stable during serial passages in FDA vaccine-approved Vero cells.
These results provide proof of concept of the safety, efficacy, and stability of
a CD-based approach for developing live-attenuated vaccine candidates against
human-pathogenic arenaviruses. IMPORTANCE: Several arenaviruses cause severe
hemorrhagic fever in humans and pose a credible bioterrorism threat. Currently,
no FDA-licensed vaccines are available to combat arenavirus infections, while
antiarenaviral therapy is limited to the off-label use of ribavirin, which is
only partially effective and is associated with side effects. Here, we describe
the generation of recombinant versions of the prototypic arenavirus LCMV encoding
codon-deoptimized viral nucleoproteins (rLCMV/NP(CD)). We identified
rLCMV/NP(CD1) and rLCMV/NP(CD2) to be highly attenuated in vivo but able to
confer protection against a subsequent lethal challenge with wild-type LCMV.
These viruses displayed an attenuated phenotype during serial amplification
passages in cultured cells. Our findings support the use of this approach for the
development of safe, stable, and protective live-attenuated arenavirus vaccines.
PMID- 25589654
TI - Demographics of natural oral infection of mosquitos by Venezuelan equine
encephalitis virus.
AB - The within-host diversity of virus populations can be drastically limited during
between-host transmission, with primary infection of hosts representing a major
constraint to diversity maintenance. However, there is an extreme paucity of
quantitative data on the demographic changes experienced by virus populations
during primary infection. Here, the multiplicity of cellular infection (MOI) and
population bottlenecks were quantified during primary mosquito infection by
Venezuelan equine encephalitis virus, an arbovirus causing neurological disease
in humans and equids.
PMID- 25589653
TI - Viral semaphorin inhibits dendritic cell phagocytosis and migration but is not
essential for gammaherpesvirus-induced lymphoproliferation in malignant catarrhal
fever.
AB - Viral semaphorins are semaphorin 7A (sema7A) mimics found in pox- and
herpesviruses. Among herpesviruses, semaphorins are encoded by gammaherpesviruses
of the Macavirus genus only. Alcelaphine herpesvirus 1 (AlHV-1) is a macavirus
that persistently infects wildebeest asymptomatically but induces malignant
catarrhal fever (MCF) when transmitted to several species of susceptible
ruminants and the rabbit model. MCF is caused by the activation/proliferation of
latently infected T lymphocytes. Viral semaphorins have been suggested to mediate
immune evasion mechanisms and/or directly alter host T cell function. We studied
AlHV-sema, the viral semaphorin encoded by the A3 gene of AlHV-1. Phylogenetic
analyses revealed independent acquisition of pox- and herpesvirus semaphorins,
suggesting that these proteins might have distinct functions. AlHV-sema showed a
predicted three-dimensional structure very similar to sema7A and conserved key
residues in sema7A-plexinC1 interaction. Expression analyses revealed that AlHV
sema is a secreted 93-kDa glycoprotein expressed during the early phase of virus
replication. Purified AlHV-sema was able to bind to fibroblasts and dendritic
cells and induce F-actin condensation and cell retraction through a plexinC1 and
Rho/cofilin-dependent mechanism. Cytoskeleton rearrangement was further
associated with inhibition of phagocytosis by dendritic cells and migration to
the draining lymph node. Next, we generated recombinant viruses and demonstrated
that the lack of A3 did not significantly affect virus growth in vitro and did
not impair MCF induction and associated lymphoproliferative lesions. In
conclusion, AlHV-sema has immune evasion functions through mechanisms similar to
poxvirus semaphorin but is not directly involved in host T cell activation during
MCF. IMPORTANCE: Whereas most poxviruses encode viral semaphorins, semaphorin
like genes have only been identified in few gammaherpesviruses belonging to the
Macavirus genus. Alcelaphine herpesvirus 1 (AlHV-1) is a macavirus carried
asymptomatically by wildebeest but induces a latency-associated
lymphoproliferative disease of T lymphocytes in various ruminant species, namely,
malignant catarrhal fever (MCF). Viral semaphorins have been hypothesized to have
immune evasion functions and/or be involved in activating latently infected T
cells. We present evidence that the viral semaphorin AlHV-sema inhibits dendritic
cell phagocytosis and migration to the draining lymph node, both being
indispensable mechanisms for protective antiviral responses. Next, we engineered
recombinant viruses unable to express AlHV-sema and demonstrated that this
protein is dispensable for the induction of MCF. In conclusion, this study
suggests that herpesvirus and poxvirus semaphorins have independently evolved
similar functions to thwart the immune system of the host while AlHV-sema is not
directly involved in MCF-associated T-cell activation.
PMID- 25589655
TI - Broadly neutralizing anti-influenza virus antibodies: enhancement of neutralizing
potency in polyclonal mixtures and IgA backbones.
AB - Current influenza virus vaccines rely upon the accurate prediction of circulating
virus strains months in advance of the actual influenza season in order to allow
time for vaccine manufacture. Unfortunately, mismatches occur frequently, and
even when perfect matches are achieved, suboptimal vaccine efficacy leaves
several high-risk populations vulnerable to infection. However, the recent
discovery of broadly neutralizing antibodies that target the hemagglutinin (HA)
stalk domain has renewed hope that the development of "universal" influenza virus
vaccines may be within reach. Here, we examine the functions of influenza A virus
hemagglutinin stalk-binding antibodies in an endogenous setting, i.e., as
polyclonal preparations isolated from human sera. Relative to monoclonal
antibodies that bind to the HA head domain, the neutralization potency of
monoclonal stalk-binding antibodies was vastly inferior in vitro but was enhanced
by several orders of magnitude in the polyclonal context. Furthermore, we
demonstrated a surprising enhancement in IgA-mediated HA stalk neutralization
relative to that achieved by antibodies of IgG isotypes. Mechanistically, this
could be explained in two ways. Identical variable regions consistently
neutralized virus more potently when in an IgA backbone compared to an IgG
backbone. In addition, HA-specific memory B cells isolated from human peripheral
blood were more likely to be stalk specific when secreting antibodies of IgA
isotypes compared to those secreting IgG. Taken together, our data provide strong
evidence that HA stalk-binding antibodies perform optimally when in a polyclonal
context and that the targeted elicitation of HA stalk-specific IgA should be an
important consideration during "universal" influenza virus vaccine design.
IMPORTANCE: Influenza viruses remain one of the most worrisome global public
health threats due to their capacity to cause pandemics. While seasonal vaccines
fail to protect against the emergence of pandemic strains, a new class of broadly
neutralizing antibodies has been recently discovered and may be the key to
developing a "universal" influenza virus vaccine. While much has been learned
about the biology of these antibodies, most studies have focused only on
monoclonal antibodies of IgG subtypes. However, the study of monoclonal
antibodies often fails to capture the complexity of antibody functions that occur
during natural polyclonal responses. Here, we provide the first detailed analyses
of the biological activity of these antibodies in polyclonal contexts, comparing
both IgG and IgA isotypes isolated from human donors. The striking differences
observed in the functional properties of broadly neutralizing antibodies in
polyclonal contexts will be essential for guiding design of "universal" influenza
virus vaccines and therapeutics.
PMID- 25589656
TI - The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine
coronavirus JHM.WU.
AB - Mouse hepatitis virus (MHV) isolates JHM.WU and JHM.SD promote severe central
nervous system disease. However, while JHM.WU replicates robustly and induces
hepatitis, JHM.SD fails to replicate or induce pathology in the liver. These two
JHM variants encode homologous proteins with few polymorphisms, and little is
known about which viral proteins(s) is responsible for the liver tropism of
JHM.WU. We constructed reverse genetic systems for JHM.SD and JHM.WU and,
utilizing these full-length cDNA clones, constructed chimeric viruses and mapped
the virulence factors involved in liver tropism. Exchanging the spike proteins of
the two viruses neither increased replication of JHM.SD in the liver nor
attenuated JHM.WU. By further mapping, we found that polymorphisms in JHM.WU
structural protein M and nonstructural replicase proteins nsp1 and nsp13 are
essential for liver pathogenesis. M protein and nsp13, the helicase, of JHM.WU
are required for efficient replication in vitro and in the liver in vivo. The
JHM.SD nsp1 protein contains a K194R substitution of Lys194, a residue conserved
among all other MHV strains. The K194R polymorphism has no effect on in vitro
replication but influences hepatotropism, and introduction of R194K into JHM.SD
promotes replication in the liver. Conversely, a K194R substitution in nsp1 of
JHM.WU or A59, another hepatotropic strain, significantly attenuates replication
of each strain in the liver and increases IFN-beta expression in macrophages in
culture. Our data indicate that both structural and nonstructural proteins
contribute to MHV liver pathogenesis and support previous reports that nsp1 is a
Betacoronavirus virulence factor. IMPORTANCE: The Betacoronavirus genus includes
human pathogens, some of which cause severe respiratory disease. The spread of
severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East
respiratory syndrome coronavirus (MERS-CoV) into human populations demonstrates
the zoonotic potential of emerging coronaviruses, and there are currently no
vaccines or effective antivirals for human coronaviruses. Thus, it is important
to understand the virus-host interaction that regulates coronavirus pathogenesis.
Murine coronavirus infection of mice provides a useful model for the study of
coronavirus-host interactions, including the determinants of tropism and
virulence. We found that very small changes in coronavirus proteins can
profoundly affect tropism and virulence. Furthermore, the hepatotropism of MHV
JHM depends not on the spike protein and viral entry but rather on a combination
of the structural protein M and nonstructural replicase-associated proteins nsp1
and nsp13, which are conserved among betacoronaviruses. Understanding virulence
determinants will aid in the design of vaccines and antiviral strategies.
PMID- 25589657
TI - A host susceptibility gene, DR1, facilitates influenza A virus replication by
suppressing host innate immunity and enhancing viral RNA replication.
AB - Influenza A virus (IAV) depends on cellular factors to complete its replication
cycle; thus, investigation of the factors utilized by IAV may facilitate
antiviral drug development. To this end, a cellular transcriptional repressor,
DR1, was identified from a genome-wide RNA interference (RNAi) screen. Knockdown
(KD) of DR1 resulted in reductions of viral RNA and protein production,
demonstrating that DR1 acts as a positive host factor in IAV replication. Genome
wide transcriptomic analysis showed that there was a strong induction of
interferon-stimulated gene (ISG) expression after prolonged DR1 KD. We found that
beta interferon (IFN-beta) was induced by DR1 KD, thereby activating the JAK-STAT
pathway to turn on ISG expression, which led to a strong inhibition of IAV
replication. This result suggests that DR1 in normal cells suppresses IFN
induction, probably to prevent undesired cytokine production, but that this
suppression may create a milieu that favors IAV replication once cells are
infected. Furthermore, biochemical assays of viral RNA replication showed that
DR1 KD suppressed viral RNA replication. We also showed that DR1 associated with
all three subunits of the viral RNA-dependent RNA polymerase (RdRp) complex,
indicating that DR1 may interact with individual components of the viral RdRp
complex to enhance viral RNA replication. Thus, DR1 may be considered a novel
host susceptibility gene for IAV replication via a dual mechanism, not only
suppressing the host defense to indirectly favor IAV replication but also
directly facilitating viral RNA replication. IMPORTANCE: Investigations of virus
host interactions involved in influenza A virus (IAV) replication are important
for understanding viral pathogenesis and host defenses, which may manipulate
influenza virus infection or prevent the emergence of drug resistance caused by a
high error rate during viral RNA replication. For this purpose, a cellular
transcriptional repressor, DR1, was identified from a genome-wide RNAi screen as
a positive regulator in IAV replication. In the current studies, we showed that
DR1 suppressed the gene expression of a large set of host innate immunity genes,
which indirectly facilitated IAV replication in the event of IAV infection.
Besides this scenario, DR1 also directly enhanced the viral RdRp activity, likely
through associating with individual components of the viral RdRp complex. Thus,
DR1 represents a novel host susceptibility gene for IAV replication via multiple
functions, not only suppressing the host defense but also enhancing viral RNA
replication. DR1 may be a potential target for drug development against influenza
virus infection.
PMID- 25589658
TI - Mining the human complexome database identifies RBM14 as an XPO1-associated
protein involved in HIV-1 Rev function.
AB - By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the
nuclear export of incompletely spliced viral transcripts. We mined data from the
recently described human nuclear complexome to identify a host protein, RBM14,
which associates with XPO1 and Rev and is involved in Rev function. Using a Rev
dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev
activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced
viral transcripts. RBM14 depletion also reduced p24 expression during viral
infection, indicating that RBM14 is limiting for Rev function. RBM14 has
previously been shown to localize to nuclear paraspeckles, a structure implicated
in retaining unspliced HIV-1 transcripts for either Rev-mediated nuclear export
or degradation. We found that depletion of NEAT1 RNA, a long noncoding RNA
required for paraspeckle integrity, abolished the ability of overexpressed RBM14
to enhance Rev function, indicating the dependence of RBM14 function on
paraspeckle integrity. Our study extends the known host cell interactome of Rev
and XPO1 and further substantiates a critical role for paraspeckles in the
mechanism of action of Rev. Our study also validates the nuclear complexome as a
database from which viral cofactors can be mined. IMPORTANCE: This study mined a
database of nuclear protein complexes to identify a cellular protein named RBM14
that is associated with XPO1 (CRM1), a nuclear protein that binds to the HIV-1
Rev protein and mediates nuclear export of incompletely spliced viral RNAs.
Functional assays demonstrated that RBM14, a protein found in paraspeckle
structures in the nucleus, is involved in HIV-1 Rev function. This study
validates the nuclear complexome database as a reference that can be mined to
identify viral cofactors.
PMID- 25589659
TI - Structural basis for host membrane remodeling induced by protein 2B of hepatitis
A virus.
AB - The complexity of viral RNA synthesis and the numerous participating factors
require a mechanism to topologically coordinate and concentrate these multiple
viral and cellular components, ensuring a concerted function. Similarly to all
other positive-strand RNA viruses, picornaviruses induce rearrangements of host
intracellular membranes to create structures that act as functional scaffolds for
genome replication. The membrane-targeting proteins 2B and 2C, their precursor
2BC, and protein 3A appear to be primarily involved in membrane remodeling.
Little is known about the structure of these proteins and the mechanisms by which
they induce massive membrane remodeling. Here we report the crystal structure of
the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two
domains: a C-terminal helical bundle preceded by an N-terminally curved five
stranded antiparallel beta-sheet that displays striking structural similarity to
the beta-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal
arrangement of the protein molecules in the crystal provides a model for 2B
induced host membrane remodeling during HAV infection. IMPORTANCE: No structural
information is currently available for the 2B protein of any picornavirus despite
it being involved in a critical process in viral factory formation: the
rearrangement of host intracellular membranes. Here we present the structure of
the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement,
both in crystals and in solution under physiological conditions, can help to
understand its function and sheds some light on the membrane rearrangement
process, a putative target of future antiviral drugs. Moreover, this first
structure of a picornaviral 2B protein also unveils a closer evolutionary
relationship between the hepatovirus and enterovirus genera within the
Picornaviridae family.
PMID- 25589660
TI - Generation of a transgenic mouse model of Middle East respiratory syndrome
coronavirus infection and disease.
AB - The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the
Middle East since 2012 has caused more than 900 human infections with ~40%
mortality to date. Animal models are needed for studying pathogenesis and for
development of preventive and therapeutic agents against MERS-CoV infection.
Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited
availability. Although a mouse lung infection model has been described using
adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is
believed that a transgenic mouse model is needed for MERS-CoV research. We have
developed this transgenic mouse model as indicated in this study. We show that
transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV
infection, resulting in relentless weight loss and death within days
postinfection. High infectious virus titers were recovered primarily from the
lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas
viral RNAs were also detected in the heart, spleen, and intestine, indicating a
disseminating viral infection. Infected Tg(+) mice developed a progressive
pneumonia, characterized by extensive inflammatory infiltration. In contrast, an
inconsistent mild perivascular cuffing was the only pathological change
associated with the infected brains. Moreover, infected Tg(+) mice were able to
activate genes encoding for many antiviral and inflammatory mediators within the
lungs and brains, coinciding with the high levels of viral replication. This new
and unique transgenic mouse model will be useful for furthering knowledge of MERS
pathogenesis and for the development of vaccine and treatments against MERS-CoV
infection. IMPORTANCE: Small and economical animal models are required for the
controlled and extensive studies needed for elucidating pathogenesis and
development of vaccines and antivirals against MERS. Mice are the most desirable
small-animal species for this purpose because of availability and the existence
of a thorough knowledge base, particularly of genetics and immunology. The
standard small animals, mice, hamsters, and ferrets, all lack the functional MERS
CoV receptor and are not susceptible to infection. So, initial studies were done
with nonhuman primates, expensive models of limited availability. A mouse lung
infection model was described where a mouse adenovirus was used to transfect lung
cells for receptor expression. Nevertheless, all generally agree that a
transgenic mouse model expressing the DPP4 receptor is needed for MERS-CoV
research. We have developed this transgenic mouse model as indicated in this
study. This new and unique transgenic mouse model will be useful for furthering
MERS research.
PMID- 25589662
TI - Emergence and evolution of H10 subtype influenza viruses in poultry in China.
AB - The cases of human infections with H10N8 viruses identified in late 2013 and
early 2014 in Jiangxi, China, have raised concerns over the origin, prevalence,
and development of these viruses in this region. Our long-term influenza
surveillance of poultry and migratory birds in southern China in the past 12
years showed that H10 influenza viruses have been introduced from migratory to
domestic ducks over several winter seasons at sentinel duck farms at Poyang Lake,
where domestic ducks share their water body with overwintering migratory birds.
H10 viruses were never detected in terrestrial poultry in our survey areas until
August 2013, when they were identified at live-poultry markets in Jiangxi. Since
then, we have isolated 124 H10N8 or H10N6 viruses from chickens at local markets,
revealing an ongoing outbreak. Phylogenetic analysis of H10 and related viruses
showed that the chicken H10N8 viruses were generated through multiple
reassortments between H10 and N8 viruses from domestic ducks and the enzootic
chicken H9N2 viruses. These chicken reassortant viruses were highly similar to
the human isolate, indicating that market chickens were the source of human
infection. Recently, the H10 viruses further reassorted, apparently with H5N6
viruses, and generated an H10N6 variant. The emergence and prevalence of H10
viruses in chickens and the occurrence of human infections provide direct
evidence of the threat from the current influenza ecosystem in China. IMPORTANCE:
After the outbreak of avian-origin H7N9 influenza viruses in China, fatal human
infections with a novel H10N8 virus were reported. Utilizing data from 12 years
of influenza surveillance in southern China, we showed that H10 viruses were
regularly introduced by migratory ducks to domestic ducks on Poyang Lake, a major
aggregative site of migratory birds in Asia. The H10 viruses were maintained and
amplified in domestic ducks and then transmitted to chickens and reassorted with
enzootic H9N2 viruses, leading to an outbreak and human infections at live
poultry markets. The emergence of the H10N8 virus, following a pathway similar to
that of the recent H7N9 virus, highlights the role of domestic ducks and the
current influenza ecosystem in China that facilitates influenza viruses moving
from their reservoir hosts through the live-poultry system to cause severe
consequences for public health.
PMID- 25589661
TI - Early function of the Abutilon mosaic virus AC2 gene as a replication brake.
AB - The C2/AC2 genes of monopartite/bipartite geminiviruses of the genera Begomovirus
and Curtovirus encode important pathogenicity factors with multiple functions
described so far. A novel function of Abutilon mosaic virus (AbMV) AC2 as a
replication brake is described, utilizing transgenic plants with dimeric inserts
of DNA B or with a reporter construct to express green fluorescent protein (GFP).
Their replicational release upon AbMV superinfection or the individual and
combined expression of epitope-tagged AbMV AC1, AC2, and AC3 was studied. In
addition, the effects were compared in the presence and in the absence of an
unrelated tombusvirus suppressor of silencing (P19). The results show that AC2
suppresses replication reproducibly in all assays and that AC3 counteracts this
effect. Examination of the topoisomer distribution of supercoiled DNA, which
indicates changes in the viral minichromosome structure, did not support any
influence of AC2 on transcriptional gene silencing and DNA methylation. The
geminiviral AC2 protein has been detected here for the first time in plants. The
experiments revealed an extremely low level of AC2, which was slightly increased
if constructs with an intron and a hemagglutinin (HA) tag in addition to P19
expression were used. AbMV AC2 properties are discussed with reference to those
of other geminiviruses with respect to charge, modification, and size in order to
delimit possible reasons for the different behaviors. IMPORTANCE: The (A)C2 genes
encode a key pathogenicity factor of begomoviruses and curtoviruses in the plant
virus family Geminiviridae. This factor has been implicated in the resistance
breaking observed in agricultural cotton production. AC2 is a multifunctional
protein involved in transcriptional control, gene silencing, and regulation of
basal biosynthesis. Here, a new function of Abutilon mosaic virus AC2 in
replication control is added as a feature of this protein in viral
multiplication, providing a novel finding on geminiviral molecular biology.
PMID- 25589663
TI - Conserved molecular signatures in gp120 are associated with the genetic
bottleneck during simian immunodeficiency virus (SIV), SIV-human immunodeficiency
virus (SHIV), and HIV type 1 (HIV-1) transmission.
AB - Human immunodeficiency virus (HIV) transmission typically results from infection
by a single transmitted/founder (T/F) variant. Are T/F variants chosen uniformly
at random from the donor pool, or are they selected based on advantageous traits
facilitating transmission? Finding evidence for selection during transmission is
of particular interest, because it would indicate that phenotypic and/or genetic
properties of the viruses might be harnessed as potential vaccine targets or
immunotherapies. Here, we systematically evaluated the differences between the
Env proteins of simian immunodeficiency virus/simian HIV (SIV/SHIV) stock and T/F
variants in search of "signature" sites of transmission. We also surveyed residue
preferences in HIV at the SIV/SHIV signature sites. Four sites of gp120 showed
significant selection, and an additional two sites showed a similar trend.
Therefore, the six sites clearly differentiate T/F viruses from the majority of
circulating variants in the stocks. The selection of SIV/SHIV could be inferred
reasonably across both vaccinated and unvaccinated subjects, with infections
resulting from vaginal, rectal, and intravenous routes of transmission and
regardless of viral dosage. The evidence for selection in SIV and SHIV T/F
variants is strong and plentiful, and in HIV the evidence is suggestive though
commensurate with the availability of suitable data for analysis. Two of the
signature residues are completely conserved across the SIV, SHIV, and HIV
variants we examined. Five of the signature residues map to the C1 region of
gp120 and one to the signal peptide. Our data raise the possibility that C1,
while governing the association between gp120 and gp41, modulates transmission
efficiency, replicative fitness, and/or host cell tropism at the level of virus
cell attachment and entry. IMPORTANCE: The present study finds significant
evidence of selection on gp120 molecules of SIV/SHIV T/F viruses. The data
provide ancillary evidence suggesting the same sites are under selection in HIV.
Our findings suggest that the signature residues are involved in increasing the
transmissibility of infecting viruses; therefore, they are potential targets for
developing a vaccine or other protective measures. A recent study identified the
same T/F signature motif but interpreted it as an effect of neutralization
resistance. Here, we show that the T/F motif has broader functional significance
beyond neutralization sensitivity, because it is present in nonimmune subjects.
Also, a vaccine regimen popular in animal trials might have increased the
transmission of variants with otherwise low transmission fitness. Our
observations might explain why many animal vaccine trials have not faithfully
predicted outcomes in human vaccine trials and suggest that current practices in
vaccine design need to be reexamined accordingly.
PMID- 25589665
TI - Resection of gliomas around language areas: can fMRI contribute?
PMID- 25589664
TI - New insights into the evolutionary rate of hepatitis B virus at different
biological scales.
AB - The evolutionary rates of hepatitis B virus (HBV) estimated using contemporary
sequences are 10(2) to 10(4) times higher than those derived from archaeological
and genetic evidence. This discrepancy makes the origin of HBV and the time scale
of its spread, both of which are critical for studying the burden of HBV
pathogenicity, largely unresolved. To evaluate whether the dual demands (i.e.,
adaptation within hosts and colonization between hosts) of the viral life cycle
affect this conundrum, the HBV quasispecies dynamics within and among hosts from
a family consisting of a grandmother, her 5 children, and her 2 granddaughters,
all of whom presumably acquired chronic HBV through mother-to-infant
transmission, were examined by PCR cloning and next-generation sequencing
methods. We found that the evolutionary rate of HBV between hosts was
considerably lower than that within hosts. Moreover, the between-host
substitution rates of HBV decreased as transmission numbers between individuals
increased. Both observations were due primarily to changes at nonsynonymous
rather than synonymous sites. There were significantly more multiple
substitutions than expected for random mutation processes, and 97% of
substitutions were changed from common to rare amino acid residues in the
database. Continual switching between colonization and adaptation resulted in a
rapid accumulation of mutations at a limited number of positions, which quickly
became saturated, whereas substitutions at the remaining regions occurred at a
much lower rate. Our study may help to explain the time-dependent HBV
substitution rates reported in the literature and provide new insights into the
origin of the virus. IMPORTANCE: It is known that the estimated hepatitis B virus
(HBV) substitution rate is time dependent, but the reason behind this observation
is still elusive. We hypothesize that owing to the small genome size of HBV,
transmission between hosts and adaptation within hosts must exhibit high levels
of fitness trade-offs for the virus. By studying the HBV quasispecies dynamics
for a chain of sequentially infected transmissions within a family, we found the
HBV substitution rate between patients to be negatively correlated with the
number of transmissions. Continual switching between hosts resulted in a rapid
accumulation of mutations at a limited number of genomic sites, which quickly
became saturated in the short term. Nevertheless, substitutions at the remaining
regions occurred at a much lower rate. Therefore, the HBV substitution rate
decreased as the divergence time increased.
PMID- 25589667
TI - Three-tesla functional MR language mapping: comparison with direct cortical
stimulation in gliomas.
AB - OBJECTIVE: To evaluate the accuracy of functional MRI (fMRI) at 3T, as currently
used in the preoperative mapping of language areas, compared with direct cortical
stimulation (DCS) during awake surgery, in patients with supratentorial gliomas;
and to identify clinical, histopathologic,and radiologic factors associated with
fMRI/DCS discrepancies. METHODS: Language mapping with fMRI and DCS of 40
consecutive patients with gliomas(24 low-grade, 16 high-grade) in functional
areas were retrospectively analyzed. Three block designed tasks were performed
during fMRI (letter word generation, category word generation,semantic
association). During awake surgery, eloquent areas were mapped using DCS, blinded
to fMRI. A site-by-site comparison of the 2 techniques was performed using a
cortical grid. fMRI sensitivity and specificity were calculated using DCS as the
reference. Associations of clinical,histopathologic, and radiologic features
(including relative cerebral blood volume [rCBV] measured with dynamic
susceptibility contrast MRI) with fMRI false-positive and false-negative
occurrence were assessed using hierarchical logistic regressions. RESULTS: Of
2,114 stimulated cortical sites, 103 were positive for language during DCS.
Sensitivity and specificity of language fMRI combining the 3 tasks reached 37.1%
(95% confidence interval [CI] 20.7-57.2) and 83.4% (95% CI 77.1-88.3),
respectively. Astrocytoma subtype(odds ratio [OR] 2.50 [1.32-4.76]; p 5 0.007),
tumor rCBV ,1.5 (OR 2.17 [1.08-4.35]; p 50.03), higher cortical rCBV (OR 2.22
[1.15-4.17]; p 5 0.02), and distance to tumor .1 cm (OR2.46 [1.82-3.32]; p #
0.001) were independently associated with fMRI false-positive occurrence.
CONCLUSIONS: There are pitfalls in preoperative fMRI as currently used in
preoperative language mapping in glioma patients, made more complicated when high
grade and hyperperfused tumors are evaluated.
PMID- 25589666
TI - Colonic mucosal a-synuclein lacks specificity as a biomarker for Parkinson
disease.
AB - OBJECTIVE: To determine the utility of detecting a-synuclein (aSyn) in colonic
mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease
(PD). METHODS: We used the paraffin-embedded tissue (PET) blot, which degrades
physiologic nonaggregated aSyn using proteinase K and enhances antigen retrieval
allowing sensitive and selective detection of remaining protein aggregates, to
detect aSyn in colonic mucosal biopsies from 15 patients with early PD (,3
years), 7 patients with later PD (.5 years), and 11 individuals without PD. aSyn
and serine 129-phosphorylated aSyn (Ser129p-aSyn) were assessed by PET blot and
conventional immunohistochemistry. RESULTS: PET blot-resistant aggregated aSyn
and Ser129p-aSyn was present in 12 of 15 individuals with early PD, 7 of 7
individuals with later PD, and 11 of 11 control subjects. The number of biopsies
positive by PET blot relative to conventional immunohistochemistry was
significantly lower in both PD groups compared with the control group for both
aSyn and Ser129p-aSyn,whereas routine immunohistochemistry was positive more
often in PD, but was positive in as many as 9 of 11 control individuals.
CONCLUSION: Strong evidence of the presence of aggregated hyperphosphorylated
aSyn in individuals with and without PD, using such a sensitive and specific
method as the PET blot, suggests that colonic deposition of aSyn is not a useful
diagnostic test for PD. The utility of detecting aSynin the colon as a biomarker
in combination with other assessments remains to be determined.
PMID- 25589668
TI - On the origin of painful somatosensory seizures.
AB - OBJECTIVE: To explore whether painful somatosensory seizures (PSS) are generated
in the primary somatosensory cortex (SI area) or in the operculo-insular cortex.
METHODS: We analyzed ictal recordings and data from stimulation using
intracerebral electrodes exploring the operculo-insular cortex (including
secondary somatosensory [SII] region), SI area,and other areas of the pain matrix
(cingulate gyrus and supplementary motor area) in a case series study of 5
patients with PSS. RESULTS: Clinical features of PSS were different from those of
seizures arising from the SI area: (1)pain intensity was higher; (2) pain
spreading was not from one somatotopic territory to adjacentones; and (3) the
spatial extent of pain was large, fitting better with the size of somatosensory
receptive fields of the insula and SII region than of the SI area. The insula and
SII region were systematically involved at the onset of seizures, rapidly
followed by the opercular portion of SI area.The upper part of SI cortex was
involved at a lesser degree, with some delay, and pain duration did not correlate
in time with that of the discharge in SI. Ictal pain was consistently reproduced
by stimulation of the insula or SII region but never by stimulating the SI area.
CONCLUSIONS: These data strongly suggest that PSS originate in the operculo
insular cortex and not in the SI area and corroborate the concept that this
region is involved in the sensory discriminative processing of pain inputs. Pain
at the onset of PSS has a high value for localizing the epileptogenic area.
PMID- 25589669
TI - Gamma oscillations precede interictal epileptiform spikes in the seizure onset
zone.
AB - OBJECTIVE: To investigate the generation, spectral characteristics, and potential
clinical significance of brain activity preceding interictal epileptiform spike
discharges (IEDs) recorded with intracranial EEG. METHODS: Seventeen adult
patients with drug-resistant temporal lobe epilepsy were implanted with
intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs
detected on clinical macro- and research microelectrodes were analyzed using time
frequency spectral analysis. RESULTS: Gamma frequency oscillations (30-100 Hz)
often preceded IEDs in spatially confined brain areas. The gamma-IEDs were
consistently observed 35 to 190 milliseconds before the epileptiform spike
waveforms on individual macro- and microelectrodes. The gamma oscillations
associated with IEDs had longer duration (p < 0.001) and slightly higher
frequency (p = 0.045) when recorded on microelectrodes compared with clinical
macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were
strongly associated with electrodes in the seizure onset zone (SOZ) compared with
the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without
preceding gamma oscillations that were often also detected outside of the SOZ.
Similar to prior studies, isolated pathologic high-frequency oscillations in the
gamma (30-100 Hz) and higher (100-600 Hz) frequency range, not associated with an
IED, were also found to be associated with SOZ. CONCLUSIONS: The occurrence of
locally generated gamma oscillations preceding IEDs suggests a mechanistic role
for gamma in pathologic network activity generating IEDs. The results show a
strong association between SOZ and gamma-IEDs. The potential clinical application
of gamma-IEDs for mapping pathologic brain regions is intriguing, but will
require future prospective studies.
PMID- 25589670
TI - Lambert-Eaton syndrome IgG inhibits transmitter release via P/Q Ca2+ channels.
AB - OBJECTIVE: To determine whether immunoglobulin G (IgG) from patients with Lambert
Eaton myasthenic syndrome (LEMS) decreases action potential-evoked synaptic
vesicle exocytosis,and whether the effect is mediated by P/Q-type voltage-gated
calcium channels (VGCCs). METHODS: IgG was obtained from 4 patients with LEMS (3
males, 1 female), including 2 patients with lung malignancy. Antibodies against
P/Q-type VGCCs were detected in all 4 patients, and against N-type VGCCs in 2. We
incubated neuronal cultures with LEMS IgG and determined the size of the total
recycling pool of synaptic vesicles and the rate of action potential-evoked
exocytosis using fluorescence imaging of the amphiphilic dye SynaptoRed C1.
Pooled IgG from healthy volunteers was used as a control. We repeated the
experiments on synapses lacking P/Q-type calcium channels from a Cacna1a knockout
mouse to determine whether these channels account for the pathogenic effect of
LEMS IgG. RESULTS: LEMS IgG had no effect on the total recycling pool size but
significantly reduced the rate of action potential-evoked synaptic exocytosis in
wild-type neurons when compared with neurons treated with control IgG. In
contrast, LEMS IgG had no effect on the rate of synaptic vesicle exocytosis in
neurons lacking P/Q-type channels. CONCLUSIONS: These data provide direct
evidence that LEMS IgG inhibits neurotransmitter release by acting on P/Q-type
VGCCs.
PMID- 25589671
TI - "Noncognitive" symptoms of early Alzheimer disease: a longitudinal analysis.
AB - OBJECTIVES: To observe the natural time course of noncognitive symptoms before
the onset of symptomatic Alzheimer disease dementia. METHODS: Using the National
Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March
2013, data from cognitively normal individuals who were aged 50 years or older at
first visit and had subsequent follow-up were analyzed. Survival analyses were
used to examine the development of particular symptoms relative to each other on
the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities
Questionnaire, and Geriatric Depression Scale, and to compare the development of
individual symptoms for persons who did and did not receive a Clinical Dementia
Rating (CDR) .0 (indicating abnormal cognition) during the follow-up period.
RESULTS: The order of symptom occurrence on the NPI-Q was similar for
participants who remained at CDR 0 and for those who received a CDR .0 over the
follow-up period, although the time to most NPI-Q symptoms was faster for
participants who received a CDR.0 (p, 0.001).With the exception of memory,
Geriatric Depression Scale symptoms reported by both CDR groups were similar.
CONCLUSIONS: We found a significantly earlier presence of positive symptoms on
the NPI-Q in cognitively normal patients who subsequently developed CDR .0. Among
participants with no depression symptoms at baseline, results suggest that
depressive symptoms may increase with aging regardless of incipient dementia.
Such findings begin to delineate the noncognitive course of Alzheimer disease
dementia in the preclinical stages. Future research must further elucidate the
correlation between noncognitive changes and distinct dementia subtypes.
PMID- 25589672
TI - Mouse models for assessing the cross-protective efficacy of oral non-typhoidal
Salmonella vaccine candidates harbouring in-frame deletions of the ATP-dependent
protease lon and other genes.
AB - In BALB/c mouse models of Salmonella enterica serovar Typhimurium infection, a
single oral immunization with a mutant strain with an insertion of the
chloramphenicol resistance gene into the ATP-dependent protease clpP or lon gene
decreased the number of salmonellae in each tissue sample 5 days after oral
challenge with virulent S. Typhimurium at weeks 26 and 54 post-immunization.
These data suggested that an oral immunization with the ClpP- or Lon-disrupted S.
Typhimurium strain could provide long-term protection against oral challenge with
virulent S. Typhimurium. Accordingly, recombinant oral non-typhoidal Salmonella
(NTS) vaccines were constructed by incorporating mutants of both S. Typhimurium
and S. enterica serovar Enteritidis harbouring stable in-frame markerless
deletions of the clpP-lon-sulA (suppressor of lon), lon-sulA or lon-msbB
(acyltransferase) genes. Amongst these orally administered vaccine candidates,
those with the lon-sulA gene deletion mutants of S. Typhimurium and S.
Enteritidis protected BALB/c and C57BL/6J mice against oral challenge with both
virulent S. Typhimurium and virulent S. Enteritidis. Therefore, the in-frame
markerless lon-sulA gene deletion mutant of S. Typhimurium or S. Enteritidis
could be a promising cross-protective NTS live vaccine candidate for practical
use in humans.
PMID- 25589673
TI - CLASP2-dependent microtubule capture at the neuromuscular junction membrane
requires LL5beta and actin for focal delivery of acetylcholine receptor vesicles.
AB - A hallmark of the neuromuscular junction (NMJ) is the high density of
acetylcholine receptors (AChRs) in the postsynaptic muscle membrane. The
postsynaptic apparatus of the NMJ is organized by agrin secreted from motor
neurons. The mechanisms that underlie the focal delivery of AChRs to the adult
NMJ are not yet understood in detail. We previously showed that microtubule (MT)
capture by the plus end-tracking protein CLASP2 regulates AChR density at agrin
induced AChR clusters in cultured myotubes via PI3 kinase acting through
GSK3beta. Here we show that knockdown of the CLASP2-interaction partner LL5beta
by RNAi and forced expression of a CLASP2 fragment blocking the CLASP2/LL5beta
interaction inhibit microtubule capture. The same treatments impair focal vesicle
delivery to the clusters. Consistent with these findings, knockdown of LL5beta at
the NMJ in vivo reduces the density and insertion of AChRs into the postsynaptic
membrane. MT capture and focal vesicle delivery to agrin-induced AChR clusters
are also inhibited by microtubule- and actin-depolymerizing drugs, invoking both
cytoskeletal systems in MT capture and in the fusion of AChR vesicles with the
cluster membrane. Combined our data identify a transport system, organized by
agrin through PI3 kinase, GSK3beta, CLASP2, and LL5beta, for precise delivery of
AChR vesicles from the subsynaptic nuclei to the overlying synaptic membrane.
PMID- 25589674
TI - PDGF-stimulated dispersal of cell clusters and disruption of fibronectin matrix
on three-dimensional collagen matrices requires matrix metalloproteinase-2.
AB - Formation of cell clusters is a common morphogenic cell behavior observed during
tissue and organ development and homeostasis, as well as during pathological
disorders. Dynamic regulation of cell clustering depends on the balance between
contraction of cells into clusters and migration of cells as dispersed
individuals. Previously we reported that under procontractile culture conditions,
fibronectin fibrillar matrix assembly by human fibroblasts functioned as a
nucleation center for cell clustering on three-dimensional collagen matrices.
Here we report that switching preformed cell clusters from procontractile to
promigratory culture conditions results in cell dispersal out of clusters and
disruption of FN matrix. Experiments using small interfering RNA silencing and
pharmacological inhibition demonstrated that matrix metalloproteinase activity
involving MMP-2 was necessary for fibronectin matrix disruption and dispersal of
cell clusters.
PMID- 25589675
TI - Involvement of general control nonderepressible kinase 2 in cancer cell apoptosis
by posttranslational mechanisms.
AB - General control nonderepressible kinase 2 (GCN2) is a promising target for cancer
therapy. However, the role of GCN2 in cancer cell survival or death is elusive;
further, small molecules targeting GCN2 signaling are not available. By using a
GCN2 level-based drug screening assay, we found that GCN2 protein level
critically determined the sensitivity of the cancer cells toward Na(+),K(+)
ATPase ligand-induced apoptosis both in vitro and in vivo, and this effect was
largely dependent on C/EBP homologous protein (CHOP) induction. Further analysis
revealed that GCN2 is a short-lived protein. In A549 lung carcinoma cells,
cellular beta-arrestin1/2 associated with GCN2 and maintained the GCN2 protein
level at a low level by recruiting the E3 ligase NEDD4L and facilitating
consequent proteasomal degradation. However, Na(+),K(+)-ATPase ligand treatment
triggered the phosphorylation of GCN2 at threonine 899, which increased the GCN2
protein level by disrupting the formation of GCN2-beta-arrestin-NEDD4L ternary
complex. The enhanced GCN2 level, in turn, aggravated Na(+),K(+)-ATPase ligand
induced cancer cell apoptosis. Our findings reveal that GCN2 can exert its
proapoptotic function in cancer cell death by posttranslational mechanisms.
Moreover, Na(+),K(+)-ATPase ligands emerge as the first identified small-molecule
drugs that can trigger cancer cell death by modulating GCN2 signaling.
PMID- 25589676
TI - Reactions to FDA-Proposed Graphic Warning Labels Affixed to U.S. Smokers'
Cigarette Packs.
AB - INTRODUCTION: Graphic warning labels have been shown to be more effective than
text-only labels in increasing attention and perceived health risks, but most
U.S. studies have involved single exposures in laboratory or Internet settings.
METHODS: We recruited a convenience sample (N = 202) of U.S. adult smokers from
population subgroups with higher rates of smoking and smoking-related deaths who
had participated in a larger survey about graphic warning labels. Participants
were randomized to get 1 of 9 graphic + text labels or a text-only label.
Research staff affixed a warning label sticker to participants' cigarette pack(s)
at enrollment. Color graphic labels covered slightly more than the lower half of
packs. Black and white labels of current U.S. text-only warnings covered the
existing side warning to prompt attention to the label (i.e., attention control).
Participants received extra stickers of the same label for subsequent packs, and
completed 3 telephone interviews in 1 week. RESULTS: Participants reported low
avoidance (<34%) and consistent use of the stickers (91%). Smokers consistently
paid more attention to graphic than text-only labels. Only 5 of the 9 graphic
warning labels were significantly associated with greater thoughts of health
risks. Thinking about quitting and stopping smoking did not differ by label.
Qualitative data illustrated differences in the "stickiness," self-referencing,
and counterarguments of graphic warning labels. CONCLUSIONS: U.S. smokers'
reactions to graphic warning labels on their own packs were similar to other,
more controlled studies. Qualitative findings underscore the need for warning
labels that encourage self-referential processing without increasing defensive
reactions.
PMID- 25589677
TI - The Nicotine Metabolite Ratio in Pregnancy Measured by trans-3'-Hydroxycotinine
to Cotinine Ratio: Characteristics and Relationship With Smoking Cessation.
AB - INTRODUCTION: Nicotine replacement therapy (NRT) helps nonpregnant smokers quit,
but there is no evidence that standard dose NRT is effective in pregnancy. As
nicotine metabolism increases in pregnancy, this could reduce NRT efficacy. Using
the ratio of trans-3'-hydroxycotinine to cotinine, the nicotine metabolite ratio
(NMR), we investigated relationships between the rate of nicotine metabolism,
maternal characteristics and smoking cessation in pregnant women recruited to a
randomized controlled trial of NRT. METHODS: Data from 1,050 pregnant smokers in
the Smoking, Nicotine and Pregnancy trial who were of 12-24 weeks gestation had
exhaled carbon monoxide readings of >=8 ppm at recruitment and who were
randomized to NRT or placebo patches were used. Linear and logistic regression
investigated associations between maternal characteristics and NMR and also
between NMR and subsequent validated cessation from smoking. RESULTS: Six hundred
and sixty-two women (63%) provided blood samples for NMR estimation. Higher NMR
was associated with increased cigarette consumption prior to pregnancy. At 1
month (odds ratio [OR] = 0.87; 95% CI = 0.76-0.99; p = .043) and delivery (OR =
0.79; 95% CI = 0.66-0.95; p = .010), there was a significant negative association
between a 0.1 unit increase in NMR and odds of achieving cessation after
adjusting for possible confounders. There was no evidence for an interaction
between a 0.1 unit increase in NMR and treatment assignment on the odds of
cessation at 1 month post-quit date (p = .556). CONCLUSION: Pregnant women who
metabolize nicotine more rapidly are less likely to achieve cessation when they
try to quit smoking. There is no evidence that NRT is more effective in women who
metabolize nicotine more slowly.
PMID- 25589678
TI - Use of E-Cigarettes Among Current Smokers: Associations Among Reasons for Use,
Quit Intentions, and Current Tobacco Use.
AB - INTRODUCTION: Research has documented growing availability and use of e
cigarettes in the United States over the last decade. METHODS: We conducted a
national panel survey of current adult cigarette smokers to assess attitudes,
beliefs, and behaviors relating to e-cigarette use in the United States (N =
2,254). RESULTS: Among current cigarette smokers, 20.4% reported current use of e
cigarettes on some days and 3.7% reported daily use. Reported reasons for e
cigarette use included: quit smoking (58.4%), reduce smoking (57.9%), and reduce
health risks (51.9%). No significant differences in sociodemographic
characteristics between e-cigarette users and nonusers were observed. Prior quit
attempts were reported more frequently among e-cigarette users (82.8%) than
nonusers (74.0%). Intention to quit was reported more frequently among e
cigarette users (64.7%) than nonusers (46.8%). Smokers intending to quit were
more likely to be e-cigarette users than those not intending to quit (odds ratio
[OR] = 1.90, CI =1.36-2.65). Those who used e-cigarettes to try to quit smoking
(OR = 2.25, CI = 1.25-4.05), reduce stress (OR = 3.66, CI = 1.11-12.09), or
because they cost less (OR = 3.42, CI = 1.64-7.13) were more likely to report
decreases in cigarette smoking than those who did not indicate these reasons.
Smokers who reported using e-cigarettes to quit smoking (OR = 16.25, CI = 8.32
31.74) or reduce stress (OR = 4.30, CI = 1.32-14.09) were significantly more
likely to report an intention to quit than those who did not indicate those
reasons for using e-cigarettes. CONCLUSIONS: Nearly a quarter of smokers in our
study reported e-cigarettes use, primarily motivated by intentions to quit or
reduce smoking. These findings identify a clinical and public health opportunity
to re-engage smokers in cessation efforts.
PMID- 25589679
TI - Smoking Among Sexual Minorities: Are There Racial Differences?
AB - INTRODUCTION: Smoking prevalence is higher among sexual minorities compared to
their heterosexual peers. However, very little is known about potential racial
differences in smoking among sexual minority populations. We examined differences
by race in smoking status among a robust sample of sexual minorities. METHODS: We
used data from the 2010 Social Justice Sexuality project, a large national
convenience sample of sexual minority adults that oversampled individuals from
racial minority groups. Log-Poisson multivariable regression models were employed
to determine the risk of current smoking among sexual minority individuals by
race after controlling for socio-demographic characteristics. RESULTS: Among
smokers, 22.35% identified as White, 26.98% identified as Black, 19.38%
identified as Latino/Hispanic, 5.58% identified as Asian American, and 25.67%
were other/multiracial. In fully adjusted gender stratified models, Black men
(adjusted risk ratio [aRR] = 0.61, 95% confidence interval [CI] = 0.50, 0.75) and
Asian American men (aRR = 0.61, 95% CI = 0.50, 0.75) were at lower risk of
smoking compared to White men. Black women were the only to remain statistically
significant for decreased risk of smoking in fully adjusted gender stratified
models (aRR = 0.78, 95 % CI = 0.65, 0.95). CONCLUSIONS: Among sexual minorities,
Black and Asian American individuals consistently were at decreased risk of
current smoking compared to their White peers. Future research should seek to
understand the mechanisms that contribute to decreased smoking status among
racial sexual minorities.
PMID- 25589681
TI - Correction.
PMID- 25589682
TI - Correction.
PMID- 25589680
TI - Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?
AB - INTRODUCTION: Understanding the mechanisms by which bupropion promotes smoking
cessation may lead to more effective treatment. To the extent that reduced
smoking reinforcement is one such mechanism, a longer duration of pre quit
bupropion treatment should promote extinction of smoking behavior. We evaluated
whether 4 weeks of pre quit bupropion (extended run-in) results in greater pre
quit reductions in smoking rate and cotinine and, secondarily, greater short-term
abstinence, than standard 1 week of pre quit bupropion (standard run-in).
METHODS: Adult smokers (n = 95; 48 females) were randomized to a standard run-in
group (n = 48; 3-week placebo, then 1-week bupropion pre quit) or an extended run
in group (4-week pre quit bupropion; n = 47). Both groups received group
behavioral counseling and 7 weeks of post quit bupropion. Smoking rate (and
craving, withdrawal, and subjective effects) was collected daily during the pre
quit period; biochemical data (cotinine and carbon monoxide) were collected at
study visits. RESULTS: During the pre quit period, the extended run-in group
exhibited a greater decrease in smoking rate, compared to the standard run-in
group, interaction p = .03. Cigarette craving and salivary cotinine followed a
similar pattern, though the latter was evident only among women. Biochemically
verified 4-week continuous abstinence rates were higher in the extended run-in
group (53%) than the standard run-in group (31%), p = .033. CONCLUSIONS: The
extended use of bupropion prior to a quit attempt reduces smoking behavior during
the pre quit period and improved short-term abstinence rates. The data are
consistent with an extinction-of-reinforcement model and support further
investigation of extended run-in bupropion therapy for smoking cessation.
PMID- 25589684
TI - Correction.
PMID- 25589683
TI - Correction.
PMID- 25589685
TI - Correction.
PMID- 25589686
TI - Correction.
PMID- 25589687
TI - Correction.
PMID- 25589689
TI - Correction.
PMID- 25589688
TI - Author's response: What characteristics of primary care and patients are
associated with early death in patients with lung cancer in the UK?
PMID- 25589690
TI - Correction.
PMID- 25589691
TI - Correction.
PMID- 25589693
TI - Recanalization of popliteal and infrapopliteal chronic total occlusions using
Viance and CrossBoss crossing catheters: a multicenter experience from the XLPAD
Registry.
AB - BACKGROUND: Chronic total occlusions (CTOs) are reported in up to 40% of patients
with symptomatic peripheral arterial disease. The Viance Crossing catheter
(Covidien) and the CrossBoss catheter (Boston Scientific) are novel devices that
facilitate either true lumen or subintimal navigation across CTOs. The purpose of
this study was to examine the acute procedural success of these devices for
popliteal and below-the-knee (BTK) CTOs. METHODS: Clinical and procedural outcome
data between Sept 2010 and October 2013 were analyzed from the ongoing
multicenter XLPAD registry. Technical success was defined as true lumen passage
of the catheter, while procedural success was defined as successful vessel
revascularization inclusive of subintimal passage and reentry. RESULTS: Twenty
nine patients underwent 31 procedures, in which 37 lesions were treated with the
Viance and CrossBoss catheters. Mean age of the group was 69.1 +/- 10.7 years and
26 patients were male (90%). All patients (100%) had hypertension, 62% were
diabetic, and 48% were active smokers. Critical limb ischemia was the indication
for the procedure in 58% of cases; mean Rutherford class was 4.2 +/- 1.2 for the
entire cohort. Target CTOs included 14 anterior tibial, 9 posterior tibial, 5
peroneal, 1 tibio-peroneal trunk, and 8 popliteal artery lesions. Mean lesion
length was 81 +/- 64 mm; 15 lesions (41%) were severely calcified. True lumen
passage was obtained in 24 lesions (65% technical success). Subintimal entry was
achieved in 5 lesions (14%). Procedural success was achieved in 26 lesions (70%).
Procedural failure was related to longer lesion length (P<.001), and mean length
of failed lesions was 136 +/- 65 mm. CONCLUSION: Viance and CrossBoss catheters
were associated with an overall 70% procedural success with predominantly true
lumen crossing in a BTK-CTO cohort. CTO length remains an important determinant
of device success.
PMID- 25589694
TI - Angiographic profile and endovascular interventions in Takayasu's arteritis.
AB - BACKGROUND: Takayasu's arteritis (TA) is a rare inflammatory, granulomatous
vasculitis primarily involving the aorta and its major branches. Clinical and
angiographic manifestations of the disease differ in various parts of the world.
OBJECTIVES: To analyze the clinical features, angiographic profile, and
endovascular interventions in TA patients (pts). METHODS: From January 2009 to
March 2013, a total of 62 consecutive pts who were diagnosed with Takayasu's
arteritis at our institute based on American College of Rheumatology Criteria
were included in the study. Thirty-four pts underwent conventional angiography,
while 28 were evaluated using computed tomographic angiography. Endovascular
interventions were attempted for 24 lesions in 23 pts who were symptomatic and
had significant stenotic lesions. RESULTS: The mean age of presentation was 28.4
+/- 9.7 years, with 69.4% female. Limb claudication (52%) was the most common
presenting symptom, followed by vertigo (35%) and constitutional symptoms. The
most common angiography class was type V (37.1%), followed by type I (32.2%),
type IV (17.7%), type IIa (8.1%), type III (3.2%), and type IIb (1.6%). The most
common artery involved was the subclavian (64.5%), with the left subclavian more
commonly involved than the right, followed by the abdominal aorta (51.6%) and
renal artery (32.2%). Stenotic lesions were present in 59 pts (95%), while
aneurysmal involvement was seen in 17 (27.4%), with isolated aneurysmal
involvement in 3 of these. CONCLUSIONS: Our cohort of TA pts had more severe and
widespread involvement. Despite a more advanced presentation, percutaneous
balloon angioplasty with stent implantation is feasible, with good immediate
results but slightly higher complication rates.
PMID- 25589695
TI - Stent and Non-Stent Based Outcomes of Infrainguinal Peripheral Artery
Interventions From the Multicenter XLPAD Registry.
AB - BACKGROUND: There are limited data regarding contemporary use of stent and non
stent based treatment strategies of infrainguinal peripheral artery disease
(PAD). METHODS: We analyzed data from the ongoing multicenter XLPAD registry
between July 2005 and October 2013 to report on the use of non-stent (atherectomy
+/- balloon angioplasty) and stent-based treatment of superficial femoral artery
(SFA), popliteal, and below-the-knee (BTK) vessels in contemporary clinical
practice. RESULTS: A total of 584 interventions (SFA, 82.5%; popliteal, 7.2%;
BTK, 9.9%) were performed in 372 patients (mean age, 63.2 years; diabetes
mellitus, 57.7%; Rutherford category 1-3, 73.5%; Rutherford category 4-6, 20.1%).
Stents were deployed in 389 lesions (66.6%; SFA, 90.5%; popliteal, 5.1%; BTK,
4.1%) and non-stent strategy (atherectomy, 49%) in 195 lesions (33.4%; SFA,
66.7%; popliteal, 11.3%; BTK, 21.5%). In the stent and non-stent groups, mean
lesion lengths were 133.9 mm and 86.0 mm (P<.001), chronic total occlusions
(CTOs) constituted 63.0% and 49.7% (P<.01), and restenotic lesions were 12.6% and
32.3% (P<.001), respectively. At a mean follow-up of 260 +/- 130 days, in the
stent and non-stent treated patients, all-cause mortality was 4.3% and 3.5%
(P=.65), clinically indicated repeat revascularization was 17.5% and 14.9%
(P=.42), and amputation was 4.6% and 9.2% (P<.01), respectively. SFA lesion
location, long lesion length, and CTO were associated with the use of stents.
Advanced Rutherford class was associated with a non-stent treatment strategy.
CONCLUSION: The majority of endovascular peripheral arterial interventions are
performed in the SFA; most include a CTO and in patients with diabetes mellitus.
Operators use stents to primarily treat complex SFA lesions with overall similar
outcomes, except for fewer amputations compared to a non-stent strategy.
PMID- 25589696
TI - Automated carbon dioxide digital angiography for lower-limb arterial disease
evaluation: safety assessment and comparison with standard iodinated contrast
media angiography.
AB - INTRODUCTION: Carbon dioxide (CO2) has been validated as a contrast agent in a
large series of studies. A particular advantages of CO2 over iodinated contrast
medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the
limitations of CO2 angiography is the difficulty of CO2 manual injection due to
its compressibility. The manual gas injection does not permit optimal control of
the gas output. Development of an automated CO2 injector has overcome these
problems. AIM: This study compares the feasibility, safety, and diagnostic
accuracy of automated CO2 digital subtraction angiography (DSA) in comparison
with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. METHODS:
We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and
directly compared the two techniques. Sixteen females and 24 males participated
in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2
in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold
standard. RESULTS: The overall diagnostic accuracy of CO2-DSA was 96.9%
(sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%;
negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3
patients. No allergic reactions or significant decline in renal function were
observed in patients receiving the CO2 injection. CONCLUSION: Carbon dioxide DSA
is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI
patients. This modality should be considered as the standard choice for CLI
patients undergoing angiographic evaluation who are known to have renal
insufficiency or contrast allergy.
PMID- 25589698
TI - The power of the story in an era of big data and huge databases.
PMID- 25589697
TI - The utility of extension catheters in transradial percutaneous coronary
intervention.
AB - OBJECTIVES: To evaluate the use of extension catheters in transradial
intervention of complex coronary lesions. BACKGROUND: Complex percutaneous
coronary intervention (PCI) via transradial approach remains a challenge for many
interventionalists, primarily due to the difficulty in obtaining adequate guide
catheter support. METHODS: A retrospective case series identified 54 patients who
presented for PCI of complex coronary lesions. A lesion was defined as complex if
it contained severe calcification, proximal tortuosity, chronic total occlusion,
or was located distal to a previously implanted stent. After identifying the
complex lesions, a conversion to femoral approach was considered, but an attempt
via the transradial approach with the use of an extension catheter was chosen as
the initial strategy. Specific cases highlighting this approach are illustrated
in detail. RESULTS: The average age of the patients was 72 years old, with male
predominance (55%). The success rate of completing the transradial intervention
with the help of an extension catheter was 96%. Stent delivery failed due to
severe tortuosity and calcification in only 2 cases. The coronary artery involved
was either the left anterior descending (n = 25), the left circumflex (n = 10),
the right coronary artery (n = 14), or a saphenous vein graft (n = 5). There were
no coronary dissections evident from use of the extension catheter. CONCLUSION:
In the treatment of complex coronary lesions via the transradial approach, the
use of an extension catheter may assist in improving successful intervention and
decrease the frequency of crossover to a femoral approach.
PMID- 25589699
TI - Transradial versus transfemoral intervention for the treatment of left main
coronary bifurcations: results from the COBIS (COronary BIfurcation Stenting) II
Registry.
AB - OBJECTIVES: We compared clinical outcomes of transradial (TR) and transfemoral
(TF) percutaneous coronary interventions (PCI) in patients with left main
coronary artery (LMCA) bifurcation lesions. BACKGROUND: The use of TR approach is
growing as an alternative to the routine use of the TF approach. However, there
are limited data comparing the outcomes of these two approaches for the treatment
of LMCA bifurcation lesions. METHODS: Between January 2003 and December 2009, a
total of 853 patients undergoing PCI using drug-eluting stent (DES) implantation
for LMCA bifurcation lesions were enrolled from 18 centers in Korea. We
classified patients into the TR group (n = 212) and TF group (n = 641) according
to the vascular approach. The primary outcome was major adverse cardiac event
(MACE) rate, including composite of cardiac death, myocardial infarction (MI),
and target lesion revascularization (TLR) in all patients and in 483 propensity
score matched patients. RESULTS: There were no significant differences between TR
and TF approaches for procedural success in the main vessel (98.6% vs. 99.7%;
P=.07) and side branches (90.6% vs. 94.4%; P=.05). Thrombolysis in Myocardial
Infarction major or minor bleeding occurred less frequently in the TR group than
in the TF group (2.4% vs. 9.4%; P=.01). Over a median follow-up of 35 months,
MACE rate did not significantly differ between TR and TF groups (9.9% vs. 14.5%;
adjusted hazard ratio, 0.80; 95% confidence interval, 0.49-1.29; P=.36). These
results were consistent after propensity-score matched analysis. CONCLUSIONS: TR
PCI is a safe and effective vascular approach, even in patients with LMCA
bifurcation lesions undergoing PCI with DES implantation.
PMID- 25589700
TI - New-onset atrial fibrillation after surgical aortic valve replacement and
transcatheter aortic valve implantation: a concise review.
AB - Surgical aortic valve replacement (SAVR) and, more recently, transcatheter aortic
valve implantation (TAVI) have been shown to be the only treatments that can
improve the natural cause of severe aortic valve stenosis. However, after SAVR
and TAVI, the incidence of new-onset atrial fibrillation (NOAF) is 31%-64% and 4%
32%, respectively. NOAF is independently associated with adverse events such as
stroke, death, and increased length of hospital stay. Increasing the knowledge of
predisposing factors, optimal postprocedural monitoring, and prophylactic
antiarrhythmic and antithrombotic therapy may reduce the risk of complications
secondary to NOAF.
PMID- 25589701
TI - A short review of catheter-based superficial venous disease management: new
directions, new paradigms.
PMID- 25589702
TI - Lesion flow coefficient: a combined anatomical and functional parameter for
detection of coronary artery disease--a clinical study.
AB - Invasive diagnosis of coronary artery disease utilizes either anatomical or
functional measurements. In this study, we tested a futuristic parameter, lesion
flow coefficient (LFC, defined as the ratio of percent coronary area stenosis
(%AS) to the square root of the ratio of the pressure drop across the stenosis to
the dynamic pressure in the throat region), that combines both the anatomical
(%AS) and functional measurements (pressure and flow) for application in a
clinical setting. In 51 vessels, simultaneous pressure and flow readings were
obtained using a 0.014" Combowire (Volcano Corporation). Anatomical details were
assessed using quantitative coronary angiography (QCA). Fractional flow reserve
(FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR),
and hyperemic microvascular index (HMR) were obtained at baseline and adenosine
induced hyperemia. QCA data were corrected for the presence of guidewire and then
the LFC values were calculated. LFC was correlated with FFR, CFR, HSR, and HMR,
individually and in combination with %AS, under both baseline and hyperemic
conditions. Further, in 5 vessels, LFC group mean values were compared between
pre-PCI and post-PCI groups. P<.05 was considered statistically significant. LFC
measured at hyperemia correlated significantly when the pressure-based FFR, flow
based CFR, and anatomically measured %AS were combined (r = 0.64; P<.05).
Similarly, LFC correlated significantly when HSR, HMR, and %AS were combined (r =
0.72; P<.05). LFC was able to significantly distinguish between pre-PCI and post
PCI groups (0.42 +/- 0.05 and 0.05 +/- 0.004, respectively; P<.05). Similar
results were obtained for the LFC at baseline conditions. LFC, a futuristic
parameter that combines both the anatomical and functional endpoints, has
potential for application in a clinical setting for stenosis evaluation, under
both hyperemic and baseline conditions.
PMID- 25589703
TI - Percutaneous closure of atrial septal defect in adults: very long-term clinical
outcome and effects on aortic and mitral valve function.
AB - AIM: To investigate the very long-term clinical outcomes of atrial septal defect
(ASD) percutaneous closure in adult patients and to evaluate the 12-month effects
of the device on aortic and mitral valve function. METHODS: Over a 12-year
period, a total of 110 consecutive patients underwent percutaneous ASD closure. A
yearly clinical follow-up was conducted and any adverse event was recorded. In a
55-patient echocardiographic subgroup, the baseline and 12-month aortic and
mitral regurgitation rate was recorded. RESULTS: Mean age was 50.9 +/- 17 years
and 75% of patients were female. Mean ASD echocardiographic dimension was 17.6 +/
6.2 mm (range, 5-36 mm). Procedural success rate was 97%. After a mean follow-up
of 61.8 +/- 34.9 months (range, 6-167 months), all-cause death occurred in 2
patients (1.8%) and the composite primary outcome of major adverse cardiovascular
event (MACE) occurred in 5 patients (4.5%): 2 non-device related cardiac deaths
occurred and 3 surgeries were required. The Kaplan-Meier analysis showed an event
free survival at 140 months of 90%. In the 12-month echocardiographic substudy,
no case of significant (moderate or severe) new-onset aortic regurgitation was
detected, while 1 case (1.8%) of worsening mild-to-moderate aortic regurgitation
was described (P=.90). No case of significant new-onset or worsening mitral
regurgitation was noted. No patient needed aortic or mitral surgical repair at
very long-term follow-up. CONCLUSIONS: Transcatheter ASD closure is a safe
procedure with satisfactory very long-term clinical outcomes. The ASD device does
not significantly affect aortic and mitral valve function.
PMID- 25589704
TI - Subintimal TRAnscatheter Withdrawal (STRAW) of hematomas compressing the distal
true lumen: a novel technique to facilitate distal reentry during recanalization
of chronic total occlusion (CTO).
AB - The development of a large hematoma impairing visualization of the distal true
lumen is a recognized complication of antegrade recanalization of chronic total
occlusions, often forcing the operator to abort the procedure or switch to a
retrograde approach. We describe a novel technique utilizing an over-the-wire
balloon inflated in the proximal occluded vessel to block inflow and allow
aspiration of the blood from the subintimal space. This decompressed the true
lumen, restored distal visualization, and allowed successful reentry using a
dedicated technology. Utilization of this novel technique may rescue antegrade
recanalization attempts complicated by large subintimal hematomas.
PMID- 25589705
TI - A case of an occlusive right coronary artery dissection after stent implantation:
dilemmas and challenges.
AB - A 53-year-old man with stable angina had a staged percutaneous coronary
intervention to a critical focal stenosis of the mid-segment of the right
coronary artery (RCA). Two hours after successful RCA stent implantation, the
patient re-presented with inferior ST elevation secondary to acute dissection
originating at the distal edge of the stent, causing subtotal occlusion of the
distal RCA. The patient had TIMI-2 flow in the posterolateral branch and
occlusion of the posterior descending artery. This case describes the procedural
challenges the operators were faced with and successful use of the "rescue STAR"
technique as a last resort.
PMID- 25589706
TI - Real-time three-dimensional intracardiac echocardiography: an early single-center
experience.
AB - As interventional procedures in structural heart diseases are coming of age,
there is a significant lag in the periinterventional imaging development for
these procedures to become safe, expedient, accurate, and well tolerated by this
patient population. Currently, transesophageal echocardiography (TEE), including
real-time three-dimensional (RT-3D), has been used for monitoring and guidance
for these procedures. Accurate identification of the pathology, its anatomy, and
its relationship with the adjoining structures along with spatial resolution is
of paramount importance for wire and catheter placement, device deployment,
evaluation of the results, and any potential complications. Two-dimensional
intracardiac echocardiography (ICE) has been used extensively for a variety of
interventional procedures that undergo conscious sedation of monitored
anesthesia. RT-3D ICE has recently become available; we describe our initial
experience with this new imaging technology.
PMID- 25589708
TI - [ApoE-containing HDL and the development of atherosclerosis].
AB - The current state of knowledge about the role of high density lipoproteins (HDL)
indicates that their anti-atherogenic function is mainly related to the
effectiveness of their actions (mostly to the participation in reverse
cholesterol transport from tissues to liver) rather than the concentration of HDL
itself. HDLs are highly heterogeneous in their structure, lipid and protein
composition and metabolic pathways and individual HDL subpopulations differ in
their biological activity and effectiveness of anti-atherogenic actions.
Apolipoproteins play a key role in HDL metabolism, therefore their presence in
lipoproteins is one of the main criterion for HDL classification. According to
this criterion HDLs containing apolipoprotein E, called HDL-apoE, are
distinguished. Although the anti-atherogenic role of apo E has been demonstrated
in many scientific reports, understanding of the mechanisms of formation,
transformation and the role of HDL-apoE is still the aim of intense research. The
results of epidemiological studies are inconclusive; some of them have
demonstrated that high HDL- -apoE concentration has been associated with lower
risk of developing coronary heart disease (CHD), while other studies have shown
that high levels of HDL-apoE has been an independent risk factor for
cardiovascular events and positively correlated with other risk factors for CHD.
PMID- 25589709
TI - [Antimicrobial peptides in asthma pathogenesis].
AB - Antimicrobial peptides exhibit activity against bacteria, viruses, fungi, and
parasites. They have been described not only as endogenous antibiotics but also
as immune modulators with an impact on innate and adaptive immune functions.
Asthma is one of the most common diseases, characterized by chronic airway
inflammation, bronchial hyperreactivity and asthma attacks. Airway inflammation
in asthma is characterized by allergic phenotypes, such as dense infiltration of
eosinophils, mast cells, Th 2 lymphocytes and monocytes. Viral infections are
often the cause of asthma exacerbation. This review highlights recent
observations on the role of antimicrobial peptides in asthma pathogenesis.
PMID- 25589710
TI - [Amylin under examination. Fibrillogenic polypeptide of pancreatic amyloid].
AB - In patients or animals affected by 2 type diabetes mellitus (diabetes mellitus
type 2, DM2, non-insulin-dependent diabetes mellitus, NIDDM) or pancreatic tumor
disease e.g., insulinoma, some pathological deposits, called amyloid, are
observed among cells of islets of Langerhans. Among other constituents,
pancreatic deposits consist of an insoluble, fibrillar form of peptide
neurohormone termed amylin, produced by pancreatic beta cells. It is thought that
formation of fibrillar deposits of misfolded and aggregated peptide is highly
toxic to beta cells and leads to cell dysfunction, cell loss, pancreas
destruction and progress of the disease. This relatively small, 37-amino acid
peptide constitutes a serious scientific, research and to some extent a medical
problem. This article presents amylin as a fibrillating molecule which
participates in formation of amyloid deposits in human and animal pancreas,
Langerhans islets as a microenvironment of pancreatic amyloid formation,
occurrence of amylin and amyloid in animals and humans, and physico-chemical
requirements to meet to name amylin deposit as amyloid.
PMID- 25589707
TI - Work and home stress: associations with anxiety and depression symptoms.
AB - BACKGROUND: In the evolving work environment of global competition, the
associations between work and home stress and psychological well-being are not
well understood. AIMS: To examine the impact of psychosocial stress at work and
at home on anxiety and depression. METHODS: In medically healthy employed men and
women (aged 30-60), serial regression analyses were used to determine the
independent association of psychosocial stress at work and at home with
depression symptoms, measured using the Beck Depression Inventory-II (BDI-II),
and anxiety symptoms, measured using the Spielberger Trait Anxiety Inventory
(STAI). Psychosocial stress at work was measured using the Job Content
Questionnaire to assess job psychological demands, job control, job social
support and job insecurity. Psychosocial stress at home was assessed by 12
questions including stress at home, personal problems, family demands and
feelings about home life. RESULTS: Serial regression analyses in 129 subjects
revealed that job insecurity and home stress were most strongly associated with
depression and anxiety symptoms. Job insecurity accounted for 9% of the variation
both in BDI-II scores and in STAI scores. Home stress accounted for 13 and 17% of
the variation in BDI-II scores and STAI scores, respectively. In addition, job
social support was significantly and independently associated with STAI scores
but not BDI-II scores. CONCLUSIONS: Work and home stress were associated with
anxiety and depression symptoms in both men and women. Both work and home stress
should be considered in studies evaluating anxiety and depression in working
populations.
PMID- 25589711
TI - [The use of various diet supplements in metabolic syndrome].
AB - Civilization development is associated with immense progress in science and
significant improvement of human living conditions but simultaneously it
contributes to many health problems including metabolic syndrome. Metabolic
syndrome is a set of mutually associated factors including insulin resistance,
hyperinsulinemia, obesity, lipids disorders and hypertension, which is the main
cause of development of coronary heart disease and type 2 diabetes. The first
line of defense against metabolic syndrome is a change of life style including
body mass reduction, application of a low-calorie diet and performance of
physical activity. In spite of the simplicity of therapy, long-term success of
the above treatment among patients is observed seldom because it is very
difficult to obey rigorous rules. Nowadays, it is considered that diet
supplements including antioxidants, polyunsaturated fatty acids and mineral
elements are helpful in metabolic syndrome treatment due to their antioxidant and
anti-inflammatory properties. It is considered that a health balanced diet
enriched with various diet supplements may be the best strategy in metabolic
syndrome treatment.
PMID- 25589712
TI - [18 kDa translocator protein--implications in cell's functions].
AB - The mitochondrial 18kDa Translocation Protein (TSPO) was first identified in 1977
by its capability to bind benzodiazepines in peripheral tissues. It is more
commonly known after its previous name - peripheral benzodiazepine receptor (PBR)
as opposed to the central benzodiazepine receptor (CBR), from which it differs by
location, structure and function. It is ubiquitous with highest expression in
steroid-producing tissues, like adrenal cortex, ovaries, testicles, and placenta.
The role of TSPO is crucial for living; its inactivation results in early
embryonic-lethal phenotype in mice. TSPO has been implicated in various functions
of cell, including steroidogenesis, cellular respiration, reactive oxygen species
production, heme biosynthesis, immunomodulation, apoptosis, and cellular
proliferation. TSPO has been shown to interact with other cellular proteins: 32
kDa voltage-dependent anion channel (VDAC), 30 kDa adenine nucleotide translocase
(ANT), cyclophilin D, hexokinase, creatinine kinase, diazepam binding inhibitor
(DBI), phosphate carrier and Bcl-2 family. They are - involved in the formation
and regulation of mitochondrial permeability transition pore (mPTP) at the
junction of the inner and outer mitochondrial membranes. While the function and
characteristics of the mPTP are known, its well defined, but its structure
remains speculative. Changes in TSPO expression are associated with multiple
disorders, including cancer, ischaemia-reperfusion injury, neurological diseases
and psychiatric disorders, atheromatosis, and others. - TSPO is able to bind
cholesterol, porphyrins and other ligands with different affinity. The current
knowledge of TSPO implicates its potential use as a diagnostic marker and
therapeutic target in different diseases and their therapies.
PMID- 25589713
TI - [Health--promoting effect of quercetin in human diet].
AB - Quercetin is a plant flavonoid phytochemical exhibiting a broad spectrum of
properties i.a. antioxidant, anti-inflammatory and immunomodulatory. However, the
effect of quercetin is not clear. This compound at low concentrations can
stimulate proliferation of human cells, so it can be a potential drug in the
treatment of neurodegenerative diseases and in high concentrations, it induces
apoptosis thereby eliminating the infected or abnormal cells and can serve as a
potential anticancer drug with wide clinical application. Action of quercetin can
be explained by its interference with cellular enzymes, receptors, transporters
and signalling system. Due to its widespread occurrence in the plant world, it is
an integral component of the human diet. The dietary quercetin occurs most often
in the form of beta-glycosides connected mostly with rutinose, rhamnose and
glucose. Depending on the nutritional habits, the daily intake of flavonoids,
including quercetin, ranges from 3 to 70 mg. Epidemiological studies confirm an
inverse correlation between the consumption of flavonoids and the incidence of
lifestyle diseases and tumor formation. Published data indicate that consumption
of foods rich in flavonoids reduces the risk of coronary heart disease. Thus,
flavonoids - including quercetin - seem to be an interesting pro-health agent.
PMID- 25589714
TI - Amyloid-beta Modulates Both AbetaPP and Tau Phosphorylation.
AB - Two histopathological hallmarks of Alzheimer's disease (AD), the tau rich
neurofibrillary tangles and the senile plaques, predominating in amyloid-beta
(Abeta), have fueled research in distinct directions. Evidence suggests that
Abeta triggers imbalanced activities of protein phosphatases and kinases thus
affecting the phosphorylation state of tau in AD. The amyloid-beta protein
precursor (AbetaPP) itself appears to be hyperphosphorylated at different
residues in AD brains, including at Thr668.The results reported in this
manuscript show, for the first time, that Abeta(42) can impact upon the AbetaPP
phosphorylation state at the Thr668 residue. This novel finding supports a
putative model, whereby Abeta can modulate the phosphorylation state of AbetaPP
regulating its processing and consequently its own production. Furthermore, the
data presented shows that in primary cortical neurons, GSK3beta and Cdk5 are
involved in AbetaPP phosphorylation at this residue and that PP1 and PP2B
participate in AbetaPP dephosphorylation. Consistent with other reports, Abeta
was reports, capable of increasing tau phosphorylation at the Ser396 and Ser262
residues. This peptide is therefore a strong candidate for promoting the cross
talk between signaling pathways, which simultaneously result in AbetaPP and tau
hyperphosphorylation. In closing, the Abeta effect on protein kinases and protein
phosphatases may constitute an alternative mechanism by which the peptide is able
to modulate the phosphorylation state of both AbetaPP and tau in AD.
PMID- 25589715
TI - Left temporal lobe epilepsy revealing left posterior cortical atrophy due to
Alzheimer's disease.
AB - Seizures can be an early symptom of Alzheimer's disease (AD) and can precede
cognitive decline. Early epilepsy in AD can mimic transient epileptic amnesic
syndrome (TEAS) or epileptic amnesic syndrome. We report the case of a patient
who started a cerebrospinal fluid (CSF)-proven AD with partial seizures and TEAS
that secondarily became a cortical posterior atrophy syndrome. CSF biomarkers
showed a high amyloid production, amyloidopathy, and high level of total tau and
p-Tau. This observation adds data to the complex AD-early epilepsy interactions
and illustrates that atypical AD can cause a TEAS. Possible red flags for an
underlying neurodegenerative process in TEAS are discussed.
PMID- 25589716
TI - Influence of oxidative stress biomarkers on cognitive decline.
AB - BACKGROUND: Abnormal oxidative stress is an established feature of Alzheimer's
disease (AD). Markers of lipoperoxidation and deficits in serum antioxidants
could have a predictive value for identifying subjects at risk of dementia and to
predict cognitive decline. OBJECTIVE: Search for relationships between the levels
of some oxidative stress biomarkers and cognitive function decline that would
help predict this decline. METHODS: The study solicited and included 97 patients
aged 63 to 93 years with various suspected neurodegenerative diseases (35 with
AD). They were followed up at six-month intervals over two years (2010-2012). The
study: i) assessed the blood levels of glutathione peroxidase, glutathione, and
malondialdehyde; ii) performed the Mini-Mental Status Examination (MMSE), the
Clock Drawing test, the free/cued recall task with 16-item lists, the cue
percentage; and the Trail Making Test; and iii) acquired brain magnetic resonance
imaging or tomodensitometry. The primary outcome measure was the MMSE score.
RESULTS: The MMSE score was correlated with the score of each neuropsychological
test, the age at baseline, and the glutathione level. On average, the decline in
the MMSE score was 1.63 points per six months. A 100 International Unit increase
in glutathione peroxidase was associated with an average loss of 1.19 MMSE points
per six months (p = 0.002). A 100 MUmol/L increase in glutathione was associated
with an average loss of 1.80 MMSE points per six months (p = 0.014). CONCLUSION:
Oxidative stress biomarkers, especially glutathione peroxidase and glutathione,
may predict the course of cognitive decline in patients with AD or other
neurodegenerative disorders.
PMID- 25589717
TI - Plasma Complement factor H in Alzheimer's Disease.
AB - Biomarkers for Alzheimer's disease (AD) should meet several criteria, including
simplicity of testing. Inappropriate activation of the complement cascade has
been implicated in the pathogenesis of AD. Complement factor H (CFH) is a
regulator of the cascade, but studies on plasma CFH levels in AD have provided
mixed results. This study compared plasma CFH levels in 317 AD cases with 254
controls using an immunodiffusion assay. The sample had an 80% power to detect a
difference of 23 mg/L between cases and controls, but no difference was evident.
Plasma CFH may not be a suitable biomarker for AD.
PMID- 25589718
TI - Inhibition of Protein Phosphatase-2A (PP2A) by I1PP2A Leads to
Hyperphosphorylation of Tau, Neurodegeneration, and Cognitive Impairment in Rats.
AB - Protein phosphatase-2A (PP2A) deficiency is a cause of the abnormal
hyperphosphorylation of tau, which composes neurofibrillary tangles (NFTs) in
Alzheimer's disease (AD) brain. We previously reported that both mRNA and protein
expression of inhibitor I of PP2A (I(1)(PP2A)) are elevated in AD brain and that
this inhibitor induces a dose-dependent inhibition of PP2A activity and tau
hyperphosphorylation in NIH3T3 cells. However, whether I(1)(PP2A) can induce AD
neurofibrillary degeneration and cognitive impairment was not known. In the
present study, we infected the brains of rat pups within 24 hours of birth with
adeno-associated virus serotype 1 (AAV1) carrying I(1)(PP2A). In the adult AAV1
I(1)(PP2A) rats, we found a decrease in PP2A activity and abnormal
hyperphosphorylation of tau in the brain. Immunohistochemistry showed a
significant reduction of MAP2 and synapsin 1 in AAV1- I(1)(PP2A) animals,
suggesting that I(1)(PP2A) can induce a loss of dendritic and synaptic plasticity
markers. Behavioral tests revealed that infection with AAV1- I(1)(PP2A) induced
deficits in exploratory activity, spatial reference memory, and memory
consolidation in adult rats. These studies suggest that I(1)(PP2A) can inhibit
PP2A activity, and in turn induce AD neurofibrillary degeneration and cognitive
deficits in rats.
PMID- 25589719
TI - A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition
and Mood in Alzheimer's Disease.
AB - BACKGROUND: Increasing evidence points toward the efficacy of nutritional
modifications in delaying cognitive decline and mood/behavioral difficulties in
Alzheimer's disease (AD). Nutritional supplementation with individual agents has
shown varied results suggesting the need for combinatorial intervention.
OBJECTIVE: We set out to determine whether nutritional intervention could
positively impact cognitive performance and behavioral difficulties for
individuals diagnosed with AD. METHODS: A double-blind, multi-site, phase II
study (ClinicalTrials.gov NCT01320527; Alzheimer's Association Trialmatch) was
conducted in which 106 individuals with AD were randomized to a nutraceutical
formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl
cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open
label extension where participants received NF for 6 additional months. RESULTS:
The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p =
0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722,
2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric
Inventory. Both cohorts improved or maintained baseline performance during open
label extensions. Activities of Daily Living did not change for either cohort.
CONCLUSIONS: These findings extend phase I studies where NF maintained or
improved cognitive performance and mood/behavior.
PMID- 25589720
TI - Neuroprotective effects of hydrated fullerene C60: cortical and hippocampal EEG
interplay in an amyloid-infused rat model of Alzheimer's disease.
AB - We studied the effects of fullerene C60 nanoparticles, namely hydrated fullerene
C60 (C60HyFn), on interrelations between EEG frequency spectra from the frontal
cortex and the dorsal hippocampus (CA1) on an amyloid-beta (Abeta) rat model of
Alzheimer's disease (AD). Infusion of Abeta1-42 protein (1.5 MUl) into the CA1
region two weeks before EEG testing diminished hippocampal theta (3.8-8.4 Hz)
predominance and eliminated cortical beta (12.9-26.2 Hz) predominance observed in
baseline EEG of rats infused with saline (control) or with C60HyFn alone. In
contrast, these Abeta1-42 effects were abolished in rats pretreated with C60HyFn,
30 min apart. Dopaminergic mediation in AD has been shown to be involved in
neuronal plasticity and Abeta transformation in different ways. To clarify its
role in the cortex-hippocampus interplay in the Abeta model of AD, we used
peripheral injection of a dopamine agonist, apomorphine (APO), at a low dose (0.1
mg/kg). In rats infused with C60HyFn or Abeta1-42 alone, APO attenuated the
cortical beta predominance, with immediate and delayed phases evident in the
Abeta1-42-rats. Pretreatment with C60HyFn diminished the APO effect in the Abeta1
42-treated rats. Thus, we show that intrahippocampal injection of Abeta1-42
dramatically disrupts cortical versus hippocampal EEG interrelations and that
pretreatment with the fullerene eliminates this abnormality. We suggest that some
effects of C60HyFn may be mediated through presynaptic dopamine receptors and
that water-soluble C60 fullerenes have a neuroprotective potential.
PMID- 25589722
TI - Localization and Trafficking of Amyloid-beta Protein Precursor and Secretases:
Impact on Alzheimer's Disease.
AB - Alzheimer's disease (AD) affects almost 35 million people worldwide. One of the
neuropathological features of AD is the presence of extracellular amyloid
plaques, which are mainly composed of amyloid-beta (Abeta) peptides. These
peptides derive from the amyloidogenic proteolytic processing of the amyloid-beta
protein precursor (AbetaPP), through the sequential action of beta- and gamma
secretases. However, AbetaPP can also be cleaved by a non-amyloidogenic pathway,
involving an alpha-secretase, and in this case the Abeta formation is precluded.
The production of Abeta and of other AbetaPP catabolites depends on the spatial
and temporal co-localization of AbetaPP with alpha- or beta-secretases and gamma
secretase, which traffic through the secretory pathway in a highly regulated
manner. Disturbances on AbetaPP and secretases intracellular trafficking and,
consequently, in their localization may affect dynamic interactions between these
proteins with consequences in the AD pathogenesis. In this article, we critically
review the recent knowledge about the trafficking and co-localization of AbetaPP
and related secretases in the brain under physiological and AD conditions. A
particular focus is given to data concerning the distribution of AbetaPP and
secretases in different types of synapses relatively to other neuronal or glial
localizations. Furthermore, we discuss some possible signals that govern the
dynamic encounter of AbetaPP with each group of secretases, such as AbetaPP
mutations, estrogen deprivation, chronic stress, metabolic impairment, and
alterations in sleep pattern-associated with aging. The knowledge of key signals
that are responsible for the shifting of AbetaPP processing away from alpha
secretases and toward the beta-secretases might be useful to develop AD
therapeutic strategies.
PMID- 25589721
TI - Calcium signaling, excitability, and synaptic plasticity defects in a mouse model
of Alzheimer's disease.
AB - Alzheimer's disease (AD) and aging result in impaired ability to store memories,
but the cellular mechanisms responsible for these defects are poorly understood.
Presenilin 1 (PS1) mutations are responsible for many early-onset familial AD
(FAD) cases. The phenomenon of hippocampal long-term potentiation (LTP) is widely
used in studies of memory formation and storage. Recent data revealed long-term
LTP maintenance (L-LTP) is impaired in PS1-M146V knock-in (KI) FAD mice. To
understand the basis for this phenomenon, in the present study we analyzed
structural synaptic plasticity in hippocampal cultures from wild type (WT) and KI
mice. We discovered that exposure to picrotoxin induces formation of mushroom
spines in both WT and KI cultures, but the maintenance of mushroom spines is
impaired in KI neurons. This maintenance defect can be explained by an abnormal
firing pattern during the consolidation phase of structural plasticity in KI
neurons. Reduced frequency of neuronal firing in KI neurons is caused by enhanced
calcium-induced calcium release (CICR), enhanced activity of calcium-activated
potassium channels, and increased afterhyperpolarization. As a result,
"consolidation" pattern of neuronal activity converted to "depotentiation"
pattern of neuronal activity in KI neurons. Consistent with this model, we
demonstrated that pharmacological inhibitors of CICR (dantrolene), of calcium
activated potassium channels (apamin), and of calcium-dependent phosphatase
calcineurin (FK506) are able to rescue structural plasticity defects in KI
neurons. Furthermore, we demonstrate that incubation with dantrolene or apamin
also rescued L-LTP defects in KI hippocampal slices, suggesting a role for a
similar mechanism. This proposed mechanism may be responsible for memory defects
in AD but also for age-related memory decline.
PMID- 25589724
TI - Clinical and Neuropsychological Comparisons of Early-Onset Versus Late-Onset
Frontotemporal Dementia: A CREDOS-FTD Study.
AB - BACKGROUND: Cognitive performance changes with chronological aging. Previous
studies investigating clinical heterogeneity in frontotemporal dementia (FTD)
according to the age of symptom onset did not consider the effect of
chronological aging on cognition. OBJECTIVE: We compared cognitive and behavioral
symptoms in patients with early-onset (EO) and late-onset (LO) FTD with
consideration of chronological aging effect. METHODS: A total of 166 FTD patients
were enrolled consecutively from multi-center memory clinics using a nationwide
FTD register. To control for the effects of chronological aging on
neuropsychological scores, seven hundred and two subjects with normal cognition
were also enrolled and regression models were set up. Neuropsychological scores
that were detrended with the regression models and the behavioral symptoms of the
EO-FTD and LO-FTD groups were compared. Subgroup analyses were performed for
three main subtypes of FTD, behavioral variant frontotemporal dementia (bvFTD),
semantic dementia (SD), and progressive non-fluent aphasia (PNFA). RESULTS: Among
166 FTD patients, there were 76 bvFTD, 57 SD, and 33 PNFA patients who met new
diagnostic criteria for bvFTD or primary progressive aphasia, respectively. LO
FTD (48.2%) was more common than previously thought and the proportions of EO and
LO groups differed across FTD subtypes. EO-FTD patients had lower memory and
frontal/executive scores and more prominent frontal/behavioral symptoms than LO
FTD patients. CONCLUSION: Our study suggested that FTD could be heterogeneous
with respect the age of symptom onset. After controlling for the effects of
chronological aging, EO-FTD patients exhibited more profound memory and
frontal/executive dysfunction and more behavioral symptoms than LO-FTD patients.
PMID- 25589723
TI - Prediction of Outcomes in Mild Cognitive Impairment by Using 18F-FDG-PET: A
Multicenter Study.
AB - BACKGROUND: 18F-FDG-PET is defined as a biomarker of neuronal injury according to
the revised National Institute on Aging-Alzheimer's Association criteria.
OBJECTIVE: The objective of this multicenter prospective cohort study was to
examine the value of 18F-FDG-PET in predicting the development of Alzheimer's
disease (AD) in patients with mild cognitive impairment (MCI). METHODS: In total,
114 patients with MCI at 9 participating institutions underwent clinical and
neuropsychological examinations, MRI, and 18F-FDG-PET at baseline. The cases were
visually classified into predefined dementia patterns by three experts.
Anautomated analysis for 18F-FDG-PET was also performed to calculate the PET
score. Subjects were followed periodically for 3 years, and progression to
dementia was evaluated. RESULTS: In 47% of the patients with MCI, progression of
symptoms justified the clinical diagnosis of "probable AD". The PET visual
interpretation predicted conversion to AD during 3-year follow-up with an overall
diagnostic accuracy of 68%. Overall diagnostic accuracy of the PET score was
better than that of PET visual interpretation at all follow-up intervals, and the
optimized PET score threshold revealed the best performance at the 2-year follow
up interval with an overall diagnostic accuracy of 83%,a sensitivity of 70%, and
a specificity of 90%. Multivariate logistic regression analysis identified the
PET score as the most significant predictive factor distinguishing AD converters
from non-converters. CONCLUSION: The PET score is the most statistically
significant predictive factor for conversion from MCI to AD, and the diagnostic
performance of the PET score is more promising for rapid converters over 2 years.
PMID- 25589725
TI - Impairment of age estimation from faces in Alzheimer's disease.
AB - A prerequisite for any function in social cognition is the perception and
processing of social cues. Age estimation is a skill that is used in everyday
life and is fundamental in social interactions. This study evaluated whether
facial age estimation is impaired in patients with mild to moderate Alzheimer's
disease (AD). The current age of faces is known to have an impact on age
estimation, and therefore stimuli belonging to different age groups (young,
middle-aged, and older adults' faces) were used. As expected, an impairment of
age estimation from faces was observed in mild to moderate AD patients. However,
the profile of impairment depended on the age of faces and stage of the disease.
Mild AD patients presented difficulties mainly in assessing the age of middle
aged adults. In moderate disease stage, these difficulties also affected the age
estimation of young adult faces. Interestingly, AD patients remained relatively
good at estimating the age of older adults' faces, compared to healthy controls.
PMID- 25589726
TI - Structural and regulatory elements of the interaction between amyloid-beta
protein precursor and Homer3.
AB - Amyloid-beta protein precursor (AbetaPP) metabolism and the accumulation of its
derivative amyloid-beta (Abeta) peptide in senile plaques have been considered
key players in the development of Alzheimer's disease (AD). However, the
mechanisms underlying the generation and the deposition of Abeta are not clear
but emphasis has been given in the role of AbetaPP protein interactions that
regulate its processing and offer a means to manipulate Abeta production. We have
previously shown that AbetaPP interacts with members of the Homer protein family,
which leads to inhibition of Abeta generation. Herein, we studied the structural
parameters of AbetaPP/Homer3 interaction by analyzing the sequences and domains
that play a role in the formation of the complex. We found that the cytoplasmic
tail of AbetaPP is necessary for the interaction. Regarding Homer3, we report
that both the EVH1 protein interacting domain and the polymerization coiled coil
domain are essential for the complex assembly. Importantly, phosphorylation of
Homers at certain serine residues seems to enhance the interaction with AbetaPP,
possibly underlying our recent work suggesting that calcium signaling also
regulates the interaction. Our results show that the regulation of AbetaPP/Homer3
interaction might be critical in the context of Alzheimer's disease pathology as
a novel target for regulating AbetaPP function and metabolism.
PMID- 25589727
TI - Different Patterns of Theory of Mind Impairment in Mild Cognitive Impairment.
AB - Theory of Mind refers to the ability to infer other's mental states, their
beliefs, intentions, or knowledge. To date, only two studies have reported the
presence of Theory of Mind impairment in mild cognitive impairment (MCI). In the
present study,we evaluated 20 MCI patients and compared them with 25 healthy
control participants using two Theory of Mind tasks. The first task was a false
belief paradigm as frequently used in the literature, and the second one was a
referential communication task,assessing Theory of Mind in a real situation of
interaction and which had never been used before in this population. The results
showed that MCI patients presented difficulties inferring another person's
beliefs about reality and attributing knowledge to them in a situation of real
life interaction. Two different patterns of Theory of Mind emerged among the
patients. In comparison with the control group, some MCI patients demonstrated
impairment only in the interaction task and presented isolated episodicmemory
impairment, while others were impaired in both Theory of Mind tasks and presented
cognitive impairment impacting both episodic memory and executive functioning.
Theory of Mind is thus altered in the very early stages of cognitive impairment
even in real social interaction, which could impact precociously relationships in
daily life.
PMID- 25589728
TI - Predictive factors of clinical response to cholinesterase inhibitors in mild and
moderate Alzheimer's disease and mixed dementia: a one-year naturalistic study.
AB - BACKGROUND: Naturalistic studies evaluate individuals in their usual way of
living, presenting more "real-life" data regarding patients and their diseases.
OBJECTIVE: To investigate demographic, clinical, and genetic factors that could
be predictive of good response to cholinesterase inhibitors (ChEI) treatment in
Alzheimer's disease (AD) and AD + cerebrovascular disease (CVD). PATIENTS AND
METHODS: A total of 129 patients were diagnosed with AD or AD + CVD and with mild
to-moderate dementia. After a 12-month treatment, 97 patients completed the
study. They were evaluated at baseline and after three, six, and 12 months of
ChEI (donepezil or rivastigmine or galantamine) use. APOE genotype and CYP2D6
polymorphisms were determined for all of the participants. In each visit, we used
cognitive, functional, mood, and behavior scales. We classified patients
according to their scores in the Mini-Mental State Examination (MMSE). Good
responders were defined as those scoring >=2 in the MMSE at 12 months. RESULTS:
The rate of good clinical response was 27.8%. In a longitudinal analysis, the
patients with mild AD and also good responders at three months were considered to
be good responders at 12 months. There was no correlation between ChEI dose, APOE
and CYP2D6 polymorphisms, and the pattern of clinical response. CONCLUSION: A
higher rate of good response was observed in this study compared to that in
previous investigations. The pharmacogenetic aspects do not seem to have an
influence in the response.
PMID- 25589730
TI - Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.
AB - The concept of molecular mimicry was established to explain commonalities of
structure which developed in response to evolutionary pressures. Most examples of
molecular mimicry in medicine have involved homologies of primary protein
structure which cause disease. Molecular mimicry can be expanded beyond amino
acid sequence to include microRNA and proteomic effects which are either
pathogenic or salutogenic (beneficial) in regard to Parkinson's disease,
Alzheimer's disease, and related disorders. Viruses of animal or plant origin may
mimic nucleotide sequences of microRNAs and influence protein expression. Both
Parkinson's and Alzheimer's diseases involve the formation of transmissible self
propagating prion-like proteins. However, the initiating factors responsible for
creation of these misfolded nucleating factors are unknown. Amyloid patterns of
protein folding are highly conserved through evolution and are widely distributed
in the world. Similarities of tertiary protein structure may be involved in the
creation of these prion-like agents through molecular mimicry. Cross-seeding of
amyloid misfolding, altered proteostasis, and oxidative stress may be induced by
amyloid proteins residing in bacteria in our microbiota in the gut and in the
diet. Pathways of molecular mimicry induced processes induced by bacterial
amyloid in neurodegeneration may involve TLR 2/1, CD14, and NFkappaB, among
others. Furthermore, priming of the innate immune system by the microbiota may
enhance the inflammatory response to cerebral amyloids (such as amyloid-beta and
alpha-synuclein). This paper describes the specific molecular pathways of these
cross-seeding and neuroinflammatory processes. Evolutionary conservation of
proteins provides the opportunity for conserved sequences and structures to
influence neurological disease through molecular mimicry.
PMID- 25589731
TI - Serum miR-206 and miR-132 as Potential Circulating Biomarkers for Mild Cognitive
Impairment.
AB - MicroRNAs (miRNAs), a class of small, non-coding RNA molecules with gene
regulatory functions, have emerged to play a critical role in the pathogenesis of
a variety of diseases. Recently, circulating miRNAs have been reported as
potential biomarkers for various pathologic conditions. The present study was
performed to investigate the potential role of circulating miRNAs as diagnostic
biomarkers for mild cognitive impairment (MCI). We collected 66 patients with MCI
and 76 normal controls from our previous cross-sectional cohort study. Seven
miRNAs (miR-206, miR-132, miR-193b, miR-130b, miR-20a, miR-296, and miR-329)
related to Alzheimer's disease (AD) were detected in serum using a quantitative
real-time PCR (qRT-PCR) method. Each miRNA's diagnostic performance was evaluated
by receiver operating characteristic curves and the areas under curves (AUC)
analysis. The levels of miR-206 and miR-132 in MCI patients' serum were
significantly elevated compared to normal controls. Combining detection of miR
206 and miR-132 achieved the highest AUC of 0.981, followed by test of miR-206
(AUC = 0.880) and miR-132 (AUC = 0.912) separately. Importantly, miR-206 and miR
132 were respectively correlated with the Montreal Cognitive Assessment score in
MCI patients. These results preliminarily indicated that circulating miR-206 and
miR-132 as novel miRNAs upregulated in MCI patient were potential biomarkers for
diagnosis of MCI.
PMID- 25589729
TI - Partial Loss of the Glutamate Transporter GLT-1 Alters Brain Akt and Insulin
Signaling in a Mouse Model of Alzheimer's Disease.
AB - The glutamate transporter GLT-1 (also called EAAT2 in humans) plays a critical
role in regulating extracellular glutamate levels in the central nervous system
(CNS). In Alzheimer's disease (AD), EAAT2 loss is associated with neuropathology
and cognitive impairment. In keeping with this, we have reported that partial GLT
1 loss (GLT-1+/-) causes early-occurring cognitive deficits in mice harboring
familial AD AbetaPPswe/PS1DeltaE9 mutations. GLT-1 plays important roles in
several molecular pathways that regulate brain metabolism, including Akt and
insulin signaling in astrocytes. Significantly, AD pathogenesis also involves
chronic Akt activation and reduced insulin signaling in the CNS. In this report
we tested the hypothesis that GLT-1 heterozygosity (which reduces GLT-1 to levels
that are comparable to losses in AD patients) in AbetaPPswe/PS1DeltaE9 mice would
induce sustained activation of Akt and disturb components of the CNS insulin
signaling cascade. We found that partial GLT-1 loss chronically increased Akt
activation (reflected by increased phosphorylation at serine 473), impaired
insulin signaling (reflected by decreased IRbeta phosphorylation of tyrosines
1150/1151 and increased IRS-1 phosphorylation at serines 632/635 - denoted as
636/639 in humans), and reduced insulin degrading enzyme (IDE) activity in brains
of mice expressing familial AbetaPPswe/PS1DeltaE9 AD mutations. GLT-1 loss also
caused an apparent compensatory increase in IDE activity in the liver, an organ
that has been shown to regulate peripheral amyloid-beta levels and expresses GLT
1. Taken together, these findings demonstrate that partial GLT-1 loss can cause
insulin/Akt signaling abnormalities that are in keeping with those observed in
AD.
PMID- 25589732
TI - Luteolin Reduces BACE1 Expression through NF-kappaB and through Estrogen Receptor
Mediated Pathways in HEK293 and SH-SY5Y Cells.
AB - Beta-secretase (BACE1) controls an essential step for the generation of amyloid-
peptide (Abeta). As Abeta forms the principle pathologies in Alzheimer's disease,
lowering A production by inhibiting BACE1 is a plausible therapeutic approach. In
the present study, we identified a natural polyphenol, luteolin, as a potent
inhibitor of BACE1 transcription inhuman embryonic kidney 293 (HEK293) and human
neuroblastoma (SH-SY5Y) cell lines. Luteolin is capable of suppressing the
activation of BACE1 promoter by NF-kappaB signaling. We further characterized
that luteolin interferes with NF-kappaB signaling by with both directly and
indirectly disrupting p65 complex formation. In addition, we discovered that
estrogen receptor mediates luteolin's effect in inhibiting NF-kappaB signaling
inhibiting and BACE1 transcription. Interestingly, the beneficial effects of
luteolin may be attributed to selective activation profiles of luteolin to
different estrogen receptor subtypes. Our study reports luteolin as a potent
BACE1-inhibiting compound, providing useful information in understanding estrogen
receptor- and NF-kappaB-mediated signaling and in regulating BACE1 expression.
PMID- 25589735
TI - Salipiger nanhaiensis sp. nov., a bacterium isolated from deep sea water.
AB - A Gram-stain-negative, facultatively anaerobic, chemoheterotrophic, moderately
halophilic, exopolysaccharide (EPS)-producing, cream, non-motile and rod-shaped
bacterium, designated strain ZH114(T), was isolated from deep water of the South
China Sea, and was subjected to a polyphasic taxonomic study. Phylogenetic
analysis, based on 16S rRNA gene sequences, indicated that this strain belongs to
the genus Salipiger with the highest sequence similarity to Salipiger mucescens
LMG 22090(T) (96.83%), followed by Pseudodonghicola xiamenensis LMG 24574(T)
(96.12%). Growth occurred at 4-37 degrees C (optimum 32 degrees C), pH 6.0-10.0
(optimum pH 9.0-10.0) and in the presence of 0-19% NaCl (w/v) (optimum 6%, w/v).
It did not produce poly-beta-hydroxyalkanoate granules or bacteriochlorophyll a.
Acid was produced from glycerol, erythrose, ribose, D-xylose, galactose, glucose,
fructose, mannitol, cellobiose, maltose, lactose, melibiose, turanose, D-lyxose,
D-tagatose, D-fucose, D-arabitol and L-arabitol after inoculating for 24 h and
weakly positive results were also detected after 48 h in API 50CH strips with D
arabinose, L-arabinose, L-xylose, adonitol, mannose, aesculin, salicin, sucrose,
mycose and L-fucose. The predominant fatty acids were C(18 : 1)omega7c and/or
C(18 : 1)omega6c, C(16 : 0), C(18 : 0) and 11-methyl C(18 : 1)omega7c. The major
polar lipids of ZH114(T) were phosphatidylglycerol, diphosphatidylglycerol,
phosphatidylethanolamine and two unidentified lipids. The major respiratory
quinone was ubiquinone Q-10. The genomic DNA G+C content of strain ZH114(T) was
63.8 mol%. Based on this phenotypic, chemotaxonomic and phylogenetic analysis,
strain ZH114(T) should be classified as a representative of a novel species of
the genus Salipiger , for which the name Salipiger nanhaiensis sp. nov. is
proposed. The type strain is ZH114(T) ( = JCM 19383(T) = KCTC 32468(T)).
PMID- 25589734
TI - Sinomonas susongensis sp. nov., isolated from the surface of weathered biotite.
AB - A novel actinomycete, designated strain A31(T), was isolated from the surface of
weathered biotite in Susong, Anhui Province, China. The organism grew optimally
at 30 degrees C, at pH 8.0 and with 1% (w/v) NaCl. Strain A31(T) had A3alpha as
the cell-wall peptidoglycan type and galactose, mannose and rhamnose as whole
cell sugars. Anteiso-C(15 : 0) and anteiso-C(17 : 0) were the major cellular
fatty acids and MK-9(H2) was the predominant respiratory quinone. In addition,
the total polar lipids were diphosphatidylglycerol, phosphatidylglycerol,
phosphatidylinositol, phosphatidylmonomethylethanolamine and four glycolipids.
The genomic DNA G+C content of strain A31(T) was 70.8 mol%. Phylogenetic analysis
based on 16S rRNA gene sequences showed that strain A31(T) was related most
closely to Sinomonas albida LC13(T) (98.3% similarity), Sinomonas atrocyanea DSM
20127(T) (98.2%), Sinomonas soli CW 59(T) (98.1%), Sinomonas flava CW 108(T)
(97.8%), 'Sinomonas mesophila' MPKL 26 (97.3%), Sinomonas echigonensis LC10(T)
(97.1%) and ' Sinomonas notoginsengisoli ' SYP-B575 (96.7%). DNA-DNA
hybridization studies with the new isolate showed relatedness values of 16.0
56.6% with its six closest neighbours. Based on phenotypic, chemotaxonomic and
phylogenetic analysis, strain A31(T) represents a novel species of the genus
Sinomonas , for which the name Sinomonas susongensis sp. nov. is proposed. The
type strain is A31(T) ( = DSM 28245(T) = CCTCC AB 2014068(T)).
PMID- 25589736
TI - Response to Tindall (2014) on the legitimacy of the names Solimonadaceae Losey et
al. 2013, Xanthomonadaceae Saddler and Bradbury 2005 and Xanthomonadales Saddler
and Bradbury 2005.
PMID- 25589737
TI - Jiella aquimaris gen. nov., sp. nov., isolated from offshore surface seawater.
AB - A Gram-stain-negative, strictly aerobic and rod-shaped motile bacterium with
peritrichous flagella, designated strain LZB041(T), was isolated from offshore
surface seawater of the East China Sea. Phylogenetic analysis based on 16S rRNA
gene sequences indicated that strain LZB041(T) formed a lineage within the family
' Aurantimonadaceae' that was distinct from the most closely related genera
Aurantimonas (96.0-96.4% 16S rRNA gene sequence similarity) and Aureimonas (94.5
96.0%). Optimal growth occurred in the presence of 1-7% (w/v) NaCl, at pH 7.0-8.0
and at 28-37 degrees C. Ubiquinone-10 was the predominant respiratory quinone.
The major fatty acids (>10% of total fatty acids) were C(18 : 1)omega7c and/or
C(18 : 1)omega6c (summed feature 8) and cyclo-C(19 : 0)omega8c. The major polar
lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine,
phosphatidylethanolamine, phosphatidylmonomethylethanolamine, one unknown
aminolipid, one unknown phospholipid and one unknown polar lipid. The DNA G+C
content of strain LZB041(T) was 71.3 mol%. On the basis of polyphasic analysis,
strain LZB041(T) is considered to represent a novel species of a new genus in the
class Alphaproteobacteria , for which the name Jiella aquimaris gen. nov., sp.
nov. is proposed. The type strain of the type species is LZB041(T) ( = JCM
30119(T) = MCCC 1K00255(T)).
PMID- 25589739
TI - Guidance of movements by prior experience: a Bayesian account of reach
performance.
PMID- 25589738
TI - A new method for estimating species age supports the coexistence of malaria
parasites and their Mammalian hosts.
AB - Species in the genus Plasmodium cause malaria in humans and infect a variety of
mammals and other vertebrates. Currently, estimated ages for several mammalian
Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy
that frustrates reliable estimation of evolutionary rates of disease-related
traits. We developed a novel statistical approach to dating the relative age of
evolutionary lineages, based on Total Least Squares regression. We validated this
lineage dating approach by applying it to the genus Drosophila. Using data from
the Drosophila 12 Genomes project, our approach accurately reconstructs the age
of well-established Drosophila clades, including the speciation event that led to
the subgenera Drosophila and Sophophora, and age of the melanogaster species
subgroup. We applied this approach to hundreds of loci from seven mammalian
Plasmodium species. We demonstrate the existence of a molecular clock specific to
individual Plasmodium proteins, and estimate the relative age of mammalian
infecting Plasmodium. These analyses indicate that: 1) the split between the
human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred
6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of
humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites
originated 22 times earlier than the split between P. falciparum and P.
reichenowi. Calibrating the absolute divergence times for Plasmodium with
eukaryotic substitution rates, we show that the split between P. falciparum and
P. reichenowi occurred 3.0-5.5 Ma, and that mammalian Plasmodium parasites
originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium
evolved contemporaneously with their hosts, with little evidence for parasite
host-switching on an evolutionary scale, and provide a solid timeframe within
which to place the evolution of new Plasmodium species.
PMID- 25589740
TI - The palmitoyl acyltransferase DHHC2 regulates recycling endosome exocytosis and
synaptic potentiation through palmitoylation of AKAP79/150.
AB - Phosphorylation and dephosphorylation of AMPA-type ionotropic glutamate receptors
(AMPARs) by kinases and phosphatases and interactions with scaffold proteins play
essential roles in regulating channel biophysical properties and trafficking
events that control synaptic strength during NMDA receptor-dependent synaptic
plasticity, such as LTP and LTD. We previously demonstrated that palmitoylation
of the AMPAR-linked scaffold protein A-kinase anchoring protein (AKAP) 79/150 is
required for its targeting to recycling endosomes in dendrites, where it
regulates exocytosis from these compartments that is required for LTP-stimulated
enlargement of postsynaptic dendritic spines, delivery of AMPARs to the plasma
membrane, and maintenance of synaptic potentiation. Here, we report that the
recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and
palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms. In
particular, RNAi-mediated knockdown of DHHC2 expression in rat hippocampal
neurons disrupted stimulation of exocytosis from recycling endosomes, enlargement
of dendritic spines, AKAP recruitment to spines, and potentiation of AMPAR
mediated synaptic currents that occur during LTP. Importantly, expression of a
palmitoylation-independent lipidated AKAP mutant in DHHC2-deficient neurons
largely restored normal plasticity regulation. Thus, we conclude that DHHC2
AKAP79/150 signaling is an essential regulator of dendritic recycling endosome
exocytosis that controls both structural and functional plasticity at excitatory
synapses.
PMID- 25589741
TI - Neuropathic pain is constitutively suppressed in early life by anti-inflammatory
neuroimmune regulation.
AB - Peripheral nerve injury can trigger neuropathic pain in adults but not in
infants; indeed, for unknown reasons, neuropathic pain is rare before
adolescence. We show here that the absence of neuropathic pain response in infant
male rats and mice following nerve injury is due to an active, constitutive
immune suppression of dorsal horn pain activity. In contrast to adult nerve
injury, which triggers a proinflammatory immune response in the spinal dorsal
horn, infant nerve injury triggers an anti-inflammatory immune response,
characterized by significant increases in IL-4 and IL-10. This immediate anti
inflammatory response can also be evoked by direct C-fiber nerve stimulation in
infant, but not adult, mice. Blockade of the anti-inflammatory activity with
intrathecal anti-IL10 unmasks neuropathic pain behavior in infant nerve injured
mice, showing that pain hypersensitivity in young mice is actively suppressed by
a dominant anti-inflammatory neuroimmune response. As infant nerve injured mice
reach adolescence (postnatal day 25-30), the dorsal horn immune profile switches
from an anti-inflammatory to a proinflammatory response characterized by
significant increases in TNF and BDNF, and this is accompanied by a late onset
neuropathic pain behavior and increased dorsal horn cell sensitivity to cutaneous
mechanical and cold stimuli. These findings show that neuropathic pain following
early life nerve injury is not absent but suppressed by neuroimmune activity and
that "latent" pain can still emerge at adolescence, when the neuroimmune profile
changes. The data may explain why neuropathic pain is rare in young children and
also why it can emerge, for no observable reason, in adolescent patients.
PMID- 25589742
TI - Necessary, yet dissociable contributions of the insular and ventromedial
prefrontal cortices to norm adaptation: computational and lesion evidence in
humans.
AB - Social norms and their enforcement are fundamental to human societies. The
ability to detect deviations from norms and to adapt to norms in a changing
environment is therefore important to individuals' normal social functioning.
Previous neuroimaging studies have highlighted the involvement of the insular and
ventromedial prefrontal (vmPFC) cortices in representing norms. However, the
necessity and dissociability of their involvement remain unclear. Using model
based computational modeling and neuropsychological lesion approaches, we
examined the contributions of the insula and vmPFC to norm adaptation in seven
human patients with focal insula lesions and six patients with focal vmPFC
lesions, in comparison with forty neurologically intact controls and six brain
damaged controls. There were three computational signals of interest as
participants played a fairness game (ultimatum game): sensitivity to the fairness
of offers, sensitivity to deviations from expected norms, and the speed at which
people adapt to norms. Significant group differences were assessed using
bootstrapping methods. Patients with insula lesions displayed abnormally low
adaptation speed to norms, yet detected norm violations with greater sensitivity
than controls. Patients with vmPFC lesions did not have such abnormalities, but
displayed reduced sensitivity to fairness and were more likely to accept the most
unfair offers. These findings provide compelling computational and lesion
evidence supporting the necessary, yet dissociable roles of the insula and vmPFC
in norm adaptation in humans: the insula is critical for learning to adapt when
reality deviates from norm expectations, and that the vmPFC is important for
valuation of fairness during social exchange.
PMID- 25589743
TI - Leptin receptor signaling in the hypothalamus regulates hepatic autonomic nerve
activity via phosphatidylinositol 3-kinase and AMP-activated protein kinase.
AB - Leptin action in the brain has emerged as an important regulator of liver
function independently from its effects on food intake and body weight. The
autonomic nervous system plays a key role in the regulation of physiological
processes by leptin. Here, we used direct recording of nerve activity from
sympathetic or vagal nerves subserving the liver to investigate how brain action
of leptin controls hepatic autonomic nerve activity. Intracerebroventricular
(ICV) administration of leptin activated hepatic sympathetic traffic in rats and
mice in dose- and receptor-dependent manners. The hepatic sympatho-excitatory
effects of leptin were also observed when leptin was microinjected directly into
the arcuate nucleus (ARC), but not into the ventromedial hypothalamus (VMH).
Moreover, using pharmacological and genetic approaches, we show that leptin
induced increase in hepatic sympathetic outflow depends on PI3K but not AMP
activated protein kinase (AMPK), STAT3, or ERK1/2. Interestingly, ICV leptin also
increased hepatic vagal nerve activity in rats. We show that this response is
reproduced by intra-ARC, but not intra-VMH, leptin administration and requires
PI3K and AMPK. We conclude that central leptin signaling conveys the information
to the liver through the sympathetic and parasympathetic branches of the
autonomic nervous system. Our data also provide important insight into the
molecular events underlying leptin's control of hepatic autonomic nerve activity
by implicating PI3K and AMPK pathways.
PMID- 25589744
TI - fMRI and EEG predictors of dynamic decision parameters during human reinforcement
learning.
AB - What are the neural dynamics of choice processes during reinforcement learning?
Two largely separate literatures have examined dynamics of reinforcement learning
(RL) as a function of experience but assuming a static choice process, or
conversely, the dynamics of choice processes in decision making but based on
static decision values. Here we show that human choice processes during RL are
well described by a drift diffusion model (DDM) of decision making in which the
learned trial-by-trial reward values are sequentially sampled, with a choice made
when the value signal crosses a decision threshold. Moreover, simultaneous fMRI
and EEG recordings revealed that this decision threshold is not fixed across
trials but varies as a function of activity in the subthalamic nucleus (STN) and
is further modulated by trial-by-trial measures of decision conflict and activity
in the dorsomedial frontal cortex (pre-SMA BOLD and mediofrontal theta in EEG).
These findings provide converging multimodal evidence for a model in which
decision threshold in reward-based tasks is adjusted as a function of
communication from pre-SMA to STN when choices differ subtly in reward values,
allowing more time to choose the statistically more rewarding option.
PMID- 25589745
TI - Accounting for the delay in the transition from acute to chronic pain: axonal and
nuclear mechanisms.
AB - Acute insults produce hyperalgesic priming, a neuroplastic change in nociceptors
that markedly prolongs inflammatory mediator-induced hyperalgesia. After an acute
initiating insult, there is a 72 h delay to the onset of priming, for which the
underlying mechanism is unknown. We hypothesized that the delay is due to the
time required for a signal to travel from the peripheral terminal to the cell
body followed by a return signal to the peripheral terminal. We report that when
an inducer of hyperalgesic priming (monocyte chemotactic protein 1) is
administered at the spinal cord of Sprague Dawley rats, priming is detected at
the peripheral terminal with a delay significantly shorter than when applied
peripherally. Spinally induced priming is detected not only when prostaglandin E2
(PGE2) is presented to the peripheral nociceptor terminals, but also when it is
presented intrathecally to the central terminals in the spinal cord. Furthermore,
when an inducer of priming is administered in the paw, priming can be detected in
spinal cord (as prolonged hyperalgesia induced by intrathecal PGE2), but only
when the mechanical stimulus is presented to the paw on the side where the
priming inducer was administered. Both spinally and peripherally induced priming
is prevented by intrathecal oligodeoxynucleotide antisense to the nuclear
transcription factor CREB mRNA. Finally, the inhibitor of protein translation
reversed hyperalgesic priming only when injected at the site where PGE2 was
administered, suggesting that the signal transmitted from the cell body to the
peripheral terminal is not a newly translated protein, but possibly a newly
expressed mRNA.
PMID- 25589746
TI - Hemisphere-dependent attentional modulation of human parietal visual field
representations.
AB - Posterior parietal cortex contains several areas defined by topographically
organized maps of the contralateral visual field. However, recent studies suggest
that ipsilateral stimuli can elicit larger responses in the right than left
hemisphere within these areas, depending on task demands. Here we determined the
effects of spatial attention on the set of visual field locations (the population
receptive field [pRF]) that evoked a response for each voxel in human topographic
parietal cortex. A two-dimensional Gaussian was used to model the pRF in each
voxel, and we measured the effects of attention on not only the center (preferred
visual field location) but also the size (visual field extent) of the pRF. In
both hemispheres, larger pRFs were associated with attending to the mapping
stimulus compared with attending to a central fixation point. In the left
hemisphere, attending to the stimulus also resulted in more peripheral preferred
locations of contralateral representations, compared with attending fixation.
These effects of attention on both pRF size and preferred location preserved
contralateral representations in the left hemisphere. In contrast, attentional
modulation of pRF size but not preferred location significantly increased
representation of the ipsilateral (right) visual hemifield in right parietal
cortex. Thus, attention effects in topographic parietal cortex exhibit
hemispheric asymmetries similar to those seen in hemispatial neglect. Our
findings suggest potential mechanisms underlying the behavioral deficits
associated with this disorder.
PMID- 25589747
TI - Biomarkers of traumatic injury are transported from brain to blood via the
glymphatic system.
AB - The nonspecific and variable presentation of traumatic brain injury (TBI) has
motivated an intense search for blood-based biomarkers that can objectively
predict the severity of injury. However, it is not known how cytosolic proteins
released from traumatized brain tissue reach the peripheral blood. Here we show
in a murine TBI model that CSF movement through the recently characterized
glymphatic pathway transports biomarkers to blood via the cervical lymphatics.
Clinically relevant manipulation of glymphatic activity, including sleep
deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in
serum S100beta, GFAP, and neuron specific enolase. We conclude that routine TBI
patient management may limit the clinical utility of blood-based biomarkers
because their brain-to-blood transport depends on glymphatic activity.
PMID- 25589749
TI - Integration of Purkinje cell inhibition by cerebellar nucleo-olivary neurons.
AB - Neurons in the cerebellar cortex, cerebellar nuclei, and inferior olive (IO) form
a trisynaptic loop critical for motor learning. IO neurons excite Purkinje cells
via climbing fibers and depress their parallel fiber inputs. Purkinje cells
inhibit diverse cells in the cerebellar nuclei, including small GABAergic nucleo
olivary neurons that project to the IO. To investigate how these neurons
integrate synaptic signals from Purkinje cells, we retrogradely labeled nucleo
olivary cells in the contralateral interpositus and lateral nuclei with cholera
toxin subunit B-Alexa Fluor 488 and recorded their electrophysiological
properties in cerebellar slices from weanling mice. Nucleo-olivary cells fired
action potentials over a relatively narrow dynamic range (maximal rate, ~ 70
spikes/s), unlike large cells that project to premotor areas (maximal rate, ~ 400
spikes/s). GABA(A) receptor-mediated IPSCs evoked by electrical or optogenetic
stimulation of Purkinje cells were more than 10-fold slower in nucleo-olivary
cells (decay time, ~ 25 ms) than in large cells (~ 2 ms), and repetitive
stimulation at 20-150 Hz evoked greatly summating IPSCs. Nucleo-olivary firing
rates varied inversely with IPSP frequency, and the timing of Purkinje IPSPs and
nucleo-olivary spikes was uncorrelated. These attributes contrast with large
cells, whose brief IPSCs and rapid firing rates can permit well timed
postinhibitory spiking. Thus, the intrinsic and synaptic properties of these two
projection neurons from the cerebellar nuclei tailor them for differential
integration and transmission of their Purkinje cell input.
PMID- 25589750
TI - Appraisal of brain connectivity in radiologically isolated syndrome by modeling
imaging measures.
AB - We hypothesized that appraisal of brain connectivity may shed light on the
substrate of the radiologically isolated syndrome (RIS), a term applied to
asymptomatic subjects with brain MRI abnormalities highly suggestive of multiple
sclerosis. We thus used a multimodal MRI approach on the human brain by modeling
measures of microstructural integrity of white matter (WM) tracts with those of
functional connectivity (FC) at the level of resting state networks in RIS
subjects, demographically matched normal controls (NC), and relapsing-remitting
(RR) MS patients, also matched with RIS for brain macrostructural damage (i.e.,
lesions and atrophy). Compared with NC, in both RIS subjects and MS patients
altered integrity of WM tracts was present. However, RIS subjects showed, at a
less conservative threshold, lower diffusivities than RRMS patients in distinct
cerebral associative, commissural, projection, and cerebellar WM tracts,
suggesting a relatively better anatomical connectivity. FC was similar in NC and
RIS subjects, even in the presence of important risk factors for MS (spinal cord
lesions, oligoclonal bands, and dissemination in time on MRI) and increased in
RRMS patients in two clinically relevant networks subserving "processing"
(sensorimotor) and "control" (working memory) functions. In RIS, the lack of
functional reorganization in key brain networks may represent a model of
"functional reserve," which may become upregulated, with an adaptive or
maladaptive role, only at a later stage in case of occurrence of clinical
deficit.
PMID- 25589748
TI - Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.
AB - In conscious mammals, hypoxia or hypercapnia stimulates breathing while
theoretically exerting opposite effects on central respiratory chemoreceptors
(CRCs). We tested this theory by examining how hypoxia and hypercapnia change the
activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex
integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly
silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby
C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory
consequences of Arch activation (10 s) in conscious rats during normoxia,
hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non
REM sleep and quiet wake. Compared with normoxia, the breathing frequency
reduction (Deltaf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2,
and absent in 12% FiO2. Tidal volume changes (DeltaV(T)) followed the same trend.
The effect of hypoxia on Deltaf(R) was not arousal-dependent but was reversed by
reacidifying the blood (acetazolamide; 3% FiCO2). Deltaf(R) was highly correlated
with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition
occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1
neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic
breathing about equally during both sleep and wake. RTN neurons are the first
putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals.
RTN neurons are silent above pHa 7.5 and increasingly active below this value.
During hyperoxia, RTN activation maintains breathing despite the inactivity of
the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation
increases breathing frequency via pathways that bypass RTN.
PMID- 25589752
TI - Agonist-dependent modulation of cell surface expression of the cold receptor
TRPM8.
AB - The spatial and temporal distribution of receptors constitutes an important
mechanism for controlling the magnitude of cellular responses. Several members of
the transient receptor potential (TRP) ion channel family can regulate their
function by modulating their expression at the plasma membrane (PM) through rapid
vesicular translocation and fusion. The mechanisms underlying this regulation are
not completely understood, and the contribution of vesicular trafficking to
physiological function is unknown. TRPM8 receptors are expressed in mammalian
peripheral sensory neurons and are essential for the detection of cold
temperatures. Previously, we showed that TRPM8-containing vesicles are segregated
into three main pools, immobile at the PM, simple diffusive and corralled
hopping. Here, we show that channel expression at the PM is modulated by TRPM8
agonists in F11 and HEK293T cells. Our results support a model in which the
activation of TRPM8 channels, located at the PM, induces a short-lived
recruitment of a TRPM8-containing vesicular pool to the cell surface causing a
transitory increase in the number of functional channels, affecting intrinsic
properties of cold receptor responses. We further demonstrate the requirement of
intact vesicular trafficking to support sustained cold responses in the skin of
mice.
PMID- 25589751
TI - Vertebrate epidermal cells are broad-specificity phagocytes that clear sensory
axon debris.
AB - Cellular debris created by developmental processes or injury must be cleared by
phagocytic cells to maintain and repair tissues. Cutaneous injuries damage not
only epidermal cells but also the axonal endings of somatosensory (touch-sensing)
neurons, which must be repaired to restore the sensory function of the skin.
Phagocytosis of neuronal debris is usually performed by macrophages or other
blood-derived professional phagocytes, but we have found that epidermal cells
phagocytose somatosensory axon debris in zebrafish. Live imaging revealed that
epidermal cells rapidly internalize debris into dynamic phosphatidylinositol 3
monophosphate-positive phagosomes that mature into phagolysosomes using a pathway
similar to that of professional phagocytes. Epidermal cells phagocytosed not only
somatosensory axon debris but also debris created by injury to other peripheral
axons that were mislocalized to the skin, neighboring skin cells, and
macrophages. Together, these results identify vertebrate epidermal cells as broad
specificity phagocytes that likely contribute to neural repair and wound healing.
PMID- 25589755
TI - Rcan1 deficiency impairs neuronal migration and causes periventricular
heterotopia.
AB - Periventricular heterotopia (PH) is a cortical malformation characterized by
aggregation of neurons lining the lateral ventricles due to abnormal neuronal
migration. The molecular mechanism underlying the pathogenesis of PH is unclear.
Here we show that Regulators of calcineurin 1 (Rcan1), a Down syndrome-related
gene, plays an important role in radial migration of rat cortical neurons.
Downregulation of Rcan1 by expressing shRNA impaired neural progenitor
proliferation and led to defects in radial migration and PH. Two isoforms of
Rcan1 (Rcan1-1 and Rcan1-4) are expressed in the rat brain. Migration defects due
to downregulation of Rcan1 could be prevented by shRNA-resistant expression of
Rcan1-1 but not Rcan1-4. Furthermore, we found that Rcan1 knockdown significantly
decreased the expression level of Flna, an F-actin cross-linking protein
essential for cytoskeleton rearrangement and cell migration, mutation of which
causes the most common form of bilateral PH in humans. Finally, overexpression of
FLNA in Rcan1 knockdown neurons prevented migration abnormalities. Together,
these findings demonstrate that Rcan1 acts upstream from Flna in regulating
radial migration and suggest that impairment of Rcan1-Flna pathway may underlie
PH pathogenesis.
PMID- 25589753
TI - DAMP signaling is a key pathway inducing immune modulation after brain injury.
AB - Acute brain lesions induce profound alterations of the peripheral immune response
comprising the opposing phenomena of early immune activation and subsequent
immunosuppression. The mechanisms underlying this brain-immune signaling are
largely unknown. We used animal models for experimental brain ischemia as a
paradigm of acute brain lesions and additionally investigated a large cohort of
stroke patients. We analyzed release of HMGB1 isoforms by mass spectrometry and
investigated its inflammatory potency and signaling pathways by immunological in
vivo and in vitro techniques. Features of the complex behavioral sickness
behavior syndrome were characterized by homecage behavior analysis. HMGB1
downstream signaling, particularly with RAGE, was studied in various transgenic
animal models and by pharmacological blockade. Our results indicate that the
cytokine-inducing, fully reduced isoform of HMGB1 was released from the ischemic
brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted
in the periphery in response to brain injury induced sickness behavior, which
could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine
neutralization. Subsequently, HMGB1-release induced bone marrow egress and
splenic proliferation of bone marrow-derived suppressor cells, inhibiting the
adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling
resulted in functional exhaustion of mature monocytes and lymphopenia, the
hallmarks of immune suppression after extensive ischemia. This study introduces
the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex
postischemic brain-immune interactions.
PMID- 25589754
TI - Topologically dissociable patterns of development of the human cerebral cortex.
AB - Over 90 years ago, anatomists noted the cortex is thinner in sulci than gyri,
suggesting that development may occur on a fine scale driven by local topology.
However, studies of brain development in youth have focused on describing how
cortical thickness varies over large-scale functional and anatomic regions. How
the relationship between thickness and local sulcal topology arises in
development is still not well understood. Here, we investigated the spatial
relationships between cortical thickness, folding, and underlying white matter
organization to elucidate the influence of local topology on human brain
development. Our approach included using both T1-weighted imaging and diffusion
tensor imaging (DTI) in a cross-sectional sample of 932 youths ages 8-21 studied
as part of the Philadelphia Neurodevelopmental Cohort. Principal components
analysis revealed separable development-related processes of regionally specific
nonlinear cortical thickening (from ages 8-14) and widespread linear cortical
thinning that have dissociable relationships with cortical topology. Whereas
cortical thinning was most prominent in the depths of the sulci, early cortical
thickening was present on the gyri. Furthermore, decline in mean diffusivity
calculated from DTI in underlying white matter was correlated with cortical
thinning, suggesting that cortical thinning is spatially associated with white
matter development. Spatial permutation tests were used to assess the
significance of these relationships. Together, these data demonstrate that
cortical remodeling during youth occurs on a local topological scale and is
associated with changes in white matter beneath the cortical surface.
PMID- 25589757
TI - Distributed neural representations of phonological features during speech
perception.
AB - A fundamental goal of the human auditory system is to map complex acoustic
signals onto stable internal representations of the basic sound patterns of
speech. Phonemes and the distinctive features that they comprise constitute the
basic building blocks from which higher-level linguistic representations, such as
words and sentences, are formed. Although the neural structures underlying
phonemic representations have been well studied, there is considerable debate
regarding frontal-motor cortical contributions to speech as well as the extent of
lateralization of phonological representations within auditory cortex. Here we
used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis
to investigate the distributed patterns of activation that are associated with
the categorical and perceptual similarity structure of 16 consonant exemplars in
the English language used in Miller and Nicely's (1955) classic study of acoustic
confusability. Participants performed an incidental task while listening to
phonemes in the MRI scanner. Neural activity in bilateral anterior superior
temporal gyrus and supratemporal plane was correlated with the first two
components derived from a multidimensional scaling analysis of a behaviorally
derived confusability matrix. We further showed that neural representations
corresponding to the categorical features of voicing, manner of articulation, and
place of articulation were widely distributed throughout bilateral primary,
secondary, and association areas of the superior temporal cortex, but not motor
cortex. Although classification of phonological features was generally bilateral,
we found that multivariate pattern information was moderately stronger in the
left compared with the right hemisphere for place but not for voicing or manner
of articulation.
PMID- 25589758
TI - Motor cortex layer V pyramidal neurons exhibit dendritic regression, spine loss,
and increased synaptic excitation in the presymptomatic hSOD1(G93A) mouse model
of amyotrophic lateral sclerosis.
AB - Motor cortex layer V pyramidal neurons (LVPNs) regulate voluntary control of
motor output and selectively degenerate (along with lower motor neurons) in
amyotrophic lateral sclerosis. Using dye-filling and whole-cell patch clamping in
brain slices, together with high-resolution spinning disk confocal z-stack
mosaics, we characterized the earliest presymptomatic cortical LVPN morphologic
and electrophysiological perturbations in hSOD1(G93A) (SOD1) mice to date. Apical
dendritic regression occurred from postnatal day (P) 28, dendritic spine loss
from P21, and increased EPSC frequency from P21 in SOD1 LVPNs. These findings
demonstrate extensive early changes in motor cortex of the SOD1 mouse model,
which thus recapitulates clinically relevant cortical pathophysiology more
faithfully than previously thought.
PMID- 25589756
TI - Different patterns of electrical activity lead to long-term potentiation by
activating different intracellular pathways.
AB - Deciphering and storing information coded in different firing patterns are
important properties of neuronal networks, as they allow organisms to respond and
adapt to external and internal events. Here we report that hippocampal CA1
pyramidal neurons respond to brief bursts of high-frequency stimulation (HFS) and
theta burst stimulation (TBS) with long-lasting enhanced responses (long-term
potentiation [LTP]), albeit by engaging different signaling pathways. TBS induces
LTP through calpain-1-mediated suprachiasmatic nucleus circadian oscillatory
protein degradation, ERK activation, and actin polymerization, whereas HFS
requires adenosine A2 receptors, PKA, and actin polymerization. TBS- but not HFS
induced LTP is impaired in calpain-1 knock-out mice. However, TBS-induced LTP and
learning impairment in knock-out mice are restored by activating the HFS pathway.
Thus, different patterns of rhythmic activities trigger potentiation by
activating different pathways, and cross talks between these can be used to
restore LTP and learning when elements of the pathways are impaired.
PMID- 25589760
TI - Task-induced modulation of intrinsic functional connectivity networks in the
behaving rat.
AB - While resting-state functional magnetic resonance imaging can probe intrinsic
network connectivity in both human and rodent brain, behavioral modulation of
these connectivity patterns has not yet been demonstrated in the rodent due to
the requirements of immobilization or anesthesia for MRI scanning. To enable the
effects of behavioral tasks on functional connectivity to be measured in freely
moving, awake rats, implanted carbon paste electrodes (CPEs) were used to monitor
low-frequency fluctuations of tissue oxygenation. Rats were implanted with CPEs
in two nodes of the default mode network (DMN) and two nodes in a lateral
cortical network, revealing amperometric oxygen correlation patterns consistent
with imaging studies. Using a block design study where rats alternated between
sustained periods of instrumental response and unscheduled spontaneous behavior,
task-induced decreases in functional connectivity were observed between the DMN
node pair, but not in the distinct lateral cortical network, demonstrating
network-specific modulation of functional connectivity.
PMID- 25589759
TI - Primary afferent and spinal cord expression of gastrin-releasing peptide:
message, protein, and antibody concerns.
AB - There is continuing controversy relating to the primary afferent neurotransmitter
that conveys itch signals to the spinal cord. Here, we investigated the DRG and
spinal cord expression of the putative primary afferent-derived "itch"
neurotransmitter, gastrin-releasing peptide (GRP). Using ISH, qPCR, and
immunohistochemistry, we conclude that GRP is expressed abundantly in spinal
cord, but not in DRG neurons. Titration of the most commonly used GRP antiserum
in tissues from wild-type and GRP mutant mice indicates that the antiserum is
only selective for GRP at high dilutions. Paralleling these observations, we
found that a GRPeGFP transgenic reporter mouse has abundant expression in
superficial dorsal horn neurons, but not in the DRG. In contrast to previous
studies, neither dorsal rhizotomy nor an intrathecal injection of capsaicin,
which completely eliminated spinal cord TRPV1-immunoreactive terminals, altered
dorsal horn GRP immunoreactivity. Unexpectedly, however, peripheral nerve injury
induced significant GRP expression in a heterogeneous population of DRG neurons.
Finally, dual labeling and retrograde tracing studies showed that GRP-expressing
neurons of the superficial dorsal horn are predominantly interneurons, that a
small number coexpress protein kinase C gamma (PKCgamma), but that none coexpress
the GRP receptor (GRPR). Our studies support the view that pruritogens engage
spinal cord "itch" circuits via excitatory superficial dorsal horn interneurons
that express GRP and that likely target GRPR-expressing interneurons. The fact
that peripheral nerve injury induced de novo GRP expression in DRG neurons points
to a novel contribution of this peptide to pruritoceptive processing in
neuropathic itch conditions.
PMID- 25589762
TI - Inflammasome-induced IL-1beta secretion in microglia is characterized by delayed
kinetics and is only partially dependent on inflammatory caspases.
AB - Inflammasomes are multiprotein complexes that link pathogen recognition and
cellular stress to the processing of the proinflammatory cytokine interleukin
1beta (IL-1beta). Whereas inflammasome-mediated activation is heavily studied in
hematopoietic macrophages and dendritic cells, much less is known about
microglia, resident tissue macrophages of the brain that originate from a
distinct progenitor. To directly compare inflammasome-mediated activation in
different types of macrophages, we isolated primary microglia and hematopoietic
macrophages from adult, healthy rhesus macaques. We analyzed the expression
profile of NOD (nucleotide-binding oligomerization domain)-like receptors,
adaptor proteins, and caspases and characterized inflammasome activation and
regulation in detail. We here demonstrate that primary microglia can respond to
the same innate stimuli as hematopoietic macrophages. However, microglial
responses are more persistent due to lack of negative regulation on pro-IL-1beta
expression. In addition, we show that while caspase 1, 4, and 5 activation is
pivotal for inflammasome-induced IL-1beta secretion by hematopoietic macrophages,
microglial secretion of IL-1beta is only partially dependent on these
inflammatory caspases. These results identify key cell type-specific differences
that may aid the development of strategies to modulate innate immune responses in
the brain.
PMID- 25589763
TI - Early and persistent abnormal decoding by glial cells at the neuromuscular
junction in an ALS model.
AB - Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease
characterized by progressive loss of motor neurons (MNs) preceded by
neuromuscular junction (NMJ) denervation. Despite the importance of NMJ
denervation in ALS, the mechanisms involved remain unexplored and ill defined.
The contribution of glial cells in the disease has been highlighted, including
axonal Schwann cell activation that precedes the decline of motor function and
the onset of hindlimb paralysis. Because NMJ denervation occurs early in the
process and that perisynaptic Schwann cells (PSCs), glial cells at the NMJ,
regulate morphological stability, integrity, and repair of the NMJ, one could
predict that PSC functions would be altered even before denervation, contributing
to NMJ malfunctions. We tested this possibility using a slowly progressive model
of ALS (SOD1(G37R) mice). We observed a normal NMJ organization at a
presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic
activity revealed by intracellular Ca(2+) changes was enhanced compared with
their wild-type littermates. This inappropriate PSC decoding ability was
associated with an increased level of neurotransmitter release and dependent on
intrinsic glial properties related to enhanced muscarinic receptor activation.
The alteration of PSC muscarinic receptor functions also persists during the
preonset stage of the disease and became dependent on MN vulnerability with age.
Together, these results suggest that PSC properties are altered in the disease
process in a manner that would be detrimental for NMJ repair. The impairments of
PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.
PMID- 25589761
TI - 5alpha-Reduced neurosteroids sex-dependently reverse central prenatal programming
of neuroendocrine stress responses in rats.
AB - Maternal social stress during late pregnancy programs hypothalamo-pituitary
adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally
stressed (PNS) offspring display exaggerated HPA axis responses to a physical
stressor (systemic interleukin-1beta; IL-1beta) in adulthood, compared with
controls. IL-1beta acts via a noradrenergic relay from the nucleus tractus
solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular
nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone
and 3beta-androstanediol (3beta-diol; 5alpha-reduced metabolites of progesterone
and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to
seek reversal of the "programmed" hyper-responsive HPA phenotype.
Allopregnanolone attenuated ACTH responses to IL-1beta (500 ng/kg, i.v.) in PNS
females, but not in PNS males. However, 3beta-diol normalized HPA axis responses
to IL-1beta in PNS males. Impaired testosterone and progesterone metabolism or
increased secretion in PNS rats was indicated by greater plasma testosterone and
progesterone concentrations in male and female PNS rats, respectively. Deficits
in central neurosteroid production were indicated by reduced 5alpha-reductase
mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in
males. In PNS females, adenovirus-mediated gene transfer was used to upregulate
expression of 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase mRNAs in
the NTS, and this normalized hyperactive HPA axis responses to IL-1beta. Thus,
downregulation of neurosteroid production in the brain may underlie HPA axis
hyper-responsiveness in prenatally programmed offspring, and administration of
5alpha-reduced steroids acutely to PNS rats overrides programming of hyperactive
HPA axis responses to immune challenge in a sex-dependent manner.
PMID- 25589766
TI - The causal role of the occipital face area (OFA) and lateral occipital (LO)
cortex in symmetry perception.
AB - Symmetry is an important cue in face and object perception. Here we used fMRI
guided transcranial magnetic stimulation (TMS) to shed light on the role of the
occipital face area (OFA), a key region in face processing, and the lateral
occipital (LO) cortex, a key area in object processing, in symmetry detection. In
the first experiment, we applied TMS over the rightOFA, its left homolog
(leftOFA), rightLO, and vertex (baseline) while participants were discriminating
between symmetric and asymmetric dot patterns. Stimulation of rightOFA and
rightLO impaired performance, causally implicating these two regions in detection
of symmetry in low-level dot configurations. TMS over rightLO but not rightOFA
also significantly impaired detection of nonsymmetric shapes defined by collinear
Gabor patches, demonstrating that rightOFA responds to symmetry but not to all
cues mediating figure-ground segregation. The second experiment showed a causal
role for rightOFA but not rightLO in facial symmetry detection. Overall, our
results demonstrate that both the rightOFA and rightLO are sensitive to symmetry
in dot patterns, whereas only rightOFA is causally involved in facial symmetry
detection.
PMID- 25589764
TI - Homeostatic dysregulation in membrane properties of masticatory motoneurons
compared with oculomotor neurons in a mouse model for amyotrophic lateral
sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron
disease with presently no cure. Motoneuron (MN) hyperexcitability is commonly
observed in ALS and is suggested to be a precursor for excitotoxic cell death.
However, it is unknown whether hyperexcitability also occurs in MNs that are
resistant to degeneration. Second, it is unclear whether all the MNs within
homogeneous motor pools would present similar susceptibility to excitability
changes since high-threshold MNs innervating fast fatigable muscle fibers
selectively degenerate compared with low-threshold MNs innervating fatigue
resistant slow muscle fibers. Therefore, we concurrently examined the
excitability of ALS-vulnerable trigeminal motoneurons (TMNs) controlling jaw
musculature and ALS-resistant oculomotor neurons (OMNs) controlling eye
musculature in a well studied SOD1(G93A) ALS mouse model using in vitro patch
clamp electrophysiology at presymptomatic ages P8-P12. Our results show that
hyperexcitability is not a global change among all the MNs, although mutant SOD1
is ubiquitously expressed. Instead, complex changes occur in ALS-vulnerable TMNs
based on motor unit type and discharge characteristics. Firing threshold
decreases among high-threshold TMNs and increases in a subpopulation of low
threshold TMNs. The latter group was identified based on their linear frequency
current responses to triangular ramp current injections. Such complex changes in
MN recruitment were absent in ALS-resistant OMNs. We simulated the observed
complex changes in TMN excitability using a computer-based jaw closer motor pool
model. Model results suggest that hypoexcitability may indeed represent emerging
disease symptomology that causes resistance in muscle force initiation.
Identifying the cellular and molecular properties of these hypoexcitable cells
may guide effective therapeutic strategies in ALS.
PMID- 25589765
TI - Dynamics of EEG rhythms support distinct visual selection mechanisms in parietal
cortex: a simultaneous transcranial magnetic stimulation and EEG study.
AB - Using repetitive transcranial magnetic stimulation (rTMS), we have recently shown
a functional anatomical distinction in human parietal cortex between regions
involved in maintaining attention to a location [ventral intraparietal sulcus
(vIPS)] and a region involved in shifting attention between locations [medial
superior parietal lobule (mSPL)]. In particular, while rTMS interference over
vIPS impaired target discrimination at contralateral attended locations,
interference over mSPL affected performance following shifts of attention
regardless of the visual field (Capotosto et al., 2013). Here, using rTMS
interference in conjunction with EEG recordings of brain rhythms during the
presentation of cues that indicate to either shift or maintain spatial attention,
we tested whether this functional anatomical segregation involves different
mechanisms of rhythm synchronization. The transient inactivation of vIPS reduced
the amplitude of the expected parieto-occipital low-alpha (8-10 Hz)
desynchronization contralateral to the cued location. Conversely, the transient
inactivation of mSPL, compared with vIPS, reduced the high-alpha (10-12 Hz)
desynchronization induced by shifting attention into both visual fields.
Furthermore, rTMS induced a frequency-specific delay of task-related modulation
of brain rhythms. Specifically, rTMS over vIPS or mSPL during maintenance (stay
cues) or shifting (shift cues) of spatial attention, respectively, caused a delay
of alpha parieto-occipital desynchronization. Moreover, rTMS over vIPS during
stay cues caused a delay of delta (2-4 Hz) frontocentral synchronization. These
findings further support the anatomo-functional subdivision of the dorsal
attention network in subsystems devoted to shifting or maintaining covert
visuospatial attention and indicate that these mechanisms operate in different
frequency channels linking frontal to parieto-occipital visual regions.
PMID- 25589767
TI - Cholinergic basal forebrain structure influences the reconfiguration of white
matter connections to support residual memory in mild cognitive impairment.
AB - The fornix and hippocampus are critical to recollection in the healthy human
brain. Fornix degeneration is a feature of aging and Alzheimer's disease. In the
presence of fornix damage in mild cognitive impairment (MCI), a recognized
prodrome of Alzheimer's disease, recall shows greater dependence on other tracts,
notably the parahippocampal cingulum (PHC). The current aims were to determine
whether this shift is adaptive and to probe its relationship to cholinergic
signaling, which is also compromised in Alzheimer's disease. Twenty-five human
participants with MCI and 20 matched healthy volunteers underwent diffusion MRI,
behavioral assessment, and volumetric measurement of the basal forebrain. In a
regression model for recall, there was a significant group * fornix interaction,
indicating that the association between recall and fornix structure was weaker in
patients. The opposite trend was present for the left PHC. To further investigate
this pattern, two regression models were generated to account for recall
performance: one based on fornix microstructure and the other on both fornix and
left PHC. The realignment to PHC was positively correlated with free recall but
not non-memory measures, implying a reconfiguration that is beneficial to
residual memory. There was a positive relationship between realignment to PHC and
basal forebrain gray matter volume despite this region demonstrating atrophy at a
group level, i.e., the cognitive realignment to left PHC was most apparent when
cholinergic areas were relatively spared. Therefore, cholinergic systems appear
to enable adaptation to injury even as they degenerate, which has implications
for functional restoration.
PMID- 25589768
TI - CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive
dysfunction induced by traumatic brain injury.
AB - Traumatic brain injury (TBI) is a major risk factor for the development of
multiple neurodegenerative diseases. With respect to the increasing prevalence of
TBI, new therapeutic strategies are urgently needed that will prevent secondary
damage to primarily unaffected tissue. Consistently, neuroinflammation has been
implicated as a key mediator of secondary damage following the initial mechanical
insult. Following injury, there is uncertainty regarding the role that
accumulating CCR2(+) macrophages play in the injury-induced neuroinflammatory
sequelae and cognitive dysfunction. Using CX3CR1(GFP/+)CCR2(RFP/+) reporter mice,
we show that TBI initiated a temporally restricted accumulation of peripherally
derived CCR2(+) macrophages, which were concentrated in the hippocampal
formation, a region necessary for learning and memory. Multivariate analysis
delineated CCR2(+) macrophages' neuroinflammatory response while identifying a
novel therapeutic treatment window. As a proof of concept, targeting CCR2(+)
macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly
reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there
was a significant reduction in multiple proinflammatory and neurotoxic mediators
with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing
of TBI-induced hippocampal-dependent cognitive dysfunction and reduced
proinflammatory activation profile 1 month after injury. Thus, therapeutically
targeting the CCR2(+) subset of monocytes/macrophages may provide a new avenue of
clinical intervention following TBI.
PMID- 25589769
TI - Cholinergic control of gamma power in the midbrain spatial attention network.
AB - The modulation of gamma power (25-90 Hz) is associated with attention and has
been observed across species and brain areas. However, mechanisms that control
these modulations are poorly understood. The midbrain spatial attention network
in birds generates high-amplitude gamma oscillations in the local field potential
that are thought to represent the highest priority location for attention. Here
we explore, in midbrain slices from chickens, mechanisms that regulate the power
of these oscillations, using high-resolution techniques including intracellular
recordings from neurons targeted by calcium imaging. The results identify a
specific subtype of neuron, expressing non-alpha7 nicotinic acetylcholine
receptors, that directly drives inhibition in the gamma-generating circuit and
switches the network into a primed state capable of producing high-amplitude
oscillations. The special properties of this mechanism enable rapid, persistent
changes in gamma power. The brain may employ this mechanism wherever rapid
modulations of gamma power are critical to information processing.
PMID- 25589771
TI - The prefrontal cortex achieves inhibitory control by facilitating subcortical
motor pathway connectivity.
AB - Communication between the prefrontal cortex and subcortical nuclei underpins the
control and inhibition of behavior. However, the interactions in such pathways
remain controversial. Using a stop-signal response inhibition task and functional
imaging with analysis of effective connectivity, we show that the lateral
prefrontal cortex influences the strength of communication between regions in the
frontostriatal motor system. We compared 20 generative models that represented
alternative interactions between the inferior frontal gyrus, presupplementary
motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during
response inhibition. Bayesian model selection revealed that during successful
response inhibition, the inferior frontal gyrus modulates an excitatory influence
of the preSMA on the STN, thereby amplifying the downstream polysynaptic
inhibition from the STN to the motor cortex. Critically, the strength of the
interaction between preSMA and STN, and the degree of modulation by the inferior
frontal gyrus, predicted individual differences in participants' stopping
performance (stop-signal reaction time). We then used diffusion-weighted imaging
with tractography to assess white matter structure in the pathways connecting
these three regions. The mean diffusivity in tracts between preSMA and the STN,
and between the inferior frontal gyrus and STN, also predicted individual
differences in stopping efficiency. Finally, we found that white matter structure
in the tract between preSMA and STN correlated with effective connectivity of the
same pathway, providing important cross-modal validation of the effective
connectivity measures. Together, the results demonstrate the network dynamics and
modulatory role of the prefrontal cortex that underpin individual differences in
inhibitory control.
PMID- 25589770
TI - PAR1-activated astrocytes in the nucleus of the solitary tract stimulate adjacent
neurons via NMDA receptors.
AB - Severe autonomic dysfunction, including the loss of control of the
cardiovascular, respiratory, and gastrointestinal systems, is a common
comorbidity of stroke and other bleeding head injuries. Previous studies suggest
that this collapse of autonomic control may be caused by thrombin acting on
astrocytic protease-activated receptors (PAR1) in the hindbrain. Using calcium
imaging and electrophysiological techniques, we evaluated the mechanisms by which
astrocytic PAR1s modulate the activity of presynaptic vagal afferent terminals
and postsynaptic neurons in the rat nucleus of the solitary tract (NST). Our
calcium-imaging data show that astrocytic and neuronal calcium levels increase
after brain slices are treated with the PAR1 agonist SFLLRN-NH2. This increase in
activity is blocked by pretreating the slices with the glial metabolic blocker
fluorocitrate. In addition, PAR1-activated astrocytes communicate directly with
NST neurons by releasing glutamate. Calcium responses to SFLLRN-NH2 in the
astrocytes and neurons significantly increase after bath application of the
excitatory amino acid transporter blocker DL-threo-beta-benzyloxyaspartic acid
(TBOA) and significantly decrease after bath application of the NMDA receptor
antagonist DL-2-amino-5-phosphonopentanoic acid (DL-AP5). Furthermore, astrocytic
glutamate activates neuronal GluN2B-containing NMDA receptors. Voltage-clamp
recordings of miniature EPSCs (mEPSCs) from NST neurons show that astrocytes
control presynaptic vagal afferent excitability directly under resting and
activated conditions. Fluorocitrate significantly decreases mEPSC frequency and
SFLLRN-NH2 significantly increases mEPSC frequency. These data show that
astrocytes act within a tripartite synapse in the NST, controlling the
excitability of both postsynaptic NST neurons and presynaptic vagal afferent
terminals.
PMID- 25589772
TI - Distinguishing the central drive to tremor in Parkinson's disease and essential
tremor.
AB - Parkinson's disease (PD) and essential tremor (ET) are the two most common
movement disorders. Both have been associated with similar patterns of network
activation leading to the suggestion that they may result from similar network
dysfunction, specifically involving the cerebellum. Here, we demonstrate that
parkinsonian tremors and ETs result from distinct patterns of interactions
between neural oscillators. These patterns are reflected in the tremors' derived
frequency tolerance, a novel measure readily attainable from bedside
accelerometry. Frequency tolerance characterizes the temporal evolution of tremor
by quantifying the range of frequencies over which the tremor may be considered
stable. We found that patients with PD (N = 24) and ET (N = 21) were separable
based on their frequency tolerance, with PD associated with a broad range of
stable frequencies whereas ET displayed characteristics consistent with a more
finely tuned oscillatory drive. Furthermore, tremor was selectively entrained by
transcranial alternating current stimulation applied over cerebellum. Narrow
frequency tolerances predicted stronger entrainment of tremor by stimulation,
providing good evidence that the cerebellum plays an important role in pacing
those tremors. The different patterns of frequency tolerance could be captured
with a simple model based on a broadly coupled set of neural oscillators for PD,
but a more finely tuned set of oscillators in ET. Together, these results reveal
a potential organizational principle of the human motor system, whose disruption
in PD and ET dictates how patients respond to empirical, and potentially
therapeutic, interventions that interact with their underlying pathophysiology.
PMID- 25589774
TI - Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal
circuits to perpetuate fear memory.
AB - Fear memories typically persist for long time periods, and persistent fear
memories contribute to post-traumatic stress disorder. However, little is known
about the cellular and synaptic mechanisms that perpetuate long-term memories.
Here, we find that mouse hippocampal CA1 neurons exhibit biphasic Arc (also known
as Arg3.1) elevations after fear experience and that the late Arc expression
regulates the perpetuation of fear memoires. An early Arc increase returned to
the baseline after 6 h, followed by a second Arc increase after 12 h in the same
neuronal subpopulation; these elevations occurred via distinct mechanisms.
Antisense-induced blockade of late Arc expression disrupted memory persistence
but not formation. Moreover, prolonged fear memories were associated with the
delayed, specific elimination of dendritic spines and the reactivation of
neuronal ensembles formed during fear experience, both of which required late Arc
expression. We propose that late Arc expression refines functional circuits in a
delayed fashion to prolong fear memory.
PMID- 25589773
TI - SIRT1 deficiency in microglia contributes to cognitive decline in aging and
neurodegeneration via epigenetic regulation of IL-1beta.
AB - Aging is the predominant risk factor for neurodegenerative diseases. One key
phenotype as the brain ages is an aberrant innate immune response characterized
by proinflammation. However, the molecular mechanisms underlying aging-associated
proinflammation are poorly defined. Whether chronic inflammation plays a causal
role in cognitive decline in aging and neurodegeneration has not been
established. Here we report a mechanistic link between chronic inflammation and
aging microglia and a causal role of aging microglia in neurodegenerative
cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia
and that microglial SIRT1 deficiency has a causative role in aging- or tau
mediated memory deficits via IL-1beta upregulation in mice. Interestingly, the
selective activation of IL-1beta transcription by SIRT1 deficiency is likely
mediated through hypomethylating the specific CpG sites on IL-1beta proximal
promoter. In humans, hypomethylation of IL-1beta is strongly associated with
chronological age and with elevated IL-1beta transcription. Our findings reveal a
novel epigenetic mechanism in aging microglia that contributes to cognitive
deficits in aging and neurodegenerative diseases.
PMID- 25589776
TI - Structure-function relationships between aldolase C/zebrin II expression and
complex spike synchrony in the cerebellum.
AB - Simple and regular anatomical structure is a hallmark of the cerebellar cortex.
Parasagittally arrayed alternate expression of aldolase C/zebrin II in Purkinje
cells (PCs) has been extensively studied, but surprisingly little is known about
its functional significance. Here we found a precise structure-function
relationship between aldolase C expression and synchrony of PC complex spike
activities that reflect climbing fiber inputs to PCs. We performed two-photon
calcium imaging in transgenic mice in which aldolase C compartments can be
visualized in vivo, and identified highly synchronous complex spike activities
among aldolase C-positive or aldolase C-negative PCs, but not across these
populations. The boundary of aldolase C compartments corresponded to that of
complex spike synchrony at single-cell resolution. Sensory stimulation evoked
aldolase C compartment-specific complex spike responses and synchrony. This
result further revealed the structure-function segregation. In awake animals,
complex spike synchrony both within and between PC populations across the
aldolase C boundary were enhanced in response to sensory stimuli, in a way that
two functionally distinct PC ensembles are coactivated. These results suggest
that PC populations characterized by aldolase C expression precisely represent
distinct functional units of the cerebellar cortex, and these functional units
can cooperate to process sensory information in awake animals.
PMID- 25589775
TI - Actions of bupivacaine, a widely used local anesthetic, on NMDA receptor
responses.
AB - NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and
play a pivotal role in the neurological disease state of chronic pain, which is
caused by central sensitization. Bupivacaine is the indicated local anesthetic in
caudal, epidural, and spinal anesthesia and is widely used clinically to manage
acute and chronic pain. In addition to blocking Na(+) channels, bupivacaine
affects the activity of many other channels, including NMDA receptors.
Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in
the dorsal horn of the spinal cord, an area critically involved in central
sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and
found that increasing concentrations of bupivacaine decreased channel open
probability in GluN2 subunit- and pH-independent manner by increasing the mean
duration of closures and decreasing the mean duration of openings. Using kinetic
modeling of one-channel currents, we attributed the observed current decrease to
two main mechanisms: a voltage-dependent "foot-in-the-door" pore block and an
allosteric gating effect. Further, the inhibition was state-independent because
it occurred to the same degree whether the drug was applied before or after
glutamate stimulation and was mediated by extracellular and intracellular
inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict
that clinical doses of bupivacaine would decrease the peak and accelerate the
decay of synaptic NMDA receptor currents during normal synaptic transmission.
These quantitative predictions inform possible applications of bupivacaine as
preventative and therapeutic approaches in chronic pain.
PMID- 25589778
TI - Prescription opioids. III. Disposition of oxycodone in oral fluid and blood
following controlled single-dose administration.
AB - Oxycodone (OC) is recommended to be included as an analyte tested in the proposed
Substance Abuse and Mental Health Services Administration (SAMHSA's) Mandatory
Guidelines for Federal Workplace Drug Testing Programs using Oral Fluid (OF)
Specimens. This study demonstrates the time course of OC and metabolites,
noroxycodone (NOC), oxymorphone (OM) and noroxymorphone (NOM), in near
simultaneous paired OF and whole blood (BL) specimens by liquid chromatography
tandem mass spectrometry (LC-MS-MS) (limit of detection = 1 ng/mL OF, 5 ng/mL
BL). A single dose of OC 20 mg controlled-release was administered to 12 healthy
subjects followed by specimen collections for 52 h. Analyte prevalence was as
follows: OF, OC > NOC > OM; and BL, OC > NOC > NOM. OC and NOC were frequently
detected within 15-30 min in OF and 30 min to 2 h in BL. NOM and OM appeared
between 1.5-5 h post-dose. The mean OF-to-BL (OF:BL) ratios and correlations were
5.4 for OC (r = 0.719) and 1.0 for NOC (r = 0.651). The period of detection for
OF exceeded BL by ~2-fold at similar cutoff concentrations. At a 1 ng/mL cutoff
for OF, the mean detection time was 34 h for OC and NOC. These data provide new
information that should facilitate interpretation of OC test results.
PMID- 25589777
TI - Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.
AB - In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc)
neurons send a dense projection to the basolateral nucleus of the amygdala (BLA).
In this study, we investigated the effect of near physiological acetylcholine
release on BLA neurons using optogenetic tools and in vitro patch-clamp
recordings. Adult transgenic mice expressing cre-recombinase under the choline
acetyltransferase promoter were used to selectively transduce BFc neurons with
channelrhodopsin-2 and a reporter through the injection of an adeno-associated
virus. Light-induced stimulation of BFc axons produced different effects
depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited
fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking
interneurons. In principal BLA neurons, two different effects were elicited
depending on their activity level. When principal BLA neurons were quiescent or
made to fire at low rates by depolarizing current injection, light-induced
activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger
depolarizing currents, eliciting firing above ~ 6-8 Hz, these muscarinic IPSPs
lost their efficacy because stimulation of BFc inputs prolonged current-evoked
afterdepolarizations. All the effects observed in principal neurons were
dependent on muscarinic receptors type 1, engaging different intracellular
mechanisms in a state-dependent manner. Overall, our results suggest that
acetylcholine enhances the signal-to-noise ratio in principal BLA neurons.
Moreover, the cholinergic engagement of afterdepolarizations may contribute to
the formation of stimulus associations during fear-conditioning tasks where the
timing of conditioned and unconditioned stimuli is not optimal for the induction
of synaptic plasticity.
PMID- 25589780
TI - Wernicke-Korsakoff syndrome not related to alcohol use: a systematic review.
AB - OBJECTIVE: Although Wernicke-Korsakoff syndrome (WKS) is a common condition,
diagnosis remains difficult. WKS not associated with alcohol is rare and thought
to present differently to alcohol-related WKS. We conducted a systematic review
of WKS not related to alcohol to enhance understanding of WKS not related to
alcohol and WKS in general. METHODS: A systematic review was conducted of case
reports, published in English, of Wernicke's encephalopathy and WKS in patients
without a history of alcohol-use disorder. Main data sources: MEDLINE, Index
Medicus. Eligible cases totaled 623. Publication dates ranged from 1867 to 2014.
Comparisons of clinical presentation were made with published data on samples
comprising, almost exclusively, alcohol-related WKS. RESULTS: A wide array of
illnesses precipitated WKS. When diagnosis of WKS was performed postmortem, non
alcohol-related cases presented a similar number of signs of the classic triad as
alcohol-related cases (p=0.662, Cohen's w=0.12) but more signs when diagnosed
antemortem (p<0.001, Cohen's w=0.46). The most common sign was altered mental
state. Korsakoff syndrome or ongoing memory impairment was reported in 25% of non
alcohol-related WKS, although cognitive status was not explicitly reported in
many cases. When duration of memory impairment was reported, 56% had clinically
obvious memory impairment lasting beyond the period of acute presentation. Non
alcohol-related WKS was more often associated with female gender, younger age,
shorter duration of precipitating illness and better survival rate compared to
alcohol-related WKS. CONCLUSIONS: Thiamine deficiency in the absence of an
alcohol-use disorder can cause the full clinical spectrum of WKS, including
chronic cognitive impairment and Korsakoff syndrome.
PMID- 25589779
TI - A panel of nine cerebrospinal fluid biomarkers may identify patients with
atypical parkinsonian syndromes.
AB - BACKGROUND: Patients presenting with parkinsonian syndromes share many clinical
features, which can make diagnosis difficult. This is important as atypical
parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP),
multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor
prognosis, compared with patients with Parkinson's disease (PD). In addition,
there is overlap between APS and dementia diseases, such as Alzheimer's disease
(AD) and frontotemporal dementia (FTD). OBJECTIVE: To use a panel of
cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD
and dementia. METHODS: A prospective cohort of 160 patients and 30 control
participants were recruited from a single specialist centre. Patients were
clinically diagnosed according to current consensus criteria. CSF samples were
obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS
(n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants
(n=30) were included as controls. Total tau (t-tau), phosphorylated tau (p-tau),
beta-amyloid 1-42 (Abeta42), neurofilament light chain (NFL), alpha-synuclein
(alpha-syn), amyloid precursor protein soluble metabolites alpha and beta
(soluble amyloid precursor protein (sAPP)alpha, sAPPbeta) and two
neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were
measured in CSF. A reverse stepwise regression analysis and the false discovery
rate procedure were used. RESULTS: CSF NFL (p<0.001), sAPPalpha (p<0.001) and a
syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these
nine biomarkers could differentiate patients with PD from APS with an area under
the curve of 0.95 and subtypes of APS from one another. There was good
discriminatory power between parkinsonian groups, dementia disorders and healthy
controls. CONCLUSIONS: A panel of nine CSF biomarkers was able to differentiate
APS from patients with PD and dementia. This may have important clinical utility
in improving diagnostic accuracy, allowing better prognostication and earlier
access to potential disease-modifying therapies.
PMID- 25589781
TI - Intracranial venous collaterals in cerebral venous thrombosis: clinical and
imaging impact.
AB - BACKGROUND AND PURPOSE: Few studies have examined collateral formation in
patients with cerebral venous thrombosis (CVT). The aim of this study was to
analyse the impact of baseline intracranial venous collaterals on the clinical
outcome and imaging features of patients with acute CVT. MATERIAL AND METHODS:
MRIs from consecutive patients with acute CVT were retrospectively analysed. The
category system described by Qureshi was used to assess the pattern of venous
collaterals. Clinical and imaging features and outcomes were analysed using
bivariate and multivariate models to assess the association of collateral
patterns with the type of parenchymal lesions and clinical outcome (modified
Rankin Scale) at 30 and 90 days. RESULTS: One hundred patients were included (77
women; median age 32 years; and median of 18 months of follow-up). Venous
collaterals were present in 88% of the patients; type I collaterals in 3
patients, type II collaterals in 27 patients, and type III collaterals in 58
patients. Twelve patients did not exhibit any collaterals. Cohen's kappa
coefficient between evaluators was 0.86. In the bivariate analysis, type III
collaterals were associated with isolated intracranial hypertension and complete
recovery, whereas type I collaterals were associated with encephalopathy.
However, in the multivariate regression analysis, the collateral pattern was not
associated with clinical presentation, type of brain lesion or outcome.
CONCLUSIONS: Intracranial venous collaterals are frequently found in patients
with CVT during the acute phase. However, they do not have an independent effect
on the type of brain damage, clinical manifestations or prognosis.
PMID- 25589783
TI - The oncogenic microRNA-21 inhibits the tumor suppressive activity of FBXO11 to
promote tumorigenesis.
AB - The microRNA miR-21 is overexpressed in most human cancers and accumulating
evidence indicates that it functions as an oncogene. Since miRNAs suppress the
expression of their target genes, we hypothesized that some miR-21 targets may
act as tumor suppressors, and thus their expression would be anticipated to be
reduced by the high miR-21 levels observed in various human cancers. By
microarray analysis and quantitative PCR we identified and validated FBXO11 (a
member of the F-box subfamily lacking a distinct unifying domain) as a miR-21
target gene. FBXO11 is a component of the SKP1-CUL1-F-box ubiquitin ligase
complex that targets proteins for ubiquitination and proteosomal degradation. By
loss of function and gain of function studies, we show that FBXO11 acts as a
tumor suppressor, promotes apoptosis and mediates the degradation of the
oncogenic protein BCL6. The critical role that FBXO11 plays in miR-21-mediated
tumorigenesis was demonstrated by a rescue experiment, in which silencing FBXO11
in miR-21KD cancer cells restored their high tumorigenicity. Expression of miR-21
and FBXO11 are inversely correlated in tumor tissue, and their expression
correlates with patient survival and tumor grade. High FBXO11 expression
correlates with better patient survival and lower tumor grade consistent with its
tumor suppressor activity. In contrast high miR-21 expression, which correlates
with poor patient survival and higher tumor grade, is consistent with its
oncogenic activity. Our results identify FBXO11 as a novel miR-21 target gene,
and demonstrate that the oncogenic miRNA miR-21 decreases the expression of
FBXO11, which normally acts as a tumor suppressor, and thereby promotes
tumorigenesis.
PMID- 25589784
TI - Anoctamin-6 controls bone mineralization by activating the calcium transporter
NCX1.
AB - Anoctamin-6 (Ano6, TMEM16F) belongs to a family of putative Ca(2+)-activated Cl(
) channels and operates as membrane phospholipid scramblase. Deletion of Ano6
leads to reduced skeleton size, skeletal deformities, and mineralization defects
in mice. However, it remains entirely unclear how a lack of Ano6 leads to a delay
in bone mineralization by osteoblasts. The Na(+)/Ca(2+) exchanger NCX1 was found
to interact with Ano6 in a two-hybrid split-ubiquitin screen. Using human
osteoblasts and osteoblasts from Ano6(-/-) and WT mice, we demonstrate that NCX1
requires Ano6 to efficiently translocate Ca(2+) out of osteoblasts into the
calcifying bone matrix. Ca(2+)-activated anion currents are missing in primary
osteoblasts isolated from Ano6 null mice. Our findings demonstrate the importance
of NCX1 for bone mineralization and explain why deletion of an ion channel leads
to the observed mineralization defect: Ano6 Cl(-) currents are probably required
to operate as a Cl(-) bypass channel, thereby compensating net Na(+) charge
movement by NCX1.
PMID- 25589785
TI - Distinct requirements for HIV-cell fusion and HIV-mediated cell-cell fusion.
AB - Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes
is a subject of active debate. The ability of HIV-1 to mediate fusion between
adjacent cells, a process referred to as "fusion-from-without" (FFWO), shows that
this virus can fuse with the plasma membrane. To compare FFWO occurring at the
cell surface with HIV-cell fusion through a conventional entry route, we designed
an experimental approach that enabled the measurements of both processes in the
same sample. The following key differences were observed. First, a very small
fraction of viruses fusing with target cells participated in FFWO. Second,
whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors,
post-CD4/coreceptor binding steps during FFWO were abrogated. A partial
dependence of HIV-cell fusion on actin remodeling was observed in CD4(+) T cells,
but this effect appeared to be due to the actin dependence of virus uptake.
Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the
ability of the virus to promote FFWO, while having a modest effect on virus-cell
fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell
fusion are consistent with the notion that, except for a minor fraction of
particles that mediate fusion between the plasma membranes of adjacent cells, HIV
1 enters through an endocytic pathway. We surmise, however, that cell-cell
contacts enabling HIV-1 fusion with the plasma membrane could be favored at the
sites of high density of target cells, such as lymph nodes.
PMID- 25589786
TI - A parallel quadruplex DNA is bound tightly but unfolded slowly by pif1 helicase.
AB - DNA sequences that can form intramolecular quadruplex structures are found in
promoters of proto-oncogenes. Many of these sequences readily fold into parallel
quadruplexes. Here we characterize the ability of yeast Pif1 to bind and unfold a
parallel quadruplex DNA substrate. We found that Pif1 binds more tightly to the
parallel quadruplex DNA than single-stranded DNA or tailed duplexes. However,
Pif1 unwinding of duplexes occurs at a much faster rate than unfolding of a
parallel intramolecular quadruplex. Pif1 readily unfolds a parallel quadruplex
DNA substrate in a multiturnover reaction and also generates some product under
single cycle conditions. The rate of ATP hydrolysis by Pif1 is reduced when bound
to a parallel quadruplex compared with single-stranded DNA. ATP hydrolysis occurs
at a faster rate than quadruplex unfolding, indicating that some ATP hydrolysis
events are non-productive during unfolding of intramolecular parallel quadruplex
DNA. However, product eventually accumulates at a slow rate.
PMID- 25589787
TI - beta-Spectrin regulates the hippo signaling pathway and modulates the basal actin
network.
AB - Emerging evidence suggests functional regulation of the Hippo pathway by the
actin cytoskeleton, although the detailed molecular mechanism remains incomplete.
In a genetic screen, we identified a requirement for beta-Spectrin in the
posterior follicle cells for the oocyte repolarization process during Drosophila
mid-oogenesis. beta-spectrin mutations lead to loss of Hippo signaling activity
in the follicle cells. A similar reduction of Hippo signaling activity was
observed after beta-Spectrin knockdown in mammalian cells. We further
demonstrated that beta-spectrin mutations disrupt the basal actin network in
follicle cells. The abnormal stress fiber-like actin structure on the basal side
of follicle cells provides a likely link between the beta-spectrin mutations and
the loss of the Hippo signaling activity phenotype.
PMID- 25589788
TI - Heparan sulfate proteoglycans mediate factor XIIa binding to the cell surface.
AB - Hageman factor (FXIIa) initiates the intrinsic coagulation pathway and triggers
the kallikrein-kinin and the complement systems. In addition, it functions as a
growth factor by expressing promitogenic activities toward several cell types.
FXIIa binds to the cell surface via a number of structurally unrelated surface
receptors; however, the underlying mechanisms are not yet fully understood. Here,
we demonstrate that FXIIa utilizes cell membrane-bound glycosaminoglycans to
interact with the cell surface of human lung fibroblasts (HLF). The combination
of enzymatic, inhibitory, and overexpression approaches identified a heparan
sulfate (HS) component of proteoglycans as an important determinant of the FXIIa
binding capacity of HLF. Moreover, cell-free assays and competition experiments
revealed preferential binding of FXIIa to HS and heparin over dextran sulfate,
dermatan sulfate, and chondroitin sulfate A and C. Finally, we demonstrate that
fibroblasts isolated from the lungs of the patients suffering from idiopathic
pulmonary fibrosis (IPF) exhibit enhanced FXIIa binding capacity. Increased
sulfation of HS resulting from elevated HS 6-O-sulfotransferase-1 expression in
IPF HLF accounted, in part, for this phenomenon. Application of RNA interference
technology and inhibitors of intracellular sulfation revealed the cooperative
action of cell surface-associated HS and urokinase-type plasminogen activator
receptor in the accumulation of FXIIa on the cell surface of IPF HLF. Moreover,
FXIIa stimulated IPF HLF migration, which was abrogated by pretreatment of cells
with heparinase I. Collectively, our study uncovers a novel role of HS-type
glycosaminoglycans in a local accumulation of FXIIa on the cell membrane. The
enhanced association of FXIIa with IPF HLF suggests its contribution to
fibrogenesis.
PMID- 25589790
TI - Deciphering the combinatorial DNA-binding code of the CCAAT-binding complex and
the iron-regulatory basic region leucine zipper (bZIP) transcription factor HapX.
AB - The heterotrimeric CCAAT-binding complex (CBC) is evolutionarily conserved in
eukaryotic organisms, including fungi, plants, and mammals. The CBC consists of
three subunits, which are named in the filamentous fungus Aspergillus nidulans
HapB, HapC, and HapE. HapX, a fourth CBC subunit, was identified exclusively in
fungi, except for Saccharomyces cerevisiae and the closely related
Saccharomycotina species. The CBC-HapX complex acts as the master regulator of
iron homeostasis. HapX belongs to the class of basic region leucine zipper
transcription factors. We demonstrated that the CBC and HapX bind cooperatively
to bipartite DNA motifs with a general HapX/CBC/DNA 2:1:1 stoichiometry in a
class of genes that are repressed by HapX-CBC in A. nidulans during iron
limitation. This combinatorial binding mode requires protein-protein interaction
between the N-terminal domain of HapE and the N-terminal CBC binding domain of
HapX as well as sequence-specific DNA binding of both the CBC and HapX. Initial
binding of the CBC to CCAAT boxes is mandatory for DNA recognition of HapX. HapX
specifically targets the minimal motif 5'-GAT-3', which is located at a distance
of 11-12 bp downstream of the respective CCAAT box. Single nucleotide
substitutions at the 5'- and 3'-end of the GAT motif as well as different spacing
between the CBC and HapX DNA-binding sites revealed a remarkable promiscuous DNA
recognition mode of HapX. This flexible DNA-binding code may have evolved as a
mechanism for fine-tuning the transcriptional activity of CBC-HapX at distinct
target promoters.
PMID- 25589789
TI - Non-thermal plasma activates human keratinocytes by stimulation of antioxidant
and phase II pathways.
AB - Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity
to control redox-based processes, e.g. wound healing, cancer, and inflammatory
diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen
species, it allows stimulation or inhibition of cellular processes in biological
systems. Our data show that both gene and protein expression is highly affected
by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase
II enzyme pathway components were found to act as key controllers orchestrating
the cellular response in keratinocytes. Additionally, glutathione metabolism,
which is a marker for NRF2-related signaling events, was affected. Among the most
robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone
oxidoreductase 1, and growth factors were found. The roles of NRF2 targets,
investigated by siRNA silencing, revealed that NRF2 acts as an important switch
for sensing oxidative stress events. Moreover, the influence of non-thermal
plasma on the NRF2 pathway prepares cells against exogenic noxae and increases
their resilience against oxidative species. Via paracrine mechanisms, distant
cells benefit from cell-cell communication. The finding that non-thermal plasma
triggers hormesis-like processes in keratinocytes facilitates the understanding
of plasma-tissue interaction and its clinical application.
PMID- 25589791
TI - Traditional serrated adenomas (TSAs) admixed with other serrated (so-called
precursor) polyps and conventional adenomas: a frequent occurrence.
AB - BACKGROUND: Traditional serrated adenoma (TSA) is a very characteristic type of
serrated polyp that has a predilection for the left colon. Recent molecular
advances have shown two molecular phenotypes of TSA: one associated with BRAF
mutations and the other with KRAS mutations. The former is associated with
hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs), while the latter
is associated with more conventional adenomatous dysplasia. AIMS: The association
of TSAs with so-called precursor lesions (HPs and SSAs) is not well recognised
and the purpose of this study was to explore the coexistent presence of HPs, SSAs
and adenomatous polyps within a large cohort of TSAs. METHODS: In total 149 TSAs
were examined for the presence of HP, SSA and adenomatous polyps. RESULTS: Seen
in 83 men and 65 women ranging in age from 32 to 89 years and 127 were left sided
with 22 in the right colon. Seventy-eight of the 149 TSAs showed evidence of
another polyp (52.34%): 32 were low-grade tubular/tubulovillous adenomas
(TAs/TVAs; 41%), 28 were HPs (36%) and 18 were SSAs (23%). Eleven of the 22 right
sided TSAs were associated with a precursor lesion (1 HP and 7 SSA). In addition,
five TSAs showed more than one polyp type: TSA with TA/TVA and HP (3); TSA with
TA/TVA and SSA (2). The TAs/TVAs were adjacent to the TSA but occurred as a
separate discrete polyp, while HPs and SSAs were intermingled with the TSA and
present at the base and surface of the lesion. CONCLUSIONS: More than 50% of TSAs
are associated with a precursor lesion or adjacent TA/TVA. Their recognition is
important as this may have surveillance and management ramifications.
PMID- 25589792
TI - Utility of bone marrow examination for workup of fever of unknown origin in
patients with HIV/AIDS.
AB - AIMS: The utility of bone marrow aspiration and biopsy (BMAB) as a diagnostic
tool in patients with HIV/AIDS and fever of unknown origin (FUO) is a subject of
debate. Because highly active antiretroviral therapy has reduced incidence of
opportunistic infections, it is important to reassess the efficacy of BMAB for
this diagnostic purpose. To our knowledge, no such studies have been performed in
Harris County which has the highest incidence of HIV in the state of Texas.
METHODS: We reviewed all BMABs from patients with HIV/AIDS and FUO or persistent
cytopenia(s) from 2007 to 2011. RESULTS: Of 57 evaluable patients, BMAB was
positive in 24 samples by acid fast bacilli (AFB) or Gomori methenamine silver
(GMS) stains (17.5%), presence of granuloma and/or lymphohistiocytic aggregates
(31.6%), culture (21.0%) or a combination. Cultures demonstrated Mycobacterium
avium/intracellulare (4), M tuberculosis (2), M gordonae (1), Histoplasma
capsulatum (3) and Cryptococcus neoformans (2). There were three cases in which a
pathogen was grown in culture but that had a negative of 'direct examination' on
tissue sections (negative AFB and GMS special stains, no morphological evidence
of granuloma/lymphohistiocytic infiltrates). CONCLUSIONS: This study supports the
use of diagnostic BMAB as a rapid decision-making tool in patients with HIV and
FUO in the proper clinical setting. BMAB demonstrated infection-related evidence
prior to positive bone marrow culture in 75% of cases. Special stains and blood
cultures had similar diagnostic yield, but BMAB offers faster results. Thus, this
procedure assists in clinical decision making and the refinement of treatment in
a more timely manner.
PMID- 25589793
TI - A dynamic model of the hypoxia-inducible factor 1a (HIF-1a) network.
PMID- 25589794
TI - Assessing Trends in Women's Violence via Data Triangulation: Arrests,
Convictions, Incarcerations, & Victim Reports.
AB - Constructionist theories suggest the national rise in female violence arrests may
be policy-generated because arrest statistics are produced by violent behavior
and changing official responses (e.g., net-widening enforcement policies).
Normative theories attribute the rise to female behavior changes (e.g., in
response to increased freedoms or hardships). We examine whether any narrowing of
the arrest gender gap is borne out across offense types of varying measurement
reliability, in victimization data, and across two post-arrest criminal justice
stages. Advanced time-series analyses over 1980-2003 support the constructionist
position - first, all sources show little or no increase in women's rates for the
more reliably measured offenses of homicide and robbery, and for rape; second,
the assault gender gap narrows for arrests, but holds stable in victimization
data; third, the assault gender gap narrows moderately for convictions, but is
stable for imprisonment, indicating spill-over effects of more expansive arrest
policies. Several factors have produced greater female representation in
"criminal assault" arrests including (i) proactive policing targeting and
formally responding to minor violence and in private contexts, (ii)
interventionist developmental epistemologies that blur distinctions among
violence types and circumstances, (iii) the rise of social movements recognizing
"hidden" victims, (iv) law and order political messages stressing greater
accountability, and (v) the somewhat greater decline in male compared to female
violence in the late 1990s. The problem of women's violence is largely a social
construction. Rather than women becoming more violent, changes in the management
of violence increasingly mask differences in the violence levels of women and
men.
PMID- 25589795
TI - Residential Segregation in Metropolitan Established Immigrant Gateways and New
Destinations, 1990-2000.
AB - In the 1990s, many immigrants bypassed established gateways like Los Angeles, New
York, Chicago, and Miami to create new immigrant destinations across the U.S. In
this paper, we examine how segregation and spatial assimilation might differ
between established gateways and new destinations among the 150 largest
metropolitan areas. Using data from the 1990 and 2000 censuses, we calculate
levels of dissimilarity for Hispanics and Asians by nativity for these two
gateway types. Our findings show that segregation levels are consistently lower
in new destinations. However, Hispanics in new destinations experienced
significant increases segregation during the 1990s, suggesting a convergence in
residential patterns by destination type. Nevertheless, in both destinations the
native-born are less segregated than the foreign born-consistent with immigrant
spatial incorporation. Finally, socioeconomic indicators are generally consistent
with predictions of spatial assimilation.
PMID- 25589796
TI - Household context, generational status, and English proficiency among the
children of African immigrants in the US.
AB - This study examines how household and parental-level determinants affect English
proficiency among the children of African immigrants in the US. Within immigrant
families, the study finds that children's level of proficiency has a stronger
positive association with the proficiency of their mothers than with that of
their fathers. Children's level of English proficiency significantly increases as
the number other English-proficient children within their household increases.
These impacts are stronger on the proficiency levels of first compared to second
generation children. Levels of proficiency are, however, lowest among children in
families from Portuguese speaking countries followed by their counterparts in
families from countries where indigenous languages and Arabic are dominant.
Although proficiency levels generally improve with increasing generational
status, these improvements are smallest for children in families from Portuguese
speaking countries. Except for children in families from English speaking
countries, the largest improvements to proficiency with increasing generational
status was observed among children in families from indigenous language
backgrounds.
PMID- 25589797
TI - Interaction of Comparative Cancer Risk and Cancer Efficacy Perceptions on Cancer
Related Information Seeking and Scanning Behaviors.
AB - This study examined the interaction between perceived cancer risk and self
efficacy related to cancer screening on cancer-related information seeking and
scanning behaviors (SSB) among the general population. Individuals completed a
cross-sectional survey, were classified into 1 of 4 clusters based on their
relative risk and self-efficacy belief scores (i.e., high relative risk and high
self-efficacy, high relative risk and low self-efficacy, low relative risk and
high self-efficacy, and low relative risk and low self-efficacy), and asked about
their information SSB related to the colonoscopy, prostate-specific antigen test,
or mammogram. A national probability sample of 2,489 adults aged 40 to 70 took
part in this study. Individuals who perceived themselves to be at high relative
risk for cancer and had high self-efficacy beliefs in performing cancer-screening
behaviors generally reported the highest amounts of SSB for cancer-screening
information, compared to the others.
PMID- 25589798
TI - Use of 99m-technetium-glucoheptonate as a tracer for brain tumor imaging: An
overview of its strengths and pitfalls.
AB - Brain tumors represent a vexing clinical problem in oncology due to their
increasing incidence, difficulties in treatment and high rates of recurrence. It
is especially challenging to evaluate the posttreatment disease status because
differentiation of recurrence from treatment-induced changes (radiation necrosis)
is not possible with the use of magnetic resonance imaging, the most commonly
used imaging method in this setting. Various functional imaging methods,
including positron emission tomography and single photon emission computed
tomography (SPECT) have been employed in this context. SPECT with 99m-technetium
(99mTc)-glucoheptonate (GHA) has shown promising results for differentiation of
recurrent brain tumor from radiation necrosis. In this review, we have discussed
in details the basics of 99mTc-GHA SPECT imaging in brain tumor along with the
available literature in this regard.
PMID- 25589799
TI - Validation of virtual spectrometer created in RADlab1.03.
AB - Spectrometer is used to perform various in vitro tests. The ability to
successfully perform these tests depends on technologist's skill. Therefore,
proper training of technologists is mandatory in gamma spectrometry. During the
training, they need to have sufficient practice to gain sound theoretical and
practical knowledge. High cost of spectrometer and risk of their damage during
independent practice may hamper the process of proper training. Hence, there is a
need of cheaper and more feasible option. Virtual spectrometer created in
RADlab1.03 can address this issue. The immediate objective of this paper is to
validate this virtual spectrometer so as to be used as an educational and
research tool for trainees. Virtual spectrometer was calibrated using Cs-137
standard source and Cs-137 spectrum was recorded by positioning 28106 Bq Cs-137
source at 2.35 cm above top surface of the well, 1 cm above from the bottom of
the well and at the bottom of the well. Ba-133 and Co-60 spectrum were also
recorded. The experiments were repeated with real spectrometer for exactly the
same conditions as applied to the virtual spectrometer. The paired t-test was
applied to find the difference in mean photopeak at 5% level of significance. The
sample data provided satisfactory evidence that mean photopeak obtained with real
as well as virtual spectrometer were same at P value of 4.641 * 10(-4),1.57 * 10(
12),1.40 * 10(-24), 1.26 * 10(-16), and 8.7 * 10(-9) for Cs-137 (photopeak: 664
keV, Co-60 (photopeak: 1181 keV), Co-60 (photopeak: Co-1348 keV), Ba-133
(photopeak: 304 keV) and Ba-133 (photopeak: 364 keV) respectively.
PMID- 25589800
TI - Does the intensity of diffuse thyroid gland uptake on F-18 fluorodeoxyglucose
positron emission tomography/computed tomography scan predict the severity of
hypothyroidism? Correlation between maximal standardized uptake value and serum
thyroid stimulating hormone levels.
AB - CONTEXT: F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed
tomography (PET/CT) scan and hypothyroidism. AIMS: The aim was to determine
whether the intensity of diffuse thyroid gland uptake on F-18 FDG PET/CT scans
predicts the severity of hypothyroidism. MATERIALS AND METHODS: A retrospective
analysis of 3868 patients who underwent F-18 FDG PET/CT scans, between October
2012 and June 2013 in our institution for various oncological indications was
done. Out of them, 106 (2.7%) patients (79 females, 27 males) presented with
bilateral diffuse thyroid gland uptake as an incidental finding. These patients
were investigated retrospectively and various parameters such as age, sex,
primary cancer site, maximal standardized uptake value (SUVmax), results of
thyroid function tests (TFTs) and fine-needle aspiration cytology results were
noted. The SUVmax values were correlated with serum thyroid stimulating hormone
(S. TSH) levels using Pearson's correlation analysis. STATISTICAL ANALYSIS USED:
Pearson's correlation analysis. RESULTS: Clinical information and TFT (serum FT3,
FT4 and TSH levels) results were available for 31 of the 106 patients (27
females, 4 males; mean age 51.5 years). Twenty-six out of 31 patients (84%) were
having abnormal TFTs with abnormal TSH levels in 24/31 patients (mean S. TSH:
22.35 MUIU/ml, median: 7.37 MUIU/ml, range: 0.074-211 MUIU/ml). Among 7 patients
with normal TSH levels, 2 patients demonstrated low FT3 and FT4 levels. No
significant correlation was found between maximum standardized uptake value and
TSH levels (r = 0.115, P > 0.05). CONCLUSIONS: Incidentally detected diffuse
thyroid gland uptake on F-18 FDG PET/CT scan was usually associated with
hypothyroidism probably caused by autoimmune thyroiditis. Patients should be
investigated promptly irrespective of the intensity of FDG uptake with TFTs to
initiate replacement therapy and a USG examination to look for any suspicious
nodules.
PMID- 25589801
TI - Role of FDG PET/CT in assessing response to targeted therapy in metastatic lung
cancers: Morphological versus metabolic criteria.
AB - INTRODUCTION: Targeted therapeutic agents are indicated in metastatic lung
cancers. These being receptor specific therapies, manifestation of response can
be best assessed by estimating the metabolic activity of tumor, rather than the
size. This retrospective analysis studied metabolic and morphological response on
Positron Emission Tomography (PET) and Computed Tomography (CT), respectively to
these agents. MATERIALS AND METHODS: Thirty-one patients (23 males, 8 females
with an age range of 42-77 years) with Epidermal Growth Factor Receptor (EGFR)
positive metastatic lung cancer on Gefitinib, who underwent PET/CT, at baseline
and at 4-6 weeks, were assessed by Response Evaluation Criteria In Solid Tumors
[RECIST] 1.1 and European Organization for Research and Treatment of Cancer
(EORTC) criteria. RESULTS: Concordance between RECIST 1.1 and EORTC was seen in
26 (83.7%) patients. Discordance was seen in 5 (16.3%) patients. In patients with
discordance, the results were confirmed by follow-up imaging. Metabolic EORTC
criteria changed the disease status from stable disease to partial response (3
out of 5) and progressive disease (2 out of 5) in these five patients.
CONCLUSIONS: Metabolic criteria using PET/CT could accurately predict response as
well as disease progression early in the course of targeted therapy, compared to
morphologic criteria. In addition, early metabolic response assessment can
predict refractoriness of therapy.
PMID- 25589802
TI - Technetium-99m dimercaptosuccinic acid scan in evaluation of renal cortical
scarring: Is it mandatory to do single photon emission computerized tomography?
AB - OBJECTIVES: Renal cortical scintigraphy with technetium-99m (Tc-99m)
dimercaptosuccinic acid (DMSA) is the method of choice to detect acute
pyelonephritis and cortical scarring. Different acquisition methods have been
used: Planar parallel-hole or pinhole collimation and single photon emission
tomography (SPECT). This study compared planar parallel-hole cortical
scintigraphy and dual-head SPECT for detection of cortical defects. PATIENTS AND
METHODS: We retrospectively reviewed 190 consecutive patients with 380 kidneys
and 200 DMSA scans referred to rule out renal cortical scarring. The diagnoses
were 52 vesicoureteric reflux, 61 recurrent urinary tract infection, 39
hydronephrosis, 20 renal impairment, and 18 hypertension. All patients were
imaged 3 h after injection of Tc-99m DMSA with SPECT and planar imaging
(posterior, anterior, left, and right posterior oblique views). For each patient,
planar and SPECT images were evaluated at different sittings, in random order.
Each kidney was divided into three cortical segments (upper, middle and lower)
and was scored as normal or reduced uptake. The linear correlation coefficient
for the number of abnormal segments detected between planner and SPECT techniques
was calculated. RESULTS: From 200 DMSA scans, 100 scans were positive for scar in
SPECT images, from which only 95 scans were positive for scar in planner imaging.
Out of the five mismatched scans, three scans were for patients with renal
impairment and high background activity and two scans were for very small scars.
No significant difference was seen in the average number of abnormal segments
detected by planar versus SPECT imaging (P = 0.31). The average correlation
coefficient between was high (r = 0.91 - 0.92). CONCLUSIONS: Tc-99m DMSA renal
cortical scanning using SPECT offers no statistically significant diagnostic
advantage over multiple views planar imaging for detection of cortical defect.
PMID- 25589804
TI - Primary breast osteosarcoma: A diagnostic challenge.
AB - Extraskeletal osteosarcomas account for < 1% of the soft tissue sarcomas and are
known to more often localize in soft tissues of the lower extremities. Primary
osteosarcomas of the breast are extremely rare. A majority of the reported cases
were in fact initially erroneously diagnosed and treated as primary breast
carcinomas. We recently got to treat an interesting case of a primary breast
osteosarcoma and discuss its evaluation and management with added emphasis on the
incremental role of technetium 99-methylene diphosphonate (Tc-99m) bone
scintigraphy in its clinical diagnosis. Tc-99m uptake can occasionally be seen in
the delayed bone scintigraphy images of extra skeletal malignancies, but the
uptakes are considered to be typically less intense than the uptakes noted in
primary skeletal malignancies. Extraskeletal osteosarcomas are however the
exceptions to this rule, the intense uptake in bone scintigraphy further aided in
an accurate preoperative diagnosis and management of our patient.
PMID- 25589803
TI - Potential role of (18)F-2-fluoro-2-deoxy-glucose positron emission
tomography/computed tomography imaging in patients presenting with generalized
lymphadenopathy.
AB - Generalized lymphadenopathy is a common and often vexing clinical problem caused
by various inflammatory, infective and malignant diseases. We aimed to review
briefly and highlight the potential role of (18)F-2-fluoro-2-deoxy-glucose ((18)F
FDG) positron emission tomography/computed tomography (PET/CT) in such patients.
(18)F-FDG PET/CT can play an important role in the management of generalized
lymphadenopathy. It can help in making an etiological diagnosis; can detect
extranodal sites of involvement and employed for monitoring response to therapy.
PMID- 25589805
TI - Solitary hypervascular liver metastasis from neuroendocrine tumor mimicking
hepatocellular cancer: All that glitters is not gold.
AB - Neuroendocrine tumor metastases to the liver can mimic primary hepatocellular
carcinoma (HCC) on imaging, cytology, and core biopsy. We present a case study
along with the literature review of a patient who presented as a solitary liver
mass mimicking HCC and subsequently underwent a partial hepatectomy. The
histopathology and immunohistochemisrty of the resected specimen revealed
metastatic neuroendocrine carcinoma. Positron emission tomography (PET) scan with
(68)Ga-DOTA-NaI-octreotide ((68)Ga-DOTANOC) localized the primary tumor in the
ileum. A curative follow-up surgery for resection of the small bowel containing
the primary tumor was carried out. This case illustrates the shortcomings of
routine imaging methods, utility of immunocytochemistry and the importance of
(68)Ga-DOTANOC PET in determining the metastatic spread as well as the origin of
neuroendocrine tumors (NETs). This case report attempts to highlight the current
imaging paradigms and management strategy of midgut and other NET's at the point
of detection, staging and follow-up.
PMID- 25589806
TI - Use of yttrium-90 hydroxyapatite radiosynovectomy as a primary modality of
treatment in diffuse pigmented villonodular synovitis of the knee joint: A first
case report.
AB - Pigmented villonodular synovitis (PVNS) is a rare, relatively benign, intra
articular lesion characterized by a slowly progressive proliferation of synovial
tissue. Knee is the most frequently involved joint. Localized and diffuse forms
of synovial involvement were reported. In extensive diffuse cases, total
synovectomy is needed, almost impossible to achieve. Hence, other treatment
modalities such as intra-articular injection of yttrium-90 have been tried and
shown to be effective in reducing the rate of local recurrence with "acceptable"
joint damage. Radiosynovectomy is based on the irradiation of the joint synovium
by the intra-articular administration of various beta-emitting
radiopharmaceuticals. We describe the first case report of use of yttrium-90
hydroxyapatite particulates in a 33-year-old male who presented with diffuse PVNS
of knee joint as a primary modality of treatment.
PMID- 25589807
TI - (18)F-fluoro-deoxyglucose positron emission tomography-computed tomography in
initial assessment and diagnosis of right atrial angiosarcoma with widespread
visceral metastases: A rare case report and review of the literature.
AB - Cardiac angiosarcoma is the most common primary cardiac sarcoma in adults.
Primary cardiac tumors are rare and have nonspecific clinical presentation, thus
making its diagnosis challenging. Clinically, patients present with advanced
disease demonstrating metastatic disease at initial presentation itself. It
commonly metastasizes to lung, liver, brain, and bone; however metastases to
lymph nodes, adrenal glands, spleen and skin has also been seen. We describe a
case of right atrial angiosarcoma with extensive visceral metastases involving
brain, lungs, liver, pancreas, kidney, and lymph nodes, demonstrated on contrast
enhanced (18)F-fluoro-deoxyglucose positron emission tomography-computed
tomography (FDG PET-CT). To the best of our knowledge metastases to pancreas and
kidney have not been reported so far in the literature. With our report, we
emphasize on the initial use of FDG PET-CT in workup of cardiac angiosarcoma for
accurate staging and prognostication of this disease.
PMID- 25589808
TI - Osteopetrosis: radiological & radionuclide imaging.
AB - Osteopetrosis is a rare inherited bone disease where bones harden and become
abnormally dense. While the diagnosis is clinical, it also greatly relies on
appearance of the skeleton radiographically. X-ray, radionuclide bone
scintigraphy and magnetic resonance imaging have been reported to identify
characteristics of osteopetrosis. We present an interesting case of a 59-year-old
man with a history of bilateral hip fractures. He underwent (99m)Tc-methylene
diphosphonate whole body scan supplemented with single-photon emission computed
tomography/computed tomography of spine, which showed increased uptake in the
humeri, tibiae and femora, which were in keeping with osteopetrosis.
PMID- 25589809
TI - Synchronous thoracic and abdominal enteric duplication cysts: Accurate detection
with (99m)Tc-pertechnetate scintigraphy.
AB - Enteric duplication cysts (EDCs) are uncommon congenital anomalies, which can
occur anywhere along the gastrointestinal tract and vary greatly in presentation,
size, location and symptoms. Ectopic gastric mucosa is reported to be found in 20
30% of these duplications. (99m)Tc-pertechnetate scintigraphy is a useful
modality for preoperative localization of the ectopic functioning gastric mucosa
in the EDCs. We report a case where (99m)Tc-pertechnetate scintigraphy was useful
in detecting synchronous thoracic and abdominal duplication cysts with
functioning gastric mucosa thus having an impact on the patient management.
PMID- 25589810
TI - Fluoro deoxyglucose positron emission tomography-computerized tomography in
primary staging and response assessment of a rare case of primary pleural
synovial sarcoma.
AB - Primary pleural sarcomas constitute <1% of all primary lung cancers. Synovial
sarcomas of the pleura are extremely rare. They may be mistaken for malignant
mesothelioma or other spindle cell tumors, but the confirmation is by histology
and immunohistochemistry. Synovial sarcomas are aggressive with a high incidence
of recurrence. In this case report, we present the 18-fluoride-fluoro
deoxyglucose (FDG) positron emission tomography-computerized tomography (PET-CT)
findings of patient with primary pleural synovial cell sarcoma. The pretreatment
and postchemotherapy FDG PET-CT scans are presented. The role of FDG PET-CT in
initial staging and response assessment in this interesting case of pleural
synovial sarcoma is presented.
PMID- 25589811
TI - Rare solitary focal tuberculous involvement of liver masquerading as hepatic
metastasis on FDG PET/CT in a case of fibular round cell tumor.
AB - Finding of focal 18F-fluoro-deoxyglucose (FDG) uptake in liver on FDG positron
emission tomography/computed tomography (FDG PET/CT) in a known case of
malignancy is often considered to be metastases. We report a similar finding on
FDG PET/CT in a case of Ewing's sarcoma of thigh, which turned out to be of
tuberculous etiology, an unusual cause of false positive FDG uptake in the liver.
PMID- 25589812
TI - (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography staging
of mucinous tubular and spindle cell carcinoma of the kidney.
AB - Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an
extremely rare carcinoma of the kidney, which develops by malignant
differentiation of the collecting ducts or the loop of Henle. The tumor can occur
at all ages, with 4 times higher prevalence in females than in males. A 62-year
old female patient presented with an asymptomatic mass lesion in the left kidney.
The ultrasound revealed a hyperechogenic mass lesion measuring 4 cm in diameter
and centrally located in the left kidney. Computed tomography (CT) revealed an
isodense mass lesion measuring 4 cm in diameter and posterolaterally located in
the left kidney. Magnetic resonance imaging revealed a renal mass of 4 cm in
diameter with hypervascular contrast uptake. For primary staging, (18)F
fluorodeoxyglucose-positron-emission tomography ((18)FDG-PET)/CT revealed left
renal cell carcinoma (RCC) with a maximum standard uptake value of 6.7. The
patient underwent transperitoneal radical nephrectomy. The immunohistochemical
examination revealed MTSCC-K. (18)FDG-PET/CT provides 81-89% sensitivity and 83
100% specificity in primary staging of the renal cancers, in diagnosing
metastatic RCC, and monitoring the response to therapy. Its use in the staging of
MTSCC of the kidney has not been previously described in the literature. This
case highlights the usefulness of (18)FDG-PET/CT in the staging of this rare
tumor.
PMID- 25589813
TI - Contrast-enhanced (18)F-fluorodeoxyglucose positron emission tomography/computed
tomography in immunoglobulin G4-related retroperitoneal fibrosis.
AB - Immunoglobulin G4 (IgG4)-related disease encompasses a wide variety of immune
disorders previously thought be distinct. IgG4-related retroperitoneal fibrosis
is one such entity. Metabolic imaging with (18)F-fluorodeoxyglucose ((18)F-FDG)
positron emission tomography/computed tomography (PET/CT) can be useful in the
management of IgG4-related retroperitoneal fibrosis. We here discuss the case of
63-year-old male with IgG4-related retroperitoneal fibrosis and the role, (18)F
FDG PET/CT played in his management.
PMID- 25589814
TI - Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography
in evaluation of residual intramuscular myxoma.
AB - Intramuscular myxoma (IM) is a rare benign neoplasm. In a patient diagnosed with
IM of left thigh, we report the utility of a postoperative fluorine-18
fluorodeoxyglucose positron emission tomography-computed tomography scan in
assessing the efficacy of surgical excision.
PMID- 25589782
TI - Higher mortality in patients with right hemispheric intracerebral haemorrhage:
INTERACT1 and 2.
AB - BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of
the affected hemisphere in stroke. We aimed to determine the relationship between
laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes.
METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies-
randomised controlled trials of patients with spontaneous acute ICH with elevated
systolic blood pressure (BP), randomly assigned to intensive (target systolic BP
<140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the
combined and separate end points of death and major disability (modified Rankin
scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total
of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90
days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death
at 90 days compared to those with left hemispheric ICH after adjustment for
potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no
differences between patients with right and left hemispheric ICH regarding the
combined end point of death or major disability or major disability in the
multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01),
respectively). CONCLUSIONS: Right hemispheric lesion was associated with
increased risk of death in patients with acute ICH. The laterality of the ICH
does not appear to affect the level of disability in survivors. TRIAL
REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier:
NCT00226096 and NCT00716079.
PMID- 25589815
TI - "Pseudo-thyroid lobe": A diagnostic conundrum caused by ossified anterior
longitudinal ligament on bone scan.
AB - Radionuclide bone imaging is one of the most commonly performed nuclear medicine
procedure around the world and characterized by its high sensitivity and
relatively low specificity. False positive findings on a bone scan are very
common; however, dense uptake over unilateral ossified anterior longitudinal
ligament appearing as single thyroid lobe on a bone scan has not been described
in the literature.
PMID- 25589816
TI - An uncommon case showing three different pathologies on (99m)technetium-methylene
diphosphonate bone scintigraphy.
AB - (99m)Technetium-methylene diphosphonate bone scintigraphy (BS) has an important
role in evaluating skeletal pathology, especially its extent. Incidental extra
osseous uptake may sometimes be seen in soft-tissue pathologies. We present a 64
year-old female with skull base osteomyelitis referred for BS which revealed
involvement of the skull base on the left side, uptake was also noted in
bilateral lungs secondary to hypercalcemia of renal failure and in the D12-L1
vertebrae as the patient had a history of Pott's spine. This is perhaps a unique
case showing three findings each of a different etiology in the same scan.
PMID- 25589817
TI - Mesenteric metastases of purely myxoid liposarcoma: An unusual behavior of
primary tumor depicted on fludeoxyglucose positron emission
tomography/computerized tomography.
AB - A 48-year-old male patient with purely myxoid liposarcoma was referred to
fludeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT)
for restaging. FDG PET/CT images showed a hypodense well-defined intermuscular
mass with mild FDG uptake in the right gluteal region. In addition, multiple mild
hypermetabolic masses that had similar characteristics with the aforementioned
lesion were also revealed in the mesenteric region of abdomen and pelvis.
PMID- 25589818
TI - Gliomatosis cerebri mimicking encephalitis evaluated using fluorine-18
fluorodeoxyglucose: Positron emission tomography/computed tomography.
AB - Gliomatosis cerebri (GC) is a rare condition in which an infiltrative glial
neoplasm spreads through the brain with preservation of the underlying structure.
F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG
PET/CT) has an important role in demonstrating the appropriate metabolism and
differentiating pathologies mimicking GC on CT and magnetic resonance imaging. We
describe imaging findings of FDG PET/CT in GC in a 9-year-old male child
mimicking encephalitis.
PMID- 25589821
TI - (175)Yb-TTHMP for bone pain palliation.
PMID- 25589820
TI - (18)F-FDG PET/CT imaging in a seldom case of primary malignant melanoma of
duodenum.
PMID- 25589822
TI - Varying Coefficient Models for Sparse Noise-contaminated Longitudinal Data.
AB - In this paper we propose a varying coefficient model for highly sparse
longitudinal data that allows for error-prone time-dependent variables and time
invariant covariates. We develop a new estimation procedure, based on covariance
representation techniques, that enables effective borrowing of information across
all subjects in sparse and irregular longitudinal data observed with measurement
error, a challenge in which there is no adequate solution currently. More
specifically, sparsity is addressed via a functional analysis approach that
considers the observed longitudinal data as noise contaminated realizations of a
random process that produces smooth trajectories. This approach allows for
estimation based on pooled data, borrowing strength from all subjects, in
targeting the mean functions and auto- and cross-covariances to overcome sparse
noisy designs. The resulting estimators are shown to be uniformly consistent.
Consistent prediction for the response trajectories are also obtained via
conditional expectation under Gaussian assumptions. Asymptotic distribution of
the predicted response trajectories are derived, allowing for construction of
asymptotic pointwise confidence bands. Efficacy of the proposed method is
investigated in simulation studies and compared to the commonly used local
polynomial smoothing method. The proposed method is illustrated with a sparse
longitudinal data set, examining the age-varying relationship between calcium
absorption and dietary calcium. Prediction of individual calcium absorption
curves as a function of age are also examined.
PMID- 25589823
TI - The Educational Attainment Process Among Adolescents with Disabilities And
Children of Parents with Disabilities.
AB - This article uses data from the National Longitudinal Survey of Youth 1997
(NLSY97) to examine the relationship between disability, parental and youth
university expectations in 1997, and youth high school completion and university
enrolment by 2003. Results indicate that educational attainment is not equal for
young adults with and without disabilities in the United States. Parents-but not
adolescents-are likely to reduce their educational expectations when adolescents
have a mild or serious disability, net of school performance. These parental-but
not adolescent-expectations are significantly associated with high school
completion. Finally, even after controlling for educational expectations and
school performance, youth with serious disabilities are much less likely to
graduate from high school than youth without disabilities. Despite the
considerable strides made in the implementation of the Individuals with
Disabilities Education Act, students with disabilities are not achieving
educational parity in graded schooling.
PMID- 25589819
TI - Forced diuresis (18)F-fluorodeoxyglucose positron emission tomography/contrast
enhanced in detection of carcinoma of urinary bladder diverticulum.
AB - Urinary bladder diverticular carcinomas are uncommon with a lesser incidence of
0.8-10% and its diagnosis still remains a challenge. Cystoscopy is the most
reliable method, but evaluating diverticulum with narrow orifices is difficult.
Before the initiation of appropriate treatment, proper detection of bladder
diverticular carcinoma and its locoregional and distant sites of involvement is
necessary. Here, we present a case of 48-year-old male with urinary bladder
diverticular carcinoma detected by forced diuretic (18)F-fluorodeoxyglucose
positron emission tomography/computerized tomography ((18)F-FDG PET/CT). This
case also highlights the significance of forced diuretic (18)F-FDG PET/CT in the
detection, staging, and response evaluation of bladder diverticular carcinoma.
PMID- 25589824
TI - Interaction of methotrexate, an anticancer agent, with copper(II) ions:
coordination pattern, DNA-cleaving properties and cytotoxic studies.
AB - The acid-base properties and the Cu(II) binding processes of methotrexate (MTX)
were characterized by selected spectroscopic techniques and potentiometric
measurements. The pH titration data showed that MTX behaves as a triprotic
ligand. The deprotonation constants were determined for alpha-COOH and gamma-COOH
groups and (N1)H+ from the pteridine ring. Taking all the obtained results into
consideration, a coordination pattern was proposed. The DNA-cleaving activity and
reactive oxygen species (ROS) generation were investigated for both MTX and the
Cu(II)-MTX system. The complex displayed a promising nuclease activity toward
plasmid DNA in the presence of hydrogen peroxide. Interestingly, the induction of
ROS, such as hydroxyl radicals, superoxide anions or singlet oxygen, was excluded
and a different mechanism of DNA degradation was proposed. As MTX is now commonly
used in anticancer therapy i.e. against lung cancer, basic cell-based studies
were carried out to establish if its Cu(II) complex exhibits higher cytotoxic
properties than the ligand alone. Activities of both compounds were also tested
against colon carcinoma. Moreover, the determined values of IC50 were confronted
with the cytotoxic activity of cisplatin.
PMID- 25589825
TI - QSPR analysis of some agonists and antagonists of alpha-adrenergic receptors.
AB - Thirty-three compounds belonging to the sympatholytics and sympathomimetics were
analyzed during the study. The biological activity data for the parameters of
binding affinity to the alpha1- and alpha2-adrenergic receptors together with
parameters of the logarithm of the partition coefficient n-octanol/water (log P)
were performed using a semi-empirical calculations methods for isolated molecules
(in vacuo) and for the molecules placed in an aqueous environment. Additionally,
the chromatographic retention data were used as extra dependent variables of the
structural parameters for a part of the considered compounds. Finally, all those
groups of parameters were analyzed using MLR, PCA, and FA methods for the
classification of studied compounds according to their chemical structures and
pharmacological activity to the adrenoceptors.
PMID- 25589826
TI - Changes in Drinking Patterns Across the Transition to College Among First-Year
College Males.
AB - Few studies examine changes in drinking behavior during the transition from high
school to college. Using a sample of 239 first-year males, we hypothesized that
participants would increase drinking from pre-college to the first month of
college. Results reveal a general trend toward increased drinking upon entering
college. Caucasians increased drinking more than non-Caucasians. Social
expectancies of alcohol moderated increases in drinking behavior. These findings
indicate that differential changes in drinking behavior occur among incoming
college males. Interventions with college students need to address both
preventing heavy consumption and alcohol-related problems in pre-college light
drinkers and in reducing these behaviors among pre-college heavy drinkers.
PMID- 25589827
TI - Methods for the morphological and functional evaluation of microvascular damage
in systemic sclerosis.
AB - Systemic sclerosis is a connective tissue disease characterized by alterations in
microvascular structure and function. In these patients, numerous studies have
demonstrated a relationship between capillary morphology and peripheral blood
perfusion. Nailfold videocapillaroscopy reveals the peripheral microvascular
morphology and thus allows classification and scoring of capillary abnormalities
with respect to different microangiopathy patterns (early, active, and late).
Laser Doppler flowmetry and laser speckle contrast analysis can be used to
estimate cutaneous blood flow through microvessels and to assess and quantify
blood perfusion at peripheral sites. These two methods are also used to identify
changes in digital blood perfusion after the infusion of vasodilators.
PMID- 25589829
TI - Major changes and improvements of dialysis therapy in Korea: review of end-stage
renal disease registry.
AB - The Korean Society of Nephrology (KSN) launched a nationwide end-stage renal
disease (ESRD) patient registry in 1985 called the Insan Prof. Byung-Suk Min
Memorial ESRD Patient Registry. KSN members voluntarily participate in this
registry, which has been collecting data through the Internet since 2000. The KSN
ESRD patient registry data were reviewed to elucidate the major changes and
improvements in dialysis therapy in Korea. The data review revealed: a rapid
increase in the number of patients with ESRD; an increase in the number of
patients with diabetic nephropathy; a decrease in the proportion of patients
undergoing peritoneal dialysis; an increase in the role of private dialysis
clinics; an increase in the number of elderly patients undergoing dialysis and
the number of patients undergoing long-term dialysis; a decrease in mean blood
pressure and an increase in pulse pressure; improvement in anemia treatment;
improvement in dialysis adequacy; and improvement in the survival of patients
undergoing dialysis. In conclusion, improvements have been made in blood pressure
control, anemia treatment, and dialysis adequacy despite increases in the number
of elderly patients, diabetic patients, and patients on long-term dialysis during
the last two decades in Korea.
PMID- 25589831
TI - Can improvements in our physiological understanding yield information on the
utility of endothelial progenitor cell capture stents?
PMID- 25589828
TI - Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes.
AB - Hypoglycemia is a major barrier to achieving the glycemic goal in patients with
type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event
that requires the assistance of another person to actively administer
carbohydrates, glucagon, or take other corrective actions, is a serious clinical
concern in patients with diabetes. If severe hypoglycemia is not managed
promptly, it can be life threatening. Hypoglycemia-associated autonomic failure
(HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective
glucose counter-regulation (altered insulin secretion, glucagon secretion, and an
attenuated increase in epinephrine during hypoglycemia) and a lack of awareness
regarding hypoglycemia (attenuated sympathoadrenal activity) are common
components of HAAF in patients with diabetes. There is considerable evidence that
hypoglycemia is an independent risk factor for cardiovascular disease. In
addition, hypoglycemia has a significant influence on the quality of life of
patients with diabetes. To prevent hypoglycemic events, the setting of glycemic
goals should be individualized, particularly in elderly individuals or patients
with complicated or advanced type 2 diabetes. Patients at high-risk for the
future development of severe hypoglycemia should be selected carefully, and
intensive education with reinforcement should be implemented.
PMID- 25589830
TI - Is tenofovir disoproxil fumarate an all-powerful weapon in the treatment of
chronic hepatitis B?
PMID- 25589832
TI - Association of metabolic syndrome with coronary artery calcification.
PMID- 25589833
TI - Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple
nucleos(t)ide analogue failure in chronic hepatitis B patients.
AB - BACKGROUND/AIMS: The efficacy of tenofovir disoproxil fumarate (TDF) for the
treatment of chronic hepatitis B (CHB) patients following prior treatment failure
with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in
Asian populations. In this study we investigated the efficacy and safety of TDF
rescue therapy in CHB patients after multiple NA treatment failure. METHODS: The
study retrospectively analyzed 52 CHB patients who experienced failure with two
or more NAs and who were switched to regimens containing TDF. The efficacy and
safety assessments included hepatitis B virus (HBV) DNA undetectability,
hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT)
normalization and changes in serum creatinine and phosphorus levels. RESULTS: The
mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration
of 34.5 months of TDF treatment, the cumulative probabilities of achieving
complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12,
24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48
patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with
elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly
associated with increased CVR rates (p < 0.001). However, CVR rates did not
differ between TDF monotherapy or combination therapy with other NAs, and were
not affected by mutations associated with resistance to NAs. No significant
adverse events were observed. CONCLUSIONS: TDF is an efficient and safe rescue
therapy for CHB patients after treatment failure with multiple NAs.
PMID- 25589834
TI - Impact of an endothelial progenitor cell capturing stent on coronary
microvascular function: comparison with drug-eluting stents.
AB - BACKGROUND/AIMS: Although drug-eluting stents (DESs) effectively reduce
restenosis following percutaneous coronary intervention (PCI), they also delay re
endothelialization and impair microvascular function, resulting in adverse
clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by
providing a functional endothelial layer on the stent, have beneficial effects on
microvascular function. However, data on coronary microvascular function in
patients with EPC stents versus DESs are lacking. METHODS: Seventy-four patients
who previously underwent PCI were enrolled in this study. Microvascular function
was evaluated 6 months after PCI based on the index of microvascular resistance
(IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the
mean distal coronary pressure at maximal hyperemia to the inverse of the
hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn
by the baseline mean transit time. RESULTS: Twenty-one patients (age, 67.2 +/-
9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 +/-
14.7 years; male:female, 40:13) with second-generation DESs were included in the
study. There were no significant differences in the baseline clinical and
angiographic characteristics of the two groups. Angiography performed 6 months
postoperatively did not show significant differences in their CFR values.
However, patients with the EPC stent had a significantly lower IMR than patients
with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18]
vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). CONCLUSIONS:
Microvascular dysfunction was significantly improved after 6 months in patients
with EPC stents compared to those with DESs. The complete re-endothelialization
achieved with the EPC stent may provide clinical benefits over DESs, especially
in patients with microvascular dysfunction.
PMID- 25589835
TI - Clinical impact of routine follow-up coronary angiography after second- or third
generation drug-eluting stent insertion in clinically stable patients.
AB - BACKGROUND/AIMS: In the bare-metal stent era, routine follow-up coronary
angiography (RFU CAG) was used to ensure stent patency. With the advent of drug
eluting stents (DESs) with better safety and efficacy profiles, RFU CAG has been
performed less often. There are few data on the clinical impact of RFU CAG after
second- or third-generation DES implantation in clinically stable patients with
coronary artery disease; the aim of this study was to examine this issue.
METHODS: We analyzed clinical outcomes retrospectively of 259 patients who were
event-free at 12-month after stent implantation and did not undergo RFU CAG
(clinical follow-up group) and 364 patients who were event-free prior to RFU CAG
(angiographic follow-up group). Baseline characteristics were compared between
the groups. RESULTS: The Kaplan-Meier estimated total survival and major adverse
cardiac event (MACE)-free survival did not differ between the groups (p = 0.100
and p = 0.461, respectively). The cumulative MACE rate was also not different
between the groups (hazard ratio, 0.85; 95% confidence interval, 0.35 to 2.02).
In the angiographic follow-up group, 8.8% revascularization was seen at RFU CAG.
CONCLUSIONS: RFU CAG did not affect long-term clinical outcome after second- or
third-generation DES implantation in clinically stable patients.
PMID- 25589836
TI - Pleural fluid characteristics of pleuropulmonary paragonimiasis masquerading as
pleural tuberculosis.
AB - BACKGROUND/AIMS: Pleuropulmonary paragonimiasis produces no specific symptoms or
radiologic findings, allowing for the possibility of misdiagnosis. We evaluated
the specific clinical and pleural fluid features of pleuropulmonary
paragonimiasis masquerading as pleural tuberculosis. METHODS: We retrospectively
analyzed the clinical and radiologic characteristics of 20 patients diagnosed
with pleuropulmonary paragonimiasis between 2001 and 2011. RESULTS: In total, 17
patients presented with respiratory symptoms, including dyspnea (30%), hemoptysis
(20%), cough (20%), and pleuritic chest pain (15%). Chest radiographs revealed
intrapulmonary parenchymal lesions, including air-space consolidation (30%),
nodular opacities (20%), cystic lesions (15%), ground-glass opacities (10%), and
pneumothorax (5%). A pleural fluid examination revealed eosinophilia, low glucose
levels, and high lactate dehydrogenase (LDH) levels in 87%, 76%, and 88% of the
patients, respectively. These traits helped to distinguish pleuropulmonary
paragonimiasis from other pleural diseases such as parapneumonic effusion,
malignancy, and pleural tuberculosis. CONCLUSIONS: Pleuropulmonary paragonimiasis
is often initially misdiagnosed as other pleural diseases. Therefore, it is
important to establish the correct diagnosis. In patients with unexplained
pleural effusion living in paragonimiasis-endemic areas, pleural fluid obtained
by thoracentesis should be examined to distinguish pleuropulmonary
paragonimiasis. When marked eosinophilia, high LDH levels, and low glucose levels
are identified in pleural fluid, physicians could consider a diagnosis of
pleuropulmonary paragonimiasis.
PMID- 25589837
TI - Proteomic differences with and without ozone-exposure in a smoking-induced
emphysema lung model.
AB - BACKGROUND/AIMS: Acute exacerbations in chronic obstructive pulmonary disease may
be related to air pollution, of which ozone is an important constituent. In this
study, we investigated the protein profiles associated with ozone-induced
exacerbations in a smoking-induced emphysema model. METHODS: Mice were divided
into the following groups: group I, no smoking and no ozone (NS + NO); group II,
no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and
group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear
intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography
tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were
performed. RESULTS: The MLIs of groups III (S + NO) and IV (S + O) (45 +/- 2 and
44 +/- 3 um, respectively) were significantly higher than those of groups I (NS +
NO) and II (NS + O) (26 +/- 2 and 23 +/- 2 um, respectively; p < 0.05). Fourteen
spots that showed significantly different intensities on image analyses of two
dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by
LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels
of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were
decreased by both smoking and ozone treatment in Western blotting and proteomic
analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased
by both smoking and ozone treatment. CONCLUSIONS: TBC1D5 could be a biomarker of
ozone-induced lung injury in emphysema.
PMID- 25589838
TI - Metabolic syndrome criteria as predictors of subclinical atherosclerosis based on
the coronary calcium score.
AB - BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic
syndrome (MetS) criteria (International Diabetes Federation [IDF], National
Cholesterol Education Program Adult Treatment Panel III [ATP III], and European
Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary
artery calcification (CAC) score in a cross-sectional study. This has not been
evaluated in previous studies. METHODS: A total of 24,060 subjects were screened
for CAC by multi-detector computed tomography. The presence of CAC was defined as
a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three
different sets of MetS criteria and according to number of MetS components.
RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS,
as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%,
25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for
multivariate regression models revealed no significant difference among the three
sets of criteria. After adjustment for risk factors, the ATP III criteria
produced a slightly higher odds ratio for CAC compared with the other criteria,
but this difference was not significant. The risk factor-adjusted odds ratio for
the presence of CAC increased from 1 to 1.679 as the number of MetS components
defined by ATP III increased from 0 to >= 3 (p for trend < 0.001). CONCLUSIONS:
The presence of MetS was associated with the presence of CAC. There was no
significant difference among the three sets of MetS criteria in terms of the
ability to predict CAC. An increase in the number of MetS components was
associated with an increased odds of CAC.
PMID- 25589839
TI - The association between an abnormal post-voiding urine volume and a lower
estimated glomerular filtration rate in patients with type 2 diabetes with no
voiding symptoms.
AB - BACKGROUND/AIMS: Diabetic cystopathy is a frequent complication of diabetes
mellitus. This study assessed the association between the post-voiding residual
(PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding
symptoms. METHODS: This study investigated 42 patients with type 2 diabetes who
were followed regularly at our outpatient clinic between July 1, 2008 and June
30, 2009. No patient had voiding problems or International Prostate Symptom
Scores (IPSSs) >= 12. An urologist performed the urological evaluations and the
PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was
considered abnormal, which was the primary study outcome. RESULTS: The mean
patient age was 60 +/- 10 years; the IPSS score was 3.7 +/- 3.3; and the diabetes
duration was 11.9 +/- 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50
mL. The presence of overt proteinuria or microalbuminuria was associated with an
increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a
significantly lower estimated glomerular filtration rate (eGFR) compared with
those with a PVR <= 50 mL (59.2 +/- 27.1 mL/min/1.73 m(2) vs. 28.7 +/- 23.3
mL/min/1.73 m(2); p < 0.001). Multivariate logistic analysis revealed that a
lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04)
was a significant risk factor for a PVR > 50 mL. CONCLUSIONS: Patients with
diabetic nephropathy had a significantly higher PVR and a lower eGFR was
associated with an abnormal PVR.
PMID- 25589840
TI - The efficacy of low-dose transdermal fentanyl in opioid-naive cancer patients
with moderate-to-severe pain.
AB - BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal
fentanyl (TDF) patches in opioid-naive patients with moderate-to-severe cancer
pain. METHODS: This study had an open-label, prospective design, and was
conducted between April 2007 and February 2009 in seven tertiary cancer
hospitals; 98 patients were enrolled. TDF was started using a low-dose
formulation (12.5 ug/hr), and the dose was adjusted according to the clinical
situation of individual patients. Pain intensity, the TDF doses used, and adverse
events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to
treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%)
completed the study. The median pain intensity decreased from 6.0 to 3.0 (p <
0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was
consistent across groups separated according to gender (p < 0.001), age (p <
0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain
intensity (p < 0.001). The decrease in pain intensity was significantly greater
in the severe group compared with the moderate group (mean +/- SD, 5.10 +/- 2.48
vs. 2.48 +/- 1.56; p < 0.001). TDF dose (27.8 ug/hr vs. 24.8 ug/hr, p = 0.423)
and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain
control were not different between the two pain-intensity groups. Patients had
AEs of only mild or moderate intensity; among these, nausea (38%) was the most
common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose
TDF was an effective treatment for patients with cancer pain of moderate-to
severe intensity. Further randomized trials assessing the efficacy of TDF for
severe pain and/or optimal starting doses are warranted.
PMID- 25589841
TI - Utilization of the respiratory virus multiplex reverse transcription-polymerase
chain reaction test for adult patients at a Korean tertiary care center.
AB - BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important
respiratory pathogens in adult patients, and the multiplex reverse transcription
polymerase chain reaction (RT-PCR) test is used frequently in adult patients with
respiratory infections. However, clinical data regarding utilization of the
multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the
utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital
in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study
period, the multiplex RT-PCR test was performed for 291 adult patients. The test
frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of
respiratory bacterial culture studies. A turnaround time of < 48 hours was
observed in 25.9% of positive tests. Most of the tests were performed for
admitted patients (97.9%) with a community-acquired infection (84.2%) during the
flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV
positivity rates for community- and hospital-acquired infections did not differ
(28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a
viral infection. Among the patients with RV-associated pneumonia, an RV other
than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT
PCR test for RVs was infrequently performed at a tertiary care center, and the
test results were often reported late. The test was most often performed for
admitted adult patients with community-acquired infections during the flu season.
The utilization of multiplex RT-PCR testing for RVs in current clinical practice
should be improved.
PMID- 25589843
TI - Cholangiocarcinoma with a paraneoplastic leukemoid reaction mimicking a pyogenic
liver abscess.
PMID- 25589842
TI - Mortality in patients with rheumatoid arthritis-associated interstitial lung
disease treated with an anti-tumor necrosis factor agent.
AB - BACKGROUND/AIMS: To evaluate the impact on mortality of anti-tumor necrosis
factor (anti-TNF) treatment of rheumatoid arthritis-associated interstitial lung
disease (RA-ILD). METHODS: We retrospectively reviewed the medical records of 100
RA-ILD patients who visited our tertiary care medical center between 2004 and
2011, identified those treated with an anti-TNF agent, divided patients into non
survivor and survivor groups and evaluated their clinical characteristics and
causes of death. RESULTS: A total of 24 RA-ILD patients received anti-TNF
therapy, of whom six died (25%). Mean age at initiation of anti-TNF therapy was
significantly higher in the nonsurvivor versus survivor group (76 years [range,
66 to 85] vs. 64 years [range, 50 to 81], respectively; p = 0.043). The mean
duration of anti-TNF treatment in the non-survivor group was shorter (7 months
[range, 2 to 14] vs. 23 months [range, 2 to 58], respectively; p = 0.030). The
duration of anti-TNF therapy in all nonsurviving patients was < 12 months.
Pulmonary function test results at ILD diagnosis, and cumulative doses of disease
modifying drugs and steroids, did not differ between groups. Five of the six
deaths (83%) were related to lung disease, including two diffuse alveolar
hemorrhages, two cases of acute exacerbation of ILD, and one of pneumonia. The
sixth patient died of septic shock following septic arthritis of the knee.
CONCLUSIONS: Lung complications can occur within months of initial anti-TNF
treatment in older RA-ILD patients; therefore, anti-TNF therapy should be used
with caution in these patients.
PMID- 25589844
TI - A functioning adrenal adenoma and pheochromocytoma in the same adrenal gland: two
discrete adrenal incidentalomas.
PMID- 25589845
TI - An insulinoma with an aberrant feeder from the splenic artery detected by super
selective arterial calcium stimulation with venous sampling.
PMID- 25589846
TI - Extranodal natural killer/T-cell lymphoma of the tenosynovium of the hand.
PMID- 25589847
TI - Occurrence of colonic liposarcoma after retroperitoneal liposarcoma.
PMID- 25589848
TI - Dual ectopic thyroid presenting with an anterior neck mass.
PMID- 25589850
TI - A new genus of soft coral (Cnidaria, Octocorallia) from the Republic of Congo
(Pointe-Noire Region).
AB - A new genus of soft coral from the Republic of Congo is described, Complexum gen.
n. Nine West African octocoral species previously described in the genus
Alcyonium by Tixier-Durivault (1955) are referred to this new genus, and a new
species is described and figured, Complexumpusillum sp. n. The new species is
characterized by having encrusting growth form and abundant spiny clubs in the
surface of the polyparium. It colonizes shallow calcareous rocky banks (5 to 20 m
depth) existing in coastal water of the region of Pointe-Noire. Based on
molecular phylogeny this new genus is well separated from Alcyonium species.
PMID- 25589851
TI - A new genus and species of Thyasiridae (Mollusca, Bivalvia) from deep-water,
Beaufort Sea, northern Alaska.
AB - Bivalve mollusk shells were collected in 2350 m depth in the Beaufort Sea, Arctic
Ocean off northern Alaska. Initial identification suggested the specimens were a
member of the bivalve family Thyasiridae, but no known eastern Pacific or Arctic
living or fossil thyasirid resembled these deep-water specimens. Comparisons were
made with the type of the genera Maorithyas Fleming, 1950, Spinaxinus Oliver &
Holmes, 2006, Axinus Sowerby, 1821, and Parathyasira Iredale, 1930. We determined
the Beaufort Sea species represents a new genus, herein described as
Wallerconcha. These specimens also represent a new species, herein named
Wallerconchasarae. These new taxa are compared with known modern and fossil
genera and species of thyasirds.
PMID- 25589852
TI - Four new species of the genus Saigona Matsumura (Hemiptera, Fulgoromorpha,
Dictyopharidae) from China.
AB - Four new species of the genus Saigona Matsumura, 1910, Saigonaanisomorpha Zheng,
Yang & Chen, sp. n., Saigonadaozhenensis Zheng, Yang & Chen, sp. n.,
Saigonadicondylica Zheng, Yang & Chen, sp. n. and Saigonatenuisa Zheng, Yang &
Chen, sp. n., from China, are described and illustrated. A key to the species of
Saigona is provided.
PMID- 25589849
TI - Rhupus syndrome.
PMID- 25589853
TI - A new replacement name for Tropidocephalaspeciosa Ding, 2006 (Hemiptera,
Fulgoromorpha, Delphacidae).
AB - A new replacement name is proposed for the species Tropidocephalaspeciosa Ding,
2006 (Hemiptera: Fulgoromorpha: Delphacidae: Tropidocephalini), preoccupied by
Tropidocephalaspeciosa (Bierman, 1908): Tropidocephaladingi Sun, Yang & Chen,
nom. n. = Tropidocephalaspeciosa Ding, 2006. The photographs and illustrations of
this species are also provided.
PMID- 25589854
TI - Revision of the planthopper genus Nycheuma Fennah (Hemiptera, Fulgoromorpha,
Delphacidae).
AB - Chinese species in the genus Nycheuma Fennah, 1964a (Hemiptera: Fulgoromorpha:
Delphacidae: Delphacinae: Delphacini) are revised to include three species:
Nycheumacognatum (Muir, 1917), Nycheumadimorpha (Matsumura, 1910) and
Nycheumanilotica Linnavuori, 1973. Nycheumacoctum Yang, 1989 is placed in
synonymy with Nycheumanilotica Linnavuori, 1973. Nycheumadimorpha (Matsumura,
1910) is newly recorded from China. The generic characteristics are redefined.
The main morphological characters, male genitalia of 3 species are described or
redescribed and illustrated. A key to Chinese species in the genus is provided.
PMID- 25589856
TI - Eucharitidae (Hymenoptera, Chalcidoidea), a family new to the fauna of Saudi
Arabia, with the description of the previously unknown male of Eucharis
(Psilogastrellus) affinis Boucek.
AB - The family Eucharitidae (Hymenoptera: Chalcidoidea) is recorded for the first
time for the fauna of Saudi Arabia based on Hydrorhoacaffra (Westwood) and
Eucharis (Psilogastrellus) affinis Boucek. The record of Hydrorhoacaffra suggests
that Al-Baha and Asir provinces should be considered as part of the Afrotropical
rather than the Palaearctic region. The previously unknown male of
Eucharisaffinis Boucek is described and figured. Macrophotographs of the species
are provided.
PMID- 25589857
TI - Circanota: a new genus of Sparganothini from the Neotropics, and its two new
species (Lepidoptera, Tortricidae).
AB - Circanota, new genus, and its two new species, Circanotaundulata sp. n. (type
species), from Costa Rica and Panama, and Circanotasimplex sp. n., from Panama
and Ecuador, are described and illustrated. Although superficially similar to
some species of Platynota Clemens, 1860, Circanota appears to be more closely
related to members of a putative clade within Sparganothini defined by a slender
crescent-shaped signum in the corpus bursae of the female genitalia. The most
conspicuous autapomorphy for Circanota is the strongly undulate costa of the male
and female forewing. Barcode sequence data (i.e., cytochrome oxidase I) from
Circanotaundulata (n = 12) form a tight cluster with exceedingly limited genetic
divergence (less than 0.1%); specimens of Circanotasimplex have not been
sequenced. In neighbor-joining trees based on COI, Circanota is portrayed nearest
Sparganothoides, which is consistent with morphological evidence.
PMID- 25589855
TI - Species delimitation using morphology, morphometrics, and molecules: definition
of the Ophionscutellaris Thomson species group, with descriptions of six new
species (Hymenoptera, Ichneumonidae).
AB - The diverse genus Ophion is almost entirely undescribed in the Nearctic region.
In this paper we define the Ophionscutellaris species group. This species group
is well-supported by analysis of DNA (ITS2, COI, and 28S D2-D3) and morphology.
It includes the Palearctic species Ophionscutellaris and the Nearctic species
Ophionidoneus. An integrative analysis of DNA, geometric wing morphometrics,
classical morphometrics and qualitative morphology indicates that this species
group contains a minimum of seven species in North America, although the full
diversity of the group has likely not been sampled. Ophionclave Schwarzfeld, sp.
n., Ophionaureus Schwarzfeld, sp. n., Ophionbrevipunctatus Schwarzfeld, sp. n.,
Ophiondombroskii Schwarzfeld, sp. n., Ophionkeala Schwarzfeld, sp. n. and
Ophionimportunus Schwarzfeld, sp. n. are described, and a key to the known
Nearctic species of the Ophionscutellaris group is provided.
PMID- 25589858
TI - Salmokottelati, a new species of trout from Alakir Stream, draining to the
Mediterranean in southern Anatolia, Turkey (Teleostei, Salmonidae).
AB - Salmokottelati sp. n., is described from Alakir Stream (Mediterranean basin) in
Turkey. It is distinguished from other Anatolian Salmo species by a combination
of the following characters (none unique to the species): general body colour
greenish to silvery in life; 7-9 parr marks along lateral line; four dark bands
on flank absent in both sexes; black ocellated spots few, present only on upper
part of flank in individuals smaller than 160 mm SL but in larger both males and
females black spots numerous and located on back and middle and upper part of
flank; red spots few to numerous, scattered on median, and half of lower and
upper part of flank; head long (length 29-33% SL in males, 26-32 in females);
mouth large (length of mouth gape 13-19% SL in males, 12-15 in females); maxilla
long (length 10-13% SL in males, 8-12 in females); 105-113 lateral line scales;
24-29 scale rows between lateral line and dorsal-fin origin, 17-19 scale rows
between lateral line and anal-fin origin; 13-15 scales between lateral line and
adipose-fin insertion.
PMID- 25589859
TI - Three new species of mygalomorph and filistatid spiders from Iran (Araneae,
Cyrtaucheniidae, Nemesiidae and Filistatidae).
AB - Three new spider species are described from Iran: Anemesiakoponeni sp. n. (?,
Cyrtaucheniidae); Raveniolamazandaranica sp. n. (?, Nemesiidae) and
Sahastatasinuspersica sp. n. (?, Filistatidae). Cyrtaucheniidae and Sahastata
Benoit, 1968 are reported from Iran for the fisrt time.
PMID- 25589860
TI - A new Eastern Asian Hycleus and key to the Chinese species of the phaleratus
group (Coleoptera, Meloidae, Mylabrini).
AB - A new species of Hycleus belonging to the phaleratus group, and close to
Hycleusphaleratus, is described. The new species, Hycleusmarcipoli, is
distributed in China (Gansu and Taiwan), Laos, and northern Thailand. A key to
the Chinese species of this group is presented.
PMID- 25589861
TI - Contribution to the knowledge of the Carabus (Archiplectes) satyrus Kurnakov,
1962, species complex in Abkhazia (Coleoptera, Carabidae, Carabini).
AB - This study is based on a comparative analysis of extensive material of Carabus
(Archiplectes) satyrus Kurnakov, 1962, its various forms and related taxa
recently collected by the authors and some other collectors in Abkhazia. The
status or specific affiliations of several subspecies are changed and a
subspecies is described. Carabus (Archiplectes) besleticus Kurnakov, 1972, stat.
n. is treated as a separate species housing six hitherto established subspecies
in addition to the nominal type: Carabus (Archiplectes) besleticusmtsaranus
Kurnakov, 1972, Carabus (Archiplectes) besleticusduripshensis Kurnakov, 1972,
Carabus (Archiplectes) besleticusnapraensis Belousov & Zamotajlov, 1993, Carabus
(Archiplectes) besleticusdsychvensis Kurnakov, 1972, Carabus (Archiplectes)
besleticusadzinbai Retezar, 2013, and Carabus (Archiplectes)
besleticusresheviensissubsp. n.Carabus (Archiplectes) satyrus is treated as
monotypical while the specific status of Carabus (Archiplectes) pseudopshuensis
Zamotajlov, 1991, earlier proposed by Fominykh and Zamotajlov (2012), is
confirmed based on the morphological and morphometric data.
PMID- 25589862
TI - Revision of Chaetocnemasemicoerulea species-group (Coleoptera, Chrysomelidae,
Galerucinae, Alticini) in China, with descriptions of three new species.
AB - Chinese species of Chaetocnemasemicoerulea group are revised and three new
species described as new: Chaetocnemasalixis sp. n., Chaetocnemayulongensis sp.
n. and Chaetocnemadeqinensis sp. n.. A key to all five species of this group
occurring in China and the illustrations of habitus and genitalia are provided. A
map of species distribution is given.
PMID- 25589863
TI - Bembidion (?Nipponobembidion) ruruy sp. n., a new brachypterous ground beetle
(Coleoptera, Carabidae) from Kunashir Island, Kuriles, Russia.
AB - A new species, Bembidion (?Nipponobembidion) ruruysp. n., is described from the
foot of Ruruy Volcano, Kunashir Island, Kuril Archipelago, Russia. It is only the
second consubgener, being characterized by the reduced wings, the rounded elytral
shoulders, and the backward position of the posterior supra-orbital pore. In this
connection, the subgenus Nipponobembidion Habu & Baba, 1968 is rediagnosed and
both of its species are keyed. It might have originated from Plataphodes
Ganglbauer, 1891, possibly in relation to volcanic activities in the region.
PMID- 25589864
TI - When DNA barcoding and morphology mesh: Ceratopogonidae diversity in Finnmark,
Norway.
AB - DNA barcoding in Ceratopogonidae has been restricted to interpreting the
medically and veterinary important members of Culicoides Latreille. Here the
technique is utilised, together with morphological study, to interpret all
members of the family in a select area. Limited sampling from the county of
Finnmark in northernmost Norway indicated the presence of 54 species, including
14 likely new to science, 16 new to Norway, and one new to Europe. No species
were previously recorded from this county. Only 93 species were known for all of
Norway before this survey, indicating how poorly studied the group is. We
evaluate and discuss morphological characters commonly used in identification of
biting midges and relate species diagnoses to released DNA barcode data from 223
specimens forming 58 barcode clusters in our dataset. DNA barcodes and morphology
were congruent for all species, except in three morphological species where
highly divergent barcode clusters indicate the possible presence of cryptic
species.
PMID- 25589865
TI - The LifeWatch approach to the exploration of distributed species information.
AB - This paper introduces a new method of automatically extracting, integrating and
presenting information regarding species from the most relevant online taxonomic
resources. First, the information is extracted and joined using data wrappers and
integration solutions. Then, an analytical tool is used to provide a visual
representation of the data. The information is then integrated into a user
friendly content management system. The proposal has been implemented using data
from the Global Biodiversity Information Facility (GBIF), the Catalogue of Life
(CoL), the World Register of Marine Species (WoRMS), the Integrated Taxonomic
Information System (ITIS) and the Global Names Index (GNI). The approach improves
data quality, avoiding taxonomic and nomenclature errors whilst increasing the
availability and accessibility of the information.
PMID- 25589866
TI - Focus stacking: Comparing commercial top-end set-ups with a semi-automatic low
budget approach. A possible solution for mass digitization of type specimens.
AB - In this manuscript we present a focus stacking system, composed of commercial
photographic equipment. The system is inexpensive compared to high-end commercial
focus stacking solutions. We tested this system and compared the results with
several different software packages (CombineZP, Auto-Montage, Helicon Focus and
Zerene Stacker). We tested our final stacked picture with a picture obtained from
two high-end focus stacking solutions: a Leica MZ16A with DFC500 and a Leica
Z6APO with DFC290. Zerene Stacker and Helicon Focus both provided satisfactory
results. However, Zerene Stacker gives the user more possibilities in terms of
control of the software, batch processing and retouching. The outcome of the test
on high-end solutions demonstrates that our approach performs better in several
ways. The resolution of the tested extended focus pictures is much higher than
those from the Leica systems. The flash lighting inside the Ikea closet creates
an evenly illuminated picture, without struggling with filters, diffusers, etc.
The largest benefit is the price of the set-up which is approximately ? 3,000,
which is 8 and 10 times less than the LeicaZ6APO and LeicaMZ16A set-up
respectively. Overall, this enables institutions to purchase multiple solutions
or to start digitising the type collection on a large scale even with a small
budget.
PMID- 25589867
TI - Three species of Hitobia Kamura, 1992 (Araneae, Gnaphosidae) from south-west
China.
AB - Two new species and one new record of the Hitobia are described from Gaoligong
Mountains, Yunnan Province, China: Hitobiatengchong sp. n. (male),
Hitobiahirtella sp. n. (male) and Hitobiamakotoi Kamura, 2011. Distributional
data and illustrations of body and copulatory organs are provided. The
differences between the new species and their related species are discussed.
PMID- 25589868
TI - A new species of tiger beetle from southeastern Arizona and Mexico (Coleoptera,
Carabidae, Cicindelini).
AB - A new tiger beetle species, Cicindelidiamelissa Duran & Roman, sp. n., of the
tribe Cicindelini, is described from high elevation montane forests of
southeastern Arizona and Mexico. It appears to be most closely related to
Cicindelidianebuligera (Bates) but is distinguished on the basis of multiple
morphological characters and geographic range. The new species is also
superficially similar to the widespread Cicindelidiasedecimpunctata (Klug), but
distinguished on the basis of multiple morphological characters and habitat.
Habitus, male and female reproductive structures, and known distribution map are
presented.
PMID- 25589869
TI - Two new species of Myrmedonota Cameron (Staphylinidae, Aleocharinae) from Mexico.
AB - Two new species of Myrmedonota are described from Mexico. Illustrations and a
distribution map are provided, as are keys to identify Myrmedonota known from the
Nearctic and Neotropics. Specimens were collected by means of mercury vapor light
traps or flight interception traps.
PMID- 25589870
TI - A new species and synonymy of the Neotropical Eucelatoria Townsend and
redescription of Myiodoriops Townsend.
AB - The New World tropics represents the most diverse region for tachinid parasitoids
(Diptera: Tachinidae), but it also contains the most narrowly defined, and
possibly the most confusing, tachinid genera of any biogeographic region. This
over-splitting of genera and taxonomic confusion has limited progress toward our
understanding the family in this region and much work is needed to revise,
redefine, and make sense of the profusion of finely split taxa. In a recent
analysis of the Neotropical genus Erythromelana Townsend, two species previously
assigned to this genus, Euptilodegeeriaobumbrata (Wulp) and Myiodoriopsmarginalis
Townsend were reinstated as monotypic genera. In the present study, we
demonstrate that Euptilodegeeriaobumbrata (Wulp), previously assigned to three
different genera, represents in fact a species of the large New World genus
Eucelatoria Townsend, in which females possess a sharp piercer for oviposition.
We also show that the species Eucelatoriacarinata (Townsend) belongs to the same
species group as Eucelatoriaobumbrata, which we here define and characterize as
the Eucelatoriaobumbrata species group. Additionally, we describe
Eucelatoriaflava sp. n. as a new species within the Eucelatoriaobumbrata species
group. Finally, we redescribe the genus Myiodoriops Townsend and the single
species Myiodoriopsmarginalis Townsend.
PMID- 25589871
TI - Taxonomic study of the genus Halolaguna Gozmany (Lepidoptera, Lecithoceridae)
from China, with descriptions of two new species.
AB - The genus Halolaguna Gozmany, 1978 is studied in China. Two new species,
Halolagunaflabellata sp. n. from Guangxi and Halolagunadiscoidea sp. n. from
Chongqing, Guangxi and Sichuan are described. The female of
Halolagunaguizhouensis Wu, 2012 is reported for the first time. Photographs of
adults and genitalia are provided. A checklist of all known Halolaguna species is
included, along with a key to the Chinese species.
PMID- 25589872
TI - The origin and early evolution of metatherian mammals: the Cretaceous record.
AB - Metatherians, which comprise marsupials and their closest fossil relatives, were
one of the most dominant clades of mammals during the Cretaceous and are the most
diverse clade of living mammals after Placentalia. Our understanding of this
group has increased greatly over the past 20 years, with the discovery of new
specimens and the application of new analytical tools. Here we provide a review
of the phylogenetic relationships of metatherians with respect to other mammals,
discuss the taxonomic definition and diagnosis of Metatheria, outline the
Cretaceous history of major metatherian clades, describe the paleobiology,
biogeography, and macroevolution of Cretaceous metatherians, and provide a
physical and climatic background of Cretaceous metatherian faunas. Metatherians
are a clade of boreosphendian mammals that must have originated by the Late
Jurassic, but the first unequivocal metatherian fossil is from the Early
Cretaceous of Asia. Metatherians have the distinctive tightly interlocking
occlusal molar pattern of tribosphenic mammals, but differ from Eutheria in their
dental formula and tooth replacement pattern, which may be related to the
metatherian reproductive process which includes an extended period of lactation
followed by birth of extremely altricial young. Metatherians were widespread over
Laurasia during the Cretaceous, with members present in Asia, Europe, and North
America by the early Late Cretaceous. In particular, they were taxonomically and
morphologically diverse and relatively abundant in the Late Cretaceous of western
North America, where they have been used to examine patterns of biogeography,
macroevolution, diversification, and extinction through the Late Cretaceous and
across the Cretaceous-Paleogene (K-Pg) boundary. Metatherian diversification
patterns suggest that they were not strongly affected by a Cretaceous Terrestrial
Revolution, but they clearly underwent a severe extinction across the K-Pg
boundary.
PMID- 25589873
TI - Distribution and habitat of the Laotian Rock Rat Laonastesaenigmamus Jenkins,
Kilpatrick, Robinson & Timmins, 2005 (Rodentia: Diatomyidae) in Vietnam.
AB - The Laotian Rock Rat Laonastesaenigmamus Jenkins, Kilpatrick, Robinson & Timmins,
2005 was originally discovered in Lao People's Democratic Republic in 2005. This
species has been recognized as the sole surviving member of the otherwise extinct
rodent family Diatomyidae. Laonastesaenigmamus was initially reported only in
limestone forests of Khammouane Province, Central Lao. A second population was
recently discovered in Phong Nha Ke Bang National Park (PNKB NP), Quang Binh
Province, Central Vietnam in 2011. The confirmed distribution range of
L.aenigmamus in Vietnam is very small, approximately 150 km(2), covering low
karst mountains in five communes of Minh Hoa District, Quang Binh Province, at
elevations between 250 and 400 m asl. The Laotian Rock Rat inhabits the lower
part of steep karst towers with many rock boulders and crevices under tall
limestone evergreen forest. They use small rock crevices for their dens. The
natural habitat of this species in PNKB NP has been affected by selected timber
harvesting, however, a complex 3-4 layer forest structure is retained. The
Laotian Rock Rat is omnivorous, feeding on parts (leaves, buds, fruits and roots)
of 18 plant species and also some insects (cicada, mantis, grasshopper). The
population of this species in PNKB NP is seriously threatened with extinction due
to its very restricted distribution, high hunting pressure, and habitat
disturbance. Laonastesaenigmamus is listed in the IUCN Red List as endangered and
in the Wildlife and Aquatic Red List of Lao, however, this species has not been
listed in the Red Data Book or any conservation legislative documents of Vietnam.
PMID- 25589874
TI - New synonym of Tipula (Vestiplex) wahlgrenana Alexander, 1968 (Diptera:
Tipulidae).
AB - Based on examination of type specimens a crane fly species Tipula (Vestiplex)
hugueniniana Alexander, 1971 is proposed as junior synonym of Tipula (V.)
wahlgrenana Alexander, 1968. The new synonymy is based on similarity of male
genitalia.
PMID- 25589875
TI - An occurence records database of French Guiana harvestmen (Arachnida, Opiliones).
AB - This dataset provides information on specimens of harvestmen (Arthropoda,
Arachnida, Opiliones) collected in French Guiana. Field collections have been
initiated in 2012 within the framework of the CEnter for the Study of
Biodiversity in Amazonia (CEBA: www.labex-ceba.fr/en/). This dataset is a work in
progress. Occurrences are recorded in an online database stored at the EDB
laboratory after each collecting trip and the dataset is updated on a monthly
basis. Voucher specimens and associated DNA are also stored at the EDB laboratory
until deposition in natural history Museums. The latest version of the dataset is
publicly and freely accessible through our Integrated Publication Toolkit at
http://130.120.204.55:8080/ipt/resource.do?r=harvestmen_of_french_guiana or
through the Global Biodiversity Information Facility data portal at
http://www.gbif.org/dataset/3c9e2297-bf20-4827-928e-7c7eefd9432c.
PMID- 25589876
TI - On the female of Gyponareversa DeLong & Martinson, 1972, with emphasis on genital
structures (Insecta: Hemiptera: Cicadellidae).
AB - Gyponareversa DeLong & Martinson, 1972 has its ovipositor described and
illustrated based on the examination of specimens from its type locality. This is
the first species of Gypona Germar, 1821 to have the female genitalia detailed
description published.
PMID- 25589877
TI - Vignayadavii (Leguminosae: Papilionoideae), a new species from Western Ghats,
India.
AB - A new species of Vigna Savi, subgenus Ceratotropis (Piper) Verdc., Vignayadavii
S.P. Gaikwad, R.D. Gore, S.D. Randive & K.U. Garad, sp. nov. is described and
illustrated here. It is morphologically close to Vignadalzelliana (Kuntze) Verdc.
but differs in its underground obligate cleistogamous flowers on positively
geotropic branches, hairy calyx, small corolla, linear style beak and dimorphic
seeds with shiny seed coat.
PMID- 25589879
TI - Isolation of acanthamoeba genotype t4 from a non-contact lens wearer from the
Philippines.
AB - We report the case of a 76-year old Filipino male who presented with pain,
redness, and blurring of vision of the right eye. Corneal scraping was done and
sent to the St. Luke's Research and Biotechnology Group for detection and
identification of the infectious agent. Morphological detection was performed by
allowing the organism from the scraping to grow in 1.5% non-nutrient agar plate
with heat-killed E. coli. Trophozoites with acanthopodia and double-walled cysts
characteristic of Acanthamoeba were observed within the first and second week of
observations, respectively. Molecular identification of the amoebae at the genus
level based on the presence of Acanthamoeba-specific amplimer S1, ASA.S1
confirmed the morphological identification. Genotyping through sequence revealed
that the organism belonged to T4, which is the genotype commonly present in the
eye of keratitis patients.
PMID- 25589878
TI - The association of cytokines with severe dengue in children.
AB - BACKGROUND: Dengue virus infection is a major public health problem. A hypothesis
put forward for severe dengue is the cytokine storm, a sudden increase in
cytokines that induces vascular permeability. Previous studies and our recent
meta-analysis showed that IL-6, IL-8, IFNgamma, TNFalpha, VEGF-A and VCAM-1 are
associated with dengue shock syndrome. Therefore, in this study we aim to
validate the association of these cytokines with severe dengue. METHODS &
FINDINGS: In a hospital based-case control study in Vietnam, children with dengue
fever, other febrile illness and healthy controls were recruited. Dengue virus
infection was confirmed by several diagnostic tests. Multiplex immunoassay using
Luminex technology was used to measure cytokines simultaneously. A positive
association with dengue shock syndrome was found for VCAM-1, whereas a negative
association was found for IFNgamma. Furthermore, multivariate logistic analysis
also showed that VCAM-1 and IFNgamma were independently correlated with dengue
shock syndrome. CONCLUSION: IFNgamma and VCAM-1 were associated with dengue shock
syndrome, although their role in the severe dengue pathogenesis remains unclear.
Additional studies are required to shed further light on the function of these
cytokines in severe dengue.
PMID- 25589880
TI - Sand fly fauna (Diptera, pcychodidae, phlebotominae) in different leishmaniasis
endemic areas of ecuador, surveyed using a newly named mini-shannon trap.
AB - To study the sand fly fauna, surveys were performed at four different
leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A
modified and simplified version of the conventional Shannon trap was named "mini
Shannon trap" and put to multiple uses at the different study sites in limited,
forested and narrow spaces. The mini-Shannon, CDC light trap and protected human
landing method were employed for sand fly collection. The species identification
of sand flies was performed mainly based on the morphology of spermathecae and
cibarium, after dissection of fresh samples. In this study, therefore, only
female samples were used for analysis. A total of 1,480 female sand flies
belonging to 25 Lutzomyia species were collected. The number of female sand flies
collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC
light trap and 804 (54.3%) by human landing. The total number of sand flies per
trap collected by the different methods was markedly affected by the study site,
probably because of the various composition of species at each locality.
Furthermore, as an additional study, the attraction of sand flies to mini-Shannon
traps powered with LED white-light and LED black-light was investigated
preliminarily, together with the CDC light trap and human landing. As a result, a
total of 426 sand flies of nine Lutzomyia species, including seven man-biting and
two non-biting species, were collected during three capture trials in May and
June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light
proved relatively superior to the white-light with regard to capture numbers, but
no significant statistical difference was observed between the two traps.
PMID- 25589881
TI - BSL-3 Laboratory User Training Program at NUITM-KEMRI.
AB - Pathogens handled in a Biosafety Level 3 (BSL-3) containment laboratory pose
significant risks to laboratory staff and the environment. It is therefore
necessary to develop competency and proficiency among laboratory workers and to
promote appropriate behavior and practices that enhance safety through biosafety
training. Following the installation of our BSL-3 laboratory at the Center for
Microbiology Research-Kenya Medical Research Institute in 2006, a biosafety
training program was developed to provide training on BSL-3 safety practices and
procedures. The training program was developed based on World Health Organization
specifications, with adjustments to fit our research activities and biosafety
needs. The program is composed of three phases, namely initial assessment, a
training phase including theory and a practicum, and a final assessment. This
article reports the content of our training program.
PMID- 25589883
TI - Epidermodysplasia Verruciformis-like Skin Eruption in an HIV-positive Patient.
AB - Epidermodysplasia Verruciformis-like skin eruption is a rare syndrome that
usually occurs in patients with immunodeficiency, predisposing them to infections
with human papilloma beta virus (HPV). We report here an HIV patient presenting
with this syndrome.
PMID- 25589882
TI - Human Cystic Echinococcosis in the Nalut District of Western Libya: A Clinico
epidemiological Study.
AB - Human cystic echinococcosis (CE) is an endemic disease in the Mediterranean area
that has not yet been fully documented in western Libya. The present study
describes the clinico-epidemiologic profile of CE in western Libya's Nalut
district. From April 2008 to July 2011, 36 cases of CE were confirmed following
surgical removal of cysts. The cysts were most frequently found in the liver
(61.1%), followed by the lungs (19.4%), kidneys (11.1%), peritoneal cavity
(11.1%), and spleen (5.6%). Among the 36 patients, 6 possessed plural cysts and 3
had cysts in 2 organs. Blood samples from this group were examined for the
presence of serum anti-hydatid IgG antibodies, which revealed positivity in 25
patients (69.4%). An additional 300 blood samples were collected randomly from
the inpatient and outpatient clinics at Nalut Hospital. Twenty-seven samples (9%)
were found to be positive for the anti-hydatid IgG antibody among which the
prevalence of infection tended to be higher in men (12%) than in women (6%). This
study demonstrates that CE is a major parasitic infectious disease of public
health significance in Libya, notably in the western part of the country, and
that disease awareness needs to be raised nationwide.
PMID- 25589884
TI - Ovipositional Behavior of Anopheles gambiae Mosquitoes.
AB - Mosquito eggs laid within two hours are necessary for transgenic (injection)
studies, because mosquito eggs become hard after that period. Thus, in order to
have eggs available within this two-hour window, it is important to understand
the ovipositional behavior of Anopheles gambiae s.s.. In the present study, the
ovipositional behavior of An. gambiae s.s. (Kisumu) was investigated in several
different conditions: age of mosquitoes, time post blood meal to access
oviposition substrate, and light conditions. Two groups of mosquitoes, 3-5 days
old and 9-11 days old were blood-fed. For those mosquito groups, an oviposition
dish was set either at 48 hours or 72 hours after the blood meal either in a
light condition or in an artificial dark condition. The number of laid eggs was
compared among the different conditions. The 3-5 day-old mosquitoes apparently
produced a higher number of eggs than 9-11 day-old mosquitoes, while there was no
significant difference between the two groups. The number of laid eggs per one
surviving blood-fed mosquito in the dark condition was significantly higher than
that in the light condition (p = 0.03). Providing an oviposition dish at 72 hours
after blood meal resulted in a significantly higher number of laid eggs per one
surviving blood-fed mosquito than at 48 hours after blood meal (p = 0.03). In
conclusion, the optimal condition to have readily available egg supply for
transgenic analysis was as follows: 3-5 day-old mosquitoes with an oviposition
dish placed at 72 hours after the blood meal in a dark environment.
PMID- 25589885
TI - Syndecan-1 expression is associated with tumor size and EGFR expression in
colorectal carcinoma: a clinicopathological study of 230 cases.
AB - BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of
tumorigenesis and has variable expression in many cancers. To date, the cause of
altered expression has not been elucidated. In this study, we compared SDC1
expression with various clinicopathological parameters and molecular markers to
evaluate its clinical significance in colorectal carcinoma. METHODS: We screened
for SDC1 expression using immunohistochemistry in 230 surgical specimens of
primary colorectal carcinoma from patients consecutively treated between 2008 and
2011 at Seoul St. Mary's Hospital, The Catholic University of Korea. The
relationship between SDC1 expression and various clinicopathological parameters
and molecular markers was analyzed. RESULTS: The tumors were principally located
in the left colon (71.3%) and rectum (33.5%). There were 216 (93.9%)
adenocarcinomas, 10 (4.3%) mucinous adenocarcinomas, and 4 other tumors. Most of
the carcinomas were pT3 (68.3%) and pT4 (22.2%). There was regional lymph node
metastasis in 140 patients. SDC1 expression was identified in the cancer cells of
212 (96.8%) colon cancer cases. Of the SDC1-positive cases, 131 showed
predominantly membranous immunopositivity, and 81 showed a predominantly
cytoplasmic staining pattern. Mixed membranous and cytoplasmic staining was
observed in 154 cases. In 93 cases, stromal SDC1 reactivity was noted. Epithelial
SDC1 immunopositivity was significantly associated with tumor size (p=0.016) and
epidermal growth factor receptor expression (p=0.006). However, it was not
significantly correlated with lymph node metastasis, distant metastasis,
lymphatic or vascular invasion, or KRAS mutation. In addition, stromal SDC1
immunopositivity was significantly associated with the male sex (p=0.018).
CONCLUSIONS: The expression profile of SDC1 may be of clinical value in
colorectal cancer and may help in identifying aggressive forms of colorectal
carcinoma. Further studies are needed in order to better understand the role of
SDC1 in the progression and invasiveness of colorectal carcinoma.
PMID- 25589887
TI - Effect of the hand antiseptic agents benzalkonium chloride, povidone-iodine,
ethanol, and chlorhexidine gluconate on atopic dermatitis in NC/Nga mice.
AB - Antiseptic agents can cause skin irritation and lead to severe problems,
especially for individuals with atopic diatheses. We investigated the effect of 4
different antiseptic agents using an atopic dermatitis (AD) model mouse. NC/Nga
mice were subcutaneously injected with mite allergen (Dp) to induce AD-like skin
lesions (ADSLs), and an application of 0.2% (w/v) benzalkonium chloride (BZK),
10% (w/v) povidone-iodine (PVP-I), 80% (v/v) ethanol (Et-OH), or 0.5% (v/v)
chlorhexidine gluconate (CHG) was applied to the ear envelope. BZK induced a
significant increase in the severity of the clinical score, infiltration of
inflammatory cells, local expression of inflammatory cytokines in subcutaneous
tissue, and total serum immunoglobulin (Ig) E. PVP-I increased the clinical
score, number of mast cells, and production of inflammatory cytokines, and total
serum IgE. Et-OH increased the clinical score and number of inflammatory cells,
but showed no effect on serum IgE levels. No differences in any parameters were
observed between CHG and the vehicle. Collectively, the results suggest the
severity of the ADSL was related in part to the strength of the immunoreaction.
These findings suggest that CHG could offer the lowest risk of inducing ADSL in
individuals with atopic dermatitis and that medical staff and food handlers with
AD could benefit from its use.
PMID- 25589888
TI - Single nucleotide polymorphism in Ag85 genes of Mycobacterium tuberculosis
complex: analysis of 178 clinical isolates from China and 13 BCG strains.
AB - Host immune pressure and associated immune evasion of pathogenic bacteria are key
features of host-pathogen co-evolution. Human T-cell epitopes of Mycobacterium
tuberculosis (M. tuberculosis) were evolutionarily hyperconserved and thus it was
deduced that M. tuberculosis lacks antigenic variation and immune evasion.
However, in our previous studies, proteins MPT64, PstS1, Rv0309 and Rv2945c all
harbored higher numbers of amino acid substitutions in their T cell epitopes,
which suggests their roles in ongoing immune evasion. Here, we used the same set
of 180 clinical M. tuberculosis complex (MTBC) isolates from China, amplified the
genes encoding Ag85 complex, and compared the sequences. The results showed that
Ag85 were hyperconserved in T/B cell epitopes and the genes were more likely to
be under purifying selection. The divergence of host immune selection on
different proteins may result from different function of the proteins. In
addition, A312G of Ag85A and T418C of Ag85B may represent special mutations in
BCG strains, which may be used to differentiate M.bovis and BCG strains from MTB
strains. Also, C714A in Ag85B seems to be a valuable phylogenetic marker for
Beijing strains.
PMID- 25589890
TI - Malignant lymphomas in the head and neck region--a retrospective, single-center
study over 41 years.
AB - OBJECTIVES: Non-Hodgkin lymphomas are malignant neoplastic proliferations of the
immune system that can manifest as nodal or extranodal lymphomas. The aim of this
study was to retrospectively investigate the site of occurrence of lymphomas in
the head and neck area and to analyze the typical symptoms of patients who
presented at an oral and maxillofacial surgical department. MATERIAL AND METHODS:
All patient files from 1971 until 2012 from an Oral and Maxillofacial Surgery of
a University were analyzed for the diagnosis non-Hodgkin lymphoma. Epidemiologic
data and data regarding the localization of the malignant lymphoma were
evaluated. RESULTS: 62 patients, 34 women and 28 men with a non-Hodgkin lymphoma
in the head and neck area were treated in the 41 years analyzed. In 87% of the
cases the lymphoma belonged to B-cell and in 12% to the T-cell lineage. The
average age at the time of diagnosis was 67 years for women (n=34) and 56 years
for men. With 22 patients each, the non-Hodgkin lymphoma was localized in either
the soft tissues or osseous structures. In the remaining 18 cases, multiple
structures were affected. In 33 patients no accompanying nodal manifestation was
noticed. In 33 cases the lymphoma was located in the oral cavity. The most common
symptoms were swelling (97%), pain (40%) and the existence of an ulcer (11%).
CONCLUSION: In the present study more than 50% of the lymphomas were located in
the oral cavity. Due to the unspecific symptoms, a histopathological verification
of the diagnosis is crucial.
PMID- 25589891
TI - Utility of kynurenic acid for non-invasive detection of metastatic spread to
lymph nodes in non-small cell lung cancer.
AB - BACKGROUND: Kynurenic acid (KYNA) is a side-stream product of the kynurenine
metabolic pathway that plays a controversial role in malignancies either enabling
escape of malignant cells from immune surveillance or exerting antiproliferative
effect on cancer cells, and is associated with differences in invasiveness
related to metastatic spread to lymph nodes in lung cancer. Nodal involvement is
a significant negative prognostic factor usually considered a contraindication
for primary surgical resection. OBJECTIVE: To assess potential value of
circulating KYNA for non-invasive identification of patients with metastatic
lymph nodes (N+) in non-small cell lung cancer (NSCLC). METHODS: KYNA level in
venous blood serum was determined with use of high performance liquid
chromatography (HPLC) in 312 subjects including 230 patients with NSCLC and 32
healthy controls. RESULTS: Circulating KYNA level in NSCLC patients was higher
than in controls (93.6+/-61.9 pmol/ml vs. 31.4+/-16.6 pmol/ml; p=2.2*10(-15)) and
positively correlated with N (R=0.326; p=2*(10-6)) but not with T or M stage
(p>0.05). In N+ patients it was higher than in N0 patients (137.7+/-51.8 pmol/ml
vs. 71.9+/-41.7 pmol/ml; p=4.8*10(-16)). KYNA effectively discriminated N+ from
N0 patients at a cut-off value 82.3 pmol/ml with sensitivity 94.7% (95%CI 87.1
98.5%), specificity 80.5% (95%CI 73.4-86.5%), negative predictive value
NPV=96.8%, PPV=70.5% and area under the ROC curve AUC=0.900 (95%CI 0.854-0.935;
p=0.0001). DISCUSSION AND CONCLUSION: Circulating KYNA level measurement offers
reliable non-invasive discrimination between N0 and N+ patients in NSCLC. Robust
discriminatory characteristics of KYNA assay predestines it for clinical use as
an adjunct facilitating selection of candidates for primary surgical resection.
PMID- 25589886
TI - Liver function parameters in hip fracture patients: relations to age, adipokines,
comorbidities and outcomes.
AB - AIM: To asses liver markers in older patients with hip fracture (HF) in relation
to age, comorbidities, metabolic characteristics and short-term outcomes.
METHODS: In 294 patients with HF (mean age 82.0+/-7.9 years, 72.1% women) serum
alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline
phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate,
magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I
were measured. RESULTS: Elevated ALT, GGT, ALP or bilirubin levels on admission
were observed in 1.7%-9.9% of patients. With age GGT, ALT and leptin decrease,
while PTH and adiponectin concentrations increase. Higher GGT (>30 U/L, median
level) was associated with coronary artery disease (CAD), diabetes mellitus (DM),
and alcohol overuse; lower ALT (<=20 U/L, median level) with dementia; total
bilirubin>20 MUmol/L with CAD and alcohol overuse; and albumin>33 g/L with CAD.
Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol
overuse and DM as independent and significant determinants of GGT (as continuous
or categorical variable); GGT for each other liver marker; and PTH for
adiponectin. The risk of prolonged hospital stay (>20 days) was about two times
higher in patients with GGT>30 U/L or adiponectin>17.14 ng/L (median level) and
4.7 times higher if both conditions coexisted. The risk of in-hospital death was
3 times higher if albumin was <33 g/L. CONCLUSIONS: In older HF patients liver
markers even within the normal range are associated with age-related disorders
and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an
independent contributor to higher GGT. Serum GGT and albumin predict prolonged
hospital stay and in-hospital death, respectively. A unifying hypothesis of the
findings presented.
PMID- 25589889
TI - Antipsychotics-associated serious adverse events in children: an analysis of the
FAERS database.
AB - OBJECTIVE: The reports submitted to the US Food and Drug Administration (FDA)
Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess
serious adverse events induced by the administration of antipsychotics to
children. METHODS: Following pre-processing of FAERS data by elimination of
duplicated records as well as adjustments to standardize drug names, reports
involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone,
risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in
the data that signified a drug-associated adverse event were detected via
quantitative data mining algorithms. The algorithms applied to this study include
the empirical Bayes geometric mean, the reporting odds ratio, the proportional
reporting ratio, and the information component of a Bayesian confidence
propagation neural network. Neuroleptic malignant syndrome (NMS), QT
prolongation, leukopenia, and suicide attempt were focused on as serious adverse
events. RESULTS: In regard to NMS, the signal scores for haloperidol and
aripiprazole were greater than for other antipsychotics. Significant signals of
the QT prolongation adverse event were detected only for ziprasidone and
risperidone. With respect to leukopenia, the association with clozapine was
noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine,
quetiapine, risperidone, and aripiprazole were detected. CONCLUSIONS: It was
suggested that there is a level of diversity in the strength of the association
between various first- and second-generation antipsychotics with associated
serious adverse events, which possibly lead to fatal outcomes. We recommend that
research be continued in order to gather a large variety and quantity of related
information, and that both available and newly reported data be placed in the
context of multiple medical viewpoints in order to lead to improved levels of
care.
PMID- 25589892
TI - New adipose tissue formation by human adipose-derived stem cells with hyaluronic
acid gel in immunodeficient mice.
AB - BACKGROUND: Currently available injectable fillers have demonstrated limited
durability. This report proposes the in vitro culture of human adipose-derived
stem cells (hASCs) on hyaluronic acid (HA) gel for in vivo growth of de novo
adipose tissue. METHODS: For in vitro studies, hASCs were isolated from human
adipose tissue and were confirmed by multi-lineage differentiation and flow
cytometry. hASCs were cultured on HA gel. The effectiveness of cell attachment
and proliferation on HA gel was surveyed by inverted light microscopy. For in
vivo studies, HA gel containing hASCs, hASCs without HA gel, HA gel alone were
allocated and subcutaneously injected into the subcutaneous pocket in the back of
nude mice (n=6) in each group. At eight weeks post-injection, the implants were
harvested for histological examination by hematoxylin and eosin (H&E) stain, Oil
Red O stain and immunohistochemical staining. The human-specific Alu gene was
examined. RESULTS: hASCs were well attachment and proliferation on the HA gel. In
vivo grafts showed well-organized new adipose tissue on the HA gel by histologic
examination and Oil-Red O stain. Analysis of neo-adipose tissues by PCR revealed
the presence of the Alu gene. This study demonstrated not only the successful
culture of hASCs on HA gel, but also their full proliferation and differentiation
into adipose tissue. CONCLUSIONS: The efficacy of injected filler could be
permanent since the reduction of the volume of the HA gel after bioabsorption
could be replaced by new adipose tissue generated by hASCs. This is a promising
approach for developing long lasting soft tissue filler.
PMID- 25589893
TI - Identification of novel compounds against an R294K substitution of influenza A
(H7N9) virus using ensemble based drug virtual screening.
AB - Influenza virus H7N9 foremost emerged in China in 2013 and killed hundreds of
people in Asia since they possessed all mutations that enable them to resist to
all existing influenza drugs, resulting in high mortality to human. In the effort
to identify novel inhibitors combat resistant strains of influenza virus H7N9; we
performed virtual screening targeting the Neuraminidase (NA) protein against
natural compounds of traditional Chinese medicine database (TCM) and ZINC natural
products. Compounds expressed high binding affinity to the target protein was
then evaluated for molecular properties to determine drug-like molecules. 4
compounds showed their binding energy less than -11 Kcal/mol were selected for
molecular dynamics (MD) simulation to capture intermolecular interactions of
ligand-protein complexes. The molecular mechanics/Poisson-Boltzmann surface area
(MM/PBSA) method was utilized to estimate binding free energy of the complex. In
term of stability, NA-7181 (IUPAC namely {9-Hydroxy-10-[3-(trifluoromrthyl)
cyclohexyl]-4.8-diazatricyclo [6.4.0.02,6]dodec-4-yl}(perhydro-1H-inden-5
yl)formaldehyde) achieved stable conformation after 20 ns and 27 ns for ligand
and protein root mean square deviation, respectively. In term of binding free
energy, 7181 gave the negative value of -30.031 (KJ/mol) indicating the compound
obtained a favourable state in the active site of the protein.
PMID- 25589894
TI - High producing tumor necrosis factor alpha gene alleles in protection against
severe manifestations of dengue.
AB - Dengue virus (DENV) infection usually presents with mild self-limiting dengue
fever (DF). Few however, would present with the more severe form of the disease,
dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present
study, the association between IL-12B, IL-10 and TNF-alpha gene polymorphisms and
dengue severity was investigated. METHODS: A case-control study was performed on
a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The
polymorphisms in IL-12B, IL-10 and TNF-alpha genes were genotyped using PCR-RFLP
and PCR-sequencing methods. RESULTS: A protective association of TNF-alpha -308A
allele and -308GA genotype against DHF/DSS was observed, while TNF-alpha -238A
allele and -238GA genotype were associated with DHF/DSS. A combination of TNF
alpha -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes
(pro1/pro1, pro2/pro2) and IL-12B 3'UTR AC were significantly correlated with
protective effects against DHF/DSS. An association between the cytokine gene
polymorphisms and protection against the clinical features of severe dengue
including thrombocytopenia and increased liver enzymes was observed in this
study. CONCLUSION: The overall findings of the study support the correlation of
high-producer TNF-alpha genotypes combined with low-producer IL-10 haplotypes and
IL-12B genotypes in reduced risk of DHF/DSS.
PMID- 25589896
TI - Predictors of spiritual care provision for patients with dementia at the end of
life as perceived by physicians: a prospective study.
AB - BACKGROUND: Spiritual caregiving is part of palliative care and may contribute to
well being at the end of life. However, it is a neglected area in the care and
treatment of patients with dementia. We aimed to examine predictors of the
provision of spiritual end-of-life care in dementia as perceived by physicians
coordinating the care. METHODS: We used data of the Dutch End of Life in Dementia
study (DEOLD; 2007-2011), in which data were collected prospectively in 28 Dutch
long-term care facilities. We enrolled newly admitted residents with dementia who
died during the course of data collection, their families, and physicians. The
outcome of Generalized Estimating Equations (GEE) regression analyses was whether
spiritual care was provided shortly before death as perceived by the on-staff
elderly care physician who was responsible for end-of-life care (last sacraments
or rites or other spiritual care provided by a spiritual counselor or staff).
Potential predictors were indicators of high-quality, person-centered, and
palliative care, demographics, and some other factors supported by the
literature. Resident-level potential predictors such as satisfaction with the
physician's communication were measured 8 weeks after admission (baseline, by
families and physicians), physician-level factors such as the physician's
religious background midway through the study, and facility-level factors such as
a palliative care unit applied throughout data collection. RESULTS: According to
the physicians, spiritual end-of-life care was provided shortly before death to
20.8% (43/207) of the residents. Independent predictors of spiritual end-of-life
care were: families' satisfaction with physicians' communication at baseline (OR
1.6, CI 1.0; 2.5 per point on 0-3 scale), and faith or spirituality very
important to resident whether (OR 19, CI 5.6; 63) or not (OR 15, CI 5.1; 47) of
importance to the physician. Further, female family caregiving was an independent
predictor (OR 2.7, CI 1.1; 6.6). CONCLUSIONS: Palliative care indicators were not
predictive of spiritual end-of-life care; palliative care in dementia may need
better defining and implementation in practice. Physician-family communication
upon admission may be important to optimize spiritual caregiving at the end of
life.
PMID- 25589897
TI - Gastric cancer review.
AB - Gastric cancer is an aggressive disease that continues to have a daunting impact
on global health. Despite an overall decline in incidence over the last several
decades, gastric cancer remains the fourth most common type of cancer and is the
second leading cause of cancer-related death worldwide. This review aims to
discuss the global distribution of the disease and the trend of decreasing
incidence of disease, delineate the different pathologic subtypes and their
immunohistochemical (IHC) staining patterns and molecular signatures and
mutations, explore the role of the pathogen H. pylori in tumorgenesis, discuss
the increasing incidence of the disease in the young, western populations and
define the role of biologic agents in the treatment of the disease.
PMID- 25589895
TI - Nanoparticle-based targeted therapeutics in head-and-neck cancer.
AB - Head-and-neck cancer is a major form of the disease worldwide. Treatment consists
of surgery, radiation therapy and chemotherapy, but these have not resulted in
improved survival rates over the past few decades. Versatile nanoparticles, with
selective tumor targeting, are considered to have the potential to improve these
poor outcomes. Application of nanoparticle-based targeted therapeutics has
extended into many areas, including gene silencing, chemotherapeutic drug
delivery, radiosensitization, photothermal therapy, and has shown much promise.
In this review, we discuss recent advances in the field of nanoparticle-mediated
targeted therapeutics for head-and-neck cancer, with an emphasis on the
description of targeting points, including future perspectives.
PMID- 25589898
TI - 28 days of creatine nitrate supplementation is apparently safe in healthy
individuals.
AB - BACKGROUND: Creatine monohydrate has become a very popular nutritional supplement
for its ergogenic effects. The safety of creatine monohydrate has previously been
confirmed. However with each novel form of creatine that emerges, its safety must
be verified. Therefore, the purpose of this study was to examine the safety of a
novel form of creatine, creatine nitrate (CN), over a 28 day period. METHODS: 58
young males and females (Pooled: 24.3 +/- 3.9 years, 144.9 +/- 8.0 cm, 74.2 +/-
13.0 kg) participated in this study across two laboratories. Subjects were
equally and randomly assigned to consume either 1 g (n = 18) or 2 g (n = 20) of
CN or remained unsupplemented (n = 20). Blood draws for full safety panels were
conducted by a trained phlebotomist prior to and at the conclusion of the
supplementation period. RESULTS: Pooled data from both laboratories revealed
significant group x time interactions for absolute lymphocytes and absolute
monocytes (p < 0.05). Analysis of the 1 g treatment revealed lab x time
differences for red blood cell distribution width, platelets, absolute monocytes,
creatinine, blood urea nitrogen (BUN):creatinine, sodium, protein, and alanine
aminotransferase (ALT) (p < 0.05). Analysis of the 2 g treatment revealed lab x
time differences for BUN:creatinine and ALT (p < 0.05). BUN and BUN:creatinine
increased beyond the clinical reference range for the 2 g treatment of Lab 2, but
BUN did not reach statistical significance. CONCLUSION: Overall, CN appears to be
safe in both 1 g and 2 g servings daily for up to a 28 day period. While those
with previously elevated BUN levels may see additional increases resulting in
post-supplementation values slightly beyond normal physiological range, these
results have minor clinical significance and are not cause for concern.
Otherwise, all hematological safety markers remained within normal range,
suggesting that CN supplementation has no adverse effects in daily doses up to 2
g over 28 days and may be an alternative to creatine monohydrate supplementation.
PMID- 25589899
TI - Antisense Modulation of RNA Processing as a Therapeutic Approach in Cancer
Therapy.
AB - Next-generation antisense technologies are re-emerging as viable and powerful
approaches to the treatment of several genetic diseases. Similar strategies are
also being applied to cancer therapy. Re-programming of the expression of
endogenous oncogenic products to replace them with functional antagonists, by
interfering with alternative splicing or polyadenylation, provides a promising
novel approach to address acquired drug resistance and previously undruggable
targets.
PMID- 25589900
TI - Alcohol-related hospitalizations of adult motorcycle riders.
AB - OBJECTIVE: To provide an overview of the demographic characteristics of adult
motorcycle riders with alcohol-related hospitalizations. METHODS: Data obtained
from the Trauma Registry System were retrospectively reviewed for trauma
admissions at a level I trauma center between January 1, 2009 and December 31,
2013. Out of 16,548 registered patients, detailed information was retrieved
regarding 1,430 (8.64%) adult motorcycle riders who underwent a blood alcohol
concentration (BAC) test. A BAC level of 50 mg/dL was defined as the cut-off
value for alcohol intoxication. RESULTS: In this study, alcohol consumption was
more frequently noted among male motorcycle riders, those aged 30-49 years, those
who had arrived at the hospital in the evening or during the night, and those who
did not wear a helmet. Alcohol consumption was associated with a lower percentage
of sustained severe injury (injury severity score >=25) and lower frequencies of
specific body injuries, including cerebral contusion (0.6; 95% confidence
interval [CI] = 0.42-0.80), lung contusion (0.5; 95% CI = 0.24-0.90), lumbar
vertebral fracture (0.1; 95% CI = 0.01-0.80), humeral fracture (0.5; 95% CI =
0.27-0.90), and radial fracture (0.6; 95% CI = 0.40-0.89). In addition, alcohol
intoxicated motorcycle riders who wore helmets had significantly lower
frequencies of cranial fracture (0.4; 95% CI = 0.29-0.67), epidural hematoma
(0.5; 95% CI = 0.29-0.79), subdural hematoma (0.4; 95% CI = 0.28-0.64),
subarachnoid hemorrhage (0.5; 95% CI = 0.32-0.72), and cerebral contusion (0.4;
95% CI = 0.25-0.78). CONCLUSIONS: Motorcycle riders who consumed alcohol
presented different characteristics and bodily injury patterns relative to sober
patients, suggesting the importance of helmet use to decrease head injuries in
alcohol-intoxicated riders.
PMID- 25589901
TI - The first case of human autochtonous subconjunctival dirofilariosis in Poland and
MALT lymphoma as possible consequence of this parasitosis.
AB - The first case of human dirofilarosis in Poland was recorded in 2007. Until that
time our country was free of Dirofilaria repens. Recent studies show that 21,4-
60% of dogs in Warsaw region harbour microfilariae, therefore it is becoming a
growing problem in Central Europe. In April 2013 a subconjunctival D. repens was
removed from the eye of 61-year-old woman. It was the twenty first case of this
disease in Poland, the third case of eye dirofilaria and the fourth autochtonous
case. The patient had never been abroad, so it was the first case of autochtonous
human ocular dirofilariosis in Poland. Nine months after the D. repens had been
removed, a MALT lymphoma was discovered. In the article we discuss whether a MALT
lymphoma of the lacrimal gland of the eye, previously affected by the parasite,
may be the consequence of the invasion.
PMID- 25589902
TI - Transcript changes in Vibrio cholerae in response to salt stress.
AB - Vibrio cholerae, which is a serious human intestinal pathogen, often resides and
thrives in estuaries but requires major self-regulation to overcome intestinal
hyperosmotic stress or high salt stress in water and food. In the present study,
we selected multiple O1 and O139 group V. cholerae strains that were isolated
from different regions and during different years to study their salt tolerance.
Based on the mechanisms that other bacteria use to respond to high salt stress,
we selected salt stress-response related genes to study the mechanisms which V.
cholerae responds to high salt stress. V. cholerae strains showed salt-resistance
characteristics that varied in salt concentrations from 4% to 6%. However, group
O1 and group O139 showed no significant difference in the degree of salt
tolerance. The primary responses of bacteria to salt stress, including Na(+)
exclusion, K(+) uptake and glutamate biosynthesis, were observed in V. cholerae
strains. In addition, some sigma factors were up-regulated in V. cholerae
strains, suggesting that V. cholerae may recruit common sigma factors to achieve
an active salt stress response. However, some changes in gene transcript levels
in response to salt stress in V. cholerae were strain-specific. In particular,
hierarchical clustering of differentially expressed genes indicated that
transcript levels of these genes were correlated with the degree of salt
tolerance. Therefore, elevated transcript levels of some genes, including sigma
factors and genes involved in peptidoglycan biosynthesis, may be due to the salt
tolerance of strains. In addition, high salt-tolerant strains may recruit common
as well as additional sigma factors to activate the salt stress response.
PMID- 25589903
TI - How could health information exchange better meet the needs of care
practitioners?
AB - BACKGROUND: Health information exchange (HIE) has the potential to improve the
quality of healthcare by enabling providers with better access to patient
information from multiple sources at the point of care. However, HIE efforts have
historically been difficult to establish in the US and the failure rates of
organizations created to foster HIE have been high. OBJECTIVES: We sought to
better understand how RHIO-based HIE systems were used in practice and the
challenges care practitioners face using them. The objective of our study were to
so investigate how HIE can better meet the needs of care practitioners. METHODS:
We performed a multiple-case study using qualitative methods in three communities
in New York State. We conducted interviews onsite and by telephone with HIE users
and non-users and observed the workflows of healthcare professionals at multiple
healthcare organizations participating in a local HIE effort in New York State.
RESULTS: The empirical data analysis suggests that challenges still remain in
increasing provider usage, optimizing HIE implementations and connecting HIE
systems across geographic regions. Important determinants of system usage and
perceived value includes users experienced level of available information and the
fit of use for physician workflows. CONCLUSIONS: Challenges still remain in
increasing provider adoption, optimizing HIE implementations, and demonstrating
value. The inability to find information reduced usage of HIE. Healthcare
organizations, HIE facilitating organizations, and states can help support HIE
adoption by ensuring patient information is accessible to providers through
increasing patient consents, fostering broader participation, and by ensuring
systems are usable.
PMID- 25589904
TI - The implementation of an integrated information system for substance use
screening in general medical settings.
AB - The Massachusetts Screening, Brief Intervention and Referral to Treatment
(MASBIRT) Program, a substance use screening program in general medical settings,
created a web-based, point-of-care (POC), application--the MASBIRT Portal (the
"Portal") to meet program goals. OBJECTIVES: We report on development and
implementation of the Portal. METHODS: Five year program process outcomes
recorded by an independent evaluator and an anonymous survey of Health Educator's
(HEs) adoption, perceptions and Portal use with a modified version of the
Technology Readiness Index are described. [8] Specific management team members,
selected based on their roles in program leadership, development and
implementation of the Portal and supervision of HEs, participated in semi
structured, qualitative interviews. RESULTS: At the conclusion of the program 73%
(24/33) of the HEs completed a survey on their experience using the Portal. HEs
reported that the Portal made recording screening information easy (96%);
improved planning their workday (83%); facilitated POC data collection (84%);
decreased time dedicated to data entry (100%); and improved job satisfaction
(59%). The top two barriers to use were "no or limited wireless connectivity"
(46%) and "the tablet was too heavy/bulky to carry" (29%). Qualitative management
team interviews identified strategies for successful HIT implementation:
importance of engaging HEs in outlining specifications and workflow needs,
collaborative testing prior to implementation and clear agreement on data
collection purpose, quality requirements and staff roles. DISCUSSION: Overall,
HEs perceived the Portal favorably with regard to time saving ability and
improved workflow. Lessons learned included identifying core requirements early
during system development and need for managers to institute and enforce
consistent behavioral work norms. CONCLUSION: Barriers and HEs' views of
technology impacted the utilization of the MASBIRT Portal. Further research is
needed to determine best approaches for HIT system implementation in general
medical settings.
PMID- 25589905
TI - A survey of nursing home physicians to determine laboratory monitoring adverse
drug event alert preferences.
AB - OBJECTIVE: We conducted a survey of nursing home physicians to learn about (1)
the laboratory value thresholds that clinical event monitors should use to
generate alerts about potential adverse drug events (ADEs); (2) the specific
information to be included in the alerts; and (3) the communication modality that
should be used for communicating them. METHODS: Nursing home physician attendees
of the 2010 Conference of AMDA: The Society for Post-Acute and Long-Term Care
Medicine. RESULTS: A total of 800 surveys were distributed; 565 completed surveys
were returned and seven surveys were excluded due to inability to verify that the
respondents were physicians (a 70% net valid response rate). Alerting threshold
preferences were identified for eight laboratory tests. For example, the majority
of respondents selected thresholds of >=5.5 mEq/L for hyperkalemia (63%) and
<=3.5 without symptoms for hypokalemia (54%). The majority of surveyed physicians
thought alerts should include the complete active medication list, current vital
signs, previous value of the triggering lab, medication change in the past 30
days, and medication allergies. Most surveyed physicians felt the best way to
communicate an ADE alert was by direct phone/voice communication (64%), followed
by email to a mobile device (59%). CONCLUSIONS: This survey of nursing home
physicians suggests that the majority prefer alerting thresholds that would
generally lead to fewer alerts than if widely accepted standardized laboratory
ranges were used. It also suggests a subset of information items to include in
alerts, and the physicians' preferred communication modalities. This information
might improve the acceptance of clinical event monitoring systems to detect ADEs
in the nursing home setting.
PMID- 25589906
TI - From bed to bench: bridging from informatics practice to theory: an exploratory
analysis.
AB - BACKGROUND: In 2009, Applied Clinical Informatics (ACI)--focused on applications
in clinical informatics--was launched as a companion journal to Methods of
Information in Medicine (MIM). Both journals are official journals of the
International Medical Informatics Association. OBJECTIVES: To explore which
congruencies and interdependencies exist in publications from theory to practice
and from practice to theory and to determine existing gaps. Major topics
discussed in ACI and MIM were analyzed. We explored if the intention of
publishing companion journals to provide an information bridge from informatics
theory to informatics practice and vice versa could be supported by this model.
In this manuscript we will report on congruencies and interdependences from
practice to theory and on major topics in MIM. METHODS: Retrospective, prolective
observational study on recent publications of ACI and MIM. All publications of
the years 2012 and 2013 were indexed and analyzed. RESULTS: Hundred and ninety
six publications were analyzed (ACI 87, MIM 109). In MIM publications, modelling
aspects as well as methodological and evaluation approaches for the analysis of
data, information, and knowledge in biomedicine and health care were frequently
raised - and often discussed from an interdisciplinary point of view. Important
themes were ambient-assisted living, anatomic spatial relations, biomedical
informatics as scientific discipline, boosting, coding, computerized physician
order entry, data analysis, grid and cloud computing, health care systems and
services, health-enabling technologies, health information search, health
information systems, imaging, knowledge-based decision support, patient records,
signal analysis, and web science. Congruencies between journals could be found in
themes, but with a different focus on content. Interdependencies from practice to
theory, found in these publications, were only limited. CONCLUSIONS: Bridging
from informatics theory to practice and vice versa remains a major component of
successful research and practice as well as a major challenge.
PMID- 25589907
TI - The process of installing REDCap, a web based database supporting biomedical
research: the first year.
AB - BACKGROUND: Clinical and research data are essential for patient care, research
and healthcare system planning. REDCapTM is a web-based tool for research data
curatorship developed at Vanderbilt University in Nashville, USA. The Faculty of
Health Sciences at the University of the Witwatersrand, Johannesburg South Africa
identified the need for a cost effective data management instrument. REDCap was
installed as per the user agreement with Vanderbilt University in August 2012.
OBJECTIVES: In order to assist other institutions that may lack the in-house
Information Technology capacity, this paper describes the installation and
support of REDCap and incorporates an analysis of user uptake over the first year
of use. METHODS: We reviewed the staffing requirements, costs of installation,
process of installation and necessary infrastructure and end-user requests
following the introduction of REDCap at Wits. The University Legal Office and
Human Research Ethics Committee were consulted regarding the REDCap end-user
agreement. Bi-monthly user meetings resulted in a training workshop in August
2013. We compared our REDCap software user numbers and records before and after
the first training workshop. RESULTS: Human resources were recruited from
existing staff. Installation costs were limited to servers and security
certificates. The total costs to provide a functional REDCap platform was less
than $9000. Eighty-one (81) users were registered in the first year. After the
first training workshop the user numbers increased by 59 in one month and the
total number of active users to 140 by the end of August 2013. Custom software
applications for REDCap were created by collaboration between clinicians and
software developers. CONCLUSION: REDCap was installed and maintained at limited
cost. A small number of people with defined skills can support multiple REDCap
users in two to four hours a week. End user training increased in the number of
users, number of projects created and the number of projects moved to production.
PMID- 25589908
TI - Increasing patient engagement: patients' responses to viewing problem lists
online.
AB - OBJECTIVE: To characterize the opinions, emotions, and actions taken by patients
who viewed their electronic problem list via an online personal health record
(PHR). MATERIALS AND METHODS: An online survey of patients who viewed their
problem lists, as maintained by their healthcare provider, in a web-based PHR
linked to an electronic health record for the first time. RESULTS: A total 3,649
patients completed the survey, yielding a response rate of 42.1%. Patient
attitudes towards the problem list function were positive overall, with 90.4%
rating it at least somewhat useful and 86.7% reporting they would probably or
definitely use it again. Nearly half (45.6%) of patients identified at least one
major or minor problem missing from their list. After viewing the list, 56.1% of
patients reported taking at least one action in response, with 32.4% of patients
reporting that they researched a condition on the Internet, 18.3% reported that
they contacted their healthcare provider and 16.7% reported changing or planning
to change a health behavior (patients could report multiple actions). 64.7% of
patients reported feeling at least somewhat happy while viewing their problem
list, though others reported feeling sad (30.4%), worried (35.7%) or scared
(23.8%) (patients could report multiple emotions). A smaller number of patients
reported feeling angry (16.6%) or ashamed (14.3%). Patients who experienced an
emotional response were more likely to take action. CONCLUSION: Overall, patients
found the ability to view their problem lists very useful and took action in
response to the information. However, some had negative emotions. More research
is needed into optimal strategies for supporting patients receiving this
information.
PMID- 25589910
TI - User-centered design and usability testing of an innovative health-related
quality of life module.
AB - OBJECTIVES: Various computerized health risk appraisals (HRAs) are available, but
few of them assess health-related quality of life (HRQoL) in a goal-directed
framework. This study describes the user-centered development and usability
testing of an innovative HRQoL module that extends a validated HRA tool in
primary care settings. METHODS: Systematic user-centered design, usability
testing, and qualitative methods were used to develop the HRQoL module in primary
care practices. Twenty two patients and 5 clinicians participated in two rounds
of interactive technology think-out-loud sessions (TOLs) and semi-structured
interviews (SSIs) to iteratively develop a four-step, computerized process that
collects information on patient goals for meaningful life activities and current
level of disability and presents a personalized and prioritized list of
preventive recommendations linked to online resources. RESULTS: Analysis of TOLs
and SSIs generated 5 categories and 11 sub-categories related to facilitators and
barriers to usability and human-technology interaction. The categories included:
Understanding the Purpose, Usability, Perceived Value, Literacy, and Participant
Motivation. Some categories were inter-connected. The technology was continually
and iteratively improved between sessions until saturation of positive feedback
was achieved in 4 categories (addressing motivation will require more research).
Usability of all screen units of the module was improved substantially. Clinician
feedback emphasized the importance of the module's ability to translate the
patient-centered HRQoL Report into actionable items for clinicians to facilitate
shared decision-making. Complete integration of the HRQoL module into the
existing HRA will require further development and testing. CONCLUSIONS:
Systematic application of user-centered design and human factors principles in
technology development and testing may significantly improve the usability and
clinical value of health information systems. This more sophisticated approach
helped us translate complex clinical concepts, goal-setting steps, and decision
support processes into an accepted and value-added technology.
PMID- 25589909
TI - Identifying consumer's needs of health information technology through an
innovative participatory design approach among English- and Spanish-speaking
urban older adults.
AB - OBJECTIVES: We describe an innovative community-centered participatory design
approach, Consumer-centered Participatory Design (C2PD), and the results of
applying C2PD to design and develop a web-based fall prevention system. METHODS:
We conducted focus groups and design sessions with English- and Spanish-speaking
community-dwelling older adults. Focus group data were summarized and used to
inform the context of the design sessions. Descriptive content analysis methods
were used to develop categorical descriptions of design session informant's needs
related to information technology. RESULTS: The C2PD approach enabled the
assessment and identification of informant's needs of health information
technology (HIT) that informed the development of a falls prevention system. We
learned that our informants needed a system that provides variation in
functions/content; differentiates between actionable/non-actionable
information/structures; and contains sensory cues that support wide-ranging and
complex tasks in a varied, simple, and clear interface to facilitate self
management. CONCLUSIONS: The C2PD approach provides community-based
organizations, academic researchers, and commercial entities with a systematic
theoretically informed approach to develop HIT innovations. Our community
centered participatory design approach focuses on consumer's technology needs
while taking into account core public health functions.
PMID- 25589911
TI - Design challenges for electronic medication administration record systems in
residential aged care facilities: a formative evaluation.
AB - INTRODUCTION: Electronic medication administration record (eMAR) systems are
promoted as a potential intervention to enhance medication safety in residential
aged care facilities (RACFs). The purpose of this study was to conduct an in
practice evaluation of an eMAR being piloted in one Australian RACF before its
roll out, and to provide recommendations for system improvements. METHODS: A
multidisciplinary team conducted direct observations of workflow (n=34 hours) in
the RACF site and the community pharmacy. Semi-structured interviews (n=5) with
RACF staff and the community pharmacist were conducted to investigate their views
of the eMAR system. Data were analysed using a grounded theory approach to
identify challenges associated with the design of the eMAR system. RESULTS: The
current eMAR system does not offer an end-to-end solution for medication
management. Many steps, including prescribing by doctors and communication with
the community pharmacist, are still performed manually using paper charts and fax
machines. Five major challenges associated with the design of eMAR system were
identified: limited interactivity; inadequate flexibility; problems related to
information layout and semantics; the lack of relevant decision support; and
system maintenance issues. We suggest recommendations to improve the design of
the eMAR system and to optimize existing workflows. DISCUSSION: Immediate value
can be achieved by improving the system interactivity, reducing inconsistencies
in data entry design and offering dedicated organisational support to minimise
connectivity issues. Longer-term benefits can be achieved by adding decision
support features and establishing system interoperability requirements with
stakeholder groups (e.g. community pharmacies) prior to system roll out. In
practice evaluations of technologies like eMAR system have great value in
identifying design weaknesses which inhibit optimal system use.
PMID- 25589912
TI - Assessment of readiness for clinical decision support to aid laboratory
monitoring of immunosuppressive care at U.S. liver transplant centers.
AB - BACKGROUND: Following liver transplantation, patients require lifelong
immunosuppressive care and monitoring. Computerized clinical decision support
(CDS) has been shown to improve post-transplant immunosuppressive care processes
and outcomes. The readiness of transplant information systems to implement
computerized CDS to support post-transplant care is unknown. OBJECTIVES: a)
Describe the current clinical information system functionality and manual and
automated processes for laboratory monitoring of immunosuppressive care, b)
describe the use of guidelines that may be used to produce computable logic and
the use of computerized alerts to support guideline adherence, and c) explore
barriers to implementation of CDS in U.S. liver transplant centers. METHODS: We
developed a web-based survey using cognitive interviewing techniques. We surveyed
119 U.S. transplant programs that performed at least five liver transplantations
per year during 2010-2012. Responses were summarized using descriptive analyses;
barriers were identified using qualitative methods. RESULTS: Respondents from 80
programs (67% response rate) completed the survey. While 98% of programs reported
having an electronic health record (EHR), all programs used paper-based manual
processes to receive or track immunosuppressive laboratory results. Most programs
(85%) reported that 30% or more of their patients used external laboratories for
routine testing. Few programs (19%) received most external laboratory results as
discrete data via electronic interfaces while most (80%) manually entered
laboratory results into the EHR; less than half (42%) could integrate internal
and external laboratory results. Nearly all programs had guidelines regarding pre
specified target ranges (92%) or testing schedules (97%) for managing
immunosuppressive care. Few programs used computerized alerting to notify
transplant coordinators of out-of-range (27%) or overdue laboratory results
(20%). CONCLUSIONS: Use of EHRs is common, yet all liver transplant programs were
largely dependent on manual paper-based processes to monitor immunosuppression
for post-liver transplant patients. Similar immunosuppression guidelines provide
opportunities for sharing CDS once integrated laboratory data are available.
PMID- 25589913
TI - Case report: patient portal versus telephone recruitment for a surgical research
study.
AB - BACKGROUND: Patient portal adoption has rapidly increased over the last decade.
Most patient portal research has been done in primary care or medical
specialties, and few studies have examined their use in surgical patients or for
recruiting research subjects. No known studies have compared portal messaging
with other approaches of recruitment. OBJECTIVES: This case report describes our
experience with patient portal versus telephone recruitment for a study involving
long-term follow up of surgical patients. METHODS: Participants were recruited
for a study of recurrence after ventral hernia repair through telephone calls and
patient portal messaging based on registration status with the portal. Potential
subjects who did not have a portal account or whose portal messages were returned
after 5 days were called. The proportion of participants enrolled with each
method was determined and demographics of eligible patients, portal users, and
participants were compared. RESULTS: 1359 patients were eligible for the hernia
study, and enrollment was 35% (n=465). Most participants were recruited by
telephone (84%, n=391); 16% (n=74) were recruited through portal messaging. Forty
four percent of eligible participants had a registered portal account, and 14% of
users responded to the recruitment message. Portal users were younger than non
users (55 vs. 58 years, p<0.001); participants recruited through the portal
versus telephone were also younger (54 vs. 59 years, p=0.001). Differences in the
sex and racial distributions between users and non-users and between portal and
telephone recruits were not significant. CONCLUSIONS: Portal versus telephone
recruitment for a surgical research study demonstrated modest portal recruitment
rates and similar demographics between recruitment methods. Published studies of
portal-only recruitment in primary care or medical-specialty patient populations
have demonstrated higher enrollment rates, but this case study demonstrates that
portal recruitment for research studies in the surgical population is feasible,
and it offers convenience to patients and researchers.
PMID- 25589915
TI - Class II but Not Second Class-Prospects for the Development of Class II PI3K
Inhibitors.
AB - The Class II PI3 kinases are emerging from the shadows of their Class I cousins.
The data emerging from PIK3C2 genetic modification studies and from siRNA
knockdown suggest important roles in physiology and pathology. With some well
studied Class I isoform inhibitors showing strong Class II activity and a wealth
of crystallographic information available, the structural similarity of these
isoforms to Class I provides both the opportunity and the challenge in design of
selective pharmacological inhibitors.
PMID- 25589916
TI - Combination of novel imidazopyridazine mps-1 kinase inhibitors and bcl-2 family
protein inhibitors.
PMID- 25589914
TI - User centered clinical decision support tools: adoption across clinician training
level.
AB - BACKGROUND: Dissemination and adoption of clinical decision support (CDS) tools
is a major initiative of the Affordable Care Act's Meaningful Use program.
Adoption of CDS tools is multipronged with personal, organizational, and clinical
settings factoring into the successful utilization rates. Specifically, the
diffusion of innovation theory implies that 'early adopters' are more inclined to
use CDS tools and younger physicians tend to be ranked in this category.
OBJECTIVE: This study examined the differences in adoption of CDS tools across
providers' training level. PARTICIPANTS: From November 2010 to 2011, 168
residents and attendings from an academic medical institution were enrolled into
a randomized controlled trial. INTERVENTION: The intervention arm had access to
the CDS tool through the electronic health record (EHR) system during strep and
pneumonia patient visits. MAIN MEASURES: The EHR system recorded details on how
intervention arm interacted with the CDS tool including acceptance of the initial
CDS alert, completion of risk-score calculators and the signing of medication
order sets. Using the EHR data, the study performed bivariate tests and general
estimating equation (GEE) modeling to examine the differences in adoption of the
CDS tool across residents and attendings. KEY RESULTS: The completion rates of
the CDS calculator and medication order sets were higher amongst first year
residents compared to all other training levels. Attendings were the less likely
to accept the initial step of the CDS tool (29.3%) or complete the medication
order sets (22.4%) that guided their prescription decisions, resulting in
attendings ordering more antibiotics (37.1%) during an CDS encounter compared to
residents. CONCLUSION: There is variation in adoption of CDS tools across
training levels. Attendings tended to accept the tool less but ordered more
medications. CDS tools should be tailored to clinicians' training levels.
PMID- 25589917
TI - Pyrrolopyrimidine Analogues as MKNK Inhibitors.
PMID- 25589918
TI - Dual leucine zipper kinase inhibitors: potential treatments for neurodegenerative
diseases.
PMID- 25589919
TI - RET Kinase Inhibitors May Treat Cancer and Gastrointestinal Disorders.
PMID- 25589920
TI - Quinalozinones as Inhibitors of Class I PI3K Kinases.
PMID- 25589921
TI - P21-Activated Kinase 4 (PAK4) Inhibitors as Potential Cancer Therapy.
PMID- 25589922
TI - Novel azaindazole sulfonamides inhibitors of serum and glucocorticoid regulated
kinase.
PMID- 25589923
TI - Pyrrolopyridines-quinazolines Inhibitors of PKR-Like ER Kinase.
PMID- 25589924
TI - Novel Disubstituted Pyrimidines as Inhibitors of Bruton's Tyrosine Kinase.
PMID- 25589927
TI - Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5
a]pyrazines as ATR Inhibitors.
AB - A saturation strategy focused on improving the selectivity and physicochemical
properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and
selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3Kalpha mutants as ATR
crystal structure surrogates was instrumental in providing cocrystal structures
to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide
and GSH as trapping agents during microsomal incubations, in addition to
deuterium-labeled compounds as mechanistic probes uncovered the molecular basis
for the observed CYP3A4 TDI in the series.
PMID- 25589925
TI - Fragment-based discovery of type I inhibitors of maternal embryonic leucine
zipper kinase.
AB - Fragment-based drug design was successfully applied to maternal embryonic leucine
zipper kinase (MELK). A low affinity (160 MUM) fragment hit was identified, which
bound to the hinge region with an atypical binding mode, and this was optimized
using structure-based design into a low-nanomolar and cell-penetrant inhibitor,
with a good selectivity profile, suitable for use as a chemical probe for
elucidation of MELK biology.
PMID- 25589926
TI - Structure-Based Design of Type II Inhibitors Applied to Maternal Embryonic
Leucine Zipper Kinase.
AB - A novel Type II kinase inhibitor chemotype has been identified for maternal
embryonic leucine zipper kinase (MELK) using structure-based ligand design. The
strategy involved structural characterization of an induced DFG-out pocket by
protein-ligand X-ray crystallography and incorporation of a slender linkage
capable of bypassing a large gate-keeper residue, thus enabling design of
molecules accessing both hinge and induced pocket regions. Optimization of an
initial hit led to the identification of a low-nanomolar, cell-penetrant Type II
inhibitor suitable for use as a chemical probe for MELK.
PMID- 25589928
TI - Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles
(ABI) as ATR Inhibitors.
AB - Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The
ABI series was potent and selective for ATR. Incorporation of a 6-azaindole
afforded a marked increase in cellular potency but was associated with poor PK
and hERG ion channel inhibition. DMPK experiments established that CYP P450 and
AO metabolism in conjunction with Pgp and BCRP efflux were major causative
mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability
driven by the presence of both a morpholine and an indole moiety. Incorporation
of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the
various medicinal chemistry issues encountered.
PMID- 25589929
TI - Quantification of a Pharmacodynamic ERK End Point in Melanoma Cell Lysates:
Toward Personalized Precision Medicine.
AB - Protein kinases are mutated or otherwise rendered constitutively active in
numerous cancers where they are attractive therapeutic targets with well over a
dozen kinase inhibitors now being used in therapy. While fluorescent sensors have
capacity to measure changes in kinase activity, surprisingly they have not been
utilized for biomarker studies. A first-generation peptide sensor for ERK based
on the Sox fluorophore is described. This sensor called ERK-sensor-D1 possesses
high activity toward ERK and more than 10-fold discrimination over other MAPKs.
The sensor can rapidly quantify ERK activity in cell lysates and monitor ERK
pathway engagement by BRAF and MEK inhibitors in cultured melanoma cell lines.
The dynamic range of the sensor assay allows ERK activities that have potential
for profound clinical consequences to be rapidly distinguished.
PMID- 25589930
TI - Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out
Conformation.
AB - The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A
series of molecules that feature both an N-phenylsulfonamide and tertiary amide
were not only very potent at LIMK2 but also were extremely selective against a
panel of other kinases. Enzymatic kinetic studies showed these molecules to be
noncompetitive with ATP, suggesting allosteric inhibition. X-ray crystallography
confirmed that these sulfonamides are a rare example of a type III kinase
inhibitor that binds away from the highly conserved hinge region and instead
resides in the hydrophobic pocket formed in the DFG-out conformation of the
kinase, thus accounting for the high level of selectivity observed.
PMID- 25589931
TI - Pyrimidine-based tricyclic molecules as potent and orally efficacious inhibitors
of wee1 kinase.
AB - Aided by molecular modeling, compounds with a pyrimidine-based tricyclic scaffold
were designed and confirmed to inhibit Wee1 kinase. Structure-activity studies
identified key pharmacophores at the aminoaryl and halo-benzene regions
responsible for binding affinity with sub-nM K i values. The potent inhibitors
demonstrated sub-MUM activities in both functional and mechanism-based cellular
assays and also possessed desirable pharmacokinetic profiles. The lead molecule,
31, showed oral efficacy in potentiating the antiproliferative activity of
irinotecan, a cytotoxic agent, in a NCI-H1299 mouse xenograft model.
PMID- 25589932
TI - Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as
Potent and Selective Pim-1 Inhibitors.
AB - Pim-1 has emerged as an attractive target for developing therapeutic agents for
treating disorders involving abnormal cell growth, especially cancers. Herein we
present lead optimization, chemical synthesis and biological evaluation of
pyrazolo[1,5-a]pyrimidine compounds as potent and selective inhibitors of Pim-1
starting from a hit from virtual screening. These pyrazolo[1,5-a]pyrimidine
compounds strongly inhibited Pim-1 and Flt-3 kinases. Selected compounds
suppressed both the phosphorylation of BAD protein in a cell-based assay and 2
dimensional colony formation in a clonogenic cell survival assay at submicromolar
potency, suggesting that cellular activity was mediated through inhibition of Pim
1. Moreover, these Pim-1 inhibitors did not show significant hERG inhibition at
30 MUM concentration. The lead compound proved to be highly selective against a
panel of 119 oncogenic kinases, indicating it had an improved safety profile
compared with the first generation Pim-1 inhibitor SGI-1776.
PMID- 25589933
TI - Unfolded Protein Response in Cancer: IRE1alpha Inhibition by Selective Kinase
Ligands Does Not Impair Tumor Cell Viability.
AB - The kinase/endonuclease inositol requiring enzyme 1 (IRE1alpha), one of the
sensors of unfolded protein accumulation in the endoplasmic reticulum that
triggers the unfolded protein response (UPR), has been investigated as an
anticancer target. We identified potent allosteric inhibitors of IRE1alpha
endonuclease activity that bound to the kinase site on the enzyme. Structure
activity relationship (SAR) studies led to 16 and 18, which were selective in
kinase screens and were potent against recombinant IRE1alpha endonuclease as well
as cellular IRE1alpha. The first X-ray crystal structure of a kinase inhibitor
(16) bound to hIRE1alpha was obtained. Screening of native tumor cell lines
(>300) against selective IRE1alpha inhibitors failed to demonstrate any effect on
cellular viability. These results suggest that IRE1alpha activity is not
essential for viability in most tumor cell lines, in vitro, and that interfering
with the survival functions of the UPR may not be an effective strategy to block
tumorigenesis.
PMID- 25589934
TI - Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly
Active and Selective SGK1 Inhibitors.
AB - From a virtual screening starting point, inhibitors of the serum and
glucocorticoid regulated kinase 1 were developed through a combination of
classical medicinal chemistry and library approaches. This resulted in highly
active small molecules with nanomolar activity and a good overall in vitro and
ADME profile. Furthermore, the compounds exhibited unusually high kinase and off
target selectivity due to their rigid structure.
PMID- 25589935
TI - Structural Analysis of the Binding of Type I, I1/2, and II Inhibitors to Eph
Tyrosine Kinases.
AB - We have solved the crystal structures of the EphA3 tyrosine kinase in complex
with nine small-molecule inhibitors, which represent five different chemotypes
and three main binding modes, i.e., types I and I1/2 (DFG in) and type II (DFG
out). The three structures with type I1/2 inhibitors show that the higher
affinity with respect to type I is due to an additional polar group (hydroxyl or
pyrazole ring of indazole) which is fully buried and is involved in the same
hydrogen bonds as the (urea or amide) linker of the type II inhibitors. Overall,
the type I and type II binding modes belong to the lock-and-key and induced fit
mechanism, respectively. In the type II binding, the scaffold in contact with the
hinge region influences the position of the Phe765 side chain of the DFG motif
and the orientation of the Gly-rich loop. The binding mode of Birb796 in the
EphA3 kinase does not involve any hydrogen bond with the hinge region, which is
different from the Birb796/p38 MAP kinase complex. Our structural analysis
emphasizes the importance of accounting for structural plasticity of the ATP
binding site in the design of type II inhibitors of tyrosine kinases.
PMID- 25589936
TI - Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the
Treatment of Glaucoma.
AB - The structure of LX7101, a dual LIM-kinase and ROCK inhibitor for the treatment
of ocular hypertension and associated glaucoma, is disclosed. Previously reported
LIM kinase inhibitors suffered from poor aqueous stability due to solvolysis of
the central urea. Replacement of the urea with a hindered amide resulted in
aqueous stable compounds, and addition of solubilizing groups resulted in a set
of compounds with good properties for topical dosing in the eye and good efficacy
in a mouse model of ocular hypertension. LX7101 was selected as a clinical
candidate from this group based on superior efficacy in lowering intraocular
pressure and a good safety profile. LX7101 completed IND enabling studies and was
tested in a Phase 1 clinical trial in glaucoma patients, where it showed efficacy
in lowering intraocular pressure.
PMID- 25589937
TI - Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical
characterization.
AB - Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular
endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic and
oncogenic pathway-related receptor tyrosine kinases. To elucidate the origin of
the potency of lenvatinib in VEGF receptor 2 (VEGFR2) inhibition, we conducted a
kinetic interaction analysis of lenvatinib with VEGFR2 and X-ray analysis of the
crystal structure of VEGFR2-lenvatinib complexes. Kinetic analysis revealed that
lenvatinib had a rapid association rate constant and a relatively slow
dissociation rate constant in complex with VEGFR2. Co-crystal structure analysis
demonstrated that lenvatinib binds at its ATP mimetic quinoline moiety to the ATP
binding site and to the neighboring region via a cyclopropane ring, adopting an
Asp-Phe-Gly (DFG)-"in" conformation. These results suggest that lenvatinib is
very distinct in its binding mode of interaction compared to the several approved
VEGFR2 kinase inhibitors.
PMID- 25589939
TI - New Frontiers in Kinases: Second Generation Inhibitors-Going beyond Cancer.
PMID- 25589938
TI - Synthesis and Structure-Activity Relationship Study of 5a-Carbasugar Analogues of
SL0101.
AB - The Ser/Thr protein kinase, RSK, is associated with oncogenesis, and therefore,
there are ongoing efforts to develop RSK inhibitors that are suitable for use in
vivo. SL0101 is a natural product that demonstrates selectivity for RSK
inhibition. However, SL0101 has a short biological half-life in vivo. To address
this issue we designed a set of eight cyclitol analogues, which should be
resistant to acid catalyzed anomeric bond hydrolysis. The analogues were
synthesized and evaluated for their ability to selectively inhibit RSK in vitro
and in cell-based assays. All the analogues were prepared using a stereodivergent
palladium-catalyzed glycosylation/cyclitolization for installing the aglycon. The
l-cyclitol analogues were found to inhibit RSK2 in in vitro kinase activity with
a similar efficacy to that of SL0101, however, the analogues were not specific
for RSK in cell-based assays. In contrast, the d-isomers showed no RSK inhibitory
activity in in vitro kinase assay.
PMID- 25589940
TI - Complex regional pain syndrome: time to study the supraspinal role?
PMID- 25589941
TI - Etifoxine for pain patients with anxiety.
AB - Etifoxine (etafenoxine, Stresam(r)) is a non-benzodiazepine anxiolytic with an
anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is
currently being studied for its ability to promote peripheral nerve healing and
to treat chemotherapy-induced pain. In addition to being mediated by GABAAalpha2
receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects
directly by binding to beta2 or beta3 subunits of the GABAA receptor complex. It
also modulates GABAA receptors indirectly via stimulation of neurosteroid
production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the
outer mitochondrial membrane in the central and peripheral nervous systems,
previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the
effects of etifoxine are not completely reversed by the benzodiazepine antagonist
flumazenil. Etifoxine is used for various emotional and bodily reactions followed
by anxiety. It is contraindicated in situations such as shock, severely impaired
liver or kidney function, and severe respiratory failure. The average dosage is
150 mg per day for no more than 12 weeks. The most common adverse effect is
drowsiness at the initial stage. It does not usually cause any withdrawal
syndromes. In conclusion, etifoxine shows less adverse effects of anterograde
amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes
than those of benzodiazepines. It potentiates GABAA receptor-function by a direct
allosteric effect and by an indirect mechanism involving the activation of TSPO.
It seems promising that non-benzodiazepine anxiolytics including etifoxine will
replenish shortcomings of benzodiazepines and selective serotonin reuptake
inhibitors according to animated studies related to TSPO.
PMID- 25589942
TI - Comparison of the efficacy of caudal, interlaminar, and transforaminal epidural
injections in managing lumbar disc herniation: is one method superior to the
other?
AB - BACKGROUND: Epidural injections are performed utilizing 3 approaches in the
lumbar spine: caudal, interlaminar, and transforaminal. The literature on the
efficacy of epidural injections has been sporadic. There are few high-quality
randomized trials performed under fluoroscopy in managing disc herniation that
have a long-term follow-up and appropriate outcome parameters. There is also a
lack of literature comparing the efficacy of these 3 approaches. METHODS: This
manuscript analyzes data from 3 randomized controlled trials that assessed a
total of 360 patients with lumbar disc herniation. There were 120 patients per
trial either receiving local anesthetic alone (60 patients) or local anesthetic
with steroids (60 patients). RESULTS: Analysis showed similar efficacy for
caudal, interlaminar, and transforaminal approaches in managing chronic pain and
disability from disc herniation. The analysis of caudal epidural injections
showed the potential superiority of steroids compared with local anesthetic alone
a 2-year follow-up, based on the average relief per procedure. In the
interlaminar group, results were somewhat superior for pain relief in the steroid
group at 6 months and functional status at 12 months. Interlaminar epidurals
provided improvement in a significantly higher proportion of patients. The
proportion of patients nonresponsive to initial injections was also lower in the
group for local anesthetic with steroid in the interlaminar trial. CONCLUSIONS:
The results of this assessment show significant improvement in patients suffering
from chronic lumbar disc herniation with 3 lumbar epidural approaches with local
anesthetic alone, or using steroids with long-term follow-up of up to 2 years, in
a contemporary interventional pain management setting.
PMID- 25589943
TI - Comparative Study of the Effects of the Retrocrural Celiac Plexus Block Versus
Splanchnic Nerve Block, C-arm Guided, for Upper Gastrointestinal Tract Tumors on
Pain Relief and the Quality of Life at a Six-month Follow Up.
AB - BACKGROUND: The celiac plexus and splanchnic nerves are targets for neurolytic
blocks for pain relief from pain caused by upper gastrointestinal tumors.
Therefore, we investigated the analgesic effect of a celiac plexus block versus a
splanchnic nerve block and the effects of these blocks on the quality of life six
months post-intervention for patients with upper GIT tumors. METHODS: Seventy
nine patients with inoperable upper GIT tumors and with severe uncontrolled
visceral pain were randomized into two groups. These were Group I, for whom a
celiac plexus block was used with a bilateral needle retrocrural technique, and
Group II, for whom a splanchnic nerve block with a bilateral needle technique was
used. The visual analogue scale for pain (0 to 100), the quality of life via the
QLQ-C30 questionnaire, and survival rates were assessed. RESULTS: Pain scores
were comparable in both groups in the first week after the block. Significantly
more patients retained good analgesia with tramadol in the splanchnic group from
16 weeks onwards (P = 0.005, 0.001, 0.005, 0.001, 0.01). Social and cognitive
scales improved significantly from the second week onwards in the splanchnic
group. Survival of both groups was comparable. CONCLUSIONS: The results of this
study demonstrate that the efficacy of the splanchnic nerve block technique
appears to be clinically comparable to a celiac block. All statistically
significant differences are of little clinical value.
PMID- 25589944
TI - A Pilot Study of the Correlation between the Numeric Rating Scale used to
Evaluate "Geop" and Questionnaires on Pain Perception.
AB - BACKGROUND: The word "geop" is a unique Korean term commonly used to describe
fright, fear and anxiety, and similar concepts. The purpose of this pilot study
is to examine the correlation between the Numeric Rating Scale (NRS) score of
geop and three different questionnaires on pain perception. METHODS: Patients
aged 20 to 70 years who visited our outpatient pain clinics were evaluated. They
were requested to rate the NRS score (range: 0-100) if they felt geop. Next, they
completed questionnaires on pain perception, in this case the Korean version of
the Pain Sensitivity Questionnaire (PSQ), the Pain Catastrophizing Scale (PCS),
and the Pain Anxiety Symptoms Scale (PASS). The correlations among each variable
were evaluated by statistical analyses. RESULTS: There was no statistically
significant correlation between the NRS score of geop and the PSQ score (r =
0.075, P = 0.5605). The NRS score of geop showed a significant correlation with
the PCS total score (r = 0.346, P = 0.0063). Among the sub-scales, Rumination (r
= 0.338, P = 0.0077) and Magnification (r = 0.343, P = 0.0069) were correlated
with the NRS score of geop. In addition, the NRS score of geop showed a
significant correlation with the PASS total score (r = 0.475, P = 0.0001). The
cognitive (r = 0.473, P = 0.0002) and fear factors (r = 0.349, P = 0.0063) also
showed significant correlations with the NRS score of geop. CONCLUSIONS: This
study marks the first attempt to introduce the concept of "geop." The NRS score
of geop showed a moderate positive correlation with the total PCS and PASS score.
However, further investigations are required before the "geop" concept can be
used practically in clinical fields.
PMID- 25589945
TI - Comparison of ramosetron plus dexamethasone with ramosetron alone on
postoperative nausea, vomiting, shivering and pain after thyroid surgery.
AB - BACKGROUND: Postoperative nausea and vomiting (PONV), postanesthetic shivering
and pain are common postoperative patient complaints that can result in adverse
physical and psychological outcomes. Some antiemetics are reported to be
effective in the management of postoperative pain and shivering, as well as PONV.
We evaluated the efficacy of dexamethasone added to ramosetron on PONV, shivering
and pain after thyroid surgery. METHODS: One hundred and eight patients scheduled
for thyroid surgery were randomly allocated to three different groups: the
control group (group C, n = 36), the ramosetron group (group R, n = 36), or the
ramosetron plus dexamethasone group (group RD, n = 36). The patients were treated
intravenously with 1 and 2 ml of 0.9% NaCl (group C); or 2 ml of 0.15 mg/ml
ramosetron plus 1 ml of 0.9% NaCl (group R); or 2 ml of 0.15 mg/ml ramosetron
plus 1 ml of 5 mg/ml dexamethasone (group RD) immediately after anesthesia.
RESULTS: Incidence of nausea and the need for rescue antiemetics, verbal rating
scale (VRS) 1 hour pain value, ketorolac consumption, and incidence of shivering
were significantly lower in group R and group RD, than in group C (P < 0.05).
Moreover, these parameters were significantly lower in group RD than in group R
(P < 0.05). CONCLUSIONS: Combination of ramosetron and dexamethasone
significantly reduced not only the incidence of nausea and need for rescue
antiemetics, but also the VRS 1 hour pain value, ketorolac consumption, and the
incidence of shivering compared to ramosetron alone in patients undergoing
thyroid surgery.
PMID- 25589946
TI - A comparison of three methods for postoperative pain control in patients
undergoing arthroscopic shoulder surgery.
AB - BACKGROUND: Arthroscopic shoulder operations (ASS) are often associated with
severe postoperative pain. Nerve blocks have been studied for pain in shoulder
surgeries. Interscalene brachial plexus blocks (ISB) and an intra-articular
injection (IA) have been reported in many studies. The aim of the present study
is to evaluate the effect of ISB, a continuous cervical epidural block (CCE) and
IA as a means of postoperative pain control and to study the influence of these
procedures on postoperative analgesic consumption and after ASS. METHODS: Fifty
seven patients who underwent ASS under general anesthesia were randomly assigned
to one of three groups: the ISB group (n = 19), the CCE group (n = 19), and the
IA group (n = 19). Patients in each group were evaluated on a postoperative
numerical rating scale (NRS), their rescue opioid dosage (ROD), and side effects.
RESULTS: Postoperative NRSs were found to be higher in the IA group than in the
ISB and CCE groups both at rest and on movement. The ROD were 1.6 +/- 2.3, 3.0 +/
4.9 and 7.1 +/- 7.9 mg morphine equivalent dose in groups CCE, ISB, and IA
groups (P = 0.001), respectively, and statistically significant differences were
noted between the CCE and IA groups (P = 0.01) but not in between the ISB and CCE
groups. CONCLUSIONS: This prospective, randomized study demonstrated that ISB is
as effective analgesic technique as a CCE for postoperative pain control in
patients undergoing ASS.
PMID- 25589947
TI - Successful Treatment of Rectus Femoris Calcification with Ultrasound-guided
Injection: A Case Report.
AB - Painful periarticular calcification most commonly occurs within the rotator cuff
of the shoulder and rarely around the elbow, hip, foot, and neck. As acute
inflammatory reaction develops, severe pain, exquisite tenderness, local
swelling, and limitation of motion with pain occur. In case of calcific
tendinitis of the shoulder, it can be easily diagnosed according to the symptoms
and with x-ray. However, in lesions of the hip, as it is a rare location and
usually involves pain in the posterolateral aspect of the thigh, which can
simulate radicular pain from a lumbar intervertebral disc, it could be difficult
to diagnose. Hence, physicians usually focus on lumbar lesions; therefore,
misdiagnosis is common and leads to a delayed management. Here, we report the
case of a 30-year-old female patient with calcific tendinitis of the rectus
femoris that was successfully managed with ultrasound-guided steroid injection.
This study offers knowledge about the rectus femoris calcification.
PMID- 25589948
TI - Spinal cord stimulation for intractable visceral pain due to sphincter of oddi
dysfunction.
AB - Sphincter of Oddi dysfunction (SOD) is a syndrome of chronic biliary pain or
recurrent pancreatitis due to the functional obstruction of the
pancreaticobiliary flow. We report a case of spinal cord stimulation (SCS) for
chronic abdominal pain due to SOD. The patient had a history of cholecystectomy
and had suffered from chronic right upper quadrant abdominal pain. The patient
had been diagnosed as having SOD. The patient was treated with opioid analgesics
and nerve blocks, including a splanchnic nerve block. However, two years later,
the pain became intractable. We implanted percutaneous SCS at the T5-7 level for
this patient. Visual analog scale (VAS) scores for pain and the amount of opioid
intake decreased. The patient was tracked for more than six months without
significant complications. From our clinical case, SCS is an effective and
alternative treatment option for SOD. Further studies and long-term follow-up are
necessary to understand the effectiveness and the limitations of SCS on SOD.
PMID- 25589949
TI - The effect of stellate ganglion block on intractable lymphedema after breast
cancer surgery.
AB - Lymphedema of the upper limb after breast cancer surgery is a disease that
carries a life-long risk and is difficult to cure once it occurs despite the
various treatments which have been developed. Two patients were referred from
general surgery department for intractable lymphedema. They were treated with
stellate ganglion blocks (SGBs), and the circumferences of the mid-point of their
each upper and lower arms were measured on every visit to the pain clinic. A
decrease of the circumference in each patient was observed starting after the
second injection. A series of blocks were established to maintain a prolonged
effect. Both patients were satisfied with less swelling and pain. This case
demonstrates the benefits of an SGB for intractable upper limb lymphedema.
PMID- 25589950
TI - Which methods of epidural steroid injections is more effective in reducing the
radicular pain; transforaminal or interlaminar?
PMID- 25589951
TI - Chronic kidney disease in the elderly: evaluation and management.
AB - Chronic kidney disease (CKD) is a very common clinical problem in elderly
patients and is associated with increased morbidity and mortality. As life
expectancy continues to improve worldwide, there is a rising prevalence of
comorbidities and risk factors such as hypertension and diabetes predisposing to
a high burden of CKD in this population. The body of knowledge on the approach to
elderly patient with CKD is still evolving. Thus, this review seeks to explore
the epidemiology and to discuss current understanding of challenges in the
diagnosis and management of elderly patients CKD.
PMID- 25589954
TI - The next challenge for VATS lobectomy surgeons.
PMID- 25589953
TI - MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release
and thrombin inhibition.
AB - MMP9-responsive bivalirudin-HPMA copolymers were synthesized for direct, local
administration in rat spinal cord contusion injury models. Polymer-conjugated
bivalirudin peptides maintained activity while demonstrating enzyme-mediated
release upon MMP9 exposure and prolonged release from hyaluronic
acid/methylcellulose (HAMC) hydrogels compared to free bivalirudin peptide.
Localized administration of bivalirudin copolymers in vivo at the site of rat
spinal cord injury decreased cellular proliferation and astrogliosis, suggesting
the bivalirudin copolymer and HAMC hydrogel system are a promising therapeutic
intervention for reducing immediate inflammatory responses and long term
scarring.
PMID- 25589952
TI - Situs inversus and ciliary abnormalities: 20 years later, what is the connection?
AB - Heterotaxy (also known as situs ambiguous) and situs inversus totalis describe
disorders of laterality in which internal organs do not display their typical
pattern of asymmetry. First described around 1600 by Girolamo Fabrizio, numerous
case reports about laterality disorders in humans were published without any idea
about the underlying cause. Then, in 1976, immotile cilia were described as the
cause of a human syndrome that was previously clinically described, both in 1904
by AK Siewert and in 1933 by Manes Kartagener, as an association of situs
inversus with chronic sinusitis and bronchiectasis, now commonly known as
Kartagener's syndrome. Despite intense research, the underlying defect of
laterality disorders remained unclear. Nearly 20 years later in 1995, Bjorn
Afzelius discussed five hypotheses to explain the connection between ciliary
defects and loss of laterality control in a paper published in the International
Journal of Developmental Biology asking: 'Situs inversus and ciliary
abnormalities: What is the connection?'. Here, nearly 20 research years later, we
revisit some of the key findings that led to the current knowledge about the
connection between situs inversus and ciliary abnormalities.
PMID- 25589955
TI - Spontaneous esophageal rupture as the underlying cause of pneumothorax: early
recognition is crucial.
AB - Boerhaave's syndrome (BS), also known as "spontaneous rupture of the esophagus",
constitutes an emergency that requires early diagnosis if death or serious
morbidity are to be prevented. First described in 1724, BS is thought to be more
common than once thought. Its true incidence remains unknown. Mortality ranges
between 20-40% with timely treatment but this rises to virtually 100% if
treatment is delayed by more than 48 hours. This is unfortunately a common
occurrence due to delayed diagnosis. The commonest precipitating factor is
vomiting but BS can be truly "spontaneous". The classical clinical presentation
described consists of vomiting, chest pain, and subcutaneous emphysema. However,
and contrary to popular belief, this triad is actually uncommon accounting for
the frequently delayed diagnosis. A less recognised presenting feature of BS is
with pneumothorax due to associated rupture of the parietal pleura. Pneumothorax
has been shown to be present in more than 20% of cases of BS-sometimes with a
coexistent pleural effusion (hydropneumothorax). This article aims to raise
awareness about pneumothorax as the sole initial presenting feature of BS and
alert clinicians to consider BS in the differential diagnosis of any patient with
respiratory symptoms and a recent history of vomiting.
PMID- 25589956
TI - Big data and clinical research: perspective from a clinician.
PMID- 25589957
TI - Endobronchial ultrasound-guided transbronchial needle aspiration: a maturing
technique.
PMID- 25589958
TI - The lung cancer epidemic in Spanish women: an analysis of mortality rates over a
37-year period.
AB - BACKGROUND: Lung cancer continues to be the leading cause of cancer-related
mortality in the European Union (EU) and deaths from lung cancer have been
projected to escalate to epidemic proportions amongst females over the next
years. We examined lung cancer mortality rates in men and women from Andalusia
(Spain) over a 37-year period [1975-2012]. METHODS: Longitudinal epidemiological
study analyzing lung cancer mortality trends in males and females. Data on lung
cancer mortality in Andalusia for the period 1975-2012 were obtained from the
official cause-of-death publications of the Institute of Statistics of Andalusia.
For each sex, age-standardized (European standard population) mortality rates
(ASR) from lung cancer were calculated for all ages and truncated at 30-64, 65
74, and >75 years using the direct method. Standardized rate trends by age and
sex were estimated by joinpoint regression analysis. RESULTS: In men, the ASR
steadily increased through the period 1993-1995, reaching a peak of 145.72
deaths/100,000 people. Subsequently, lung cancer deaths decreased to a rate of
125.47 in the 2011-2012 period. A moderate increase was seen in women until the
late 1990s and early 2000s. Thereafter, a very notable rise was observed in
females for all age groups, the only exception being older subjects. The sex
differences decreased from 8.6:1 in the 1975-1977 period to 6.8:1 in the 2011
2012 period. CONCLUSIONS: Lung cancer mortality rates decreased significantly in
Andalusian men from 1975 to 2012. More importantly, we demonstrate for the first
time the beginning of the lung cancer epidemics in Andalusian women as previously
predicted for this area.
PMID- 25589959
TI - Treatment of giant emphysamous bulla with endobronchial valves in patients with
chronic obstructive pulmonary disease: a case series.
AB - BACKGROUND: Giant emphysamtous bulla (GEB) can negatively affect the pulmonary
functions of chronic obstructive pulmonary diseases (COPD) patients, including
decreased forced expiratory volume in 1 s (FEV1) and increased functional
residual capacity (FRC). The aim of this study was to evaluate the efficacy of
endobronchial valve (EBV) to treat bullae and to find efficacy predictors of
successful treatment. METHODS: Five COPD patients with giant bulla were treated
using EBVs. Before the EBV deployment, collateral ventilation (CV) between the
targeted and adjacent lobes was evaluated with Chartis system. RESULTS: In the
two patients with negative CV, the mean value of FEV1 increased from 27.1+/-11.4%
of predicted value before EBV treatment to 32.8+/-12.0% (P>0.05) at 1 month after
EBV treatment, than to 31.7+/-24.5% (P>0.05) at 6 months after EBV treatment.
Only one patient, whose bulla occupied the whole right middle lung, displayed
sustained improvement of FEV1 at 6 months after EBV treatment. In the three
patients with positive CV, the mean value of FEV1 decreased from 28.8+/-19.0% of
predicted value before EBV treatment to 24.8+/-12.6% (P>0.05) at 1 month after
EBV treatment, than to 22.1+/-10.8% (P>0.05) at 6 months after EBV treatment.
CONCLUSIONS: EBV is an effective measure to treat highly selected COPD patients
with giant bulla. Although, EBV treatment can achieve transient improvement of
lung function at patients with CV negative bulla, long-term benefit was merely
observed at the patient with a bulla at right middle lobe (RML).
PMID- 25589960
TI - Effect of a neutrophil elastase inhibitor on ventilator-induced lung injury in
rats.
AB - OBJECTIVE: We hypothesized that pretreatment with sivelestat therapy could
attenuate ventilator-induced lung injury (VILI) and lung inflammation in a rat
model. METHODS: The neutrophil elastase inhibitor was administered
intraperitoneally 30 min before and at the initiation of ventilation. The rats
were categorized as (I) sham group; (II) VILI group; (III) sivelestat group; (IV)
early sivelestat group. Wet-to-dry weight ratio, bronchoalveolar lavage fluid
(BALF) neutrophil and protein, tissue malondialdehyde (MDA) and histologic VILI
scores were investigated. RESULTS: The ratio of wet-to-dry weight, BALF
neutrophil and protein, tissue MDA and VILI scores were significantly increased
in the VILI group compared to the sham group [3.85+/-0.32 vs. 9.05+/-1.02,
P<0.001; (0.89+/-0.93)*10(4) vs. (7.67+/-1.41)*10(4) cells/mL, P<0.001; 2.34+/
0.47 vs. 23.01+/-3.96 mg/mL, P<0.001; 14.43+/-1.01 vs. 36.56+/-5.45 nmol/mg
protein, P<0.001; 3.78+/-0.67 vs. 7.00+/-1.41, P<0.001]. This increase was
attenuated in the early sivelestat group compared with the sivelestat group [wet
to-dry ratio: 6.76+/-2.01 vs. 7.39+/-0.32, P=0.032; BALF neutrophil: (5.56+/
1.13)*10(4) vs. (3.89+/-1.05)*10(4) cells/mL, P=0.021; BALF protein: 15.57+/-2.32
vs. 18.38+/-2.00 mg/mL, P=0.024; tissue MDA: 29.16+/-3.01 vs. 26.31+/-2.58,
P=0.049; VILI scores: 6.33+/-1.41 vs. 5.00+/-0.50, P=0.024]. CONCLUSIONS:
Pretreatment with a neutrophil elastase inhibitor attenuates VILI in a rat model.
PMID- 25589961
TI - Cost and effectiveness of video-assisted thoracoscopic surgery for clinical stage
I non-small cell lung cancer: a population-based analysis.
AB - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive
alternative to conventional surgery (CS). We aimed to estimate the short-term
cost-effectiveness of VATS vs. CS for clinical stage I non-small cell lung cancer
(NSCLC-c-stage-I) patients from the payer's perspective (National Health
Insurance). METHODS: We identified NSCLC-c-stage-I patients diagnosed and
received surgery within 2007-2009 through a comprehensive population-based
database containing cancer and death registries, and reimbursement data. The
duration of interest was 1 year. We included potential confounding covariables
through literature searching and our own experience, and used a propensity score
to construct a 1:1 population for adjustment. RESULTS: Our study population
constituted 966 patients. The mean hospital stay [days, standard deviation (SD)]
were 14.4 [7] and 16.1 (7.7) for VATS and CS respectively (P=0.002). The mean
cost (2013 USD) and survival (year) was $22,316 vs. $21,976 and 0.98 vs. 0.974
for VATS vs. CS. The probability for VATS to be cost-effective (i.e., positive
net benefit) was 0.49 & 0.56 at willingness-to-pay (WTP) 50,000 & 100,000
USD/life-year, respectively. CONCLUSIONS: We provide the first empirical evidence
that when compared to CS, VATS was potentially cost-effective in the short term
(1 year) within the common WTP levels in Taiwan.
PMID- 25589962
TI - Predictive risk factors for lymph node metastasis in patients with small size non
small cell lung cancer.
AB - BACKGROUND: Accurate clinical staging of non-small cell lung cancer (NSCLC) is
essential for developing an optimal treatment strategy. This study aimed to
determine the predictive risk factors for lymph node metastasis, including both
N1 and N2 metastases, in clinical T1aN0 NSCLC patients. METHODS: We
retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no
radiologic evidence of lymph node metastasis, and who had undergone surgical
pulmonary resection with systematic mediastinal node dissection or sampling at
the First Affiliated Hospital of Zhejiang University between January 2011 and
June 2013. Univariate and multivariate logistic regression analyses were
performed to identify predictive factors for node metastasis. RESULTS:
Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients.
Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2
nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of
the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients
had nodal skip metastasis. Variables of preoperative radiographic tumor size, non
upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and
micropapillary predominant adenocarcinoma (AC) were identified as predictors for
positive N1 or N2 node multivariate analysis. CONCLUSIONS: Pathologically
positive lymph nodes were common in small size NSCLC patients with clinical
negative lymph nodes. Therefore, preoperative staging should be performed more
thoroughly to increase accuracy, especially for patients who have the larger
size, non-upper lobe located, high CEA level or micropapillary predominant ACs.
PMID- 25589963
TI - The protective effects of glutamine in a rat model of ventilator-induced lung
injury.
AB - BACKGROUND: The mortality rate of patients with acute respiratory distress
syndrome (ARDS) is still high despite the use of protective ventilatory
strategies. We sought to examine the pharmacological effects of glutamine (GLN)
in a two-hit model of endotoxin-induced inflammation followed by ventilator
induced lung injury (VILI). We hypothesized that the administration of GLN
ameliorates the VILI. METHODS: Sprague-Dawley rats were anesthetized and given
lipopolysaccharide (LPS) intratracheally as a first hit to induce lung
inflammation, followed 24 h later by a second hit of mechanical ventilation (MV)
with either low tidal volume (6 mL/kg) with 5 cmH2O of positive end-expiratory
pressure (PEEP) or high tidal volume (22 mL/kg) with zero PEEP for 4 h. GLN or
lactated Ringer's solution as the placebo was administered intravenously 15 min
prior to MV. RESULTS: In the LPS-challenged rats ventilated with high tidal
volume, the treatment with GLN improved lung injury indices, lung mechanics and
cytokine responses compared with the placebo group. CONCLUSIONS: The
administration of GLN given immediately prior to MV may be beneficial in the
context of reducing VILI.
PMID- 25589964
TI - Lung cancer staging: the value of PET depends on the clinical setting.
AB - BACKGROUND: Although positron emission tomography (PET) imaging is widely
recommended in the evaluation of patients with lung cancer, randomized controlled
trials (RCTs) assessing this have demonstrated inconsistent results. We asked
whether differences in the clinical context and endpoints could explain these
discrepancies. METHODS: We used realist synthesis methods to analyze how
contextual differences among RCTs affected the results. We focused on RCTs to
minimize confounding yet permit evaluation of differences by comparing across
studies. RESULTS: This analysis suggests that the impact of PET depends on the
clinical setting. PET is of greatest benefit in identifying M1 disease in
patients with a high chance of such involvement and when little traditional
imaging [e.g., abdominal/pelvis computed tomography (CT) and bone scan] is used.
Identification of N2,3 involvement by PET prior to resection is seen primarily
when there is at least a moderate probability of such and the rate of invasive
staging is high. The rate of N2 disease not identified preoperatively appears to
increase if PET is used to avoid invasive mediastinal staging in clinical
settings in which the risk of N2,3 involvement is moderately high. There is both
a potential benefit in avoiding stage-inappropriate resection as well as a risk
of missed (stage-appropriate) resection if PET findings are not evaluated
carefully. CONCLUSIONS: A blanket recommendation for PET may be too simplistic
without considering nuances of the clinical setting.
PMID- 25589965
TI - Five-year epidemiological survey of valvular heart disease: changes in morbidity,
etiological spectrum and management in a cardiovascular center of Southern China.
AB - OBJECTIVE: The objective of the present study is to analyze the epidemiological
profile of patients with abnormal valvular structure and function and highlight
the etiological spectrum and management of valvular heart disease (VHD) in a
single cardiovascular center of Southern China in five years. METHODS: The
retrospective study included 19,428 consecutive patients (9,441 men and 9,987
women with a mean age of 52.03+/-20.50 years) with abnormal valvular structure
and function who were screened by transthoracic echocardiography (TTE) or
transesophageal echocardiography (TEE) at the in-patient department of Guangdong
General Hospital from January 2009 to December 2013. Data on baseline
characteristics, potential etiology, treatment strategies and discharge outcomes
were collected from electronic medical records. RESULTS: There were 13,549
(69.7%) patients with relatively definite etiology for VHD. VHD was rheumatic in
7,197 (37.0%) patients, congenital in 2,697 (13.9%), degenerative in 2,241
(11.5%), ischemic in 2,460 (12.7%). The prevalence decreased significantly in
rheumatic VHD from 2009 to 2013 (from 42.8% to 32.8%, P<0.001), but increased
markedly in congenital VHD (from 9.0% to 12.3%, P<0.001), ischemic VHD (from 9.2%
to 11.3%, P=0.003) and degenerative VHD (from 8.8% to 14.5%, P<0.001). Meantime,
the prevalence of ischemic VHD increased after the age of 45, similar to that of
degenerative VHD. From 2009 to 2013, the proportion of patients with VHD
undergoing open cardiac valvular surgery decreased (from 49.5% to 44.3%, P<0.001)
and that of patients treated with general medication increased (from 49.2% to
54.1%, P<0.001). However, there was markedly increment in video-assisted
thoracoscopic surgery (VATS) from 2009 to 2013 (from 0.3% to 4.4%, P<0.001).
Increasing tendencies were showed in aortic mechanical valve replacement (from
32.1% to 34.5%, P=0.001) and double mechanical valve replacement (from 20.9% to
22.3%, P=0.035), especially in mitral valvuloplasty (from 8.5% to 15.7%,
P<0.001). However, the proportion of patients undergoing bioprosthetic valve
replacement decreased from 2009 to 2013 (from 26.3% to 15.5%, P<0.001).
CONCLUSIONS: Despite a significant shift from rheumatic towards degenerative
etiology from 2009 to 2013, rheumatic VHD remains the leading etiology in
Southern China, with a significant increase in the prevalence of ischemic,
congenital and degenerative VHD. General medication and cardiac valvular surgery
remain the main treatment options. The proportion of VATS increased markedly from
2009 to 2013, and mechanical valve replacement and mitral valvuloplasty showed an
increasing tendency.
PMID- 25589966
TI - Rapid pleurodesis is an outpatient alternative in patients with malignant pleural
effusions: a prospective randomized controlled trial.
AB - BACKGROUND: Chemical pleurodesis can be palliative for recurrent, symptomatic
pleural effusions in patients who are not candidate for a thoracic surgical
procedure. We hypothesized that effective pleurodesis could be accomplished with
a rapid method of pleurodesis as effective as the standard method. METHODS: A
prospective randomized 'non-inferiority' trial was conducted in 96 patients with
malignant pleural effusion (MPE) who are not potentially curable and/or not
amenable to any other surgical intervention. They were randomly allocated to
group 1 (rapid pleurodesis) and to group 2 (standard protocol). In group 1,
following complete fluid evacuation, talc slurry was instilled into the pleural
space. This was accomplished within 2 h of thoracic catheter insertion, unless
the drained fluid was more than 1,500 mL. After clamping the tube for 30 min, the
pleural space was drained for 1 h, after which the thoracic catheter was removed.
In group 2, talc-slurry was administered when the daily drainage was lower than
300 mL/day. RESULTS: No-complication developed due to talc-slurry in two groups.
Complete or partial response was achieved in 35 (87.5%) and 33 (84.6%) patients
in group 1 and group 2 respectively (P=0.670). The mean drainage time was 40.7
and 165.2 h in group 1 and group 2 respectively (P<0.001). CONCLUSIONS: Rapid
pleurodesis with talc slurry is safe and effective and it can be performed in an
outpatient basis.
PMID- 25589967
TI - Overnight fluid shifts in subjects with and without obstructive sleep apnea.
AB - OBJECTIVE: To investigate the characteristics of baseline body fluid content and
overnight fluid shifts between non-obstructive sleep apnea (non-OSA) and
obstructive sleep apnea (OSA) subjects. METHODS: A case-controlled study was
performed between February 2013 and January 2014, with 36 (18 OSA and 18 non-OSA)
outpatients enrolled in this study. Polysomnographic parameters and results of
body fluid were compared between the two groups. RESULTS: There were no
differences in age, weight, and body mass index (BMI) between groups. Compared
with the non-OSA group, OSA group had significantly higher neck circumference
(NC) and fluid volume shift in the legs. OSA patients had higher left and right
leg fluid indices than non-OSA subjects. There were significant correlations
between apnoea-hypopnoea index and baseline fluid indices in both legs as well as
the reduction in overnight change in both legs fluid volume. The increase in NC
was also significantly correlated with the reduction in overnight change in both
legs fluid volume, but not with the change in head and neck fluid volume. There
were significant correlations between change in NC and increased fluid shifts in
head and neck volume. CONCLUSIONS: OSA patients had a higher baseline fluid
content in both legs as compared with non-OSA subjects, which may be the basic
factor with regards to fluid shifts in OSA patients. The increase in head and
neck fluid shift volume did not directly correlate with the severity of OSA.
PMID- 25589968
TI - The changes of vaccinia related kinase 1 in grafted heart after rat heart
transplantation.
AB - OBJECTIVE: To assess the expression and significance of vaccinia-related kinase 1
(VRK1) after rat heart transplantation. MATERIALS AND METHODS: Lewis and Wistar
rats weighing 250 to 300 g were used as donors and recipients. Allografts were
from Wistar transplanted into Lewis, and isografts were transplanted from Lewis
into Lewis. Grafts were harvested at 1, 3, 5, and 7 days after transplantation.
We performed Western Blot of heart tissues after cardiac transplantation. To
analyze VRK1 express between the isografts and allografts for immunohistochemical
staining. At 5th day after heart transplantation use related cytokines VRK1 for
immunohistochemical. We used double immunofluorescent staining on transverse
cryosections of graft tissues by co-labeling with different markers, including
those for VRK1, activate caspase-3, alpha-actinin, VCAM-1, CD4. RESULTS: Compared
with rare expression in syngeneic Lewis rat hearts, VRK1 protein level in
allogeneic hearts were detected at various survival times after heterotopic heart
transplantation, which observably expressed on day 5 postoperative. In addition,
we examined the expression of activate caspase-3 in allogeneic hearts, which has
a similar expression with VRK1. Immunohistochemical and immunofluorescent method
displayed that VRK1 was widely expressed in cytoplasm of cardiac tissue and
activate caspase-3 was also expressed in cardiomyocytes. However, the VRK1 wasn't
express in inflammation. CONCLUSIONS: The VRK1 expression has increased after
heart transplantation in allograft and isograft, and VRK1 may play a significant
role in myocardial apoptosis after heterotopic heart transplantation in rats.
PMID- 25589969
TI - Uniportal video assisted thoracoscopic lobectomy: primary experience from an
Eastern center.
AB - BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy is an
emerging technique for the surgical resection of non-small cell lung cancer
(NSCLC). Besides its wide debates on safety and efficacy throughout the world,
there were few report on uniportal VATS from the Eastern countries. In this
article, we summarized our primary experience on uniportal VATS lobectomy in an
Eastern center. METHODS: From October 2013 till February 2014, 54 consecutive
uniportal VATS lobectomy were performed in the Department of Thoracic Surgery,
Zhongshan Hospital of Fudan University. Patients' clinical features and operative
details were recorded. Post-operatively, the morbidity and mortality were
recorded to analyze the safety and efficacy of uniportal VATS lobectomy for
NSCLCs. RESULTS: Among the 54 planned uniportal VATS lobectomy, there was one
conversion to mini-thoracotomy due to lymph node sticking. Extra ports were
required in two patients. The uniportal VATS lobectomy was achieved in 51 out of
54 patients (94.4%). The average operation duration was 122.2+/-37.5 min (90-160
min). The average volume of estimated blood loss during the operation was 88.8+/
47.1 mL (50-200 mL). The mean chest tube duration and hospital stay were 3.2+/
1.9 days and 4.6+/-2.0 days, respectively. There was no postoperative mortality
in this study. Two patients suffered from prolonged air leakage (5 and 7 days),
and one atrial fibrillation was observed in this cohort. CONCLUSIONS: Based on
our primary experience, uniportal VATS lobectomy is a safe and effective
procedure for the surgical resection of NSCLCs. The surgical refinements and
instrumental improvements would facilitate the technique. Further studies based
on larger population are required to determine its benefits towards patients with
NSCLCs.
PMID- 25589970
TI - Differences in the clinical and radiological characteristics of lung-involved
toxocariasis between toxocariasis with eosinophilia and those without
eosinophilia.
AB - BACKGROUND: Previously, most studies did not discuss about the characteristics of
lung-involved toxocariasis without eosinophilia. However, the patients are not
always accompanied by eosinophilia, so it is necessary to learn about the
clinical and radiologic features that may predict pulmonary toxocariasis without
eosinophilia. In addition, we also want to check the differences in
characteristics between the two groups based on the presence of eosinophilia.
METHODS: We investigated patients from October 2009 to February 2014 with
antibody against Toxocara positive using enzyme-linked immunosorbent assay
(ELISA), abnormal chest X-ray, and computed tomography (CT) findings. This
retrospective study included patients diagnosed as toxocariasis with pulmonary
involvement, using the results of laboratory findings, symptoms, and CT at the
time of diagnosis. RESULTS: Out of 88 patients, 78% were male and 22% were
female; and the mean age was 51 years. The mean eosinophil fraction in peripheral
blood was 11.8%. The most common chest CT findings of patients with eosinophilia
were nodules plus ground glass opacity (GGO) pattern, and nodules were found in
patients with no eosinophilia. Pure GGO was the most common predominant subtype
in GGO lesions of patients with eosinophilia. In terms of anatomical
distribution, random distribution was seen more in patients with eosinophilia
than those without eosinophilia, with statistically significance (P=0.042). In
patients who underwent additional CT scans, 44% of those with eosinophilia had
migrating lesions and had significant differences from patients without
eosinophilia (P=0.008). CONCLUSIONS: There were no significant differences in
lesion characteristics with the exception of random anatomic distribution between
patients with and without eosinophilia. However, there was a significant
difference between the fixation and migration of the lesion in patients with and
without eosinophilia.
PMID- 25589971
TI - Antihypertensive therapy with nicardipine for patients with aortic disease is
associated with more esmolol usage than urapidil.
AB - BACKGROUND: Acute aortic disease is a common but challenging entity in clinical
practice. Titration the blood pressure and heart rate to a target level is of
paramount importance in the acute phase regardless of whether the patient will
undergo a surgery or not eventually. In addition to the initially intravenous
beta-blockers, parenteral infusion of nicardipine and urapidil are the most
common used antihypertensive therapy currently in mainland China. However, few
empirical data was available with respect to the different effect on patients'
outcome of the two antihypertensive strategies. Specifically given the
deleterious reflex tachycardia of vasodilators which may increase force of
ventricular contraction and potentially worsen aortic disease. Therefore, this
study was aimed to evaluate the difference of the abovementioned two
antihypertensive strategies on the outcome of patients with aortic disease.
METHODS: All patients with new diagnosed aortic diseases presented to our
hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed.
The antihypertensive strategies and their association with patients' outcomes
were evaluated with logistics regression. RESULTS: A total of 120 patients with
new diagnosed aortic disease were included in the study. Of them, 47 patients
received urapidil while 73 patients received nicardipine antihypertensive
therapy. Patients with nicardipine were more quickly to reach the target blood
pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024).
After adjustment for patient demographics, co-morbidity, involved extend of
aorta, interventional strategies, antihypertensive therapy with nicardipine (with
urapidil as reference) for patients with aortic disease was significantly
associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval
(CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI,
1.5-10.3, P=0.006). However, there was no significant correlation between
nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123).
CONCLUSIONS: Although nicardipine achieved the target blood pressure level more
quickly than urapidil for patients with aortic disease, it was associated with
more esmolol use and longer ICU LOS.
PMID- 25589972
TI - In vitro study of coronary flow occlusion in transcatheter aortic valve
implantation.
AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been developed
recently for patients with high morbidities and who are believed to be not
tolerate standard surgical aortic valve replacement. Nevertheless, the TAVI is
associated with complications such as potential obstruction of coronary ostia,
mitral valve insufficiency, and stent migration although it seems promising.
Impairment of the coronary blood flow after TAVI is catastrophic and it was
believed to be associated with the close position of the coronary orifice and the
aortic leaflets and valve stent. However, few data was available as to the
anatomic relationship between valve stent and aortic root anatomic structures
including the coronary arterial ostia, aortic leaflets. METHODS: The aortic roots
were observed in 40 hearts specimens. The width of aortic leaflet, height of
aortic sinus annulus to the sinutubular junction (STJ), distance between aortic
sinus annulus to its corresponding coronary ostia, and coronary arterial ostia to
its corresponding STJ level were measured. Moreover, the relationships of valve
stent, aortic leaflets and coronary ostia before/post stent implantation and
after the open of aorta were evaluated respectively. RESULTS: Approximate three
quarters of the coronary ostia were located below the STJ level. The mean
distances from left, right and posterior aortic sinus annulus to the related STJ
level was comparable, which was 18.5+/-2.7, 18.9+/-2.6, 18.7+/-2.6 mm,
respectively. Meanwhile, the height of left and right aortic sinus annulus to its
corresponding coronary ostia was 16.6+/-2.8 and 17.2+/-3.1 mm for left and right
side respectively. CONCLUSIONS: Most of the coronary ostia were located below the
STJ level and could be covered by the leaflets. This highlights the need of
modified stents to prevent occlusion of coronary flow after TAVI.
PMID- 25589973
TI - Adrenergic regulation of the rapid component of delayed rectifier K+ currents in
guinea pig cardiomyocytes.
AB - BACKGROUND: Guinea pig ventricular cardiomyocytes display the rapid component of
the delayed rectifier potassium current (Ikr) that contributes to ventricular
repolarization and promotes stress-induced arrhythmias. Adrenergic stimulation
favors ventricular arrhythmogenesis but its effects on Ikr are poorly understood.
METHODS: Adrenergic modulation of Ikr was studied in isolated guinea pig
ventricular cardiomyocytes using whole-cell patch clamping. RESULTS: We found
that the Ikr amplitude was reduced to 0.66+/-0.02 and 0.62+/-0.03 in response to
0.1 uM phenylephrine (PE), an alpha1AR agonist, and 10 uM isoproterenol (ISO), a
betaAR agonist, respectively. The effect of PE can be blocked by the selective
alpha1A-adrenoceptor antagonist 5-methylurapidil, but not by the alpha1B
adrenoceptor antagonist chloroethylclonidine or alpha1D-adrenoceptor antagonist
BMY7378. Additionally, the effect of ISO can be blocked by the beta1-selective AR
antagonist CGP-20712A, but not by the beta2-selective AR antagonist ICI-118551.
Although PE and ISO was continuously added to cells, ISO did not decrease the
current to a greater extent when cells were first given PE. In addition, PE's
effect on Ikr was suppressed by beta1AR stimulation. CONCLUSIONS: Ikr can by
regulated by both the alpha1 and beta ARs system, and that in addition to direct
regulation by each receptor system, crosstalk may exist between the two systems.
PMID- 25589975
TI - Sodium tanshinone IIA silate as an add-on therapy in patients with unstable
angina pectoris.
AB - OBJECTIVE: To investigate whether sodium tanshinone IIA silate (STS) as an add-on
therapy to conventional treatment may provide additional benefits for patients
with unstable angina pectoris (UAP) and is associated with changes in profiles of
serum inflammatory factors. METHODS: Eighty patients diagnosed with UAP were
randomly divided into two groups for the 2-week treatment. The control group
received conventional therapy, while the treatment group was given intravenous
STS (0.06 mg in 250 mL, once daily) as an add-on therapy to the conventional
medications. The therapeutic efficacy and changes in serum levels of several
inflammatory cytokines, including monocyte chemotactic protein 1 (MCP-1), tumor
necrosis factor alpha (TNF-alpha), peroxisome proliferator-activated receptor
(PPAR-gamma), and high-sensitivity C-reactive protein (hs-CRP) from baseline were
determined and compared between the two group. RESULTS: The clinical symptoms of
all patients in both groups were improved after treatment. The overall rate of
effectiveness was 97.5% in the treatment group vs. 80.0% in the control group.
Serum levels of MCP-1, TNF-alpha, and hs-CRP levels were significantly reduced in
both groups (P<0.01), whereas the reduction was greater in patients receiving
additional STS (P<0.05). PPAR-gamma was significantly elevated in both groups
(P<0.01). CONCLUSIONS: STS in combination with conventional treatment may be
associated with better outcomes in patients with UAP.
PMID- 25589974
TI - Epidemiological and viral genome characteristics of the first human H7N9
influenza infection in Guangdong Province, China.
AB - BACKGROUND: The first H7N9 human case in south of China was confirmed in
Guangdong Province on August 2013, outside of the typical influenza season. For
investigating the H7N9 virus source and transmission in the local community, we
analyze the epidemiology and genome features of the virus isolated from the first
human infection detected in Guangdong Province. METHODS: The data including
medical records, exposure history and time line of events for the H7N9 patient
and close contacts was collected. Variation and genetic signatures of H7N9 virus
in Guangdong was analyzed using ClustalW algorithm and comparison with mutations
associated with changes in biological characteristics of the virus. RESULTS: The
female patient had a history of poultry exposure, and she was transferred from a
local primary hospital to an intensive care unit (ICU) upon deterioration. No
additional cases were reported. Similar to previous infections with avian
influenza A (H7N9) virus, the patient presented with both upper and lower
respiratory tract symptoms. Respiratory failure progressed quickly, and the
patient recovered 4 weeks after the onset of symptoms. Genome analysis of the
virus indicated that the predicted antigen city and internal genes of the virus
are similar to previously reported H7N9 viruses. The isolated virus is
susceptible to neuraminidase (NA) inhibitors but resistant to adamantine.
Although this virus contains some unique mutations that were only detected in
avian or environment-origin avian influenza A (H7N9) viruses, it is still quite
similar to other human H7N9 isolates. CONCLUSIONS: The epidemiological features
and genome of the first H7N9 virus in Guangdong Province are similar to other
human H7N9 infections. This virus may have existed in the environment and live
poultry locally; therefore, it is important to be alert of the risk of H7N9 re
emergence in China, including emergence outside the typical influenza season.
PMID- 25589976
TI - Lung protective effects of budesonide nebulization during perioperative period of
thoracolumbar fusion.
AB - OBJECTIVE: To determine the pulmonary protective effect of budesonide
nebulization in patients undergoing spinal fusion for thoracolumbar degenerative
disorders. METHODS: Forty patients who underwent spinal fusion at our hospital
from January 2013 to December 2013 for the treatment of thoracolumbar
degenerative disorders were randomly allocated into a budesonide intervention
group (budesonide group) and a control group. The control group received routine
supportive therapy including rehydration, analgesia, and neurotrophic drug
treatment; in addition to these, the budesonide group was administered with
budesonide nebulization (1-mg budesonide/2-mL saline, twice daily) from 1 day
preoperatively through 3 days postoperatively. Respiratory symptoms, arterial
blood gas, and pulmonary complication before and after the operations were
observed and compared between the two groups. RESULTS: The patients ranged in age
from 46 to 81 years old (mean, 62.4+/-9.4 years), and comprised 20 men and 20
women. There were no significant differences in postoperative body temperature,
heart rate, and respiratory rate between the groups (P>0.05). The change in
arterial partial pressure of oxygen (PaO2) from baseline was significantly lower
in the budesonide group than in the control group (at 2.4+/-12.4 vs. 16.0+/-11.3
mmHg) (P=0.002), so was the findings for oxygen saturation (SpO2) (0.2%+/-2.3%
vs. 2.6%+/-3.3%), respectively (P=0.047). The incidence of postoperative
pulmonary symptoms and complications, such as coughing, shortness of breath, and
dyspnea, was 0% in the budesonide group and 15% in the control group; overall,
the budesonide group performed better than control group in all pulmonary
parameters. None of the patients in the budesonide group experienced severe
events associated with glucocorticoid therapy. CONCLUSIONS: Perioperative
budesonide nebulization may reduce the postoperative pulmonary complications in
middle-aged and elderly patients undergoing thoracolumbar fusion to treat
thoracolumbar degeneration, with favorable efficacy and safety.
PMID- 25589977
TI - Chemotherapy with paclitaxel plus carboplatin for relapsed advanced thymic
carcinoma.
AB - OBJECTIVE: For rarity of thymic carcinoma, no definitive chemotherapeutic regimen
has been established in second- or further-line settings. The aim of this study
was to evaluate the feasibility and safety of paclitaxel plus carboplatin in
advanced thymic carcinoma as second- or further-line treatment in our institute.
METHODS: We evaluated the efficacy and toxicity of paclitaxel plus carboplatin as
salvage therapy in 12 patients with previously treated advanced thymic carcinoma
from 2005 to 2012 in Zhejiang Cancer Hospital. Survival analysis was evaluated by
Kaplan-Meier method. RESULTS: Twelve patients were included in current study.
Four patients achieved stable disease (SD), and three achieved partial response
(PR), representing a response rate of 25.0% and disease control rate (DCR) of
58.3%. Median progression-free survival (PFS) and overall survival (OS) were 3.5
and 24.0 months, respectively. The toxicities associated with the paclitaxel plus
carboplatin was generally acceptable. CONCLUSIONS: Paclitaxel plus carboplatin
appears to have some activity against thymic carcinoma as second-line or later
chemotherapy in advanced thymic carcinoma.
PMID- 25589978
TI - Video-assisted thoracoscopic left upper lobe sleeve lobectomy combined with
pulmonary arterioplasty via two-port approach.
AB - Here we report a case of left upper lobe sleeve lobectomy with pulmonary
arterioplasty via video-assisted thoracoscopy surgery (VATS) two-port approach. A
squamous cell carcinoma with stage T3N1M0 was identified on pathological
examination. The bronchial anastomosis was performed using running suture with a
3-0 prolene. Two bulldog clamps were used to gain adequate vascular control.
Partial pulmonary artery resection was achieved tangentially with a stapler. The
postoperative course was uneventful.
PMID- 25589979
TI - Total thoracoscopic combined lingulectomy and pericardial cystectomy.
AB - Thoracoscopic anatomic segmentectomy is usually more complex than lobectomy. This
video shows a 58-year-old female who suffered from limited bronchiectasis of the
lingular segment of the left upper lung and a pericardial cyst on the same side.
Both of these benign thoracic diseases can cause pleural adhesions. Repeated
chronic inflammation contributes to hypervascularity and lymph node enlargement,
making surgery more difficult. We used single-direction thoracoscopic
segmentectomy via a three-port approach and successfully removed the lingula and
pericardial cyst.
PMID- 25589980
TI - Video-assisted thoracoscopic surgery right upper posterior segmentectomywith
systemic mediastinal lymph node dissection.
AB - Video-assisted thoracoscopic surgery (VATS) segmentectomy is a promising
treatment option for rigorously selected patients with earlystage non-small cell
lung cancer. In the presented video, a 66-year-old male with a 1.6 cm suspicious
nodule located at the posterior segment of the right upper lobe was treated with
anatomic segmentectomy and systemic mediastinal lymph node (LN) dissection
successfully.
PMID- 25589981
TI - Video-assisted thoracoscopic left upper lobe apical trisegmentectomy with the
Harmonic scalpel.
AB - Segmental resection is a useful procedure to preserve respiratory function. A 56
year-old woman presented with a finding of a left upper lobe lesion on CT
scanning. She was performed video-assisted thoracoscopic left upper lobe apical
trisegmentectomy with the Harmonic scalpel. Video-assisted thoracoscopy surgery
(VATS) segmentectomy is associated with safe and feasible procedure. With the
Harmonic scalpel dissection, blood loss is minimal and this speeds patient
recovery.
PMID- 25589982
TI - Left lower sleeve lobectomy and systematic lymph node dissection by complete
video-assisted thoracic surgery.
AB - Sleeve lobectomy for selected cases of central lung cancer has better functional
outcomes comparing to pneumonectomy. With improved technology and increased
experiences in complete video-assisted thoracic surgery (VATS) lobectomy,
complete VATS sleeve lobectomy has been applied in major medical centers
recently. A 64-year-old male patient with left lower central lung cancer
underwent thoracoscopic sleeve lobectomy and systemic mediastinal lymph node
dissection. The major incision, of four incisions in total, was a 4 cm mini
incision in the 4th intercostal space of anterior axillary line. The patient had
recovered uneventfully after the surgery.
PMID- 25589983
TI - Video-assisted thoracic surgery right sleeve lobectomy.
AB - A 50-year-old active male with a smoking history of 30 years (20 cigarettes per
day) was admitted to hospital because of more than one month's cough without
sputum. No comorbidity was present. The preoperative examination showed: blood
test normal, ECG normal, cardio-pulmonary function normal, chest computed
tomography (CT) display right upper lobe (RUL) mass of 5 cm diameter.
Bronchoscopy examination and biopsy indicated large cell neuroendocrine carcinoma
(LCNEC) in the take-off of RUL bronchus. No metastatic focus was found after
emission computed tomography (ECT) scan of whole body bone, abdominal US scanning
and brain MR. After initial evaluation, the clinical stage before operation was
cT2bN0M0 (IIA stage). A selective video-assisted thoracic surgery (VATS)
operation was arranged after 9 days of smoking cessation. Lateral position, one
10 mm trocar for camera in the 7th intercostals space in the mid-auxiliary line,
4 cm trocar for operation in the 4th intercostal space in the anterior axillary
line, 15 mm trocar for auxiliary operation in the 8th intercostal space in the
scapula line, the patient received VATS RUL lobectomy, plus systemic mediastinal
lymph nodes dissection. The procedure of 200 minutes operation was smooth with
blood loss of about 150 mL. Chest tube was removed 6 days after operation, and
the patient discharged 11 days after the operation; The post-operation
pathological examination showed RUL LCNEC, and the pathological stage was
pT2bN0M0R0 (IIA stage). The patient has received four cycles of EP adjuvant
chemotherapy per 21 days and is still alive without disease recurrence and
metastasis after re-examination.
PMID- 25589984
TI - Uniportal video-assisted thoracoscopic left basilar segmentectomy.
AB - Uniportal video-assisted thoracoscopic surgery (VATS) has recently been
introduced as an acceptable alternative to the traditional three-port VATS.
Uniportal VATS lobectomy and segmentectomy actually gained increasing popularity.
Until now there have been few reports about uniportal VATS basilar segmentectomy;
we herein reported our experience with a patient who suffered from recurrent
hemoptysis with 1-cm nodule in the basilar segment of the left lower lobe. A left
basilar segmentectomy was performed through a single port. Operating time was 90
minutes, and postoperative course was uneventful. Pathology revealed
cryptococcosis. Follow-up at 6 months after surgery demonstrated a normal chest
computed tomographic (CT) scan and complete recovery without complications.
PMID- 25589985
TI - Video-assisted thoracic surgery left S1+2+3 segmentectomy for lung cancer.
AB - A 49-year-old female presented with a solitary pulmonary nodule on the chest
screening computed tomography (CT) scan. The nodule was 1.3 cm in diameter and
located in the apical segment of left upper lobe. The lesion was considered to be
cT1aN0M0 non-small cell lung cancer (NSCLC) and a 3-port video-assisted thoracic
surgery (VATS) wedge resection was performed. Intraoperative frozen sections
revealed a lung adenocarcinoma. Therefore, sequential S1+2+3 segmentectomy of the
left upper lobe was performed, also systematic lymph node dissection was carried
out. The final pathological stage was pT1aN0M0 (Ia).
PMID- 25589986
TI - Uniportal video-assisted thoracoscopic surgery right upper lobectomy with
systematic lymphadenectomy in a semiprone position.
AB - A 53-year-old male smoker was referred to our hospital with an enlarged lesion in
the right upper lung. Computed tomography (CT) showed a 1.5 cm solid lesion with
pleural indentation in the right upper lobe adjacent to the oblique fissure. The
preoperative clinical diagnosis was stage I primary lung cancer. Uniportal video
assisted thoracoscopic surgery (VATS) right upper lobectomy in a semiprone
position was performed in this case. Frozen section examination confirmed the
diagnosis of lung adenocarcinoma, and systematic lymphadenectomy was then
performed. A chest tube was placed at the posterior part of the incision through
the dorsal thoracic cavity to the apex. The postoperative pathologic diagnosis
was T2aN0M0 adenocarcinoma.
PMID- 25589987
TI - Unidirectionally progressive resection of left upper pulmonary lobe under video
assisted thoracoscopy.
AB - The case is a nodule in the upper left lobe, and intraoperative frozen section
pathological diagnosis on the removed nodule confirmed well differentiated
mucinous adenocarcinoma. Unidirectionally progressive resection of the left upper
pulmonary lobe under video-assisted thoracoscopy is selected as the surgical
method. Right below the operation hole, surgeons gradually advanced in one
direction, and dissociated and divided in such order: the upper left pulmonary
vein, the upper left lobe bronchus, the upper left pulmonary arterial branches
and the fissures. Endoscopic linear cutters and hem-o-lok clip applicator were
used to deal with the blood vessels, bronchus, and under-differentiated fissures.
At last, the removed upper left lobe was put into a size eight sterile glove and
taken out through the main operation hole. General anesthesia with double-lumen
endotracheal intubation is used. The patient took a 90 degree decubitus on his
contralateral side. The surgeons were on the ventral side of the patient, and
operated with endoscope apparatus under the monitor.
PMID- 25589988
TI - Video-assisted thoracic surgery left upper lobectomy with systematic
lymphadenectomy.
AB - A 43-year-old man was referred to our hospital after chest computed tomography
revealed a 2.5-cm mixed ground-glass opacity peripherally in the left upper lobe
of the lung. No metastasis or contraindication for surgery was found. Video
assisted thoracic surgery (VATS) left upper lobectomy was performed, and analysis
of the intraoperative frozen section confirmed the diagnosis of adenocarcinoma.
Subsequently, systematic lymphadenectomy was performed. By using this method,
suction and harmonic scalpel were the only two major instruments needed
throughout the operation. The use of suction ensures a clear view, and the
harmonic scalpel functions as a combined dissector, grasper, and cutter, which
helps avoid changing instruments during the surgery and saves time. Moreover, the
use of this technique for three-port VATS lobectomy facilitates the conversion
into single-port VATS if needed.
PMID- 25589989
TI - Autogenous rib graft for reconstruction of sternal defects.
AB - Those who have undergone sternum resection need graft to stabilize the sternum
with steel wire, titanium mesh or polypropylene mesh. The current study reports a
case of using autogenous rib graft to reconstruct the sternum after resection. A
53-year-old man, whose chest computed tomography (CT) identified expansive
lesions and the presence of osteocytes lesions in the sternum, with no apparent
involvement of the mediastina structures, come to our medical center due to pain
and a lump of the anterior chest wall. The patient underwent tumor radical
resection and sternal reconstruction with autogenous rib graft, and the
histopathological examination of the surgical specimen determined the diagnosis
of osteosarcoma. The patient has recovered well after the surgery.
PMID- 25589990
TI - VATS right upper lobectomy.
AB - A 56-year-old male patient was admitted due to one small pulmonary nodule in the
apicoposterior segment of the right upper lobe, which was found on his health
screening one month ago. Preoperative examinations showed no distant metastasis,
and his heart and lung functions could tolerate the lobectomy. Chest computed
tomography (CT) showed one small pulmonary nodules on the apicoposterior segment
of the right upper lobe, which was considered to be malignant lesions. No
remarkably swollen lymph node was visible in the mediastinum. Therefore, VATS
right upper lobectomy was performed and intraoperative frozen section confirmed
the diagnosis of adenocarcinoma.
PMID- 25589991
TI - Thoracoscopic left upper lobectomy with systematic lymph nodes dissection under
left pulmonary artery clamping.
AB - Video-assisted thoracoscopic surgery (VATS) has become a routine procedure for
stage I and II lung cancers. However, in the presence of multiple metastasized
lymph nodes invading the pulmonary artery or its major branches, the pulmonary
artery have to be resected partially or sleeve resected, which could be extremely
risky under thoracoscopic conditions. In order to reduce the risk of bleeding, an
experienced thoracic surgeon would occlude the inflow and outflow of the
pulmonary artery before anatomically dissecting the area of the pulmonary artery
with tumor invasion. Different centers may use different clamping techniques and
devices. Here, we report our technique of totally thoracoscopic left upper
lobectomy with systematic lymph nodes dissection under pulmonary artery clamping
for a 49-year-old woman with left upper lobe carcinoma. The video demonstrates
our thinking and surgical process.
PMID- 25589992
TI - Thoracoscopic resection of functional posterior mediastinal paraganglioma: a case
report.
AB - A 48-year-old man with posterior mediastinal mass was diagnosed as functional
mediastinal paraganglioma during surgical exploration via open thoracotomy in
another hospital. The operation was terminated because of severe hypertension
when touching the tumor. He was transferred to our center later. After systemic
evaluation, the patient was medicated with oral alpha- and beta-blockades, as
well as intravenous fluid resuscitation for two weeks. His blood pressure became
stable and a second operation was planned. The tumor was removed completely via
the thoracoscopic approach, and was finally confirmed as functional paraganglioma
by immunohistochemistry. The patient recovered uneventfully after surgery, with
no recurrence during one year follow-up visit.
PMID- 25589993
TI - Optimization of lymph node dissection with VATS right upper lobectomy.
AB - Video-assisted thoracoscopic lobectomy (VATSL) has developed rapidly. As per the
requirements of tumor staging and oncotherapy, the technique of VATS mediastinal
lymph node dissection plays an important role. With our experience, lymph node
dissection can be performed very well on the condition that surgical process and
skills be optimized.
PMID- 25589995
TI - Basic statistics (the fundamental concepts).
AB - An appreciation and understanding of statistics is import to all practising
clinicians, not simply researchers. This is because mathematics is the
fundamental basis to which we base clinical decisions, usually with reference to
the benefit in relation to risk. Unless a clinician has a basic understanding of
statistics, he or she will never be in a position to question healthcare
management decisions that have been handed down from generation to generation,
will not be able to conduct research effectively nor evaluate the validity of
published evidence (usually making an assumption that most published work is
either all good or all bad). This article provides a brief introduction to basic
statistical methods and illustrates its use in common clinical scenarios. In
addition, pitfalls of incorrect usage have been highlighted. However, it is not
meant to be a substitute for formal training or consultation with a qualified and
experienced medical statistician prior to starting any research project.
PMID- 25589994
TI - Nonintubated anesthesia for thoracic surgery.
AB - Nonintubated thoracic surgery has been used in procedures including pleura, lungs
and mediastinum. Appropriate anesthesia techniques with or without sedation allow
thoracic surgery patients to avoid the potential risks of intubated general
anesthesia, particularly for the high-risk patients. However, nonintubated
anesthesia for thoracic surgery has some benefits as well as problems. In this
review, the background, indication, perioperative anesthetic consideration and
management, and advantages and disadvantages are discussed and summarized.
PMID- 25589996
TI - A synopsis of resampling techniques.
AB - Bootstrap is a computer intensive technique of resampling with replacement, which
can be applied in many statistical analytical tests. The article describes the
most frequent situations where bootstrap resampling can be applied in thoracic
surgical research: variable selection for multivariable regression analysis,
internal validation of regression equations, model validation. Practical examples
for programming bootstrap in commercially available statistical software are
finally reported.
PMID- 25589997
TI - Professor I-wen Wang: better life supported through mechanical circulatory
devices-a dream within reach.
PMID- 25589998
TI - Professor Mario Cazzola: prospect of the COPD medicine.
PMID- 25589999
TI - Buyer beware: understanding the assumptions behind health economic assessments in
personalized cancer care.
PMID- 25590000
TI - Pyrexia in patients with uncontrolled systemic hypertension: could they have an
aortic dissection?
AB - Aortic dissection can present in a variety of ways and one of the most documented
risk factors includes systemic hypertension. Occasionally aortic dissection can
be diagnosed late due to an insidious presentation. Fever has been described in
people with aortic dissection but rarely as the main presenting feature. We
present the cases of two patients with type B aortic dissections who shared three
pertinent features which could have alerted the clinicians of the potential
diagnosis; systemic hypertension, small left sided pleural effusion and a fever
of unknown origin.
PMID- 25590001
TI - Primary synovial sarcoma of the lung: can haemothorax be the first manifestation?
AB - Primary pulmonary synovial sarcomas represent a rare clinical entity and account
for approximately 0.5% of lung malignancies. We report the case of a 30-year-old
male who presented clinically with haemothorax. Imaging revealed a complex
collection obscuring a multi-lobulated mass in the right lower lobe of the lung.
He underwent a right thoracotomy for evacuation of collection and surgical
resection of his pulmonary mass. Histological analysis confirmed a grade 3
monophasic fibrous synovial sarcoma of the lung with infiltration to adjacent
pleura, causing his initial haemothorax. Postoperative period was uneventful and
patient was referred to the oncology team for further management. Primary
pulmonary synovial sarcoma, though rare, should remain an important differential
when considering lung malignancies, as complete surgical resection is the
mainstay of treatment.
PMID- 25590002
TI - Palliative stent graft placement combined with subsequent open surgery for
retrograde ascending dissection intra-thoracic endovascular aortic repair.
AB - Thoracic endovascular aortic repair (TEVAR) is an effective strategy for type B
dissection. Retrograde ascending dissection (RAD) intra-TEVAR is a rare
complication on clinic. In this case, a 48-year-old Chinese man with Stanford
type B aortic dissection suffered acute RAD during the TEVAR. And palliative
stent grafts placement was performed in a local hospital, which earned the time
for transfer and subsequent total arch replacement surgery in Zhongshan Hospital
Fudan University. This report suggests that the palliative strategy may be an
option for RAD in some specific situation.
PMID- 25590003
TI - Induced airway obstruction under extracorporeal membrane oxygenation during
treatment of life-threatening massive hemoptysis due to severe blunt chest
trauma.
AB - Simultaneous improvement in respiratory maintenance and bleeding control
increases survival of patients with life-threatening hemoptysis. Endobronchial
blockade is an effective method and is preferred for emergency hemostasis.
However, when the volume of hemoptysis is high, emergency hemostasis and airway
maintenance are impossible due to flooding of blood into the airway. We used
extracorporeal membrane oxygenation (ECMO) to overcome these limitations in a
patient with massive hemoptysis due to severe blunt trauma and succeeded in
saving the life by inducing a near-total airway obstruction.
PMID- 25590004
TI - Unexpectedly long intravenous and intracardiac extension of a small-sized
pulmonary pleomorphic carcinoma.
AB - Pleomorphic carcinoma of the lung is one of the uncommon histological types of
lung cancers, which shows an aggressive behavior. Intravenous extension (not
metastasis or direct invasion) of the tumor into the heart is a rare complication
of lung cancers. We present a case of a 64-year-old man, who was admitted to
hospital due to severe dyspnea. Chest CT scan revealed a 2-cm nodule in the upper
lobe of the right lung. Echocardiography demonstrated a giant mass in the left
atrium. Because of a considerable distance between the lung nodule and heart, the
relation of these two lesions was unclear. He died four days after the admission.
At autopsy, the lung nodule was pleomorphic carcinoma composed of spindle and
giant cells, which invaded the pulmonary vein and extended intravenously to the
left atrium. The intravenous component of the tumor measured approximately ten cm
in length. At the tip of the extension, an 8 cm * 5 cm * 3 cm mass was formed in
the left atrium, which obstructed the mitral valve. This case highlights a
possibility that even a small-sized, peripherally located pleomorphic carcinoma
of the lung could extend for an unexpectedly long distance to the heart, causing
cardiac complications.
PMID- 25590005
TI - Beware of arteria lusoria during lymph node dissection of the right paratracheal
fossa for lung cancer surgery.
AB - An asymptomatic elderly woman presented with a solitary right upper lobe mass
revealed to be non-small cell lung cancer following routine surveillance post
mastectomy. Upon review of CT with contrast in preparation for rigid bronchoscopy
and right upper lobectomy, we noticed that the patient had a rare case of arteria
lusoria. This is the presence of an aberrant right subclavian artery extending
from the left side of the aortic arch, crossing posteriorly across the midline to
supply the upper limb. We suggest that with a documented 100% diagnostic
sensitivity on 64 multislice computed tomography, the presence of arteria lusoria
within the posterior paratracheal fossa may cause life-threatening complications
in the unaware during systematic lymph node dissection for non-small cell lung
cancer (NSCLC).
PMID- 25590006
TI - Fatal interstitial lung disease associated with icotinib.
AB - The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and
erlotinib is drug-associated interstitial lung disease (ILD), which has been
often described. However, it has been less well described for icotinib, a similar
orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old
female patient with stage IV lung adenocarcinoma who developed fatal ILD is
reported here. She denied chemotherapy, and received palliative treatment with
icotinib (125 mg po, three times daily) on March 1, 2013. One month after
treatment initiation, the patient complained of continuous dry cough and rapid
progressive dyspnea. Forty one days after icotinib treatment, icotinib associated
ILD was suspected when the patient became increasingly dyspnoeic despite of
treatment of pericardial effusion, left pleural effusion and lower respiratory
tract infection, and X-ray computed tomography (CT) of chest revealed multiple
effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib
was discontinued and intravenous corticosteroid was started (methylprednisolone
40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after
icotinib treatment, the patient died of hypoxic respiratory failure. ILD should
be considered as a rare, but often fatal side effect associated with icotinib
treatment.
PMID- 25590007
TI - Primary malignant pericardial mesothelioma-a rare cause of superior vena cava
thrombosis and constrictive pericarditis.
AB - Primary malignant pericardial mesothelioma (PMPM) is an extremely rare, highly
lethal and often misdiagnosed tumor. We report a 60-year-old woman complaining of
dry cough, shortness of breath and exertional dyspnea due to a large pericardial
effusion. The pericardial fluid volume declined after pericardiocentesis;
analysis of the fluid revealed malignant cells and was negative for tuberculosis.
Subsequently, the patient developed a compression of the superior vena cava and
pericardial constriction. The patient's symptoms marginally improved after
partial pericardiectomy, and a diagnosis of pericardial mesothelioma was made on
pathology. However, her symptoms continued to aggravate, and she died 8 months
after presentation. Pericardial mesothelioma should be discovered earlier to
treat patients who develop repeatedly pericardial effusion after
pericardiocentesis and pericardial tamponade or those develop constrictive
pericarditis.
PMID- 25590008
TI - IgG4-related lung disease with atypical CT imaging: a case report.
AB - IgG4-related lung disease is a rare disease, diagnosed when typical pathologic
features are seen in the context of increased serum levels of IgG4 and the
elevated tissue's IgG4-positive plasma cells. Here we reported the case of a 24
year-old woman with IgG4-related lung disease. This patient presented with fever,
cough and shortness of breath. Thoracic computed tomography (CT) images
demonstrated multiple nodules or masses with high density in both lungs, and
thickened interlobular septa. The 'halo sign' was observed around the high
density lesions of the upper lobes. This range of CT images' characteristics is
atypical, which differs from previous reports of this condition.
PMID- 25590009
TI - Rare and persistent Rhodococcus equi infection in a diffuse large B cell lymphoma
patient: case report and review of the literature.
AB - Rhodococcus equi (R. equi) is an uncommon gram positive organism. It is a rare
but recognized pathogen in humans and has emerged as an important cause of
morbidity and mortality among immunocompromised patients. Generally, R. equi
infection needs combined treatment with effective antibiotics, and often requires
the immune adjuvant therapy. Here we reported a 49-year-old man presented dyspnea
with fever, skin ulcer for 5 months, and the final diagnosis was diffuse large B
cell lymphoma with R. equi septicemia and pneumonia, the treatment was failure,
the blood culture was always positive during the course of disease, though he was
given combined treatment with effective antibiotics, perhaps the immune
reconstitution or immune supportive treatment was more important.
PMID- 25590011
TI - The pure distal left main bronchial sleeve resection with total lung parenchymal
preservation: report of two cases and literature review.
AB - Pure bronchial sleeve resection and reconstruction is a type of rare thoracic
surgery, especially for the second carina reconstruction on the left side, needs
more exquisite surgical techniques, and patient selection to such surgery often
requires rigorous screening. We present two cases of left main bronchial adenoid
cystic carcinoma with the second carina reconstruction. The purpose of this paper
is to recommend a useful supplement to conventional surgery for some very
selected patients.
PMID- 25590010
TI - Good neurological recovery after rescue thrombolysis of presumed pulmonary
embolism despite prior 100 minutes CPR.
AB - We reported the case of a 70-year-old man who was admitted to neurologic wards
for recurrent syncope for 3 years. Unfortunately, just 2 hours after his
admission, he suddenly collapsed and failed to return of spontaneous circulation
(ROSC) after a 100-minute standard cardiopulmonary resuscitation (CPR).
Fortunately, he was timely suspected to have pulmonary embolism (PE) based on his
sedentary lifestyle, elevated D-dimer and markedly enlarged right ventricle
chamber on bedside echocardiography. After a rescue thrombolytic alteplase
therapy, he was successfully resuscitated and good neurological recovery was
achieved.
PMID- 25590012
TI - Pleural fluid is surrogate for time.
PMID- 25590013
TI - 3-1-5 implementation for 2015.
PMID- 25590014
TI - Panhellenic Congress News: innovation in the academic world.
PMID- 25590015
TI - Keep calm in an emergency: an unexpected case with poisoning.
PMID- 25590016
TI - Oxygen.
PMID- 25590017
TI - Clinical Research Environment in India: Challenges and Proposed Solutions.
AB - India has compelling need and keen aspirations for indigenous clinical research.
Notwithstanding this need and previously reported growth the expected expansion
of Indian clinical research has not materialized. We reviewed the scientific
literature, lay press reports, and ClinicalTrials.gov data for information and
commentary on projections, progress, and impediments associated with clinical
trials in India. We also propose targeted solutions to identified challenges. The
Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate)
between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013.
Phase-1 trials grew by (+) 43.5% CAGR from 2005-2013, phase-2 trials grew by (+)
19.8% CAGR from 2005-2009 and contracted by (-) 12.6% CAGR from 2009-2013, and
phase-3 trials grew by (+) 13.0% CAGR from 2005-2010 and contracted by (-) 28.8%
CAGR from 2010-2013. This was associated with a slowing of the regulatory
approval process, increased media coverage and activist engagement, and
accelerated development of regulatory guidelines and recuperative initiatives. We
propose the following as potential targets for restorative interventions:
Regulatory overhaul (leadership and enforcement of regulations, resolution of
ambiguity in regulations, staffing, training, guidelines, and ethical principles
[e.g., compensation]).Education and training of research professionals,
clinicians, and regulators.Public awareness and empowerment. After a peak in 2009
2010, the clinical research sector in India appears to be experiencing a
contraction. There are indications of challenges in regulatory enforcement of
guidelines; training of clinical research professionals; and awareness,
participation, partnership, and the general image amongst the non-professional
media and public. Preventative and corrective principles and interventions are
outlined with the goal of realizing the clinical research potential in India.
PMID- 25590018
TI - Histoplasmosis Masquerading as a Rheumatoid Nodule in an Immunocompromised Host:
A Case Report.
PMID- 25590019
TI - Interprofessional and Interdisciplinary Approach from Undergraduate Health and
Pre-Medical Students in Children's Health Educational Initiative.
AB - The importance of interprofessional training in healthcare to improve quality of
care and health outcomes has been increasingly recognized. This pilot study used
an interprofessional and interdisciplinary team of undergraduate health and pre
health students to establish a unique community partnership with a local
elementary school in developing and implementing a nutrition/exercise educational
intervention. Our results suggest that children as young as 8 years old are
capable of learning new information related to the benefits of particular food
groups, are capable of retaining this knowledge for 6 months, and that an
intervention program as short as one hour every few months stand to make
significant impact on children's knowledge about proper nutrition and healthy
lifestyles. Our results suggest the potential benefits of further expanding the
short-term intervention into a longer-term community-based curriculum targeting a
younger age group previously or currently practiced.. Furthermore, this pilot
study suggests that undergraduate health and pre-health students can form an
interprofessional and collaborative team to take an active role in the
dissemination of nutrition knowledge in the community.
PMID- 25590021
TI - Comparing the Relationship Between Stature and Later Life Health in Six Low and
Middle Income Countries.
AB - This paper examines the relationship between stature and later life health in 6
emerging economies, each of which are expected to experience significant
increases in the mean age of their populations over the coming decades. Using
data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data
from the Longitudinal Ageing Study in India (LASI), I show that various measures
of health are associated with height, a commonly used proxy for childhood
environment. In the pooled sample, an additional 10cm increase in height is
associated with between a 2 and 3 percentage point increase in the probability of
being in very good or good self-reported health, a 3 percentage point increase in
the probability of reporting no difficulties with activities of daily living or
instrumental activities of daily living, and between a fifth and a quarter of a
standard deviation increase in grip strength and lung function. Adopting a
methodology previously used in the research on inequality, I also summarise the
height-grip strength gradient for each country using the concentration index, and
provide a decomposition analysis.
PMID- 25590023
TI - Comparison between antibiotic therapy of Brucellosis with and without vitamin A.
AB - BACKGROUND: Brucellosis is one of the endemic diseases in our country and it can
be in the types of acute, sub-acute or chronic. It estimates that about 20% of
Brucellosis may change from acute to chronic. Because cell mediated immunity
(CMI) is the main defense of body against Brucella species, it seems that some
degree of Immunologic disorders existed in the patients with chronic form of
diseases and some supplements such as Vitamin A (Vit A) as an immunomodulator can
stimulate CMI and may decrease the rate of chronicity. MATERIALS AND METHODS: In
a single-blind randomized clinical trial 120 patients with the clinical and
serological diagnosed Brucellosis were randomized. A total of 60 patients
received streptomycin and Doxycycline as standard therapy for 6 weeks and others
in addition to this Regimen received Vit A for about 4 weeks. RESULTS: In the
case group, only 1 case (1.6%) relapsed and in the control group 8 (13.5%) with
significant difference (P < 0.005) between two groups. Morbidity of disease was
different between two groups. CONCLUSION: Vit A therapy in the patients with
Brucellosis with may reduce the disease morbidity and rate of chronicity.
PMID- 25590024
TI - The Serum and salivary level of malondialdehyde, vitamins A, E, and C in patient
with recurrent aphthous stomatitis.
AB - BACKGROUND: Oral recurrent aphthous stomatitis (RAS) is a chronic inflammatory
disease affected oral mucosa which has afflicted about 20% of the society.
Etiology of this disease is unknown. Three main factors influencing aphthous
stomatitis are genetic, hematologic, and immunologic factors. Another proposed
factor that may be considered in etiology of aphthous ulcer is oxidant, anti
oxidant imbalance in the body. The purpose of this study was the evaluation of
lipid peroxide enzyme as an important oxidant agent and anti-oxidant vitamins in
the saliva and serum of the patients suffering from RAS and compare it to healthy
people. MATERIALS AND METHODS: In this cross-sectional, descriptive - analytical
study, 25 patients suffering from RAS were compared to 24 healthy individuals.
Applying enzyme-linked immunosorbent assay method, the amount of malondialdehyde
(MDA) as well as Vitamins A, E, and C were measured in the saliva and serum of
two groups. The results were analyzed by Statistical Package for the Social
Sciences (SPSS) software version (11.5), t-test and chi(2). RESULTS: No
significant difference was detected between salivary and serum levels of
antioxidant vitamins (A, E, and C) and MDA in both experimental groups (P >
0.05). CONCLUSION: According to the results of this study, RAS is not associated
with oxidant-antioxidant imbalance in the body. However, it seems quite necessary
to carry out more studies in this area.
PMID- 25590020
TI - Overview and Historical Perspectives.
AB - In this overview, we describe the history of Shiga toxin (Stx)-producing
Escherichia coli (STEC) in two phases. In phase one, between 1977 and 2011, we
learned that E. coli could produce Shiga toxin and cause both hemorrhagic colitis
and the hemolytic-uremic syndrome in humans and that the prototype STEC-E. coli
O157:H7-adheres to and effaces intestinal epithelial cells by a mechanism similar
to that of enteropathogenic E. coli. We also recognized that the genes for Stx
are typically encoded on a lysogenic phage; that STEC O157:H7 harbors a large
pathogenicity island that encodes the elements needed for the characteristic
attaching and effacing lesion; and that the most severe cases of human disease
are linked to production of Stx type 2a, not Stx type 1a. Phase two began with a
large food-borne outbreak of hemorrhagic colitis and hemolytic-uremic syndrome in
Germany in 2011. That outbreak was caused by a novel strain consisting of
enteroaggregative E. coli O104:H4 transduced by a Stx2a-converting phage. From
this outbreak we learned that any E. coli strain that can adhere tightly to the
human bowel (either by a biofilm-like mechanism as in E. coli O104:H4 or by an
attaching and effacing mechanism as in E. coli O157:H7) can cause severe
diarrheal and systemic illness when it acquires the capacity to produce Stx2a.
This overview provides the basis for the review of current information regarding
these fascinating and complex pathogens.
PMID- 25590025
TI - Immunocontraceptives: How far from reality?
AB - Despite high expectations of safer, effective, economical, longer acting
contraceptives, to date, there are no licensed contraceptive vaccines available
in the market. Nevertheless, a role for vaccines undoubtedly exists as an aid to
birth spacing and as a nonsurgical means of generating sterility. The research
concerned in the area so far has been successful on the feline population, with
room still for exhaustive studies on humans. The future of contraceptive vaccines
holds great promise in terms of comfort, price, efficacy, rare complications, and
possibly nonselective action on animal populations as well as on humans. This
brief review deals with the basic aspects of immunocontraceptives along with the
efforts done so far. There is a need for further research in aspects involving
the rate of evolution of contraception resistance based on genetics, resistance
phenotypes, or cross generation effects. Gonadotropin-releasing hormone and
luteinizing-hormone have not been investigated in humans, as both reported
impotency in animals; the follicle-stimulating hormone has been shown to cause
oligospermia; zona pellucida has also not been studied in humans as it causes
irreversible oophoritis, while the sperm has the potential for success in humans
based on the data from immunoreproductive studies. Even as the position of the
human chorionic gonadotropin vaccine looks hopeful, research on other possible
targets continue with an eventual aim of discovering a vaccine that is more
immunogenically effective.
PMID- 25590022
TI - Ocular drug delivery systems: An overview.
AB - The major challenge faced by today's pharmacologist and formulation scientist is
ocular drug delivery. Topical eye drop is the most convenient and patient
compliant route of drug administration, especially for the treatment of anterior
segment diseases. Delivery of drugs to the targeted ocular tissues is restricted
by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug
levels are not maintained for longer duration in target tissues. In the past two
decades, ocular drug delivery research acceleratedly advanced towards developing
a novel, safe and patient compliant formulation and drug delivery
devices/techniques, which may surpass these barriers and maintain drug levels in
tissues. Anterior segment drug delivery advances are witnessed by modulation of
conventional topical solutions with permeation and viscosity enhancers. Also, it
includes development of conventional topical formulations such as suspensions,
emulsions and ointments. Various nanoformulations have also been introduced for
anterior segment ocular drug delivery. On the other hand, for posterior ocular
delivery, research has been immensely focused towards development of drug
releasing devices and nanoformulations for treating chronic vitreoretinal
diseases. These novel devices and/or formulations may help to surpass ocular
barriers and associated side effects with conventional topical drops. Also, these
novel devices and/or formulations are easy to formulate, no/negligibly
irritating, possess high precorneal residence time, sustain the drug release, and
enhance ocular bioavailability of therapeutics. An update of current research
advancement in ocular drug delivery necessitates and helps drug delivery
scientists to modulate their think process and develop novel and safe drug
delivery strategies. Current review intends to summarize the existing
conventional formulations for ocular delivery and their advancements followed by
current nanotechnology based formulation developments. Also, recent developments
with other ocular drug delivery strategies employing in situ gels, implants,
contact lens and microneedles have been discussed.
PMID- 25590027
TI - The frequency of agitation due to inappropriate use of naltrexone in addicts.
AB - BACKGROUND: There is a high tendency among specialists to treat the addicts with
naltrexone; withdrawal symptoms are frequent after taking naltrexone along with
opioids. This study investigated the frequency of agitation due to inappropriate
use of naltrexone in addicts. MATERIALS AND METHODS: This was a cross-sectional
study, conducted in Noor and Aliasghar hospitals in Isfahan city. The study
population included the addicts who were agitated as a result of naltrexone
abuse. Scores of patients with agitation were measured with Richmond Agitation
Sedation Scale (RASS). Patient outcomes including recovery without complications,
recovery with complications (rhabdomyolysis), and mortality were recorded.
RESULTS: All the patients with agitation caused by naltrexone abuse during 1 year
were 40 people, of whom nine were excluded due to their comorbid diseases
(diabetes or cardiovascular disease). Among the remaining 31 patients, 30 were
male. The patients' mean age was 29.93 (5.24) years. The most common symptoms
observed besides agitation was midriasis (41.9%), and vomiting (41.9%), A 38.8%
of the patients scored 3 or 4, and, 61.2% scored 1 or 2 for agitation. The mean
time for patients' restlessness scores to reach zero was 9.30 (3.71) h (min: 3 h,
max: 18 h). All the patients in both groups were discharged with recovery without
complication. CONCLUSION: Considering the high prevalence of agitation in the
poisoning emergency department due to inappropriate use of naltrexone, more
accurate planning for administration of naltrexone in addicts seems necessary.
PMID- 25590028
TI - Preoperative evaluation of pelvic kidney renal cell carcinoma with 64-slice CT
and 3D-CT angiography.
AB - We report a case of a 55-year-old woman, who presented with a vague pelvic pain
and was found to have an ectopic pelvic kidney involved by a mass. Preoperative
assessment was done by multi-slice CT and 3D-CT angiography. According to our
knowledge only eight cases of pelvic kidney tumor have been reported in the
literature and our case is the first report of using multi-slice CT and 3D-CT
angiography in the preoperative evaluation of these cases.
PMID- 25590026
TI - A comparison between standard triple therapy and sequential therapy on
eradication of Helicobacter pylori in uremic patients: A randomized clinical
trial.
AB - BACKGROUND: The prevalence of peptic ulcer disease in hemodialysis dependent
patients is higher than the general population. These patients are also more
prone to upper gastrointestinal bleeding. The aim of this study was to compare
the effects of a standard triple therapy with a sequential therapy on
Helicobacter pylori eradication in azotemic and hemodialysis patients. MATERIALS
AND METHODS: Forty nine hemodialysis and azotemic patients, naive to H. pylori
treatment, were randomized into two groups to receive either standard triple
therapy (pantoprazole 40 mg, amoxicillin 500 mg and clarithromycin 250 mg twice a
day for 14 days) or a sequential therapy (pantoprazole 40 mg for 10 days,
amoxicillin 500 mg twice a day for the first 5 days and clarithromycin 250 mg +
tinidazole 500 mg twice a day just during the second 5 days). H. pylori
eradication was evaluated by fecal H. pylori antigen assessment 8 weeks after the
treatment. RESULTS: Of 49 patients, 45 patients (21 in triple therapy group and
24 in the sequential group) completed the study. Based on intention to treat
analysis, H. pylori eradication rates were 66.7% (95% confidence interval [CI]:
47.8-85.5%) in standard triple therapy group and 84% (95% CI: 69.6-98.3%) in
sequential therapy group (P = 0.34). Per-protocol (PP) eradication rates were
(95% CI: 76.2%. 6-89.3%) 54 and 87.5% (95% CI: 68.8-95.5%), respectively (P =
0.32). CONCLUSION: According to Maastricht III consensus report, the results of
our study showed that sequential therapy might be a better choice compared with
the standard triple therapy in azotemic and hemodialysis patients Iran. We
propose to assess the effects of shorter-duration sequential therapy (less than
10 days) for H. pylori eradication.
PMID- 25590029
TI - Kefir protective effects against nicotine cessation-induced anxiety and cognition
impairments in rats.
AB - BACKGROUND: Nicotine as one of the potent psychostimulant drugs is characterized
by its parasympathomimetic activity. Upon the abrupt discontinuation of nicotine
intake, a number of symptoms such as anxiety, depression and cognition impairment
develop. Kefir as a food supplement is rich in tryptophan. In this study, we have
evaluated the effects of Kefir on nicotine cessation-induced anxiety, depression
and cognition impairment. MATERIALS AND METHODS: Forty adult male rats were
divided into four groups. All the groups received 6 mg/kg/day of nicotine for 17
days and then the negative control groups got 5 mg/kg/day of normal saline. The
positive control groups were given 40 mg/kg/day of Sertraline HCl for 7 days. The
group treated with Cow Milk Kefir (CMK) and Soy Milk Kefir (SMK) received 5
mg/kg/day for 7 days. On the 25(th) day, Elevated Plus Maze (EPM), Open Field
Test (OFT) and Forced Swim Test (FST) were used to investigate anxiety and
depression. In addition, Moris Water Maze was applied to evaluate learning and
memory in the animals between the 20(th) and 25(th) days. RESULTS: The results
showed that administration of CMK, SMK and Sertraline had higher anti-depression
and anxiolytic effects on nicotine withdrawal-induced depression and anxiety in
rats (P < 0.05). Moreover, CMK and SMK improved learning and memory impairment
results in the nicotine withdrawal period (P < 0.05). CONCLUSION: This study
revealed that Kefir had a potential effect on the treatment of nicotine cessation
induced depression, anxiety and cognition impairment in the animal model. Kefir
may be useful for adjunct therapy for nicotine abandonment treatment protocols.
PMID- 25590030
TI - Placement of long-term hemodialysis catheter (permcath) in patients with end
stage renal disease through external jugular vein.
AB - BACKGROUND: The number of patients with End-Stage Renal Disease (ESRD) has
progressively increased in the population. Kidney transplantation is the specific
treatment for such patients; however a majority of patients will require
hemodialysis before kidney transplantation. The present study aims to investigate
using the external jugular vein (EJV) for Permcath placement in these patients.
MATERIALS AND METHODS: This descriptive and analytical study was conducted in
Alzahra Medical Center, Isfahan, in 2012. Catheters were inserted by cutting down
the right EJV. The patency rate and potential complications were studied. The
obtained data was analyzed using SPSS 21.0. RESULTS: Out of 45 live patients,
within three months of surgery, 40 patients (81.6%) had no complications and
dialysis continued through Permcath. Permcath Thrombosis occurred in two patients
(4.4%). Catheter infection led to the removal of it in one patient (2.2%) 1.5
months after surgery. And accidental catheter removal occurred in one patient.
CONCLUSION: Placement of the permcath in the external jugular vein can be a safe,
uncomplicated, and reliable method for patients requiring hemodialysis, and can
be a life-saving alternative in patients without accessible internal jugular
vein.
PMID- 25590031
TI - Comparing the treatment results of proximal humerus fracture based on surgical or
nonsurgical methods.
AB - BACKGROUND: A common type of Humerus fractures is about proximal. This study
aimed to compare the results of surgical and non-surgical methods in treatment
the Fracture of Proximal Humerus for decisions based on high-performance and less
side effect. MATERIALS AND METHODS: This prospective clinical trial study was
done on 114 patients 30-80 years old with proximal humerus fracture referred to
the Isfahan hospital universities (Ayatollah Kashani and Al Zahra hospitals) in
2007-2012. They were divided into two groups of 57 and treated surgically or non
surgically. The self provided questionnaires were used to assess the consequences
of the side effects. The patients returned for trial check up during 6 weeks, 3
months, 6 months and one year after intervention. RESULT: In two parts fracture
with displacement, nonsurgical treatment had lead to more complications rather
than surgical treatment. In three-parts fracture non-union was seen in
nonsurgical method in 6 weeks and in surgical method in 3, 6 months and one year
after treatment, malunion was seen more in nonsurgical method rather than
surgical method. In four-part fracture none-union results was seen more in
nonsurgical method in 6 weeks, 3 months and one year and in surgical method in 6
months after treatment, mal union was seen more in nonsurgical method rather than
surgical method. CONCLUSION: The surgery in three and four parts fractures had
fewer complications in the patients under 50 but not in the elders.
PMID- 25590032
TI - Perspective on the hospital incidence rate of deep venous coagulopathy: Clinical
and biochemical diagnostic markers.
AB - BACKGROUND: Identifying factors contributing to the increased risk of deep venous
thrombosis (DVT) in each population is vital, because of its life-threatening
outcome. The current study aims to find the diagnostic performance of some
laboratory coagulation markers for predicting DVT in an Iranian population
complaining of DVT in the lower limbs. PATIENTS AND METHODS: For this study, 66
consecutive patients with documented DVT, admitted to the Al-Zahra Hospital in
Isfahan for the first time, were considered as the case group and 33 patients
without DVT documentations were included as the control group. DVT was considered
when there was visualization of thrombus or non-compressibility of the vein,
confirmed by bilateral lower extremity compression Doppler ultrasonographic
examination. Homocysteine, antiphospholipid, and anticardiolipin antibodies were
measured in both groups by using sensitive ELISA kits. Protein C was measured via
a functional clotting method, and prothrombin was measured by a kinetic,
enzymatic assay. RESULTS: Multivariable analysis showed that the serum
homocysteine levels was potentially associated with the presence of DVT after
adjusting for age and gender (OR: 1.038, 95% CI: 1.007-1.070, P = 0.017).
Comparison of the C statistic showed a partially good discrimination of
homocysteine for DVT, with the area under the receiver operating characteristic
(ROC) curve being 0.614 and with the optimal cut-off value of 16.5 micromol/L
(MUmol/L) for men and 14.5 MUmol/L for women. CONCLUSION: Hyperhomocysteinemia
could be considered as an independent risk factor for DVT, with an actual
acceptable prognostic value, in the Iran population.
PMID- 25590033
TI - Case report on the administration of an eighty milligram diazepam injection
without respiratory depression.
AB - Nowadays one of the most challenging problems in Medicine is addiction -
addiction to sedative drugs such as benzodiazepines. In this article, we are
going to describe a case of diazepam addiction that has tolerated a high dose of
intravenous diazepam.
PMID- 25590034
TI - Comparison of Bristow procedure and Bankart arthroscopic method as the treatment
of recurrent shoulder instability.
AB - BACKGROUND: Anterior shoulder dislocation is the most common major joint
dislocation. In patients with recurrent shoulder dislocation, surgical
intervention is necessary. In this study, two methods of treatment, Bankart
arthroscopic method and open Bristow procedure, were compared. MATERIALS AND
METHODS: This clinical trial survey had been done in the orthopedic department of
Alzahra and Kashani hospitals of Isfahan during 2008-2011. Patients with
recurrent anterior shoulder dislocation who were candidates for surgical
treatment were randomly divided into two groups, one treated by Bankart
arthroscopic technique and the other treated by Bristow method. All the patients
were assessed after the surgery using the criteria of ROWE, CONSTANT, UCLA, and
ASES. Data were analyzed by SPSS software. RESULTS: Six patients (16.22%) had
inappropriate condition with ROWE score (score less than 75); of them, one had
been treated with Bristow and five with Bankart (5.26 vs. 27.78). Nine patients
(24.32%) had appropriate condition, which included six from Bristow group and
three treated by Bankart technique (31.58 vs. 16.67). Finally, 22 patients
(59.46%) showed great improvement with this score, which included 12 from Bristow
and 10 from Bankart groups (63.16 vs. 55.56). According to Fisher's exact test,
there were no significant differences between the two groups (P = 0.15).
CONCLUSION: The two mentioned techniques did not differ significantly, although
some parameters such as level of performance, pain intensity, use of analgesics,
and range of internal rotation showed more improvement in Bristow procedure.
Therefore, if there is no contraindication for Bristow procedure, it is preferred
to use this method.
PMID- 25590035
TI - Comparison of the effects of two different formulas of fluids in craniotomy
patients.
AB - BACKGROUND: Intraoperative fluid management of the patients who had undergone
neurosurgery presents special challenges for the anesthesiologist. In this study,
we aimed to compare the effects of two fluid combinations (half-normal +
bicarbonate with saline + Ringer's lactate) on brain relaxation, and acid, base,
and hemodynamic balance in patients undergoing elective craniotomy surgery.
MATERIALS AND METHODS: This randomized double-blind controlled clinical trial
study was done on 50 patients, of age 20-60 years, undergoing craniotomy in
Alzahra Hospital in 2012. They were divided in two groups of 25 patients each. In
the control group, after the patients received hypertonic saline, normal saline
serum and Ringer's lactate was administered, and in the half-normal study group,
80 ml of sodium bicarbonate for every liter of it was added. Arterial blood gas
(ABG) was taken before the last suture. Brain relaxation before dura opening was
registered. RESULTS: There was no significant difference in heart rate changes (P
= 0.054). No significant difference was observed in the mean arterial pressure
between the two groups (P = 0.99). Changes in pH, HCO3, and BE were not
significantly different (P = 0.99) between the two groups. Urine output in half
normal saline group was significantly higher than in normal saline group. The
mean bleeding volume was higher in normal saline group, but was not significantly
different (P = 0.54). The mean volume of injected blood was higher in half-normal
group with a significant difference (P = 0.54). The injected blood volume mean in
half-normal group was higher with no significant difference (P = 0.55). The mean
of brain relaxation was not different (P = 0.5). CONCLUSION: These two fluids did
not show any significant differences in the studied variables in this research.
PMID- 25590036
TI - From Measurement to Analysis Reporting: Grand Challenges in Nutritional
Methodology.
PMID- 25590038
TI - Biogenic amine metabolism in juvenile neurocardiogenic syncope with dysautonomia.
AB - OBJECTIVE: Biogenic amine brain levels and their cerebral metabolism are
frequently studied by quantitation of biogenic amine metabolites in cerebrospinal
fluid (CSF) compared to age-matched controls. There is a paucity of studies in
adolescents and young adults investigating the potential role of disordered
cerebral biogenic amine metabolism in young patients who have dysautonomia based
on abnormal head-up tilt table (HUTT). METHODS: In a cohort of juvenile patients
with neurocardiogenic syncope and dysautonomia documented by abnormal HUTT,
biogenic amine metabolites of dopamine and serotonin were quantitated in 18
patients (15 females). HUTT testing is an effective clinical method to evaluate
posturally induced physiological events in patients suspected of neurocardiogenic
syncope with dysautonomia. RESULTS: Levels of the dopamine metabolite
(homovanillic acid: HVA) and/or the serotonin metabolite (5-hydroxyindoleacetic
acid: 5HIAA) were significantly reduced in 13 patients compared to age-matched
controls. INTERPRETATION: Peripheral biogenic amines and their metabolites have
been extensively studied in adults with dysautonomia due to various
neurodegenerative disorders (Parkinson disease, multiple system atrophy, primary
autonomic failure). Our findings indicate that more than two-thirds of this
cohort of young patients with dysautonomia of variable severity have a defect in
cerebral biogenic amines, particularly in dopamine and serotonin metabolism.
PMID- 25590037
TI - Identification of Srp9 as a febrile seizure susceptibility gene.
AB - OBJECTIVE: Febrile seizures (FS) are the most common seizure type in young
children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE).
To identify new FS susceptibility genes we used a forward genetic strategy in
mice and subsequently analyzed candidate genes in humans. METHODS: We mapped a
quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome
1, containing the signal recognition particle 9 (Srp9) gene. Effects of
differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9
expression and genetic association were analyzed in FS and mTLE patients.
RESULTS: Srp9 was differentially expressed between parental strains C57BL/6J and
A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS
susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain
Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS
susceptibility, exhibited reduced hippocampal AMPA and NMDA currents.
Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor
subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than
patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated
with FS and mTLE. INTERPRETATION: Our findings identify SRP9 as a novel FS
susceptibility gene and indicate that SRP9 conveys its effects through
endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane
proteins, such as glutamate receptors. Discovery of this new FS gene and
mechanism may provide new leads for early diagnosis and treatment of children
with complex FS at risk for mTLE.
PMID- 25590040
TI - Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.
AB - Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be
responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here
we examined the signal intensity of the four alleles of each mtDNA nucleotide
position (np) in whole blood of AD patients and age-matched controls using
MitoChip v2.0 array. Our analysis identified 270 significantly different nps
which, with one exception, showed an increased contribution of non-reference
alleles in AD patients. Principal component analysis (PCA) and cluster analysis
showed that five of these nps could discriminate AD from control subjects with
80% of cases correctly classified. Our data support the hypothesis of mtDNA
alterations as an important factor in the etiology of AD.
PMID- 25590039
TI - Heterogeneity of oligodendrocyte progenitor cells in adult human brain.
AB - OBJECTIVE: Remyelination in multiple sclerosis has been attributed to the
presence of oligodendrocyte progenitor cells (OPCs) in brain parenchyma. However,
the precise identity of these progenitors is poorly defined. Here, we
characterized populations of OPCs in the adult human brain and examined their
myelination capacity and profile of miRNAs. Comparisons were made with fetal OPCs
and mature oligodendrocytes. METHODS: We isolated human adult and fetal (early-to
mid second trimester) OPCs from surgically resected brain tissues using O4-, A2B5
, and MOG-directed fluorescence activated cell sorting and transplanted them into
dysmyelinated shiverer slices to examine their myelination capacity. We used qRT
PCR to analyze expression of selective miRNAs implicated in OPC biology. RESULTS:
Three subsets of putative OPCs were identified in adult brains: (1) A2B5(+), (2)
O4(low), and (3) A2B5(+)O4(high)MOG(+) progenitors. In comparison, fetal brains
contained (1) A2B5(+), (2) O4(+), and (3) A2B5(+)O4(+) progenitors, but no MOG(+)
cells. We demonstrate that like fetal OPCs, adult OPCs have the capacity to
ensheathe cerebellar axons. However, adult OPCs exhibit low to undetectable
expression of miRNAs that were highly expressed in O4-expressing fetal OPCs.
Adult OPCs also express different miRNAs compared to mature oligodendrocytes.
INTERPRETATION: We conclude that phenotypically distinct subsets of OPCs are
present in adult human brain and these OPCs show differential miRNA expression
compared to fetal OPCs and mature oligodendrocytes. These suggest that
remyelination in adult brain may involve multiple populations of progenitors
within the brain and that OPC differentiation in adulthood may be differentially
regulated compared to development.
PMID- 25590042
TI - Discharge responses of the optic tract to flash stimuli in Parkinson's disease.
AB - Dopamine has a significant role in retinal processing, and it has been
demonstrated that retinal dopamine content is decreased in parkinsonian patients.
We measured the latency of the evoked discharges in the optic tract (OT) to flash
stimuli during stereotactic pallidal neurosurgery in 25 patients with Parkinson's
disease (PD) (13 women and 12 men, age 38-78 years, unified Parkinson's disease
rating scale (UPDRS) Motor Score in the Off state 11-54, Hoehn and Yahr stage in
the Off state 1.5-5) and investigated the effects of age at surgery, disease
duration, levodopa dose, and severity of parkinsonian symptoms on the latency. OT
discharges were evoked by monocular flash stimuli delivered from a flashlight
with a krypton bulb with a tungsten filament. The luminance at the eye measured
~4 * 10(4) cd/m(2). The light wavelength of the stimulus was composed of a wide
spectrum with its peak at around 800 nm or longer. The latency of OT discharges
ranged 49-79 msec, and there was a significant positive correlation between the
latencies of evoked activities in the OT to a flashlight and age (r = 0.59, P <
0.001, by Pearson correlation), but no correlation between the latency and the
severity of parkinsonian symptoms and between the latency and duration of
illness. These results indicate that the delay in visual processing and
conduction at the level of the retina and the OT are substantially derived from
age-related degenerative changes in the retina and visual pathway which are
apparently unrelated to the striatal dopamine deficiency in PD.
PMID- 25590041
TI - Subtle retinal pathology in amyotrophic lateral sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is characterized by neuro-ophthalmological
abnormalities beyond disturbed oculomotor control such as decreased visual acuity
and disturbed visual evoked potentials. Here we report retinal alterations in a
cohort of 24 patients with clinically definite (n = 20) or probable (n = 4) ALS
as compared to matched controls. High-resolution spectral domain optical
coherence tomography with retinal segmentation revealed a subtle reduction in the
macular thickness and the retinal nerve fiber layer (RNFL) as well as a marked
thinning of the inner nuclear layer (INL). Our data indicate an unprecedented
retinal damage pattern and suggest neurodegeneration beyond the motor system in
this disease.
PMID- 25590043
TI - Spinal cord atrophy in early Huntington's disease.
AB - Despite evidence for spinal cord involvement, it remains unclear whether spinal
cord atrophy exists in early Huntington's disease. We studied magnetic resonance
images, covering both brain and upper cervical cord, in two cohorts of
Huntington's patients and in one cohort of Alzheimer's patients. All cohorts
included healthy controls comparable with regard to age and gender. We found
significant spinal cord atrophy in both cohorts of Huntington's patients but not
in the cohort of Alzheimer's patients. Furthermore, spinal cord atrophy
correlated with motor symptoms indicating that spinal cord atrophy occurs in the
clinical stages and does not result from abnormal development.
PMID- 25590046
TI - Head accelerometry may be useful as a test of psychogenic head tremor.
PMID- 25590045
TI - Beta-2-Adrenergic Receptor Methylation Influences Asthma Phenotype in The School
Inner City Asthma Study.
AB - Asthma is the most common chronic illness of childhood and inner city residents
suffer a disproportionately high rate of asthma diagnosis and asthma morbidity.
The School Inner City Asthma Study investigates the school classroom based
environmental exposures that may lead to asthma morbidity in inner city school
children with asthma. Within this cohort, we investigated the role of methylation
at the promoter region of the beta-2-adrenergic receptor in relation to asthma
morbidity. We found that high levels of methylation in the region studied was
significantly associated with decreased report of dyspnea and trended towards
significance for lower levels of asthma symptoms and airway obstruction. This
Research Highlight discusses the findings of the recent study and the
investigators' active research endeavors.
PMID- 25590047
TI - Biodemographic Analyses of Longitudinal Data on Aging, Health, and Longevity:
Recent Advances and Future Perspectives.
AB - Biodemography became one of the most innovative and fastest growing areas in
demography. This progress is fueled by the growing variability and amount of
relevant data available for analyses as well as by methodological developments
allowing for addressing new research questions using new approaches that can
better utilize the potential of these data. In this review paper, we summarize
recent methodological advances in biodemography and their diverse practical
applications. Three major topics are covered: (1) computational approaches to
reconstruction of age patterns of incidence of geriatric diseases and other
characteristics such as recovery rates at the population level using Medicare
claims data; (2) methodological advances in genetic and genomic biodemography and
applications to research on genetic determinants of longevity and health; and (3)
biodemographic models for joint analyses of time-to-event data and longitudinal
measurements of biomarkers collected in longitudinal studies on aging. We discuss
how such data and methodology can be used in a comprehensive prediction model for
joint analyses of incomplete datasets that take into account the wide spectrum of
factors affecting health and mortality transitions including genetic factors and
hidden mechanisms of aging-related changes in physiological variables in their
dynamic connection with health and survival.
PMID- 25590048
TI - Astrocyte mediated MMP-9 activation in the synapse dysfunction: An implication in
Alzheimer disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs
due to spasms of the neurons, resulting in loss of memory and behavioral changes.
In particular, synaptic loss has been described as an early event in the
pathogenesis of AD. The increasing evidences have suggested the role of many
matrix metalloproteinase (MMPs) in central nervous system (CNS) pathology. Many
studies showed that MMPs enzymes are important for the pathophysiological process
during Alzheimer's disease (AD). It is usually believed that the synaptic
dysfunction and synapse loss contribute to the cognitive deficits of patients
with AD. Cerebrovascular events such as blood-brain barrier (BBB) disruption lead
to neuronal damage as well as neuroinflammation. BBB dysfunctions are observed at
an early post injury time point, and are associated with activation of proteases,
such as MMPs especially MMP-9 which is actively engage in a neuronal injury in
the most of the neurodegenerative disorders. BBB opening is accompanied by
astrocytic activation, BBB injury and dysregulation of cerebral blood flow.
Activated MMPs disrupt neurovascular unit (NVU) which may starve the neurons and
affect the synapse function by altering synaptic plasticity and ultimately lead
to cognitive decline. However, how MMPs implicated in synaptic dysfunction what
are the mechanism associated with this disparity needs to discuss for better
understanding the role of MMP-9 in pathogenesis of AD. In this review, we focused
on the role of astrocytes and MMP-9 in synaptic dysfunction. We also, underlined
possible pharmacological strategies for drug development that might offer more
insight into the pathogenesis of cerebrovascular disease such as stroke and
Vascular dementia.
PMID- 25590049
TI - Pre-Clinical Models of Acquired Neonatal Seizures: Differential Effects of Injury
on Function of Chloride Co-Transporters.
AB - Hypoxic-ischemic encephalopathy [HIE] represents the most common acquired
pathology associated with neonatal seizures. HIE-associated neonatal seizures are
often difficult to control, due to their refractoriness to traditional anti
seizure agents. Developmentally regulated chloride gradients during early
development make the neonatal brain more seizure-susceptible by depolarizing
GABAAR-mediated currents, and therefore hindering inhibition by conventional anti
seizure drugs such as phenobarbital [PB] and benzodiazepines. Pharmaco-modulation
of chloride co-transporters has become a current field of research in treating
refractory neonatal seizures, and the basis of two clinical trials [NCT01434225;
NCT00380531]. However, the recent termination of NEMO study [NCT01434225] on
bumetanide, an NKCC1 antagonist, suggests that clinical utilization of bumetanide
as an adjunct to treat neonatal seizures with PB may not be a viable option.
Hence, re-evaluation of bumetanide as an adjunct through pre-clinical studies is
warranted. Additionally, the model-specific variability in the efficacy of
bumetanide in the pre-clinical models of neonatal seizures highlights the
differential consequences of insults used to induce seizures in each pre-clinical
model as worth exploration. Injury itself can significantly alter the function of
chloride co-transporters, and therefore the efficacy of anti-seizure agents that
follow.
PMID- 25590051
TI - Degradation of two fluoroquinolone antibiotics photoinduced by Fe(III)-microalgae
suspension in an aqueous solution.
AB - The widespread presence of fluoroquinolone antibiotics (FQs) in natural
ecosystems is a health hazard for humans and other living organisms. In this
work, the photochemical degradation process of two antibiotics in the presence of
Fe(III) and marine microalgae has been studied. Two fluoroquinolone (FQ)
antibiotics, enrofloxacin (ENR) and ciprofloxacin hydrochloride (CIP), and two
marine microalgae, Platymonas subcordiformis and Isochrysis galbana, were
investigated under irradiation with a high-pressure mercury lamp (HPML) in a
laboratory-scale experiment. The effects of the initial concentration of
antibiotics on the degradation of these two FQs in Fe(III)-algae suspensions were
also investigated. On the basis of the information in this study, compared to
other systems, the efficiency of photo-degradation of the two FQs is better at
lower FQ concentrations in the Fe(III)-algae system. Moreover, the low initial
concentration of antibiotics benefits the photochemical process of antibiotics.
This work demonstrated that the Fe(III)-algae system is an interesting and
valuable research area and could be considered as a promising photochemical
system for seawater remediation.
PMID- 25590053
TI - Proceedings of the 11th Annual MCBIOS Conference, March 6-8, 2014, Stillwater,
Oklahoma.
PMID- 25590050
TI - Replication of SCN5A Associations with Electrocardio-graphic Traits in African
Americans from Clinical and Epidemiologic Studies.
AB - The NAv1.5 sodium channel alpha subunit is the predominant alpha-subunit
expressed in the heart and is associated with cardiac arrhythmias. We tested five
previously identified SCN5A variants (rs7374138, rs7637849, rs7637849, rs7629265,
and rs11129796) for an association with PR interval and QRS duration in two
unique study populations: the Third National Health and Nutrition Examination
Survey (NHANES III, n= 552) accessed by the Epidemiologic Architecture for Genes
Linked to Environment (EAGLE) and a combined dataset (n= 455) from two biobanks
linked to electronic medical records from Vanderbilt University (BioVU) and
Northwestern University (NUgene) as part of the electronic Medical Records &
Genomics (eMERGE) network. A meta-analysis including all three study populations
(n~4,000) suggests that eight SCN5A associations were significant for both QRS
duration and PR interval (p<5.0E-3) with little evidence for heterogeneity across
the study populations. These results suggest that published SCN5A associations
replicate across different study designs in a meta-analysis and represent an
important first step in utility of multiple study designs for genetic studies and
the identification/characterization of genetic variants associated with ECG
traits in African-descent populations.
PMID- 25590054
TI - Proceedings of the the 5th Symposium on Antimicrobial Resistance in Animals and
the Environment (ARAE 2013), June 30-July 3, 2013, Ghent, Belgium.
PMID- 25590052
TI - Proceedings of the 13th European Conference on Computational Biology (ECCB'14),
September 7-10, 2014, Strasbourg, France.
PMID- 25590056
TI - European Society of Cardiology European Affairs: bringing science to policy
makers.
PMID- 25590055
TI - Efficacy and safety of human placental extract for alcoholic and nonalcoholic
steatohepatitis: an open-label, randomized, comparative study.
AB - Human placental extract (HPE) is a traditional medicine that has been used for
the symptomatic treatment of liver disease without any verifying clinical
evidence. This study aimed to evaluate the efficacy and safety of HPE in patients
with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this
clinical trial as a multicenter, open-label, randomized, comparative
noninferiority study to improve the reliability of analyses. The enrollment
criteria were limited to ASH or NASH patients with serum alanine aminotransferase
(ALT) 1.5-fold higher than the normal level. Patients in the control group were
treated with a commercially available mixture of liver extract and flavin adenine
dinucleotide (LE-FAD). Intention-to-treat (ITT) analysis was applied to 194
patients, and per-protocol (PP) analysis was available for 154 patients. The rate
of primary goal achievement of treatment efficacy was arbitrarily defined as 20%
or greater improvement in ALT level compared with the pretreatment level and did
not differ significantly between the HPE and control groups [62.9% (44/70) vs.
48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to
those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree
occurred in 3.1% of patients. The ADR and treatment compliance rates were similar
in both groups. In conclusion, the clinical value of HPE in the treatment of ASH
and NASH is equivalent to that of LE-FAD.
PMID- 25590057
TI - Taskforce QRS.
PMID- 25590059
TI - The pinch patch technique.
PMID- 25590058
TI - Influence of serum albumin levels during opioid rotation from morphine or
oxycodone to fentanyl for cancer pain.
AB - Morphine, oxycodone, and fentanyl are commonly used to control cancer pain.
Because these drugs have differences in receptor affinity or pharmacokinetic
parameters, changing the opioid formulation may result in an unexpected outcome,
depending on the patient's condition. This study investigated whether low serum
protein levels influence the effectiveness of opioid rotation by determining the
impact of serum albumin levels on the analgesic effect before and after opioid
rotation from morphine or oxycodone to fentanyl in cancer patients. The patients
were classified into 3 groups according to their serum albumin levels before
opioid rotation: group 1, <2.5 g/dL; group 2, from 2.5 g/dL to <3.0 g/dL; and
group 3, >=3.0 g/dL. There was no significant change in the percentage of
patients with good pain control after rotation in group 1 or group 2; however,
the percentage of patients with good pain control increased significantly in
group 3. When the percentage of patients whose numerical rating scale scores
increased, were unchanged, or decreased after rotation were compared, a
significant difference in the percentage of those showing improvement was noted
among the 3 groups and between groups 1 and 3. These findings suggest that
monitoring serum albumin levels during fentanyl therapy is useful for pain
management, and that the effectiveness of opioid rotation to fentanyl in patients
with serum albumin levels of <2.5 g/dL should be carefully evaluated after
rotation.
PMID- 25590060
TI - Novel use of the retinoscope in visualization of the anterior segment.
PMID- 25590061
TI - In Memoriam: Hans von Leden.
PMID- 25590062
TI - Proceedings of The 8th World Congress on Vaccines, Immunisation and
Immunotherapy, June 5-7, 2012, Barcelona, Spain.
PMID- 25590065
TI - Rating the planet's oceans.
PMID- 25590063
TI - Proceedings of the Fifth International Brain-Computer Interface Meeting, June 3
7, 2013, Pacific Grove, CA.
PMID- 25590066
TI - Using bacteria to reduce impact of diazepam in UK rivers.
PMID- 25590067
TI - Nanoparticles accumulate quickly in wetland sediment.
PMID- 25590068
TI - Pollution linked to lethal sea turtle tumours.
PMID- 25590069
TI - Coral's best defender against an army of sea stars.
PMID- 25590070
TI - Proceedings and abstracts of the 29th International Workshop on Surfactant
Replacement, May 30-31, 2014, Valencia, Spain.
PMID- 25590071
TI - Whaling commission shifts toward conservation agenda.
PMID- 25590072
TI - Recreational activity a major pollutant on Canadian Pacific coast.
PMID- 25590073
TI - Changing Antarctic waters could trigger steep rise in sea levels.
PMID- 25590074
TI - Big changes in the Sargasso Sea.
PMID- 25590075
TI - Microplastic pollution discovered in St. Lawrence River sediments.
PMID- 25590077
TI - Changes in coastal upwelling linked to temporary declines in marine ecosystem.
PMID- 25590076
TI - Tropical fish a threat to Mediterranean Sea ecosystems.
PMID- 25590079
TI - Proceedings of the 6th ANIRCEF National Congress - Headache and Social Context,
29-31 May, 2014, Asti, Italy.
PMID- 25590081
TI - Oncology scan--primary central nervous system lymphoma.
PMID- 25590083
TI - The challenges faced by the Korean Society for Radiation Oncology in the national
healthcare system in Korea.
PMID- 25590084
TI - Puerarin enhances bone mass by promoting osteoblastogenesis and slightly lowering
bone marrow adiposity in ovariectomized rats.
AB - We investigated the effect of puerarin on bone mass and marrow adiposity in
ovariectomy (OVX)- induced osteoporosis. The rats were divided into four groups:
control; OVX; OVX+estradiol (OVX-E); and OVX+puerarin treatment (OVX-GE). In
vivo, bone mineral density (BMD) and histomorphometry were measured under
microCT. The mechanical properties of tibia were obtained in 3-point bending
test. Plasma osteocalcin and adiponectin were determined using enzyme-linked
immunosorbent assay (ELISA). Alkaline phosphatase (ALP) were measured using
biochemical methods. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) and Oil Red O staining were used to compare
osteoblast proliferation and adipocyte differentiation, respectively. Osteocalcin
and adiponectin in culture supernatants were determined using ELISA. The results
showed that puerarin significantly enhanced bone volume density and trabecular
number compared with OVX and OVX-E groups (p<0.05, p<0.05, respectively).
Puerarin increased energy to ultimate load, plasma osteocalcin and ALP (p<0.01).
However, BMD in OVX-GE group was less than that in control (p<0.01) and OVX-E
groups (p<0.05). The culture supernatants from OVX-GE group showed increased
osteocalcin compared with those from OVX (p<0.01) and OVX-E groups (p<0.05).
Puerarin lowered adiponectin in culture supernatant compared with supernatant
from OVX group and inhibited the increase in adipocytes caused by OVX (p<0.01).
However, the amount of lipids did not differ between OVX-GE and OVX groups. These
findings suggest that puerarin likely enhances bone formation by stimulating the
proliferation and differentiation of osteoblasts while slightly inhibiting the
adipotic differentiation.
PMID- 25590086
TI - Role of simplex lattice statistical design in the formulation and optimization of
microemulsions for transdermal delivery.
AB - Microemulsions (ME) have gained attention as an alternative pharmaceutical
formulation for transdermal delivery systems. However, the complicated
relationships between various ME compositions (causal factors) and their
characteristics (response variable) have not been fully comprehended. To overcome
this problem, the design and development of ME for transdermal delivery was
performed in our study using Design Expert((r)) Software. The model formulations
of ME were prepared according to the ME region obtained from pseudo-ternary phase
diagrams using the simplex lattice design as an optimization technique. In this
study, ketoprofen-loaded ME composed of oleic acid, Cremophor((r)) RH40, ethanol
and water were prepared, and their characteristics (e.g., size, charge,
conductivity, pH, viscosity, drug content, loading capacity and skin permeation
flux) were evaluated. The ME having an appropriate skin permeation flux was used
as the basis for optimization. The skin permeation flux of the experimental ME
was very close to the flux predicted by Design Expert((r)) Software and was
significantly greater than that for the commercial product. Possible mechanisms
for the enhancement of the skin permeation of the ME were also investigated using
Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD). This
finding provided an understanding of the relationship between the causal factors
and response variables, as shown in the response surfaces. Moreover, these
results indicated that the simple lattice design was beneficial for the
pharmaceutical development of ME for transdermal delivery.
PMID- 25590089
TI - Nephrotoxicity induced by piperacillin-tazobactam in late elderly Japanese
patients with nursing and healthcare associated pneumonia.
AB - This study aimed to clarify the efficacy, safety, and pharmacokinetics of
piperacillin-tazobactam (PIPC- TAZ) in late elderly Japanese patients. This is
the first antimicrobial pilot study in late elderly patients with nursing and
healthcare associated pneumonia. After PIPC-TAZ administration, PIPC
concentrations in plasma were measured chromatographically and the
pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological
evaluations were also carried out. The mean age was 85.0 years old and most of
the patients were late elderly. Chest X-rays, body temperature, white blood cell
count, and C reactive protein all improved significantly, and a high efficacy
ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases
(18.2%) after administration of PIPC-TAZ. Creatinine clearance (meanS.D.)
measured before PIPC-TAZ therapy was significantly lower in the nephrotoxicity
group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min),
although the ages were not different between the 2 groups. In the pharmacokinetic
parameters for PIPC, total clearance was slightly lower in the nephrotoxicity
group than in the non-nephrotoxicity group. However, no significant difference
was observed in plasma PIPC levels between the 2 groups. In patients with renal
impairment, especially with a creatinine clearance of <40 mL/ min, renal
impairment was found to be an influencing factor for severe nephrotoxicity
following PIPC-TAZ administration. In conclusion, the results suggest that
physicians should pay close attention in order to avoid possible toxicity, and
that deliberate administration planning and careful follow-up are required in
late elderly patients with comprised organ dysfunction.
PMID- 25590090
TI - Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in
mice.
AB - The skeletal renin-angiotensin system (RAS) is involved in the progression of
osteoporosis and the active peptide within the RAS, angiotensin II (ANG II), has
deleterious effects on bones. This study was performed to investigate whether
suppression of the rate-limiting step of the RAS cascade by the renin inhibitor
aliskiren has a benefit on trabecular bone in osteoporotic mice. A postmenopausal
osteoporosis model was induced by bilateral ovariectomy. The ovariectomized (OVX)
mice were treated with a low (5 mg/kg) or high (25 mg/kg) dose of aliskiren for 6
weeks. Micro-computed tomography was performed to detect trabecular bone
parameters of lumbar vertebra and to obtain 3-dimensional (3D) images. Treatment
with aliskiren markedly increased bone volume over total volume (p<0.05),
trabecular bone number (p<0.05), connectivity density (p<0.05), and bone mineral
density (p<0.05) and reduced trabecular bone separation (p<0.05) compared to
vehicle-treated OVX mice. Similarly, the 3D images were consistent with the
quantitative data that showed aliskiren could markedly reverse the ovariectomy
induced pathological changes of trabecular bone. Thus, this study indicated that
the treatment of estrogen-deficient mice with aliskiren could markedly increase
bone mass and improve trabecular bone structure, suggesting its potential
application in treating postmenopausal osteoporosis.
PMID- 25590091
TI - [Does prolonged ceftaroline therapy frequently cause neutropenia?].
PMID- 25590092
TI - Preface. Insoluble proteins.
PMID- 25590102
TI - Proceedings of the 7th Copenhagen Workshop on Endocrine Disrupters, 28-31 May,
2013,Copenhagen, Denmark.
PMID- 25590096
TI - State trends in the cost of employer health insurance coverage, 2003-2013.
AB - From 2010 to 2013--the years following the implementation of the Affordable Care
Act--there has been a marked slowdown in premium growth in 31 states and the
District of Columbia. Yet, the costs employees and their families pay out-of
pocket for deductibles and their share of premiums continued to rise, consuming a
greater share of incomes across the country. In all but a handful of states,
average deductibles more than doubled over the past decade for employees working
in large and small firms. Workers are paying more but getting less protective
benefits. Costs are particularly high, compared with median income, in Southern
and South Central states, where incomes are below the national average. Based on
recent forecasts that predict an uptick in private insurance growth rates
starting in 2015, securing slow cost growth for workers, families, and employers
will likely require action to address rising costs of medical care services.
PMID- 25590103
TI - Homage to Professor Jean-Michel Thomine.
PMID- 25590104
TI - Jean-Michel Thomine has left us.
PMID- 25590128
TI - Perfluoroalkyl acids and their precursors in Swedish food: The relative
importance of direct and indirect dietary exposure.
AB - We analyzed food market basket samples obtained in Sweden from 1999, 2005, and
2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds.
Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year
pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate
diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2)
were detected in the year pools with the highest ?diPAP concentrations in 1999
and 2005. All precursors were predominantly found in meat, fish, and/or eggs
based on analysis of individual food groups from 1999. Based on year pools, PFOS
precursors contributed between 4 and 1% as an indirect source to total dietary
PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure
originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and
perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total
exposure. The lowest precursor contributions were generally seen in food samples
from 2010.
PMID- 25590129
TI - Chemical composition of vegetation along urbanisation gradients in two European
cities.
AB - Accumulation of particulate matter (PM) and metals on leaves of three deciduous
woody species was studied along urbanisation gradients in Stavanger and Warsaw.
Differences between rural and urban sites explained most of the observed
variation in leaf chemistry, followed by differences between regions. Highest
leaf accumulation of elements was found in Warsaw, but also composition of
elements differed between the cities. Overall, species showed similar patterns of
element accumulation, but differed in accumulation of specific elements. These
differences could in part be explained by differences in epicuticular waxes and
PM accumulation. Expected source of elements and their chemical characteristics
did not explain the observed accumulation patterns. A better differentiation
between elements taken up from soil and air would be required for his. Species
specific accumulation of elements has to be taken into consideration using leaf
samples for biomonitoring.
PMID- 25590130
TI - Human exposure to mercury in a compact fluorescent lamp manufacturing area: By
food (rice and fish) consumption and occupational exposure.
AB - To investigate human Hg exposure by food consumption and occupation exposure in a
compact fluorescent lamp (CFL) manufacturing area, human hair and rice samples
were collected from Gaohong town, Zhejiang Province, China. The mean values of
total mercury (THg) and methylmercury (MeHg) concentrations in local cultivated
rice samples were significantly higher than in commercial rice samples which
indicated that CFL manufacturing activities resulted in Hg accumulation in local
rice samples. For all of the study participants, significantly higher THg
concentrations in human hair were observed in CFL workers compared with other
residents. In comparison, MeHg concentrations in human hair of residents whose
diet consisted of local cultivated rice were significantly higher than those who
consumed commercial rice. These results demonstrated that CFL manufacturing
activities resulted in THg accumulation in the hair of CFL workers. However, MeHg
in hair were mainly affected by the sources of rice of the residents.
PMID- 25590131
TI - Promiscuous RNA binding ensures effective encapsidation of APOBEC3 proteins by
HIV-1.
AB - The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)
proteins are cell-encoded cytidine deaminases, some of which, such as APOBEC3G
(A3G) and APOBEC3F (A3F), act as potent human immunodeficiency virus type-1 (HIV
1) restriction factors. These proteins require packaging into HIV-1 particles to
exert their antiviral activities, but the molecular mechanism by which this
occurs is incompletely understood. The nucleocapsid (NC) region of HIV-1 Gag is
required for efficient incorporation of A3G and A3F, and the interaction between
A3G and NC has previously been shown to be RNA-dependent. Here, we address this
issue in detail by first determining which RNAs are able to bind to A3G and A3F
in HV-1 infected cells, as well as in cell-free virions, using the unbiased
individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP)
method. We show that A3G and A3F bind many different types of RNA, including HIV
1 RNA, cellular mRNAs and small non-coding RNAs such as the Y or 7SL RNAs.
Interestingly, A3G/F incorporation is unaffected when the levels of packaged HIV
1 genomic RNA (gRNA) and 7SL RNA are reduced, implying that these RNAs are not
essential for efficient A3G/F packaging. Confirming earlier work, HIV-1 particles
formed with Gag lacking the NC domain (Gag DeltaNC) fail to encapsidate A3G/F.
Here, we exploit this system by demonstrating that the addition of an assortment
of heterologous RNA-binding proteins and domains to Gag DeltaNC efficiently
restored A3G/F packaging, indicating that A3G and A3F have the ability to engage
multiple RNAs to ensure viral encapsidation. We propose that the rather
indiscriminate RNA binding characteristics of A3G and A3F promote functionality
by enabling recruitment into a wide range of retroviral particles whose packaged
RNA genomes comprise divergent sequences.
PMID- 25590133
TI - Overexpression of tau downregulated the mRNA levels of Kv channels and improved
proliferation in N2A cells.
AB - Microtubule binding protein tau has a crucial function in promoting the assembly
and stabilization of microtubule. Besides tuning the action potentials, voltage
gated K+ channels (Kv) are important for cell proliferation and appear to play a
role in the development of cancer. However, little is known about the possible
interaction of tau with Kv channels in various tissues. In the present study, tau
plasmids were transiently transfected into mouse neuroblastoma N2A cells to
explore the possible linkages between tau and Kv channels. This treatment led to
a downregulation of mRNA levels of several Kv channels, including Kv2.1, Kv3.1,
Kv4.1, Kv9.2, and KCNH4, but no significant alteration was observed for Kv5.1 and
KCNQ4. Furthermore, the macroscopic currents through Kv channels were reduced by
36.5% at +60 mV in tau-transfected N2A cells. The proliferation rates of N2A
cells were also improved by the induction of tau expression and the incubation of
TEA (tetraethylammonium) for 48 h by 120.9% and 149.3%, respectively. Following
the cotransfection with tau in HEK293 cells, the mRNA levels and corresponding
currents of Kv2.1 were significantly declined compared with single Kv2.1
transfection. Our data indicated that overexpression of tau declined the mRNA
levels of Kv channels and related currents. The effects of tau overexpression on
Kv channels provided an alternative explanation for low sensitivity to anti
cancer chemicals in some specific cancer tissues.
PMID- 25590132
TI - Considerations on the current universal vaccination policy against hepatitis A in
Greece after recent outbreaks.
AB - Greece is the only European Union member state that in 2008 included hepatitis A
(HAV) vaccine in the routine national childhood immunization program (NCIP).
Given that the resources allocated to public health have dramatically decreased
since 2008 and that Greece is a low endemicity country for the disease, the
benefit from universal vaccination has been questioned. The aim of this paper is
to summarize the available epidemiological data of the disease for 1982-2013, and
discuss the effects of universal vaccination on disease morbidity. Descriptive
analysis, ARIMA modeling and time series intervention analysis were conducted
using surveillance data of acute HAV. A decreasing trend of HAV notification rate
over the years was identified (p<0.001). However, universal vaccination (~ 80%
vaccine coverage of children) had no significant effect on the annual number of
reported cases (p = 0.261) and has resulted to a progressive increase of the
average age of infection in the general population. The mean age of cases before
the inclusion of the vaccine to NCIP (24.1 years, SD = 1.5) was significantly
lower than the mean age of cases after 2008 (31.7 years, SD = 2.1) (p<0.001). In
the last decade, one third of all reported cases were Roma (a population
accounting for 1.5% of the country's total population) and in 2013 three
outbreaks with 16, 9 and 25 Roma cases respectively, were recorded, indicating
the decreased effectiveness of the current immunization strategy in this group.
Data suggest that universal vaccination may need to be re-considered. Probably a
more cost effective approach would be to implement a program that will include:
a) vaccination of high risk groups, b) universal vaccination of Roma children and
improving conditions at Roma camps, c) education of the population and travel
advice, and d) enhancement of the control measures to increase safety of
shellfish and other foods.
PMID- 25590135
TI - Evaluation of the effect of c.2946+1G>T mutation on splicing in the SCN1A gene.
AB - Mutations in the SCN1A gene have commonly been associated with a wide range of
mild to severe epileptic syndromes. They generate a wide spectrum of phenotypes
ranging from the relatively mild generalized epilepsy with febrile seizures plus
(GEFS+) to other severe epileptic encephalopathies, including myoclonic epilepsy
in infancy (SMEI), cryptogenic focal epilepsy (CFE), cryptogenic generalized
epilepsy (CGE) and a distinctive subgroup termed as severe infantile multifocal
epilepsy (SIMFE). The present study was undertaken to investigate the potential
effects of a transition in the first nucleotide at the donor splice site of
intron 15 of the SCN1A gene leading to CGES. Functional analyses using site
directed mutagenesis by PCR and subsequent ex-vivo splicing assays, revealed that
the c.2946+1G>T mutation lead to a total skipping of exon 15. The exclusion of
this exon did not alter the reading frame but induced the deletion of the amino
acids (853 Leu -971 Val) which are a major part in the fourth, fifth and sixth
transmembrane segments of the SCN1A protein. The theoretical implications of the
splice site mutations predicted with the bioinformatic tool human splice finder
were investigated and compared with the results obtained by the cellular assay.
PMID- 25590134
TI - Dynamic ocular surface and lacrimal gland changes induced in experimental murine
dry eye.
AB - Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjogren's
Syndrome or increased tear film evaporation despite normal lacrimal gland
function. To determine if there is a correlation between severity effects in
these models and underlying pathophysiological responses, we compared the time
dependent changes in each of these parameters that occur during a 6 week period.
Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an
Intelligently Controlled Environmental System (ICES). Sixty mice were housed in
ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal
environment and received subcutaneous injections of scopolamine hydrobromide
(SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal
environment and received no treatment. Corneal fluorescein staining along with
corneal MMP-9 and caspase-3 level measurements were performed in parallel with
the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-alpha, IFN-gamma
and TGF-beta2 levels were estimated by real-time PCR measurements of conjunctival
and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with
flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light
and transmission electron microscopy studies evaluated LGs cytoarchitectural
changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2
weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland
proinflammatory cytokine level increases were much lower than those in the SCOP
group. In accord with the lower proinflammatory cytokine levels, in the ICES
group, lacrimal gland cytosolic vesicular density and size exceeded that in the
SCOP group. ICES and SCOP induced murine dry eye effects became progressively
more severe over a two week period. Subsequently, the disease process stabilized
for the next four weeks. ICES induced local effects in the ocular surface, but
failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which
accounts for less dry eye severity in the ICES model than that in the SCOP model.
PMID- 25590137
TI - Rewriting the mechanism of JAK2 activation.
PMID- 25590136
TI - The Use of a Circular Side Stapling Technique in Laparoscopic Low Anterior
Resection for Rectal Cancer: Experience of 30 Serial Cases.
AB - The double-stapling technique using a circular stapler (CS) to create an end-to
end anastomosis is currently used widely in laparoscopic-assisted rectal surgery.
However, a high rate of anastomotic failure has been reported. We report new side
to-side anastomosis creation using a CS, the so-called circular side stapling
technique (CST). After excising the rectum at the oral and anal sides of the
tumor with a linear stapler, a side-to-side colorectal anastomosis was made on
the anterior wall of the rectosigmoid colon and the anterior or posterior wall of
the rectum with a CS. Between 2012 and 2013, we recorded 30 serial cases of
rectal-sigmoid or rectal cancer that were treated with laparoscopic-assisted
surgeries using this method. In the 30 cases, the mean age was 68 +/- 12 years,
operating time was 288 +/- 80 minutes, and blood loss was 66 +/- 67 mL. None of
the patients suffered from anastomosis leakage or postoperative anastomotic
bleeding, and none complained of their stool habits. Three months after the last
surgery in this cohort, no anastomosis strictures were reported. Based on these
results, we propose an alternative method of side-to-side anastomosis for low
anterior resection by using a CS to prevent staple overlap. Our experience
indicates that the CST is easy and safe. Therefore, this method is a useful
alternative to the current method used in laparoscopic surgery.
PMID- 25590138
TI - Synthesis and properties of SmO0.5F0.5BiS2 and enhancement in Tc in La1
ySmyO0.5F0.5BiS2.
AB - The crystal structure and properties of a new member of the oxybismuth sulfide
family SmO(0.5)F(0.5)BiS(2) are reported here. The compounds SmO(1-x)F(x)BiS(2)
(x = 0.0 and 0.5) are isostructural with LaOBiS(2) and crystallize in the
CeOBiS(2)-type structure (P4/nmm). Sm substitution in LaO(0.5)F(0.5)BiS(2) (La1
ySmyO(0.5)F(0.5)BiS(2)) leads to a gradual decrease in the a-lattice constant;
however, the c-lattice constant does not show such a gradual trend. Enhancement
in T(c) is achieved upon partial substitution of La by the smaller Sm ion. A
maximum T(c) ~ 4.6 K was observed for composition with y = 0.8. Disobeying this
trend, Tc disappears unexpectedly in the composition SmO(0.5)F(0.5)BiS(2) (y =
1.0). Both the undoped and F-doped (x = 0.0 and 0.5) compounds are paramagnetic,
exhibiting semiconducting behavior down to 2 K.
PMID- 25590139
TI - The association between breast tissue optical content and mammographic density in
pre- and post-menopausal women.
AB - Mammographic density (MD), associated with higher water and lower fat content in
the breast, is strongly related to breast cancer risk. Optical attenuation
spectroscopy (OS) is a non-imaging method of evaluating breast tissue composition
by red and near-infrared light transmitted through the breast that, unlike
mammography, does not involve radiation. OS provides information on wavelength
dependent light scattering of tissue and on absorption by water, lipid, oxy-,
deoxy-hemoglobin. We propose that OS could be an alternative marker of breast
cancer risk and that OS breast tissue measures will be associated with MD. In the
present analysis, we developed an algorithm to estimate breast tissue composition
and light scattering parameters using a spectrally constrained global fitting
procedure employing a diffuse light transport model. OS measurements were
obtained from 202 pre- and post-menopausal women with normal mammograms. Percent
density (PD) and dense area (DA) were measured using Cumulus. The association
between OS tissue composition and PD and DA was analyzed using linear regression
adjusted for body mass index. Among pre-menopausal women, lipid content was
significantly inversely associated with square root transformed PD (beta = -0.05,
p = 0.0002) and DA (beta = -0.05, p = 0.019); water content was significantly
positively associated with PD (beta = 0.06, p = 0.008). Tissue oxygen saturation
was marginally inversely associated with PD (beta = -0.03, p = 0.057) but
significantly inversely associated with DA (beta = -0.10, p = 0.002). Among post
menopausal women lipid and water content were significantly associated
(negatively and positively, respectively) with PD (beta lipid = -0.08, beta water
= 0.14, both p<0.0001) and DA (beta lipid = -0.10, p<0.0001; beta water = 0.11, p
= 0.001). The association between OS breast content and PD and DA is consistent
with more proliferation in dense tissue of younger women, greater lipid content
in low density tissue and higher water content in high density tissue. OS may be
useful for assessing physiologic tissue differences related to breast cancer
risk, particularly when mammography is not feasible or easily accessible.
PMID- 25590140
TI - alpha-Actinin-3: why gene loss is an evolutionary gain.
PMID- 25590143
TI - Triggers and signaling cross-talk controlling cell death commitment.
PMID- 25590144
TI - Flexible graphene based microwave attenuators.
AB - We demonstrate flexible 3 dB and 6 dB microwave attenuators using multilayer
graphene grown by the chemical vapor deposition method. On the basis of the
characterized results of multilayer graphene and graphene-Au ohmic contacts, the
graphene attenuators are designed and measured. The flexible graphene-based
attenuators have 3 dB and 6 dB attenuation with a return loss of less than -15 dB
at higher than 5 GHz. The devices have shown durability in a bending cycling test
of 100 times. The circuit model of the attenuator based on the characterized
results matches the experimental results well.
PMID- 25590142
TI - Associations between schistosomiasis and the use of human waste as an
agricultural fertilizer in China.
AB - BACKGROUND: Human waste is used as an agricultural fertilizer in China and
elsewhere. Because the eggs of many helminth species can survive in environmental
media, reuse of untreated or partially treated human waste, commonly called night
soil, may promote transmission of human helminthiases. METHODOLOGY/PRINCIPAL
FINDINGS: We conducted an open cohort study in 36 villages to evaluate the
association between night soil use and schistosomiasis in a region of China where
schistosomiasis has reemerged and persisted despite control activities. We tested
2,005 residents for Schistosoma japonicum infection in 2007 and 1,365 residents
in 2010 and interviewed heads of household about agricultural practices each
study year. We used an intervention attributable ratio framework to estimate the
association between night soil use and S. japonicum infection. Night soil use was
reported by half of households (56% in 2007 and 46% in 2010). Village night soil
use was strongly associated with human S. japonicum infection in 2007. We
estimate cessation of night soil use would lead to a 49% reduction in infection
prevalence in 2007 (95% CI: 12%, 71%). However, no association between night soil
and schistosomiasis was observed in 2010. These inconsistent findings may be due
to unmeasured confounding or temporal shifts in the importance of different
sources of S. japonicum eggs on the margins of disease elimination.
CONCLUSIONS/SIGNIFICANCE: The use of untreated or partially treated human waste
as an agricultural fertilizer may be a barrier to permanent reductions in human
helminthiases. This practice warrants further attention by the public health
community.
PMID- 25590141
TI - Inference of quantitative models of bacterial promoters from time-series reporter
gene data.
AB - The inference of regulatory interactions and quantitative models of gene
regulation from time-series transcriptomics data has been extensively studied and
applied to a range of problems in drug discovery, cancer research, and
biotechnology. The application of existing methods is commonly based on implicit
assumptions on the biological processes under study. First, the measurements of
mRNA abundance obtained in transcriptomics experiments are taken to be
representative of protein concentrations. Second, the observed changes in gene
expression are assumed to be solely due to transcription factors and other
specific regulators, while changes in the activity of the gene expression
machinery and other global physiological effects are neglected. While convenient
in practice, these assumptions are often not valid and bias the reverse
engineering process. Here we systematically investigate, using a combination of
models and experiments, the importance of this bias and possible corrections. We
measure in real time and in vivo the activity of genes involved in the FliA-FlgM
module of the E. coli motility network. From these data, we estimate protein
concentrations and global physiological effects by means of kinetic models of
gene expression. Our results indicate that correcting for the bias of commonly
made assumptions improves the quality of the models inferred from the data.
Moreover, we show by simulation that these improvements are expected to be even
stronger for systems in which protein concentrations have longer half-lives and
the activity of the gene expression machinery varies more strongly across
conditions than in the FliA-FlgM module. The approach proposed in this study is
broadly applicable when using time-series transcriptome data to learn about the
structure and dynamics of regulatory networks. In the case of the FliA-FlgM
module, our results demonstrate the importance of global physiological effects
and the active regulation of FliA and FlgM half-lives for the dynamics of FliA
dependent promoters.
PMID- 25590145
TI - Detection of pathogenic Escherichia coli in samples collected at an abattoir in
Zaria, Nigeria and at different points in the surrounding environment.
AB - Pathogenic Escherichia coli can be released with the wastes coming from
slaughterhouses into the environment, where they can persist. We investigated the
presence of diarrheagenic E. coli in specimens taken at an abattoir located in
the Zaria region, Nigeria, in samples of water from the river Koreye, where the
effluent from the abattoir spills in, and vegetable specimens taken at a nearby
farm. All the isolated E. coli were assayed for the production of Shiga toxins
(Stx) by using the Ridascreen verotoxin Immunoassay and by PCR amplification of
genes associated with the diarrheagenic E. coli. Three strains from the rectal
content of two slaughtered animals and a cabbage were positive for the presence
of the Stx-coding genes. Additionally we have isolated one Enteroaggregative E.
coli (EAggEC) from the abattoir effluent and two Subtilase-producing E. coli from
the slaughterhouse's effluent and a sample of carrots. Our results provide
evidence that pathogenic E. coli can contaminate the environment as a result of
the discharge into the environment of untreated abattoir effluent, representing a
reservoir for STEC and other diarrheagenic E. coli favouring their spread to
crops.
PMID- 25590146
TI - Reducing environmental tobacco smoke exposure of preschool children: a randomized
controlled trial of class-based health education and smoking cessation counseling
for caregivers.
AB - OBJECTIVES: To assess counseling to caregivers and classroom health education
interventions to reduce environmental tobacco smoke exposure of children aged 5-6
years in China. METHODS: In a randomized controlled trial in two preschools in
Changsha, China, 65 children aged 5-6 years old and their smoker caregivers (65)
were randomly assigned to intervention (n = 33) and control (no intervention)
groups (n = 32). In the intervention group, caregivers received self-help
materials and smoking cessation counseling from a trained counselor, while their
children were given classroom-based participatory health education. Children's
urinary cotinine level and the point prevalence of caregiver quitting were
measured at baseline and after 6 months. RESULTS: At the 6-month follow-up,
children's urinary cotinine was significantly lower (Z = -3.136; p = 0.002) and
caregivers' 7-day quit rate was significantly higher (34.4% versus 0%) (p <
0.001; adjusted OR = 1.13; 95% CI: 1.02-1.26) in the intervention than control
group. CONCLUSIONS: Helping caregivers quitting smoke combined with classroom
based health education was effective in reducing children's environmental tobacco
smoke exposure. Larger-scale trials are warranted.
PMID- 25590147
TI - Substance use, mental disorders and physical health of Caribbeans at-home
compared to those residing in the United States.
AB - This study compares the health conditions of domestic Caribbeans with those
living in the United States to explore how national context and migration
experiences might influence substance use (i.e., alcohol or drug) and other
mental and physical health conditions. The study is based upon probability
samples of non-institutionalized Caribbeans living in the United States (1621),
Jamaica (1216) and Guyana (2068) 18 years of age and over. Employing descriptive
statistics and multivariate analytic procedures, the results revealed that
substance use and other physical health conditions and major depressive disorder
and mania vary by national context, with higher rates among Caribbeans living in
the United States. Context and generation status influenced health outcomes.
Among first generation black Caribbeans, residing in the United States for a
longer length of time is linked to poorer health outcomes. There were different
socio-demographic correlates of health among at-home and abroad Caribbeans. The
results of this study support the need for additional research to explain how
national context, migratory experiences and generation status contribute to
understanding substance use and mental disorders and physical health outcomes
among Caribbean first generation and descendants within the United States,
compared to those remaining in the Caribbean region.
PMID- 25590148
TI - The effect of PM10 on allergy symptoms in allergic rhinitis patients during
spring season.
AB - BACKGROUND: Asian sand dust (ASD) that originates in the Mongolian Desert in the
spring induces serious respiratory health problems throughout East Asia (China,
Korea, Japan). PM10 (particulate matter with an aerodynamic diameter <10 MUm) is
a major air pollutant component in ASD. We studied the effects of PM10 on allergy
symptoms in patients with allergic rhinitis during the spring season, when ASD
frequently develops. METHODS: We investigated the changes in allergic symptoms in
108 allergic patients and 47 healthy subjects by comparing their 120-day symptom
scores from February to May 2012. At the same time, the contributions of pollen
count and PM10 concentration were also assessed. We also compared symptom scores
before and 2 days after the daily PM10 concentration was >100 MUg/m3. RESULTS:
The PM10 concentration during the 120 days was <150 MUg/m3. No significant
correlations were observed between changes in the PM10 concentration and allergic
symptom scores (p > 0.05). However, allergic symptoms were significantly
correlated with outdoor activity time (p < 0.001). CONCLUSIONS: These results
demonstrate that a PM10 concentration <150 MUg/m3 did not influence allergy
symptoms in patients with allergic rhinitis during the 2012 ASD season.
PMID- 25590150
TI - Metabolic dysregulation. Driving the obese asthma phenotype in adolescents?
PMID- 25590149
TI - Integrative proteomics and targeted transcriptomics analyses in cardiac
endothelial cells unravel mechanisms of long-term radiation-induced vascular
dysfunction.
AB - Epidemiological data from radiotherapy patients show the damaging effect of
ionizing radiation on heart and vasculature. The endothelium is the main target
of radiation damage and contributes essentially to the development of cardiac
injury. However, the molecular mechanisms behind the radiation-induced
endothelial dysfunction are not fully understood. In the present study, 10-week
old C57Bl/6 mice received local X-ray heart doses of 8 or 16 Gy and were
sacrificed after 16 weeks; the controls were sham-irradiated. The cardiac
microvascular endothelial cells were isolated from the heart tissue using
streptavidin-CD31-coated microbeads. The cells were lysed and proteins were
labeled with duplex isotope-coded protein label methodology for quantification.
All samples were analyzed by LC-ESI-MS/MS and Proteome Discoverer software. The
proteomics data were further studied by bioinformatics tools and validated by
targeted transcriptomics, immunoblotting, immunohistochemistry, and serum
profiling. Radiation-induced endothelial dysfunction was characterized by
impaired energy metabolism and perturbation of the insulin/IGF-PI3K-Akt signaling
pathway. The data also strongly suggested premature endothelial senescence,
increased oxidative stress, decreased NO availability, and enhanced inflammation
as main causes of radiation-induced long-term vascular dysfunction. Detailed data
on molecular mechanisms of radiation-induced vascular injury as compiled here are
essential in developing radiotherapy strategies that minimize cardiovascular
complications.
PMID- 25590151
TI - Clearing the air. Smoking and incident asthma in adults.
PMID- 25590152
TI - Lung-protective ventilation in acute respiratory distress syndrome. How soon is
now?
PMID- 25590153
TI - Toward improved diagnosis of early asthma.
PMID- 25590154
TI - Novel approaches are needed to develop tomorrow's antibacterial therapies.
AB - Society faces a crisis of rising antibiotic resistance even as the pipeline of
new antibiotics has been drying up. Antibiotics are a public trust; every
individual's use of antibiotics affects their efficacy for everyone else. As
such, responses to the antibiotic crisis must take a societal perspective. The
market failure of antibiotics is due to a combination of scientific challenges to
discovering and developing new antibiotics, unfavorable economics, and a hostile
regulatory environment. Scientific solutions include changing the way we screen
for new antibiotics. More transformationally, developing new treatments that seek
to disarm pathogens without killing them, or that modulate the host inflammatory
response to infection, will reduce selective pressure and hence minimize
resistance emergence. Economic transformation will require new business models to
support antibiotic development. Finally, regulatory reform is needed so that
clinical development programs are feasible, rigorous, and clinically relevant.
Pulmonary and critical care specialists can have tremendous impact on the
continued availability of effective antibiotics. Encouraging use of molecular
diagnostic tests to allow pathogen-targeted, narrow-spectrum antibiotic therapy,
using short rather than unnecessarily long course therapy, reducing inappropriate
antibiotic use for probable viral infections, and reducing infection rates will
help preserve the antibiotics we have for future generations.
PMID- 25590155
TI - An official American Thoracic Society policy statement: managing conscientious
objections in intensive care medicine.
AB - RATIONALE: Intensive care unit (ICU) clinicians sometimes have a conscientious
objection (CO) to providing or disclosing information about a legal,
professionally accepted, and otherwise available medical service. There is little
guidance about how to manage COs in ICUs. OBJECTIVES: To provide clinicians,
hospital administrators, and policymakers with recommendations for managing COs
in the critical care setting. METHODS: This policy statement was developed by a
multidisciplinary expert committee using an iterative process with a diverse
working group representing adult medicine, pediatrics, nursing, patient advocacy,
bioethics, philosophy, and law. MAIN RESULTS: The policy recommendations are
based on the dual goals of protecting patients' access to medical services and
protecting the moral integrity of clinicians. Conceptually, accommodating COs
should be considered a "shield" to protect individual clinicians' moral integrity
rather than as a "sword" to impose clinicians' judgments on patients. The
committee recommends that: (1) COs in ICUs be managed through institutional
mechanisms, (2) institutions accommodate COs, provided doing so will not impede a
patient's or surrogate's timely access to medical services or information or
create excessive hardships for other clinicians or the institution, (3) a
clinician's CO to providing potentially inappropriate or futile medical services
should not be considered sufficient justification to forgo the treatment against
the objections of the patient or surrogate, and (4) institutions promote open
moral dialogue and foster a culture that respects diverse values in the critical
care setting. CONCLUSIONS: This American Thoracic Society statement provides
guidance for clinicians, hospital administrators, and policymakers to address
clinicians' COs in the critical care setting.
PMID- 25590156
TI - Severe adult respiratory distress syndrome from Goodpasture syndrome. Survival
using extracorporeal membrane oxygenation.
PMID- 25590157
TI - A solemn declaration from the World Alliance against Antibiotic Resistance.
PMID- 25590158
TI - Development of a hypercoagulable status in patients undergoing off-pump lung
transplantation despite prolonged conventional coagulation tests.
PMID- 25590160
TI - IL-33-dependent Th2 response after rhinovirus infection in asthma: more
information needed.
PMID- 25590159
TI - Measurement of serum calprotectin in stable patients predicts exacerbation and
lung function decline in cystic fibrosis.
PMID- 25590161
TI - IL-33-dependent type 2 inflammation in asthma exacerbations.
PMID- 25590162
TI - Reply: IL-33-dependent type 2 inflammation in asthma exacerbations.
PMID- 25590163
TI - American Thoracic Society patient information series. Other therapies for sleep
apnea.
AB - Treatment is needed for obstructive sleep apnea (OSA) because untreated OSA can
result in serious health problems. Continuous positive airway pressure (CPAP)
therapy is the most common treatment used for obstructive sleep apnea (OSA). (see
ATS Patient Series http://patients.thoracic.org/wp-content/uploads/
2014/03/obstructive-sleep-apnea.pdf) For those who cannot use CPAP or want to try
another option, there are other therapies that can work for people with OSA.
PMID- 25590168
TI - Correction to "assessing the dual activity of a chalcone-phthalocyanine
conjugate: design, synthesis, and antivascular and photodynamic properties".
PMID- 25590169
TI - Innovative use of membrane contactor as condenser for heat recovery in carbon
capture.
AB - The gas-liquid membrane contactor generally used as a nonselective gas absorption
enhancement device is innovatively proposed as a condenser for heat recovery in
liquid-absorbent-based carbon capture. The membrane condenser is used as a heat
exchanger to recover the latent heat of the exiting vapor from the desorber, and
it can help achieve significant energy savings when proper membranes with high
heat-transfer coefficients are used. Theoretical thermodynamic analysis of mass
and heat transfer in the membrane condensation system shows that heat recovery
increases dramatically as inlet gas temperature rises and outlet gas temperature
falls. The optimal split mass flow rate is determined by the inlet gas
temperature and the overall heat-transfer coefficient in the condensation system.
The required membrane area is also strongly dependent on the overall heat
transfer coefficient, particularly at higher inlet gas temperatures. Mass
transfer across the membrane has an insignificant effect on heat transfer and
heat recovery, suggesting that membrane wetting may not be an issue when a
membrane condenser is used for heat recovery. Our analysis provides important
insights into the energy recovery performance of the membrane condensation system
as well as selection of operational parameters, such as split mass flow rate and
membrane area, thickness, and thermal conductivity.
PMID- 25590170
TI - Elaboration, validation and standardization of the five to fifteen (FTF)
questionnaire in a Danish population sample.
AB - The five to fifteen (FTF) is a parent questionnaire developed to assess ADHD, its
common comorbid conditions and associated problems in children and adolescents.
The present study examined (1) the psychometric properties of scores on the new
teacher version of the FTF, (2) competing models of the FTF subdomain structure
and (3) the psychometric properties and utility of scores on the newly developed
FTF impact questions. Parents (n=4258) and teachers (n=1298) of Danish children
and adolescents (ages 5 to 17 years), selected using simple random sampling,
completed the FTF. In the largest study of the FTF to date, parent and teacher
scores had acceptable psychometric properties. The FTF subdomains were organized
into six domains labelled cognitive skills, motor/perception,
emotion/socialization/behaviour, attention, literacy skills and activity control
and analysis of these domains may provide additional information when applying
the FTF in the future. The impact questions yielded information above and beyond
that provided by symptom count alone and appeared to increase the ability of the
FTF to identify at risk children and adolescents.
PMID- 25590164
TI - mTOR coordinates protein synthesis, mitochondrial activity and proliferation.
AB - Protein synthesis is one of the most energy consuming processes in the cell. The
mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine kinase
that integrates a multitude of extracellular signals and intracellular cues to
drive growth and proliferation. mTOR activity is altered in numerous pathological
conditions, including metabolic syndrome and cancer. In addition to its well
established role in regulating mRNA translation, emerging studies indicate that
mTOR modulates mitochondrial functions. In mammals, mTOR coordinates energy
consumption by the mRNA translation machinery and mitochondrial energy production
by stimulating synthesis of nucleus-encoded mitochondria-related proteins
including TFAM, mitochondrial ribosomal proteins and components of complexes I
and V. In this review, we highlight findings that link mTOR, mRNA translation and
mitochondrial functions.
PMID- 25590171
TI - Oculomotor performance in children with high-functioning Autism Spectrum
Disorders.
AB - Sensorimotor issues are of increasing focus in the assessment and treatment of
Autism Spectrum Disorders (ASD). The oculomotor system is a sensorimotor network
that can provide insights into functional neurobiology and has well-established
methodologies for investigation. In this study, we assessed oculomotor
performance among children with high functioning ASD and typically developing
children, ages 6-12 years. Children with ASD exhibited greater horizontal saccade
latency and greater phase lag during vertical smooth pursuit. Saccades and smooth
pursuit are mediated by spatially distant brain regions and the long-fiber tracts
connecting them, many of which are implicated in ASD. Training paradigms for
oculomotor deficits have shown positive outcomes in other clinical populations,
and deficits described here may provide useful targets for interventions.
PMID- 25590172
TI - Postural control during standing reach in children with Down syndrome.
AB - The purpose of the present study was to investigate the dynamic postural control
of children with Down syndrome (DS). Specifically, we compared postural control
and goal-directed reaching performance between children with DS and typically
developing children during standing reach. Standing reach performance was
analyzed in three main phases using the kinematic and kinetic data collected from
a force plate and a motion capture system. Fourteen children with DS, age and
gender matched with fourteen typically developing children, were recruited for
this study. The results showed that the demand of the standing reach task
affected both dynamic postural control and reaching performance in children with
DS, especially in the condition of beyond arm's length reaching. More postural
adjustment strategies were recruited when reaching distance was beyond arm's
length. Children with DS tended to use inefficient and conservative strategies
for postural stability and reaching. That is, children with DS perform standing
reach with increased reaction and execution time and decreased amplitudes of
center of pressure displacements. Standing reach resembled functional balance
that is required in daily activities. It is suggested to be considered as a part
of strength and balance training program with graded task difficulty.
PMID- 25590173
TI - Variations in cognitive demand affect heart rate in typically developing children
and children at risk for developmental coordination disorder.
AB - BACKGROUND: Developmental coordination disorder (DCD) is a diagnosis for children
who present with movement difficulties, but are of normal intelligence without
neurological deficits. Previous studies have demonstrated that children with DCD
exhibit perceptual deficits and lower cognition performance. To date, their
autonomic nervous system (ANS) responses during tasks requiring cognitive and
perceptual effort have not been compared to typically developing children (TDC).
OBJECTIVE: The present study investigated heart rate variability (HRV) as a
marker for ANS response differences between DCD and TDC, and the impact of
different levels of task difficulty. METHODS: Participants were 60 individuals (9
10 years); 30 children at risk for DCD, and 30 TDC. Each participant performed
two tasks each of which demanded enhanced cognitive effort: a visual signal
detection task and a digit memory task-each task had two levels of difficulty,
low (LD) and high (HD). Heart rate responses were continuously recorded during
performance of each task. Frequency domain analysis and heart rate sample entropy
(SampEn) were computed to determine ANS responses in each of the tasks. RESULTS:
HRV differences were detected between the two levels of task difficulty, LD and
HD, for the visual signal detection task, but not for the digit memory task. HRV
differences between LD and HD conditions were greater for TDC children than DCD
when engaged in visual signal detection task, compare to the memory task.
INTERPRETATION: The results suggest that children at risk for DCD may show
decreased HRV as a marker for altered ANS responses and potential deficits in the
linkage between their perceptions and actions.
PMID- 25590174
TI - Initial evaluation of a new plastic pancreatic duct stent for endoscopic
ultrasonography-guided placement.
AB - There are currently no plastic pancreatic duct stents that have been designed for
endoscopic ultrasonography (EUS)-guided placement. This study prospectively
evaluated the feasibility and efficacy of a new, single-pigtail, plastic stent.
Eight patients with main pancreatic duct stricture or stenotic
pancreatojejunostomy underwent EUS-guided placement of the pancreatic duct stent.
The stent was placed successfully in all cases (8/8). Treatment success was
achieved in all cases (8/8). A mild adverse event associated with the procedure
was observed in one patient but there were no other adverse events during a mean
follow-up of 7.4 months. This new pancreatic duct stent appears to be feasible
and effective for EUS-guided stenting.
PMID- 25590175
TI - A two-step multidisciplinary approach to treat recurrent esophageal strictures in
children with epidermolysis bullosa dystrophica.
AB - In children with severe generalized recessive dystrophic epidermolysis bullosa
(RDEB), esophageal scarring leads to esophageal strictures with dysphagia,
followed by malnutrition and delayed development. We describe a two-step
multidisciplinary therapeutic approach to overcome malnutrition and growth
retardation. In Step 1, under general anesthesia, orthograde balloon dilation of
the esophagus is followed by gastrostomy creation using a direct puncture
technique. In Step 2, further esophageal strictures are treated by retrograde
dilation via the established gastrostomy; this step requires only a short
sedation period. A total of 12 patients (median age 7.8 years, range 6 weeks to
17 years) underwent successful orthograde balloon dilation of esophageal
strictures combined with direct puncture gastrostomy. After 12 and 24 months in
11 children, a substantial improvement of growth and nutrition was achieved (body
mass index [BMI] standard deviation score [SDS] + 0.59 and + 0.61, respectively).
In one child, gastrostomy was removed because of skin ulcerations after 10 days.
Recurrent esophageal strictures were treated successfully in five children. The
combined approach of balloon dilation and gastrostomy is technically safe in
children with RDEB, and helps to promote catch-up growth and body weight. In
addition, recurrent esophageal strictures can be treated successfully without
general anesthesia in a retrograde manner via the established gastrostomy.
PMID- 25590176
TI - EUS-guided sutured gastropexy for transgastric ERCP (ESTER) in patients with Roux
en-Y gastric bypass: a novel, single-session, minimally invasive approach.
AB - BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP)
in patients with Roux-en-Y gastric bypass (RYGB) is a challenging procedure.
Available techniques are hampered by limited success, need for a separate delayed
session for ERCP, potential complications,and/or invasiveness. This paper reports
on a novel technique that involves endoscopic ultrasound(EUS)-guided access into
the remnant stomach and sutured gastropexy for transgastric ERCP in a single
combined session. PATIENTS AND METHODS: A total of 10 patients with RYGB
underwent transgastric ERCP using the novel technique. EUS was used to puncture
the excluded stomach through the gastric pouch or jejunum,the stomach was
insufflated, and a direct percutaneous gastrostomy puncture followed by sutured
gastropexy was performed. ERCP was performed by passing a duodenoscope through
the gastrostomy. RESULTS: Technical success of EUS-assisted sutured gastropexy
was achieved in nine patients (90 %),with immediate, same-session ERCP in all
nine.There were no adverse events. CONCLUSIONS: EUS-assisted, fluoroscopically
guided sutured gastropexy is a safe and effective method to obtain access into
the excluded gastric remnant for same-session transgastric ERCP inpatients with
Roux-en-Y gastric bypass anatomy.
PMID- 25590177
TI - Magnetic-controlled capsule endoscopy vs. gastroscopy for gastric diseases: a two
center self-controlled comparative trial.
AB - BACKGROUND AND STUDY AIMS: We developed a novel magnetic-controlled capsule
endoscopy (MCE) system for use in the human stomach. The aim of the current study
was to compare the diagnostic accuracy of MCE with that of standard gastroscopy
for gastric diseases. PATIENTS AND METHODS: A total of 68 patients were enrolled
in this self-controlled trial. Patients were evaluated by both MCE and
gastroscopy. Gastroscopy was performed 4 - 24 hours after completion of the MCE
examination. RESULTS: The positive percent agreement between MCE and gastroscopy
was 96.0 %, and the negative percent agreement was 77.8 %. The overall agreement
was 91.2 % with a kappa value of 0.765 (P < 0.001). A total of 68 pathological
findings were detected, of which 53 were identified by both methods. The MCE and
standard gastroscopy missed seven and eight findings, respectively. CONCLUSIONS:
MCE showed a diagnostic accuracy similar to that of standard gastroscopy. These
results suggest that MCE is a promising alternative to gastroscopy for
noninvasive screening of gastric diseases.Clinical trial registration number:
NCT01903629.
PMID- 25590178
TI - Prophylactic somatostatin can reduce incidence of post-ERCP pancreatitis:
multicenter randomized controlled trial.
AB - BACKGROUND AND STUDY AIM: Post-endoscopic retrograde cholangiopancreatography
(ERCP) pancreatitis (PEP) remains the most common complication of ERCP.
Somatostatin may inhibit pancreatic secretion and has been tested for PEP
prophylaxis. However, the results of previous studies are inconsistent. The aim
of the current study was to investigate whether somatostatin can reduce the
incidence of PEP. PATIENTS AND METHODS: The study was a multicenter, open-label,
randomized controlled trial. A total of 908 patients with normal amylase levels
who were undergoing ERCP were randomized to receive somatostatin 250 MUg bolus
injection before ERCP and 250 MUg/hour intravenous infusion for 11 hours after
ERCP (somatostatin group) or no somatostatin treatments (control group). The
incidences of PEP and hyperamylasemia were compared in the two groups. RESULTS:
The full analysis set included 900 patients (445 in the somatostatin group, 455
in the control group). PEP developed in 34 patients (7.5 %) in the control group
(95 % confidence interval [CI] 5.4 % - 10.3 %) and in 18 patients (4.0 %) in the
somatostatin group (95 %CI 2.6 % - 6.3 %; P = 0.03). Hyperamylasemia occurred in
46 patients (10.1 %) in the control group (95 %CI 7.7 % - 13.2 %) and in 27
patients (6.1 %) in the somatostatin group (95 %CI 4.2 % - 8.7 %; P = 0.03). No
perforation or death occurred during the study. CONCLUSIONS: This study showed
that somatostatin was effective and safe for the prevention of PEP and
hyperamylasemia in ERCP patients.(ClinicalTrials.gov number, NCT01431781).
PMID- 25590179
TI - Self-expandable metallic stents vs. plastic stents for endoscopic biliary
drainage in hepatocellular carcinoma.
AB - BACKGROUND AND STUDY AIMS: The patency of self-expandable metallic stents (SEMS)
is known to be better than plastic stents in the palliation of malignant biliary
obstruction. However, data are scarce for obstructive jaundice caused by
hepatocellular carcinoma (HCC). This study aimed to compare SEMSs and plastic
stents for the palliation of obstructive jaundice in unresectable HCC. PATIENTS
AND METHODS: A total of 96 patients who underwent endoscopic retrograde biliary
drainage with SEMSs or plastic stents were included in this retrospective
analysis. The rate of successful biliary drainage, adverse events, stent patency
duration, and patient survival were compared between the SEMS (n = 36) and
plastic stent (n = 60) groups. RESULTS: The rate of successful biliary drainage
was similar between the SEMS and plastic stent groups (25/36 [69.4 %] vs. 39/60
[65.0 %]; P = 0.655). Adverse events occurred in 6 patients (16.7 %) in the SEMS
group and 13 patients (21.7 %) in the plastic stent group (P = 0.552). The median
patency duration was also similar between the two groups (60 vs. 68 days; P =
0.396). The median patient survival was longer in the plastic stent group than in
the SEMS group (123 vs. 48 days; P = 0.005). CONCLUSIONS: SEMSs were not superior
to plastic stents for the palliation of malignant biliary obstruction in HCC with
regard to successful drainage, stent patency, and adverse events. Patient
survival was better in the plastic stent group. Given the lower cost, plastic
stents could be a favorable option for malignant biliary obstruction caused by
HCC.
PMID- 25590180
TI - Prospective evaluation of ERCP performance: results of a nationwide quality
registry.
AB - BACKGROUND AND STUDY AIMS: Despite significant interest from health care
authorities, patient organizations, and insurance companies, data on procedural
outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in
general and academic practice are sparse. The aims of this study were to assess
procedural outcome of ERCP within a large prospective registry in The
Netherlands, and to evaluate associations between endoscopist-related factors and
procedural outcome. METHODS: All endoscopists performing ERCP in The Netherlands
were invited to register their ERCPs over a 1-year period using the Rotterdam
Assessment Form for ERCP (RAF-E). The primary outcome measure was procedural
success. A priori difficulty level of the procedure was classified according to
Schutz. Baseline characteristics of the endoscopist (e. g. previous experience)
were recorded at study entry. Regression analysis was performed to identify
predictors of procedural outcome. RESULTS: A total of 8575 ERCPs were registered
by 171 endoscopists from 61 centers, constituting about 50 % of all ERCPs
performed nationally during the study period. Overall procedural success was 85.8
%. Intact papillary anatomy was present in 5106 patients (59.5 %): procedural
success in this subgroup of patients was 83.4 % vs. 89.4 % after sphincterotomy
(P < 0.001). Multivariate logistic regression identified "degree of difficulty,"
"intact papillary anatomy," and "previous ERCP failure" to be independently
associated with procedural failure. "Yearly volume of ERCPs" and "trainee
involvement" were independently associated with success. CONCLUSIONS: The
nationwide prospective RAF-E registry proved to be a valuable tool to gain
insight into procedural outcome of ERCPs.
PMID- 25590181
TI - Long-term mortality and recurrence after colorectal cancer surgery with
preoperative stenting: a Danish nationwide cohort study.
AB - BACKGROUND AND STUDY AIMS: Self-expanding metal stents (SEMS) used as a bridge to
surgery for obstructive colorectal cancer (CRC) have fallen under suspicion for
inducing tumor dissemination, and thereby increasing recurrence risk and long
term mortality. The aim of this study was to compare overall mortality and CRC
recurrence in patients receiving preoperative SEMS vs. patients undergoing urgent
resection. PATIENTS AND METHODS: This was a Danish, nationwide, population-based
cohort study (2005 - 2010). For patients with CRC who survived the first 30 days
after resection, the long-term survival in terms of mortality rate ratios was
assessed using Cox regression with adjustment for important covariates. For
patients with Dukes' A - C disease only, recurrence risk was similarly assessed
using incidence rate ratios. RESULTS: The 5-year survival was 49 % among 581
patients with preoperative SEMS and 40 % among 3333 patients undergoing urgent
resection, corresponding to an adjusted mortality rate ratio of 0.98 (95 %
confidence interval [CI] 0.90 to 1.07). For patients with Dukes' stage A - C
disease, the 5-year recurrence risk was 39 % among 286 patients after
preoperative SEMS and 30 % among 1627 patients after urgent resection,
corresponding to an adjusted incidence rate ratio of 1.12 (95 %CI 0.99 to 1.28).
CONCLUSIONS: Long-term mortality associated with the use of SEMS as a bridge to
surgery was comparable to that of urgent resection. SEMS use may be associated
with an increased CRC recurrence risk.
PMID- 25590183
TI - Effects of a hemostatic powder hemospray on coagulation and clot formation.
AB - BACKGROUND AND STUDY AIMS: Hemospray (Cook Medical Inc., Winston-Salem, North
Carolina, USA) is a novel, hemostatic, powder spray that has been developed for
gastrointestinal use. The powder is thought to achieve hemostasis by
concentrating clotting factors and forming a mechanical plug on the injured blood
vessel. However, no detailed studies on the hemostatic mode of action have been
performed. The aim of this study was to examine the effects of Hemospray on
coagulation and clot formation both in vitro and in vivo. MATERIALS AND METHODS:
Recalcification time, thromboelastometry using EXTEM and INTEM assays, and plasma
coagulation tests (activated partial thromboplastin time and prothrombin time)
were carried out on blood samples mixed with Hemospray, and compared with talcum
powder (negative control) and kaolin (positive control) at 1 mg/mL and 10 mg/mL.
Scanning electron microscopy (SEM) and light microscopy were performed on in
vitro thrombi and on gastric thrombi from an animal model of gastrointestinal
hemorrhage treated with Hemospray. RESULTS: The median recalcification time of
whole blood was 187.5 seconds. The addition of 1 mg/mL and 10 mg/mL Hemospray
significantly shortened this time (median 60 and 45 seconds, respectively; P <
0.05). The median clotting time of whole blood, measured using the INTEM assay,
was 160 seconds (interquartile range [IQR] 159 - 176.5) and this was also
significantly reduced by the addition of Hemospray (91 seconds [IQR 84 - 102]; P
= 0.005). The plasma prothrombin time of 11.6 seconds was significantly reduced
by Hemospray (9.5 seconds; P = 0.011). SEM of in vivo clots demonstrated that
Hemospray rapidly interacted with whole blood, forming one confluent mass over
the bleeding site. In sufficient amounts, Hemospray was able to deform and pack
erythrocytes. CONCLUSIONS: Hemospray covered the bleeding site and enhanced clot
formation in vivo, and shortened coagulation time in vitro. Elaboration of these
unique properties in clinical practice will help to optimize future endoscopic
hemostasis with Hemospray.
PMID- 25590182
TI - Randomized multicenter study of multiple plastic stents vs. covered self
expandable metallic stent in the treatment of biliary stricture in chronic
pancreatitis.
AB - BACKGROUND AND STUDY AIMS: The use of covered self-expandable metallic stents
(cSEMS) in benign biliary indications is evolving. The aim of the study was to
assess the safety and feasibility of cSEMS compared with multiple plastic stents
in the treatment of benign biliary stricture (BBS) caused by chronic
pancreatitis. PATIENTS AND METHODS: This was a prospective, multicenter,
randomized study of 60 patients with BBS caused by chronic pancreatitis. All
patients received an initial plastic stent before randomization. At
randomization, the stent was replaced either with a single cSEMS or three plastic
stents. After 3 months, the position of the cSEMS was checked or another three
plastic stents were added. At 6 months after randomization, all stents were
removed. Clinical follow-up including abdominal ultrasound and laboratory tests
were performed at 6 months and 2 years after stent removal. RESULTS: Two patients
dropped out of the cSEMS group before stent removal. In April 2014, the median
follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success
rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent
group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one
late recurrence in the plastic stent group 50 months after stent removal. Stent
migration occurred three times (10 %) in the plastic stent group and twice in the
cSEMS group (7 %; P = 1.000). CONCLUSION: A 6-month treatment with either six 10
Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of
biliary stricture caused by chronic pancreatitis.Study registered at
ClinicalTrials.gov (NCT01085747).
PMID- 25590184
TI - Thienopyridine derivatives as risk factors for bleeding following high risk
endoscopic treatments: Safe Treatment on Antiplatelets (STRAP) study.
AB - BACKGROUND AND STUDY AIMS: The optimal method of perioperative management of
antiplatelet agents during endoscopic procedures that carry a high risk of
bleeding is still controversial. The aim of this study was to evaluate the safety
of continuing aspirin treatment during these procedures in an Asian population.
PATIENTS AND METHODS: A multicenter, prospective, observational cohort study was
conducted at six high volume endoscopy centers in Japan. The study included
patients at high risk of thromboembolism who were regularly taking antiplatelet
agents (e. g. thienopyridine derivatives and aspirin). Enrolled patients
continued their aspirin therapy, and underwent endoscopic procedures that had a
high risk of bleeding for treatment of lesions in the upper and lower
gastrointestinal tracts. The primary end point was the rate of major bleeding
complications after endoscopic procedures. RESULTS: The study was terminated in
accordance with predetermined safety criteria because 7 of 28 consecutive
patients experienced major bleeding complications (25.0 %; 95 % confidence
interval 10.7 % - 44.9 %). All major bleeding complications occurred following
endoscopic submucosal dissection (ESD; 6 stomach, 1 colon). Univariate analysis
showed that postoperative administration of thienopyridine derivatives was the
only significant factor associated with postoperative bleeding (P = 0.01).
Subanalysis of gastric ESD (23 lesions in 19 patients) confirmed that the
administration of thienopyridine derivatives (P = 0.01) and that of multiple
agents (P = 0.02) were the significant factors. All bleeding complications
(postoperative day 11.2 +/- 3.5) occurred after resuming thienopyridine
derivative therapy postoperatively (postoperative day 2.3 +/- 2.4). CONCLUSION:
In Asian patients taking thienopyridine derivatives with aspirin, cautious
postoperative care is necessary for those undergoing endoscopic procedures that
are associated with a high risk of bleeding, especially gastric ESD. Continuation
of aspirin alone during these endoscopic procedures may be acceptable. STUDY
REGISTRATION: UMIN000009176.
PMID- 25590185
TI - Determining the adenoma detection rate and adenomas per colonoscopy by
photography alone: proof-of-concept study.
AB - BACKGROUND AND STUDY AIMS: The adenoma detection rate (ADR) and adenomas detected
per colonoscopy (APC) are measures of the quality of mucosal inspection during
colonoscopy. In a resect and discard policy, pathologic assessment for
calculation of ADR and APC would not be available. The aim of this study was to
determine whether ADR and APC calculation based on photography alone is adequate
compared with the pathology-based gold standard. PATIENTS AND METHODS: A
prospective, observational, proof-of-concept study was performed in an academic
endoscopy unit. High definition photographs of consecutive polyps were taken, and
pathology was estimated by the colonoscopist. Among 121 consecutive patients aged
>= 50 years who underwent colonoscopy, 268 polyps were removed from 97 patients.
Photographs of consecutive polyps were reviewed by a second endoscopist. RESULTS:
The resect and discard policy applied to lesions that were <= 5 mm in size. When
only photographs of lesions that were ultimately proven to be adenomas were
included, the reviewer assessed ADR and APC to be lower than that determined by
pathology (absolute reductions of 6.6 % and 0.17, and relative reductions of 12.6
% and 13.1 % in ADR and APC, respectively). When all photographs were included
for calculation of ADR and APC, the reviewer determined the ADR to be 3.3 % lower
(absolute reduction) and the APC to be the same as the rates determined by
pathology. CONCLUSIONS: In a simulated resect and discard strategy, a high-level
detector can document adequate ADR and APC by photography alone.
PMID- 25590186
TI - Early use of double-guidewire technique to facilitate selective bile duct
cannulation: the multicenter randomized controlled EDUCATION trial.
AB - BACKGROUND AND STUDY AIMS: There are no guidelines for the timing of conversion
from a single-guidewire to a double-guidewire technique to facilitate selective
bile duct cannulation and reduce post-endoscopic retrograde
cholangiopancreatography pancreatitis (PEP), when using wire-guided cannulation.
We investigated whether early conversion to the double-guidewire method, at first
unintentional insertion of a guidewire into the pancreatic duct, facilitated
selective bile duct cannulation and reduced PEP compared with repeated single
guidewire attempts. PATIENTS AND METHODS: A multicenter prospective randomized
controlled trial included 274 patients with a naive papilla, undergoing
endoscopic retrograde cholangiography (ERC) using wire-guided cannulation in whom
there was unintentional insertion of the guidewire into the pancreatic duct. With
the guidewire still in the duct, patients were randomly assigned to undergo the
double-guidewire technique or repeated single-wire cannulation. Main outcomes
were success rates for selective bile duct cannulation and PEP frequency.
RESULTS: Success rates for selective bile duct cannulation within 10 attempts and
10 minutes were 75 % and 70 %, respectively, for the early double-guidewire (EDG)
and repeated single-guidewire (RSG) cannulation groups (relative rate 1.07, 95 %
confidence interval [95 %CI] 0.93 - 1.24, P = 0.42). Corresponding final
selective bile duct cannulation rates were 98 % and 97 % (relative rate 1.01, 95
%CI 0.97 - 1.05, P = 1.00). PEP rates were 20 % and 17 %, respectively, for the
EDG and RSG cannulation groups (relative risk 1.17, 95 %CI 0.71 - 1.94, P =
0.53). Double-guidewire cannulation was more effective in patients with malignant
biliary stricture (relative rate 1.36, 95 %CI 1.05 - 1.77, P = 0.02).
CONCLUSIONS: During therapeutic ERC using wire-guided cannulation, converting to
a double-guidewire technique neither facilitated selective bile duct cannulation
nor decreased PEP incidence compared with repeated use of a single-wire
technique.
PMID- 25590187
TI - Utility of intrapapillary capillary loops seen on magnifying narrow-band imaging
in estimating invasive depth of esophageal squamous cell carcinoma.
AB - BACKGROUND AND STUDY AIMS: Intrapapillary capillary loops (IPCLs) have been used
to estimate histopathological atypia and the invasion depth of squamous cell
carcinoma (SCC). The aim of this study was to evaluate the clinical significance
of IPCLs. PATIENTS AND METHODS: A total of 358 consecutive patients with
esophageal neoplasia on magnifying narrow-band imaging (M-NBI) were studied. The
lesions were categorized according to the IPCL classification of Inoue et al. and
were subsequently resected. Resected specimens were histopathologically analyzed
to determine the invasion depth. The inter- and intraobserver agreements in the
interpretation of IPCL images were also investigated. RESULTS: A total of 446
lesions were diagnosed on M-NBI as IPCL type V lesions, which were further
classified as 185 IPCL type V1, 109 type V2, 104 type V3, and 48 type Vn.
Sensitivity and specificity of IPCL type V1-2 for invasion confined to the
epithelium or lamina propria mucosa (m1-2) were 89.5 % (95 % confidence interval
[CI] 85.4 % - 92.7 %) and 79.6 % (95 %CI 72.3 % - 85.7 %), respectively.
Sensitivity and specificity of IPCL type V3 for invasion confined to the
muscularis mucosa or slight submucosal invasion (m3-sm1) were 58.7 % and 83.8 %,
respectively. Sensitivity and specificity of IPCL type Vn for deeper invasion
(sm2-3) were 55.8 % and 98.6 %, respectively. Interobserver agreement was
substantial (kappa = 0.609, 0.641, and 0.705), as was intraobserver agreement
(kappa = 0.705 and kappa = 0.819). CONCLUSION: Changes in the morphology of IPCLs
on M-NBI correlated with the depth of SCC invasion, and results were reproducible
and reliable among observers. Identification of IPCL type V1-2 proved useful for
the intraprocedural identification of m1-2 lesions, which are considered an
absolute indication for endoscopic resection.
PMID- 25590188
TI - Wing-shaped plastic stents vs. self-expandable metal stents for palliative
drainage of malignant distal biliary obstruction: a randomized multicenter study.
AB - BACKGROUND AND STUDY AIMS: Previous studies have shown superior patency rates for
self-expandable metal stents (SEMS) compared with plastic stents in patients with
malignant biliary obstruction. The aim of this study was to compare stent
patency, patient survival, and complication rates between a newly designed, wing
shaped, plastic stent and SEMSs in patients with unresectable, malignant, distal,
biliary obstruction. PATIENTS AND METHODS: A randomized, multicenter trial was
conducted at four tertiary care centers in Germany. A total of 37 patients
underwent randomization between March 2010 and January 2013. Patients underwent
endoscopic retrograde cholangiography with insertion of either a wing-shaped,
plastic stent without lumen or an SEMS. RESULTS: Stent failure occurred in 10/16
patients (62.5 %) in the winged-stent group vs. 4/18 patients (22.2 %) in the
SEMS group (P = 0.034). The median time to stent failure was 51 days (range 2 -
92 days) for the winged stent and 80 days (range 28 - 266 days) for the SEMS (P =
0.002). Early stent failure (< 8 weeks after placement) occurred in 8 patients
(50 %) vs. 2 patients (11.1 %), respectively (P = 0.022). After obtaining the
results from this interim analysis, the study was discontinued because of safety
concerns. CONCLUSIONS: The frequency of stent failure was significantly higher in
the winged-stent group compared with the SEMS group. A high incidence of early
stent failure within 8 weeks was observed in the winged-stent group. Thus, the
winged, plastic stent without central lumen may not be appropriate for mid or
long term drainage of malignant biliary obstruction. Study registration
ClinicalTrials.gov (NCT01063634).
PMID- 25590189
TI - Evaluation of cellular proliferative activity in patients with oral lichen planus
and hepatitis C through AgNOR method.
AB - The objective of this study was to evaluate the cellular proliferative potential
of oral lichen planus (OLP) lesions from patients without hepatitis C virus (HCV)
by means of AgNOR method, as well as the cellular proliferative potential of the
normal oral mucosa from patients with HCV, treated or untreated by interferon and
ribavirin. A cross-sectional study was developed to investigate four groups: 10
HCV+ patients without clinical signs of OLP who had never been treated for HCV
infection - Group 1; 10 HCV+ patients that were under interferon and ribavirin
treatment - Group 2; 15 patients with reticular OLP lesions histopathologically
confirmed, without HCV - Group 3; and 15 blood donors without HCV infection and
no clinical signs of OLP GROUP 4 Control Group. The cytological material of all
groups was collected by the liquid-based cytology technique. Then, the sedimented
material from each patient was filled with the Nucleolar Organizer Regions
impregnation by silver method (AgNOR). The count of NORs was performed on 100
epithelial cell nuclei per patient using the Image Tool(tm) software. The Tukey
HSD test was used to compare the median value of NORs among the groups and showed
that the oral mucosa of HCV+ patients previously treated with anti-HCV drugs
(GROUP 2), presented a higher average number of NORs in relation to others
(p<0.05). The anti-HCV treatment may be related to increased cell proliferation
of oral mucosa, indicating a possible relationship between OLP and HCV+ patients
treated with interferon and ribavirin.
PMID- 25590190
TI - Correlation between radiographic area and immunolocation of MMP-2 and MMP-9 in
unilocular radiographic lesions.
AB - Unilocular bone cysts are the most common entities affecting the maxillofacial
region. The mechanism of proliferation and expansion remains unclear.
Metalloproteinases (MMPs) are associated to diverse pathological conditions. The
aim of the present study was to correlate the radiographic aspect (area) and the
presence of MMP-2 and MMP-9 in dentigerous cysts, radicular cysts and
keratocystic odontogenic tumors. The radiographic area of each lesion was
calculated using the mathematical formula of the ellipse area. All specimens were
subjected to immunohistochemical analysis for these enzymes. The average
radiographic area was 284.17 mm2, 235.81 mm2 and 381.81 mm2, respectively.
Statistical analyses revealed no association between the immunoreactivity of MMPs
and radiographic area of the lesions in all pathologies studied, except for MMP-2
and radicular cysts, for which smaller lesions had increased immunostaining for
this enzyme. The results demonstrate that quantities of MMP-2 and MMP-9 are
especially involved with dentigerous and radicular cysts in expansion, whereas
these enzymes seem to be related to the biological behavior of keratocystic
odontogenic tumors, indicating invasion and cell proliferation. Moreover, there
is an inverse association between MMP-2 and MMP-9 in keratocystic odontogenic
tumors (p=0.03; rs=-0.660), indicating activity in different regions.
PMID- 25590192
TI - Effect of trimetaphosphate and fluoride association on hydroxyapatite dissolution
and precipitation in vitro.
AB - The present study analyzed the action of sodium trimetaphosphate (TMP) and/or
fluoride on hydroxyapatite. Hydroxyapatite powder was suspended in different
solutions: deionized water, 500 ug F/mL, 1,100 ug F/mL, 1%TMP, 3%TMP, 500 ug F/mL
plus 1%TMP and 500 ug F/mL plus 3%TMP. The pH value of the solutions was reduced
to 4.0 and after 30 min, raised to 7.0 (three times). After pH-cycling, the
samples were analyzed by X-ray diffraction and infrared spectroscopy. The
concentrations of calcium fluoride, fluoride, calcium and phosphorus were also
determined. Adding 1% or 3% TMP to the solution containing 500 ug F/mL produced a
higher quantity of calcium fluoride compared to samples prepared in a 1,100 ug
F/mL solution. Regarding the calcium concentration, samples prepared in solutions
of 1,100 ug F/mL and 500 ug F/mL plus TMP were statistically similar and showed
higher values. Using solutions of 1,100 ug F/mL and 500 ug F/mL plus TMP resulted
in a calcium/phosphorus ratio close to that of hydroxyapatite. It is concluded
that the association of TMP and fluoride favored the precipitation of a more
stable hydroxyapatite.
PMID- 25590193
TI - Recolonization of mutans Streptococci after application of chlorhexidine gel.
AB - Streptococcus mutans is specifically suppressed by intensive treatment with
chlorhexidine gel, but the time for recolonization and the effect on other oral
bacteria are not totally clear. In this study, recolonization of mutans
streptococci was evaluated in nine healthy adult volunteers, who were highly
colonized with this microorganism. Stimulated saliva was collected before
(baseline) and at 1, 7, 14, 21 and 28 days after application of 1% chlorhexidine
gel on volunteers' teeth for two consecutive days. On each day, the gel was
applied using disposable trays for 3 x 5 min with intervals of 5 min between each
application. Saliva was plated on blood agar to determine total microorganisms
(TM); on mitis salivarius agar to determine total streptococci (TS) and on mitis
salivarius agar plus bacitracin to determine mutans streptococci (MS).
Chlorhexidine was capable of reducing the counts of MS and the proportion of MS
with regard to total microorganisms (%MS/TM) (p<0.05), but these values did not
differ statistically from baseline (p>0.05) after 14 days for MS and 21 days for
%MS/TM. The counts of TM and TS and the proportion of MS to total streptococci
did not differ statistically from baseline (p>0.05) after chlorhexidine
treatment. The results suggest that the effect of chlorhexidine gel treatment on
suppression of mutans streptococci is limited to less than a month in highly
colonized individuals.
PMID- 25590191
TI - Dentin bond strength of a fluoride-releasing adhesive system submitted to pH
cycling.
AB - To evaluate the microtensile bond strength (uTBS) of a fluoride-containing
adhesive system submitted to a pH-cycling and storage time regimen for primary
outcomes. As secondary outcomes the fluoride released amount was evaluated.
Twelve dentin surfaces from sound third molar were divided into 2 groups
according to adhesive systems: Clearfil SE Protect (PB) and Clearfil SE Bond
(SE). Sticks obtained (1.0 mm2) from teeth were randomly divided into 3 subgroups
according to storage regimen model: immediate (24h); 5-month deionized water (W);
and pH-cycling model (C). All sticks were tested for uTBS in a universal testing
machine. Fluoride concentration was obtained from 1-4 days and 30-day in W and 1
4 days in demineralization (DE)/remineralization (RE) solutions from C, using a
fluoride-specific electrode. uTBS and fluoride released data were, respectively,
submitted to ANOVA in a split plot design and Tukey, and Friedman' tests
(a=0.05). There was no significant interaction between adhesive system and
storage regimen for uTBS. W showed the lowest uTBS values. There was no
significant difference between 24 h and C models for uTBS. There was no
significant difference between adhesive systems. Failure mode was predominantly
cohesive within composite for the 24 h and W, for the C group it was mixed for SE
and cohesive within composite for PB adhesive system. Fluoride concentrations in
the DE/RE solutions were less than 0.03125 ppm and not detected in W. In
conclusion, the fluoride-containing adhesive system performed similarly to the
regular one. Hydrolytic degradation is the main problem with both adhesive
systems, regardless of fluoride contents.
PMID- 25590194
TI - Root canal penetration of a sodium hypochlorite mixture using sonic or ultrasonic
activation.
AB - The purpose of this ex vivo study was to determine, in "open" and "closed"
systems, whether the design has an influence on the penetration length of sodium
hypochlorite mixed with a radiopaque contrast medium, measured in millimeters,
when delivered using positive pressure (PP) and using sonic (SI) or passive
ultrasonic (PUI) activation. Sixty single-rooted teeth were divided into two
groups: open and closed systems (n=30). Root canal shaping was performed to a
working length of 17 mm. The samples were divided into three sub-groups (n=10)
according to irrigant delivery and activation: PP, and SI or PUI activation. By
using radiographs, penetration length was measured, and vapor lock was assessed.
For the closed group, the penetration distance means were: PP 15.715 (+/-0.898)
mm, SI 16.299 (+/-0.738) mm and PUI 16.813 (+/-0.465) mm, with vapor lock
occurring in 53.3% of the specimens. In the open group, penetration to 17 mm
occurred in 97.6% of the samples, and no vapor lock occurred. Irrigant
penetration and distribution evaluation using open and closed systems provide
significantly different results. For closed systems, PUI is the most effective in
delivering the irrigant to working length, followed by SI.
PMID- 25590195
TI - Monitoring nonsurgical and surgical root canal treatment of teeth with primary
and secondary infections.
AB - The aim of this study was to monitor nonsurgical and surgical root canal
treatment (RCT) of teeth with primary and secondary infections and apical
periodontitis (AP). This prospective clinical study comprised the treatment of 80
patients with primary and persistent secondary infections and AP. Of this initial
sample, forty patients did not return. Periapical index using cone beam computed
tomography scans (CBCTPAI) was used to aid diagnosis, planning and to determine
the better therapeutic strategy. Twenty patients (26 teeth) diagnosed with
primary infection and AP received conventional RCT and were followed up for 10 to
36 months. Twenty patients (31 teeth) diagnosed with persistent secondary
infection were submitted to periapical surgical and followed up for 6 to 30
months. The results showed RCT successful in 19/26 cases with complete AP healing
(5/26 with partial repair) in 10-36 months of follow up. For the surgically
managed cases, effectiveness of surgical therapy was detected in 10/31 cases with
complete healing (10/31 cases with partial repair) within 6-30 months follow up.
The return of patients for clinical and radiographic follow-up, and obedience to
the proposed time period was very short from ideal. The levels of success in both
therapeutic protocols were high. RCT failures were detected even with rigorous
standard clinical protocols.
PMID- 25590196
TI - Manual and rotary instrumentation ability to reduce Enterococcus faecalis
associated with photodynamic therapy in deciduous molars.
AB - This aim of this study was to assess the ability of manual or rotary
instrumentation associated with photodynamic therapy (PDT) to reduce Enterococcus
faecalis using three combinations of light/photosensitizers: toluidine blue
O/laser, fuchsin/halogen light and fuchsin/LED. Twenty deciduous molars were
selected and contaminated with Enterococcus faecalis (McFarland 0.5 scale).
Working length determination was performed by visual method. The teeth were
randomly divided into two groups: G1 (n=10): manual instrumentation (Kerr-type
files) and G2 (n=10): rotary instrumentation (ProTaper system). The bacteria were
collected three times using sterile paper cones compatible with the anatomic
diameter of the root canal for 30 s before and after instrumentation and after
PDT. The samples were diluted in peptone water, seeded on blood agar plates and
incubated in an oven at 37 degrees C for colony-forming units counting. The
decrease of E. faecalis counts after instrumentation and after PDT was compared
using the Wilcoxon test, t-test and Kruskal Wallis test. A significant reduction
of E. faecalis occurred after manual and rotary instrumentation and after PDT
using the three combinations of light/photosensitizer (p<0.05). It may be
concluded that both rotary and manual instrumentation reduced E. faecalis.
Fuchsin with halogen light or LED irradiation and toluidine blue O with laser
irradiation can be used to reduce E. faecalis in root canals of primary molars.
PDT can be used as an adjuvant to conventional endodontic treatment.
PMID- 25590197
TI - Analysis of endodontist posture utilizing cinemetry, surface electromyography and
ergonomic checklists.
AB - The postural risk factors for dentists include the ease of vision in the
workplace, cold, vibration and mechanical pressure in tissues, incorrect posture,
functional fixity, cognitive requirements and work-related organizational and
psychosocial factors. The objective was to analyze the posture of endodontists at
the workplace. Eighteen right-handed endodontists aged 25 to 60 years (34+/-3)
participated in the study. Electromyography, kinemetry, ergonomic scales (RULA
and Couto's checklist) and biophotogrammetry were used to analyze the posture of
endodontists during root canal treatment of the maxillary right first and second
molars using rotary and manual instrumentation. The variations observed in the
electromyographic activities during the performance of rotary and manual
techniques suggest that the fibers of the longissimus region, anterior and medium
deltoid, medium trapezium, biceps, triceps brachii, brachioradialis and short
thumb abductor muscles underwent adaptations to provide more accurate functional
movements. Computerized kinemetry and biophotogrammetry showed that, as far as
posture is concerned, rotary technique was more demanding than the manual
technique. In conclusion, the group of endodontists evaluated in this study
exhibited posture disorders regardless of whether the rotary or manual technique
was used.
PMID- 25590198
TI - Impact of intracoronal dentin treatment prior to bleaching on bond strength of
restorative materials.
AB - Surface treatment of dentin before the bleaching procedure may affect its
permeability and influence the bond strength of restorative materials. This study
evaluated the influence of surface treatment before the bleaching on shear bond
strength (SBT) of restorative materials to intracoronal dentin. Dentin slabs were
subjected to surface treatment: no bleaching (control - CON), no surface
treatment + bleaching (HP), 37% phosphoric acid + bleaching (PA) and Er:YAG laser
+ bleaching (L). After the bleaching procedure, specimens (n=10) were restored
with: microhybrid composite resin (MH), flowable composite resin (F), and resin
modified glass-ionomer cement (RMGIC). The shear test was carried out. ANOVA and
Tukey's test (alpha=0.05) showed significant difference for surface treatment and
restorative materials (p<0.05). CON presented higher STB and was statistically
different from HP (p<0.05). PA and L showed intermediate values and were
statistically similar to CON and HP (p>0.05). STB for MH and F were higher than
RMGIC (p<0.05), and did not differ from each other (p>0.05). The surface
treatments with phosphoric acid and Er:YAG laser before the bleaching procedure
provided shear bond strength at the same level of unbleached dentin and the
composite resins presented superior bond strength to the intracoronal dentin.
PMID- 25590199
TI - A comparison of the bleaching effectiveness of chlorine dioxide and hydrogen
peroxide on dental composite.
AB - This study was carried out to verify if composites could be bleached using
chlorine dioxide as compared with hydrogen peroxide. 3M ESPE Filtek Z350
Universal Restorative discs were prepared (n=40), with dimensions 5 mm diameter x
2 mm thickness. The discs were divided into 4 groups of 10 discs each. Color
assessment was performed by CIEDE2000. The discs were stained with coffee, tea,
wine and distilled water (control) solutions for 14 days, 5 hours daily. Color
assessment was repeated on stained discs and followed by bleaching of 5 discs
from each group using chlorine dioxide and hydrogen peroxide in-office systems.
Finally, a last color assessment was performed and compared statistically. DE2000
after bleaching was very close to baseline for both the bleaching agents,
although chlorine dioxide showed better results than hydrogen peroxide. After
staining, there was a clinically significant discoloration (?E2000>=3.43) for the
tea, coffee and wine groups, and discoloration (?E2000) was seen more in the wine
group as compared to tea and coffee. Overall, the control group (distilled water)
had the least color change in the three intervals. After bleaching, the color in
all specimens returned close to the baseline. The color differences between
bleaching and baseline were less than 3.43 for all groups. The obtained results
show that chlorine dioxide is slightly superior to hydrogen peroxide in the
bleaching of composites, while maintaining the shade of the composite close to
the baseline.
PMID- 25590200
TI - Physicochemical properties of a methacrylate-based dental adhesive incorporated
with epigallocatechin-3-gallate.
AB - This study aimed to evaluate the influence of epigallocatechin-3-gallate (EGCG)
incorporation on the physicochemical properties of a methacrylate-based dental
adhesive. EGCG was added to Adper Easy One (3M-ESPE) except in control group, to
obtain concentrations of 0.01% w/w and 0.1% w/w of EGCG-doped adhesives. For
water sorption (WS) and solubility (SL) surveys, resin discs were assayed
following ISO recommendations (n=10). The degree of conversion (DC) was analyzed
by FTIR whereas flexural strength (FS) was tested by three-point bending with bar
specimens (n=10). Data were subjected to one-way ANOVA and Tukey's test (p<0.05).
No significant difference in the DC, WS and FS were found between the different
concentrations of EGCG (p>0.05). Adhesives containing 0.1% or 0.01% of EGCC
demonstrated similar values of SL (p>0.05) and higher than those found for
adhesive without EGCC (p<0.05). In conclusion, the addition of EGCC to adhesive
reduced the solubility without affecting the other evaluated properties.
PMID- 25590201
TI - Degradation of resin composites in a simulated deep cavity.
AB - The aim of this study was to analyze the sorption and solubility of a nanofilled
(Filtek Z350) and a midifilled (Filtek P60) resin composite in oral environment
like substances, in a simulated deep cavity. A cylindrical cavity prepared in a
bovine incisor root was incrementally filled with resin composites. The obtained
resin composite cylinders were cut perpendicularly to the axis to obtain 1-mm
thick discs that were divided into fifteen groups (n=5) according to depth (1, 2,
3, 4 and 5 mm) and immersion media (distilled water - DW, artificial saliva - AS
and lactic acid - LA). The sorption and solubility were calculated based on ISO
4049:2000. Additionally, the degree of conversion (DC%) was calculated by FT-IR
spectroscopy. Data were analyzed using multifactor analysis of variance (MANOVA)
followed by Tukey's HSD post-hoc test and linear regression analysis (a=0.05).
The DC% was higher for the midifilled resin composite and was negatively
influenced by cavity depth (p<0.05). The nanofilled resin composite presented
higher sorption and solubility than did the midifilled (p<0.05). The immersion
media influenced the sorption and the solubility as follows: LA>AS>DW, (p<0.05).
Both phenomena were influenced by cavity depth, with the sorption and solubility
increasing from 1 to 5 mm (p<0.05). The degradation of resin composite
restorations may be greater in the deepest regions of class II restorations when
the composite is exposed to organic acids present in the oral biofilm (lactic
acid).
PMID- 25590202
TI - Effect of 4-(N,N-dimethylamino)phenethyl alcohol on degree of conversion and
cytotoxicity of photo-polymerized CQ-based resin composites.
AB - The aim of this study was to evaluate the degree of conversion (DC) and the
cytotoxicity of photo-cured experimental resin composites containing 4-(N,N
dimethylamino)phenethyl alcohol (DMPOH) combined to the camphorquinone (CQ)
compared with ethylamine benzoate (EDAB). The resin composites were mechanically
blended using 35 wt% of an organic matrix and 65 wt% of filler loading. To this
matrix was added 0.2 wt% of CQ and 0.2 wt% of one of the reducing agents tested.
5x1 mm samples (n=5) were previously submitted to DC measurement and then pre
immersed in complete culture medium without 10% (v/v) bovine serum for 1 h or 24
h at 37 degrees C in a humidifier incubator with 5% CO2 and 95% humidity to
evaluate the cytotoxic effects of experimental resin composites using the MTT
assay on immortalized human keratinocytes cells. As a result of absence of normal
distribution, the statistical analysis was performed using the nonparametric
Kruskal-Wallis to evaluate the cytotoxicity and one-way analysis of variance to
evaluate the DC. For multiple comparisons, cytotoxicity statistical analyses were
submitted to Student-Newman-Keuls and DC analysis to Tukey's HSD post-hoc test
(?=0.05). No significant differences were found between the DC of DMPOH (49.9%)
and EDAB (50.7%). 1 h outcomes showed no significant difference of the cell
viability between EDAB (99.26%), DMPOH (94.85%) and the control group (100%).
After 24 h no significant difference were found between EDAB (48.44%) and DMPOH
(38.06%), but significant difference was found compared with the control group
(p>0.05). DMPOH presented similar DC and cytotoxicity compared with EDAB when
associated with CQ.
PMID- 25590203
TI - Does maintaining a bottle of adhesive without the lid significantly reduce the
solvent content?
AB - This study aimed to evaluate the effect of maintaining a bottle of adhesive
without its lid on the solvent loss of the etch-and-rinse adhesive systems. Three
2-step etch-and-rinse adhesives with different solvents (acetone, ethanol or
butanol) were used in this study. Drops of each adhesive were placed on an
analytical balance and the adhesive mass was recorded until equilibrium was
achieved (no significant mass alteration within time). The solvent content of
each adhesive and evaporation rate of solvents were measured (n=3). Two bottles
of each adhesive were weighted. The bottles were maintained without their lids
for 8 h in a stove at 37 oC, after which the mass loss was measured. Based on
mass alteration of drops, acetone-based adhesive showed the highest solvent
content (46.5%, CI 95%: 35.8-54.7) and evaporation rate (1.11 %/s, CI95%: 0.63
1.60), whereas ethanol-based adhesive had the lowest values (10.1%, CI95%: 4.3
16.0; 0.03 %/s CI95%: 0.01-0.05). However, none of the adhesives bottles
exhibited significant mass loss after sitting for 8 h without their lids (% from
initial content; acetone - 96.5, CI 95%: 91.8-101.5; ethanol - 99.4, CI 95%: 98.4
100.4; and butanol - 99.3, CI 95%: 98.1-100.5). In conclusion, maintaining the
adhesive bottle without lid did not induce significant solvent loss, irrespective
the concentration and evaporation rate of solvent.
PMID- 25590204
TI - Toothache, associated factors, and its impact on Oral Health-Related Quality of
Life (OHRQoL) in preschool children.
AB - The aim of this study was to assess the prevalence of toothache, associated
factors and impact of this condition on the Child Oral Health Related Quality of
Life (COHRQoL) in preschoolers. The study was carried out in Santa Maria, Brazil,
during the National Children's Vaccination Day, and 534 children aged 0 to 5
years were included. Clinical variables included dental caries and dental trauma.
A questionnaire was responded by the parents and provided information about
several socioeconomic indicators, dental service use and toothache. Toothache was
collected by the question: "Has your child ever had a toothache - Yes or no?".
Data on COHRQoL were assessed using the Brazilian version of the Early Childhood
Oral Health Impact Scale (ECOHIS). Multivariable Logistic regression models were
performed to assess the association between the predictor variables and outcomes.
The prevalence of toothache was 10.11% (95% CI: 7.55% - 12.68%). Older children
had a higher chance of presenting dental pain (OR 2.72; 95% CI: 1.01 - 7.56), as
well as children with caries experience (OR 3.43; 95% CI: 1.81 - 6.52). Moreover,
children who had not visited the dental service in the last 6 months were less
likely to present toothache (OR 0.51; 95% CI: 0.28 - 0.95). The presence of
dental pain negatively affects the COHRQoL; those with toothache presented a
higher chance of having higher impact on the total scores of ECOHIS (OR 4.18; 95%
CI: 1.76 - 9.95) than those without toothache. Similar observation was found for
the child section of the questionnaire (OR 5.54; 95% CI: 2.15 - 14.24). Toothache
negatively affects COHRQoL and is associated with caries experience, age and use
of dental service.
PMID- 25590205
TI - Effect of the parafunctional occlusal loading and crown height on stress
distribution.
AB - The aim of this study was to assess, by the three-dimensional finite element
method, the influence of crown-to-implant ratio and parafunctional occlusal
loading on stress distribution in single external hexagon implant-supported
prosthesis. Computer-aided design software was used to confection three models.
Each model was composed of a block bone and an external hexagon implant (5x10.0
mm) with screw-retained implant prostheses, varying the height crown: 10, 12.5
and 15 mm. Finite element analysis software was used to generate the finite
element mesh and to establish the loading and boundary conditions. Normal (200 N
axial and 100 N oblique load) and parafunctional forces (1,000 N axial and 500 N
oblique load) were applied. The results were visualized by von Mises and maximum
principal stress. In comparison with the normal occlusal force, the
parafunctional occlusal force induced an increase in stress concentration and
magnitude on implant (platform and first threads) and screw (neck). The cortical
bone showed the highest tensile stress under parafunctional force (oblique load).
The stress concentration increased as the crown height increased. It was
concluded that: increasing the C/I increased stress concentration in both implant
components and cortical bone; parafunctional loading increased between 4-5 times
the value of stresses in bone tissue compared with functional loading; the type
of loading variation factor is more influential than the crown-to-implant factor.
PMID- 25590206
TI - Pattern of maxillofacial fractures in severe multiple trauma patients: a 7-year
prospective study.
AB - The incidence of facial trauma is high. This study has the primary objective of
documenting and cataloging maxillofacial fractures in polytrauma patients. From a
total of 1229 multiple trauma cases treated at the Emergency Room of the Santo
Antonio Hospital - Oporto Hospital Center, Portugal, between August 2001 and
December 2007, 251 patients had facial wounds and 209 had maxillofacial
fractures. Aged ranged form 13 to 86 years. The applied selective method was
based on the presence of facial wound with Abbreviated Injury Scale >=1. Men had
a higher incidence of maxillofacial fractures among multiple trauma patients
(86.6%) and road traffic accidents were the primary cause of injuries (69.38%).
Nasoorbitoethmoid complex was the most affected region (67.46%) followed by the
maxilla (57.42%). The pattern and presentation of maxillofacial fractures had
been studied in many parts of the world with varying results. Severe multiple
trauma patients had different patterns of maxillofacial injuries. The number of
maxillofacial trauma is on the rise worldwide as well as the incidence of
associated sequelae. Maxillofacial fractures on multiple trauma patients were
more frequent among males and in road traffic crashes. Knowing such data is
elementary. The society should have a key role in the awareness of individuals
and in prevention of road traffic accidents.
PMID- 25590207
TI - Technique of framework cemented on prepared abutments to obtain passive fit at
fixed complete denture: a 2-year follow-up report.
AB - The passive fit of implant-supported dentures is fundamental to the
rehabilitation success due the absence of the periodontal ligament in
osseointegrated implants. Many techniques to obtain passive fit have been
reported in the literature, some inaccessible for the clinicians and dental
laboratories. This case report presents a technique to fabricate fixed complete
dentures aiming at obtain passive fit with reduced time and cost, but without
demerit for the aesthetics, function and longevity. A 40-year-old woman was
referred for treatment presenting some teeth in the maxilla and an edentulous
mandible, reporting eating problems related to instability and little retention
of the mandibular complete denture. Treatment based on the reverse planning was
performed to guide the rehabilitation with a complete mandibular fixed complete
denture and maxillary occlusal plane adjustment. The framework of the fixed
complete denture was manufactured luting a cast metal bar above the prepared
titanium cylinder abutments using resin cement. The aim of this technique was to
obtain a fixed complete denture with passive fit presenting positive esthetic and
functional outcomes after 2 years of follow-up.
PMID- 25590208
TI - Obturation over an S1 ProTaper instrument fragment in a mandibular molar with
three years of follow-up.
AB - This case report describes root canal filling performed over a large S1 ProTaper
file fragment in a second mandibular molar with irreversible pulpitis. An S1
ProTaper file was fractured during the instrumentation of the mesiobuccal canal.
Approximately 10 mm of file fragment remained in the apical and middle thirds of
the canal. The obturation was performed over this fragment using
thermomechanically compacted gutta-percha and sealer. Radiographic findings and
the absence of clinical signs and symptoms at 3-year follow up indicated
successful treatment. Cone-beam computed tomography images revealed absence of
periapical lesion and details of intracanal file fragment related to root
fillings and apex morphology. In this case, the presence of a large intracanal
fractured instrument did not have a negative impact on the endodontic prognosis
during the follow up evaluation period.
PMID- 25590209
TI - Effects of Aerosolized Adenosine 5'-Triphosphate in Smokers and Patients With
COPD.
AB - BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) stimulates vagal C and
Adelta fibers in the lung, resulting in pronounced bronchoconstriction and cough
mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We
investigated the effects of nebulized ATP on cough and symptoms in control
subjects, healthy smokers, and patients with COPD and compared these responses to
the effects of inhaled adenosine, the metabolite of ATP. METHODS: We studied the
effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber,
perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in
exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n =
14), and patients with COPD (n = 7). RESULTS: In comparison with healthy
subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and
patients with COPD, and the effects of ATP were more pronounced than those of
AMP. The concentration of ATP in the exhaled breath condensate of patients with
COPD was elevated compared with that of healthy subjects. CONCLUSIONS: Smokers
and patients with COPD manifest hypersensitivity to extracellular ATP, which may
play a mechanistic role in COPD.
PMID- 25590210
TI - Two-step cyanomethylation protocol: convenient access to functionalized aryl- and
heteroarylacetonitriles.
AB - A two-step protocol has been developed for the introduction of cyanomethylene
groups to metalated aromatics through the intermediacy of substituted isoxazoles.
A palladium-mediated cross-coupling reaction was used to introduce the isoxazole
unit, followed by release of the cyanomethylene function under thermal or
microwave-assisted conditions. The intermediate isoxazoles were shown to be
amenable to further functionalization prior to deprotection of the sensitive
cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl
substituted acetonitrile building blocks.
PMID- 25590211
TI - Metformin reverts the secretion of CXCL8 induced by TNF-alpha in primary cultures
of human thyroid cells: an additional indirect anti-tumor effect of the drug.
AB - CONTEXT: Metformin displays both direct and indirect anti-tumor effects. CXCL8 is
a crucial downstream mediator of Nuclear-Factor-kappaB signaling related to the
growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged
survival and reduced metastatic spread in in-vivo animal models of thyroid
tumors. OBJECTIVE: This study aimed to evaluate whether metformin inhibits the
secretion of CXCL8 induced by Tumor-Necrosis-Factor-alpha (TNF-alpha) in primary
cultures of normal and tumor human thyroid cells as well as in thyroid cancer
cell lines. METHODS: Normal human thyrocytes, papillary thyroid cancer cells, and
thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-alpha (10
ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM).
CXCL8 levels were measured in the cell supernatants after 24 hours. RESULTS:
Metformin significantly and dose-dependently inhibited the TNF-alpha-induced
CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and
papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1
and BCPAP cell lines. CONCLUSION: Metformin inhibits the TNF-alpha-induced CXCL8
secretion in primary cultures of normal thyroid cells and differentiated thyroid
cancer cells at least of the most frequent poorly aggressive phenotype. The
recruitment of neutrophils within the thyroid gland is a crucial metastasis
promoting factor, and it depends on the amount of CXCL8 produced by both tumor
cells and by the more abundant normal thyroid cells exposed to TNF-alpha. Thus,
the here-reported inhibiting effect of metformin on TNF-alpha-induced CXCL8
secretion could be considered as a further indirect anticancer property of the
drug.
PMID- 25590212
TI - Pharmacological management of obesity: an endocrine Society clinical practice
guideline.
AB - OBJECTIVE: To formulate clinical practice guidelines for the pharmacological
management of obesity. PARTICIPANTS: An Endocrine Society-appointed Task Force of
experts, a methodologist, and a medical writer. This guideline was co-sponsored
by the European Society of Endocrinology and The Obesity Society. EVIDENCE: This
evidence-based guideline was developed using the Grading of Recommendations,
Assessment, Development, and Evaluation (GRADE) system to describe the strength
of recommendations and the quality of evidence. CONSENSUS PROCESS: One group
meeting, several conference calls, and e-mail communications enabled consensus.
Committees and members of the Endocrine Society, the European Society of
Endocrinology, and The Obesity Society reviewed and commented on preliminary
drafts of these guidelines. Two systematic reviews were conducted to summarize
some of the supporting evidence. CONCLUSIONS: Weight loss is a pathway to health
improvement for patients with obesity-associated risk factors and comorbidities.
Medications approved for chronic weight management can be useful adjuncts to
lifestyle change for patients who have been unsuccessful with diet and exercise
alone. Many medications commonly prescribed for diabetes, depression, and other
chronic diseases have weight effects, either to promote weight gain or produce
weight loss. Knowledgeable prescribing of medications, choosing whenever possible
those with favorable weight profiles, can aid in the prevention and management of
obesity and thus improve health.
PMID- 25590214
TI - Arterial norepinephrine concentration is inversely and independently associated
with insulin clearance in obese individuals with metabolic syndrome.
AB - CONTEXT: Impaired insulin clearance contributes to the hyperinsulinemia of
obesity, yet relatively little is known concerning the pathophysiological
determinants of insulin clearance in obese populations. OBJECTIVE: To examine the
cross-sectional relationship between insulin clearance and resting sympathetic
nervous system activity in a cohort of obese subjects with metabolic syndrome.
PARTICIPANTS AND METHODS: Unmedicated, nonsmoking subjects (31 male, 27 female;
aged 56 +/- 1 year; body mass index 33.7 +/- 0.6 kg/m(2)) underwent euglycemic
hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin
clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry,
Doppler echocardiography, and oral glucose tolerance test. RESULTS: Univariate
correlation analyses showed inverse associations between insulin clearance and
arterial norepinephrine concentration (r = -0.44, P = .0006), calculated
norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r =
0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda
insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P =
.04). Insulin clearance and sensitivity did not differ between genders, however
females had higher AI compared to males (35 +/- 3% versus 14 +/- 2%, P < .001).
In age and gender adjusted stepwise regression analyses, arterial norepinephrine
concentration alone explained 19% of the variance in insulin clearance. When all
significant variables were entered into the regression model, arterial
norepinephrine, AI, gender, and M were independent predictors of insulin
clearance, together explaining 41% of the variance. CONCLUSIONS: Arterial
norepinephrine concentration is inversely and independently associated with whole
body insulin clearance rate in obese individuals with metabolic syndrome.
Prospective studies are needed to determine the direction of causality and the
chronology of interactions between insulin clearance and sympathetic neural
activity.
PMID- 25590213
TI - Clinical review: Drugs commonly associated with weight change: a systematic
review and meta-analysis.
AB - CONTEXT: Various drugs affect body weight as a side effect. OBJECTIVE: We
conducted this systematic review and meta-analysis to summarize the evidence
about commonly prescribed drugs and their association with weight change. DATA
SOURCES: MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were
searched to identify published systematic reviews as a source for trials. STUDY
SELECTION: We included randomized trials that compared an a priori selected list
of drugs to placebo and measured weight change. DATA EXTRACTION: We extracted
data in duplicate and assessed the methodological quality using the Cochrane risk
of bias tool. RESULTS: We included 257 randomized trials (54 different drugs; 84
696 patients enrolled). Weight gain was associated with the use of amitriptyline
(1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg),
risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone
(2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg),
glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss
was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol
(0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg),
zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3
kg). For many other remaining drugs (including antihypertensives and
antihistamines), the weight change was either statistically nonsignificant or
supported by very low-quality evidence. CONCLUSIONS: Several drugs are associated
with weight change of varying magnitude. Data are provided to guide the choice of
drug when several options exist and institute preemptive weight loss strategies
when obesogenic drugs are prescribed.
PMID- 25590216
TI - Percutaneous autologous pancreatic islet cell transplantation for traumatic
pancreatic injury.
AB - CONTEXT: Traumatic pancreatic injury with pancreatic duct disruption is
surgically managed with at least a partial pancreatectomy, often leading to poor
blood glucose control and the subsequent development of diabetes mellitus.
Autologous beta-islet cell transplantation may therefore help to preserve
pancreatic endocrine function. CASE DESCRIPTION: We describe 3 patients with
pancreatic duct disruption from traumatic pancreatic injury who were treated with
a partial pancreatectomy followed by autologous beta-islet cell transplantation
via a percutaneous transhepatic approach. Immediately after trauma, 2 of the 3
patients had difficulty with glucose control that resolved after autologous beta
islet cell transplantation. At follow-up, all patients remained normoglycemic.
CONCLUSION: In patients requiring partial pancreatectomy after pancreatic trauma,
percutaneous transhepatic autologous beta-islet cell transplantation should be
considered to minimize the risk of development of diabetes mellitus.
PMID- 25590215
TI - Prophylactic central compartment lymph node dissection in papillary thyroid
carcinoma: clinical implications derived from the first prospective randomized
controlled single institution study.
AB - BACKGROUND: The benefits of prophylactic central compartment lymph node
dissection (pCCND) in papillary thyroid cancer (PTC) are still under
investigation. This treatment seems to reduce PTC recurrence/mortality rates but
has a higher risk of surgical complications. The lack of prospective randomized
trials does not allow definitive recommendations. The aim of this prospective
randomized controlled study was to evaluate the clinical advantages and
disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without
evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly
assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or
Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of
followup, no difference was observed in the outcome of the two groups. However, a
higher percentage of Group A were treated with a higher number of (131)I courses
(P = .002), whereas a higher prevalence of permanent hypoparathyroidism was
observed in Group B (P = .02). No preoperative predictors of central compartment
lymph node metastases (N1a) were identified. Only three patients were upstaged,
and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients
with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One
advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but
the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost
50% of patients with PTC had micrometastatic lymph nodes in the central
compartment, but none of the presurgical features analyzed, including BRAF
mutation, was able to predict their presence; moreover, to be aware of their
presence does not seem to have any effect on the outcome.
PMID- 25590217
TI - In postmenopausal female subjects with type 2 diabetes mellitus, vertebral
fractures are independently associated with cortisol secretion and sensitivity.
AB - CONTEXT: In type 2 diabetes (T2D), the vertebral fracture (VFx) prevalence and
cortisol secretion are increased. OBJECTIVE: The objective of this study was to
evaluate the role of glucocorticoid secretion and sensitivity in T2D-related
osteoporosis. DESIGN AND SETTING: This was a case-control study in an outpatient
setting. PATIENTS: The patients were ninety-nine well-compensated T2D
postmenopausal women (age, 65.7 +/- 7.3 y) and 107 controls (age, 64.5 +/- 8.2
y). MAIN OUTCOME MEASURES: We assessed osteocalcin, C-terminal telopeptide of
type I collagen, ACTH, cortisol after the dexamethasone suppression test (F
1mgDST), BclI and N363S single-nucleotide polymorphisms (SNPs) of glucocorticoid
receptor, lumbar spine and femoral neck bone mineral density by dual x-ray
absorptiometry, and VFx by radiography. RESULTS: Compared with controls, T2D
subjects had increased VFx prevalence (20 vs 34.3%, respectively; P = .031), bone
mineral density (Z-scores, lumbar spine, 0.16 +/- 1.28 vs 0.78 +/- 1.43, P =
.001; femoral neck, -0.03 +/- 0.87 vs 0.32 +/- 0.98, P = .008, respectively), and
F-1mgDST (1.06 +/- 0.42 vs 1.21 +/- 0.44 MUg/dL, 29.2 +/- 1.2 vs 33.3 +/- 1.2
nmol/L, respectively; P = .01), and decreased osteocalcin (10.6 +/- 6.4 vs 4.9 +/
3.2 ng/mL, 10.6 +/- 6.4 vs 4.9 +/- 3.2 MUg/L, respectively; P < .0001) and C
terminal telopeptide of type I collagen (0.28 +/- 0.12 vs 0.14 +/- 0.08 ng/mL,
0.28 +/- 0.12 vs 0.14 +/- 0.08 mcg/L, respectively; P < .0001). Fractured
controls or T2D patients had increased sensitizing N363S SNP prevalence (20 and
17.6%, respectively) compared to non-fractured subjects (3.4 and 3.1%,
respectively; P = .02 for both comparisons), and similar BclI SNP prevalence. The
VFx presence was associated with the sensitizing variant of N363S SNPs in
controls (odds ratio [OR] = 10.6; 95% confidence interval [CI], 1.8-63.3; P =
.01) and in T2D patients (OR = 12.5; 95% CI, 1.8-88.7; P = .01), and with the F
1mgDST levels (OR = 2.1; 95% CI, 1.1-4.1; P = .03) only in T2D patients.
CONCLUSIONS: In postmenopausal T2D women, VFx are associated with cortisol
secretion and the sensitizing variant of N363S SNPs.
PMID- 25590218
TI - The smallest of the small: short-term outcomes of profoundly growth restricted
and profoundly low birth weight preterm infants.
AB - OBJECTIVE: Survival of preterm and very low birth weight (VLBW) infants has
steadily improved. However, the rates of mortality and morbidity among the very
smallest infants are poorly characterized. STUDY DESIGN: Data from the California
Perinatal Quality Care Collaborative for the years 2005 to 2012 were used to
compare the mortality and morbidity of profoundly low birth weight (ProLBW, birth
weight 300 to 500 g) and profoundly small for gestational age (ProSGA, <1st
centile for weight-for-age) infants with very low birth weight (VLBW, birth
weight 500 to 1500 g) and appropriate for gestational age (AGA, 5th to 95th
centile for weight-for-age) infants, respectively. RESULT: Data were available
for 44 561 neonates of birth weight <1500 g. Of these, 1824 were ProLBW and 648
were ProSGA. ProLBW and ProSGA differed in their antenatal risk factors from the
comparison groups and were less likely to receive antenatal steroids or to be
delivered by cesarean section. Only 14% of ProSGA and 21% of ProLBW infants
survived to hospital discharge, compared with >80% of AGA and VLBW infants. The
largest increase in mortality in ProSGA and ProLBW infants occurred prior to 12 h
of age, and most mortality happened in this time period. Survival of the ProLBW
and ProSGA infants was positively associated with higher gestational age, receipt
of antenatal steroids, cesarean section delivery and singleton birth. CONCLUSION:
Survival of ProLBW and ProSGA infants is uncommon, and survival without
substantial morbidity is rare. Survival is positively associated with receipt of
antenatal steroids and cesarean delivery.
PMID- 25590219
TI - Prone positioning decreases cardiac output and increases systemic vascular
resistance in neonates.
AB - OBJECTIVE: To evaluate the cardiovascular response to short-term prone
positioning in neonates. STUDY DESIGN: In this prospective study, we continuously
monitored heart rate (HR), stroke volume (SV) and cardiac output (CO) by
electrical velocimetry in hemodynamically stable neonates in each of the
following positions for 10 min: supine, prone and back-to-supine position. Skin
blood flow (SBF) was also continuously assessed on the forehead or foot using
Laser Doppler technology. Systemic vascular resistance (SVR) index was calculated
as mean blood pressure (BP)/CO. Data were analyzed using repeated measures
analysis of variance. RESULTS: Thirty neonates (gestational age: 35+/-4 weeks;
postmenstrual age: 36+/-3 weeks) were enrolled. HR did not change in response to
positioning. However, in prone position, SV, CO and SBF decreased and SVR index
increased from 1.5+/-0.3 to 1.3+/-0.3 ml kg(-1) (mean +/-s.d., P<0.01), 206+/-44
to 180+/-41 ml kg(-1) min(-1) (P<0.01), 0.54+/-0.30 to 0.44+/-0.29 perfusion
units (P<0.01) and 0.25+/-0.06 to 0.30+/-0.07 mm Hg ml(-1) kg(-1) min(-1)
(P<0.01), respectively. After placing the infants back-to-supine position, SV,
CO, SBF and SVR index returned to baseline. The above pattern of cardiovascular
changes was consistent in vast majority of the studied neonates. CONCLUSIONS:
Short-term prone positioning is associated with decreased SV, CO and SBF and
increased calculated SVR index.
PMID- 25590220
TI - Nutritional outcomes with implementation of probiotics in preterm infants.
AB - OBJECTIVE: To assess nutritional outcomes in preterm infants after the
implementation of probiotics. STUDY DESIGN: Retrospective chart review of infants
with birth weight?1250 grams and/or?28 weeks of gestational age admitted to the
KCH-Neonatal Intensive Care Unit was done. Data were collected over two periods,
period 1 (before probiotics) and period 2 (after probiotics) and included
demographic data, daily weight gain, feeding strategies (type, amount, caloric
content and frequency of feeds) and comorbidities affecting feedings (Patent
ductus arteriosus, Sepsis). Primary outcomes-extra uterine growth restriction
(EUGR) status and incidence of necrotizing enterocolitis (NEC) as well as
secondary outcomes-time to reach full feeds, feeding intolerance episodes and
weight gain were compared between the two groups. RESULTS: A total of 113 infants
(period 1) were compared with 108 infants (period 2). The odds of EUGR was
significantly lower with probiotics (odds ratio: 0.3, 95% confidence interval
0.138 to 0.611). Time to reach full feeds was significantly reduced and weight
gain was significantly better in period 2. Significant reduction was also noted
in number of total parental nutrition days, central line days, nil per os days
and number of feeding intolerance episodes in period 2. There was no significant
difference in the incidence of NEC. CONCLUSION: Probiotics improve feeding
tolerance leading to better overall growth and decreases the incidence of EUGR in
preterm infants.
PMID- 25590222
TI - Correction to "What a Difference a Decade Has Not Made: The Murky Electronic
Structure of Iron Monocyanide (FeCN) and Iron Monoisocyanide (FeNC)".
PMID- 25590221
TI - Relationship of maternal creatinine to first neonatal creatinine in infants <30
weeks gestation.
AB - OBJECTIVE: To examine the relationship between maternal and neonatal creatinine
(Cr) in preterm infants in the context of antenatal and intrapartum maternal and
neonatal factors. STUDY DESIGN: In this 51/2-year, single-center, retrospective
study, paired maternal and neonatal Cr were compared by t-test. Linear regression
for correlated outcomes employing generalized estimating equations was used to
examine neonatal Cr as a function of antenatal maternal Cr and potential
confounders. RESULT: A total of 157 neonates of 124 mothers met study criteria.
Neonatal Cr values in the first 24 h of life were significantly higher than
antenatal maternal values. Linear regression modeling showed that maternal Cr,
neonatal lactate, hypoxic-ischemic villous changes on placental pathology and
multiple gestation were each significant determinants of the first neonatal Cr.
CONCLUSION: No neonatal Cr was less than its paired maternal value. Maternal Cr,
neonatal lactate, hypoxic-ischemic villous changes in the placenta and multiple
gestation were each significantly associated with neonatal Cr.
PMID- 25590225
TI - Contrasting performance of donor-acceptor copolymer pairs in ternary blend solar
cells and two-acceptor copolymers in binary blend solar cells.
AB - Here two contrasting approaches to polymer-fullerene solar cells are compared. In
the first approach, two distinct semi-random donor-acceptor copolymers are
blended with phenyl-C61-butyric acid methyl ester (PC61BM) to form ternary blend
solar cells. The two poly(3-hexylthiophene)-based polymers contain either the
acceptor thienopyrroledione (TPD) or diketopyrrolopyrrole (DPP). In the second
approach, semi-random donor-acceptor copolymers containing both TPD and DPP
acceptors in the same polymer backbone, termed two-acceptor polymers, are blended
with PC61BM to give binary blend solar cells. The two approaches result in bulk
heterojunction solar cells that have the same molecular active-layer components
but differ in the manner in which these molecular components are mixed, either by
physical mixing (ternary blend) or chemical "mixing" in the two-acceptor (binary
blend) case. Optical properties and photon-to-electron conversion efficiencies of
the binary and ternary blends were found to have similar features and were
described as a linear combination of the individual components. At the same time,
significant differences were observed in the open-circuit voltage (Voc) behaviors
of binary and ternary blend solar cells. While in case of two-acceptor polymers,
the Voc was found to be in the range of 0.495-0.552 V, ternary blend solar cells
showed behavior inherent to organic alloy formation, displaying an intermediate,
composition-dependent and tunable Voc in the range from 0.582 to 0.684 V,
significantly exceeding the values achieved in the two-acceptor containing binary
blend solar cells. Despite the differences between the physical and chemical
mixing approaches, both pathways provided solar cells with similar power
conversion efficiencies, highlighting the advantages of both pathways toward
highly efficient organic solar cells.
PMID- 25590223
TI - Phaeohyphomycosis caused by Exophiala spinifera: an increasing disease in young
females in mainland China? Two case reports and review of five cases reported
from mainland China.
AB - No more than 30 cases of phaeohyphomycosis caused by Exophiala spinifera have
been reported up to now in English and Chinese literature over the past half
century. Here, we reported two cases of phaeohyphomycosis caused by E. spinifera
and reviewed all the five cases reported from mainland China. These two involved
were both young female, one patient experiencing recurrence during pregnancy and
the other developing multiple-site infections without apparent immunodeficiency.
The aetiological agents were both identified as E. spinifera by molecular
analysis. Oral itraconazole was proved effective enough for the first patient,
while the combination of itraconazole and terbinafine was needed for the second
patient. It seems that infections due to E. spiniferais increasing in China
mainland nowadays, usually involving young female.
PMID- 25590224
TI - Let there be light: regulation of gene expression in plants.
AB - Gene expression regulation relies on a variety of molecular mechanisms affecting
different steps of a messenger RNA (mRNA) life: transcription, processing,
splicing, alternative splicing, transport, translation, storage and decay. Light
induces massive reprogramming of gene expression in plants. Differences in
alternative splicing patterns in response to environmental stimuli suggest that
alternative splicing plays an important role in plant adaptation to changing life
conditions. In a recent publication, our laboratories showed that light regulates
alternative splicing of a subset of Arabidopsis genes encoding proteins involved
in RNA processing by chloroplast retrograde signals. The light effect on
alternative splicing is also observed in roots when the communication with the
photosynthetic tissues is not interrupted, suggesting that a signaling molecule
travels through the plant. These results point at alternative splicing regulation
by retrograde signals as an important mechanism for plant adaptation to their
environment.
PMID- 25590226
TI - Subcloning plus insertion (SPI)--a novel recombineering method for the rapid
construction of gene targeting vectors.
AB - Gene targeting refers to the precise modification of a genetic locus using
homologous recombination. The generation of novel cell lines and transgenic mouse
models using this method necessitates the construction of a 'targeting' vector,
which contains homologous DNA sequences to the target gene, and has for many
years been a limiting step in the process. Vector construction can be performed
in vivo in Escherichia coli cells using homologous recombination mediated by
phage recombinases using a technique termed recombineering. Recombineering is the
preferred technique to subclone the long homology sequences (>4 kb) and various
targeting elements including selection markers that are required to mediate
efficient allelic exchange between a targeting vector and its cognate genomic
locus. Typical recombineering protocols follow an iterative scheme of step-wise
integration of the targeting elements and require intermediate purification and
transformation steps. Here, we present a novel recombineering methodology of
vector assembly using a multiplex approach. Plasmid gap repair is performed by
the simultaneous capture of genomic sequence from mouse Bacterial Artificial
Chromosome libraries and the insertion of dual bacterial and mammalian selection
markers. This subcloning plus insertion method is highly efficient and yields a
majority of correct recombinants. We present data for the construction of
different types of conditional gene knockout, or knock-in, vectors and BAC
reporter vectors that have been constructed using this method. SPI vector
construction greatly extends the repertoire of the recombineering toolbox and
provides a simple, rapid and cost-effective method of constructing these highly
complex vectors.
PMID- 25590227
TI - From a cracking facade to a total escape: maladaptive perfectionism and suicide.
AB - This study explored the final stages of the suicide process among six men
characterized as maladaptive perfectionists. These men, aged 22 to 58, had no
history of suicide attempts or mental health treatment. In-depth interviews with
5 to 9 informants for each person were analyzed by using interpretative
phenomenological analysis. Three themes emerged from the analysis: (a) a cracking
facade; (b) a total loss of coping ability; and (c) a total escape. Suicide was
related to a shameful defeat that was not reversible, and a loss of the ability
to handle such feelings of defeat and shame.
PMID- 25590228
TI - Trichosporon asahii infection presenting as chronic meningo-ventriculitis and
intra ventricular fungal ball: a case report and literature review.
AB - Central nervous system trichosporonosis is a rare clinical entity and so far only
six cases including three each of brain abscess and meningitis has been on
record. We report a rare case of chronic meningo-ventriculitis and
intraventricular fungal ball due to Trichosporon asahii in an 18-year-old
immunocompetent male from Burundi, east Africa. Neuroendoscopy showed multiple
nodules and a fungal ball within the ventricle, which on culture grew T. asahii.
He was initially empirically treated with liposomal amphotericin B. However, the
antifungal susceptibility testing of T. asahii isolate revealed high minimum
inhibitory concentration for amphotericin B (2 MUg ml-1), flucytosine (16 MUg ml
1) and caspofungin (2 MUg ml-1) but exhibited potent activity for voriconazole,
posaconazole, itraconazole and fluconazole. The patient rapidly succumbed to
cardiac arrest before antifungal therapy could be changed. Although disseminated
trichosporonosis has been increasingly reported the diagnosis represents a
challenge especially in rare clinical settings such as intraventricular fungal
ball in the present case, which has not been described previously.
PMID- 25590229
TI - Radiation-induced second primary cancer risks from modern external beam
radiotherapy for early prostate cancer: impact of stereotactic ablative
radiotherapy (SABR), volumetric modulated arc therapy (VMAT) and flattening
filter free (FFF) radiotherapy.
AB - Risks of radiation-induced second primary cancer following prostate radiotherapy
using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy
(IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and
stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were
created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy
in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy
matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and
energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans
of three prostate patients, each planned using all 6 techniques, were used to
calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second
rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using
mechanistic, bell-shaped and plateau models. For organs distant to the treatment
field, chamber measurements recorded in an anthropomorphic phantom were used to
calculate OEDs and EARs using a linear model. Ratios of OED give relative
radiation-induced second cancer risks. SABR resulted in lower second cancer risks
at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out
of-field tissues relative to equivalent flattened techniques, with increasing
impact in organs at greater distances from the field. For example, FFF reduced
second cancer risk by up to 20% in the stomach and up to 56% in the brain,
relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV
IMRT or VMAT with flattening filter increased second cancer risks in several out
of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs
were consistently low. The observed large relative differences between
techniques, in absolute terms, were very low, highlighting the importance of
considering absolute risks alongside the corresponding relative risks, since when
absolute risks are very low, large relative risks become less meaningful. A
calculated relative radiation-induced second cancer risk benefit from SABR and
FFF techniques was theoretically predicted, although absolute radiation-induced
second cancer risks were low for all techniques, and absolute differences between
techniques were small.
PMID- 25590230
TI - Activation of cellular apoptosis in the caecal epithelium is associated with
increased oxidative reactions in lactating goats after feeding a high-concentrate
diet.
AB - NEW FINDINGS: What is the central question of this study? What are the
ultrastructural changes of the caecal mucosa and the status of epithelial
cellular apoptosis and oxidative reactions in lactating goats after prolonged
feeding with a high-concentrate diet? What is the main finding and its
importance? High-concentrate diet results in ultrastructural damage to the
caprine caecal epithelium. Increased oxidative and decreased antioxidative
reactions are involved in the process of activating epithelial apoptosis in the
caecal epithelium of goats fed a high-concentrate diet. Our results provide new
insight into the relationship between abnormal fermentation in the hindgut and
damage to the intestinal mucosal barrier. The effect of feeding a high
concentrate diet (HC) to lactating ruminants on their hindgut epithelial
structure remains unknown. In this study, 12 lactating goats were randomly
assigned to either HC (65% of dry matter as concentrate; n = 6) or a low
concentrate diet (LC; 35% of dry matter as concentrate; n = 6). After 10 weeks,
the epithelial ultrastructure and cell apoptotic status in the caecal mucosa were
determined by transmission electron microscopy and TUNEL, respectively. The
results showed that the level of free lipopolysaccharide (P < 0.05), total
volatile fatty acid concentrations (P < 0.1) and starch content (P < 0.05) in the
caecal digesta were significantly increased in HC- compared with LC-fed goats.
The HC-fed goats exhibited obvious epithelial cellular damage, with widened tight
junction spaces, nuclear breakdown and mitochondrial swelling. Compared with
their LC-fed counterparts, HC-fed goats showed greater apoptosis in the caecal
epithelium, as evidenced by more TUNEL-positive apoptotic cells. Western blot
analysis showed that there was no significant difference in activated caspase-3,
Bax protein expression in caecal epithelial mucosa between HC- and LC-fed goats
(P > 0.05). However, the level of malondialdehyde content in the caecal
epithelium from HC-fed goats was markedly higher than that in LC-fed goats (P <
0.05), whereas the level of glutathione peroxidase and the superoxide dismutase
activity were significantly decreased. Gene expressions of cytokines, including
interleukin-1beta, interleukin-6, interleukin-10, tumour necrosis factor-alpha
and interferon-gamma, as well as myeloperoxidase activity in the caecal mucosa
did not show any significant difference between HC- and LC-fed goats. These
results indicate that feeding a high-concentrate diet to lactating goats for a
prolonged period results in abnormal fermentation and structural disruption in
the hindgut, which is accompanied by greater cellular apoptosis and an enhanced
oxidative stress response.
PMID- 25590231
TI - The neuromuscular junction: measuring synapse size, fragmentation and changes in
synaptic protein density using confocal fluorescence microscopy.
AB - The neuromuscular junction (NMJ) is the large, cholinergic relay synapse through
which mammalian motor neurons control voluntary muscle contraction. Structural
changes at the NMJ can result in neurotransmission failure, resulting in
weakness, atrophy and even death of the muscle fiber. Many studies have
investigated how genetic modifications or disease can alter the structure of the
mouse NMJ. Unfortunately, it can be difficult to directly compare findings from
these studies because they often employed different parameters and analytical
methods. Three protocols are described here. The first uses maximum intensity
projection confocal images to measure the area of acetylcholine receptor (AChR)
rich postsynaptic membrane domains at the endplate and the area of synaptic
vesicle staining in the overlying presynaptic nerve terminal. The second protocol
compares the relative intensities of immunostaining for synaptic proteins in the
postsynaptic membrane. The third protocol uses Fluorescence Resonance Energy
Transfer (FRET) to detect changes in the packing of postsynaptic AChRs at the
endplate. The protocols have been developed and refined over a series of studies.
Factors that influence the quality and consistency of results are discussed and
normative data are provided for NMJs in healthy young adult mice.
PMID- 25590235
TI - Profiling the preterm or VLBW born adolescent; implications of the Dutch POPS
cohort follow-up studies.
AB - In 1983, data of a unique nationwide cohort of 1338 very preterm (<32 weeks of
gestation) or VLBW (birth weight<1500g) infants in the Netherlands was collected
and followed at several ages until they reached the age of 19 years. At 19 years
of age a more extensive follow-up study was done, including questionnaires, tests
on a computer and a full physical exam. These studies provide insight into how
Dutch adolescents at 19 years of age, who were born very preterm or with a very
low birth weight (VLBW), reach adulthood. At 19 years, 705 POPS participants
participated (74% of 959 still alive). Outcome measures at 19 years included:
physical outcomes (e.g. blood pressure), cognition, behavior, quality of life,
and impact of handicaps. The POPS participants showed more impairments on most
outcome measures at various ages, compared to norm data. Major handicaps remained
stable as the children grew older, but minor handicaps and disabilities
increased. At 19 years of age, only half (47.1%) of the survivors had no
disabilities and no minor or major handicaps. Especially those born small for
gestational age (SGA) seem most vulnerable. These long-term results help to
support preterm and SGA born children and adolescents in reaching independent
adulthood, and stress the need for long term follow-up studies and to promote
prevention of disabilities and of preterm birth itself.
PMID- 25590236
TI - Precious life-blood of a master-spirit.
AB - Recent books on microscopy and related topics, including bad writing, are
examined.
PMID- 25590237
TI - Representation of Disease: What's in a Name?
PMID- 25590233
TI - New strategy for in vitro activation of primordial follicles with mTOR and PI3K
stimulators.
AB - It had been known for decades that primordial follicles in mammalian ovaries are
assembled with definite numbers and represent the ovarian reserve throughout the
reproductive life. Intra-oocyte PI3K/mTOR pathways have been indicated to play a
central role on the activation of primordial follicles. Genetic modified mouse
models with chronic activation of PI3K/mTOR signals in primordial oocytes showed
premature activation of all primordial follicles and eventually their exhaustion.
On the other hand, this may suggest that, unlike chronic activation of PI3K/mTOR,
its acute activation in infertility would activate primordial follicles,
permitting fertility during the treatment. Previously, PI3K stimulators were
reported as a temporary measure to accelerate primordial follicle activation and
follicular development in both mouse and human, and were applied in the treatment
of infertility in premature ovarian failure (POF) patients. To address whether
mTOR stimulators could play similar role in the process, we transiently treated
neonatal and aged mouse ovaries with mTOR stimulators-phosphatidic acid (PA) and
propranolol. Our results demonstrated the stimulators increased activation of
primordial follicles and the production of progeny. Human ovarian cortex cubes
were also treated with mTOR or/and PI3K stimulators in vitro. When they were used
separately, both of them showed similar promotive effects on primordial
follicles. Surprisingly, after joint-treatment with the 2 kinds of stimulators
together, synergistic effects on follicular development were observed. Based on
increased efficiency of follicular activation in humans, here we propose in vitro
transient treatment with mTOR and PI3K stimulators as an optimized protocol for
the application in different clinical conditions with limited follicle reserve.
PMID- 25590232
TI - NK cell-based immunotherapies in Pediatric Oncology.
AB - The past decade has seen several anticancer immunotherapeutic strategies
transition from "promising preclinical models" to treatments with proven clinical
activity or benefit. In 2013, the journal Science selected the field of Cancer
Immunotherapy as the overall number-1 breakthrough for the year in all of
scientific research. In the setting of cancer immunotherapy for adult
malignancies, many of these immunotherapy strategies have relied on the cancer
patient's endogenous antitumor T-cell response. Although much promising research
in pediatric oncology is similarly focused on T-cell reactivity, several
pediatric malignancies themselves, or the chemo-radiotherapy used to achieve
initial responses, can be associated with profound immune suppression,
particularly of the T-cell system. A separate component of the immune system,
also able to mediate antitumor effects and less suppressed by conventional cancer
treatment, is the NK-cell system. In recent years, several distinct
immunotherapeutic approaches that rely on the activity of NK cells have moved
from preclinical development into clinical testing, and some have shown clear
antitumor benefit. This review provides an overview of NK cell-based
immunotherapy efforts that are directed toward childhood malignancies, with an
emphasis on protocols that are already in clinical testing.
PMID- 25590238
TI - Polyacrylamide gels for invadopodia and traction force assays on cancer cells.
AB - Rigid tumor tissues have been strongly implicated in regulating cancer cell
migration and invasion. Invasive migration through cross-linked tissues is
facilitated by actin-rich protrusions called invadopodia that proteolytically
degrade the extracellular matrix (ECM). Invadopodia activity has been shown to be
dependent on ECM rigidity and cancer cell contractile forces suggesting that
rigidity signals can regulate these subcellular structures through actomyosin
contractility. Invasive and contractile properties of cancer cells can be
correlated in vitro using invadopodia and traction force assays based on
polyacrylamide gels (PAAs) of different rigidities. Invasive and contractile
properties of cancer cells can be correlated in vitro using invadopodia and
traction force assays based on polyacrylamide gels (PAAs) of different
rigidities. While some variations between the two assays exist, the protocol
presented here provides a method for creating PAAs that can be used in both
assays and are easily adaptable to the user's specific biological and technical
needs.
PMID- 25590239
TI - Photochemical nitrogen conversion to ammonia in ambient conditions with FeMoS
chalcogels.
AB - In nature, nitrogen fixation is one of the most important life processes and
occurs primarily in microbial organisms containing enzymes called nitrogenases.
These complex proteins contain two distinct subunits with different active sites,
with the primary N2 binding site being a FeMoS core cluster that can be reduced
by other nearby iron-sulfur clusters. Although nitrogen reduction to ammonia in
biology does not require the absorption of light, there is considerable interest
in developing catalyst materials that could drive the formation of ammonia from
nitrogen photochemically. Here, we report that chalcogels containing FeMoS
inorganic clusters are capable of photochemically reducing N2 to NH3 under white
light irradiation, in aqueous media, under ambient pressure and room temperature.
The chalcogels are composed of [Mo2Fe6S8(SPh)3](3+) and [Sn2S6](4-) clusters in
solution and have strong optical absorption, high surface area, and good aqueous
stability. Our results demonstrate that light-driven nitrogen conversion to
ammonia by MoFe sulfides is a viable process with implications in solar energy
utilization and our understanding of primordial processes on earth.
PMID- 25590241
TI - Rapid discrimination and feature extraction of three Chamaecyparis species by
static-HS/GC-MS.
AB - This study aimed to develop a rapid and accurate analytical method for
discriminating three Chamaecyparis species (C. formosensis, C. obtusa, and C.
obtusa var. formosana) that could not be easily distinguished by volatile
compounds. A total of 23 leaf samples from three species were analyzed by static
headspace (static-HS) coupled with gas chromatography-mass spectrometry (GC-MS).
The static-HS procedure, whose experimental parameters were properly optimized,
yielded a high Pearson correlation-based similarity between essential oil and VOC
composition (r = 0.555-0.999). Thirty-six major constituents were identified;
along with the results of cluster analysis (CA), a large variation in contents
among the three different species was observed. Principal component analysis
(PCA) methods illustrated graphically the relationships between characteristic
components and tree species. It was clearly demonstrated that the static-HS-based
procedure enhanced greatly the speed of precise analysis of chemical fingerprint
in small sample amounts, thus providing a fast and reliable tool for the
prediction of constituent characteristics in essential oil, and also offering
good opportunities for studying the role of these feature compounds in
chemotaxonomy or ecophysiology.
PMID- 25590240
TI - PCDH10, a novel p53 transcriptional target in regulating cell migration.
AB - Cell cycle arrest, senescence and apoptosis are commonly regarded as the major
tumor suppression mechanisms of p53. However, accumulating evidence indicates
that loss of these canonical functions is not sufficient for tumor formation,
highlighting the complexity of p53-mediated tumor suppression. PCDH10 belongs to
a proto cadherin protein family and is a potential tumor suppressor protein as
the dysregulation of PCDH10 gene frequently existed in multiple human tumors.
Here, we found that PCDH10 is a transcriptional target of p53 and that the levels
of PCDH10 expression can be induced by wild type p53 but not mutant p53 in a
number of human cancer cell lines. Moreover, we identified a p53 consensus
binding site located in the PCDH10 promoter region that is responsive to p53
regulation. Although upregulation of PCDH10 has no obvious effect on growth
arrest or apoptosis in human cells, PCDH10 exhibits inhibitory roles in cancer
cell motility and cell migration. These results suggest an important role of p53
in regulating tumor cell migration through activating PCDH10 expression and
support the notion that non-canonical activities of p53 may contribute to its
tumor suppressor function in vivo.
PMID- 25590242
TI - Maternal adiponectin controls milk composition to prevent neonatal inflammation.
AB - Adiponectin is an important adipokine. Increasing evidence suggests that altered
adiponectin levels are linked with metabolic and inflammatory disorders. Here we
report an important yet previously unrecognized function of adiponectin in
lactation by which maternal adiponectin determines the inflammatory status in the
nursing neonates. Surprisingly, both maternal adiponectin overexpression in the
transgenic mice and maternal adiponectin deletion in the knockout mice lead to
systemic inflammation in the pups, manifested as transient hair loss. However,
distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte
infiltration and production of inflammatory cytokines in the lactating mammary
gland. In contrast, adiponectin overabundance increases lipid accumulation in the
lactating mammary gland, resulting in excessive long-chain saturated fatty acids
in milk. Interestingly, in both cases, the inflammation and alopecia in the pups
can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double
knockout pups are resistant. Mechanistically, long-chain saturated fatty acid
activation of inflammatory genes is TLR2/4 dependent and can be potentiated by
proinflammatory cytokines, indicating that the inflammatory stimuli in both
scenarios functionally converge by activating the TLR2/4 signaling. Therefore,
our findings reveal adiponectin as a dosage-dependent regulator of lactation
homeostasis and milk quality that critically controls inflammation in the nursing
neonates. Furthermore, these results suggest that inflammatory infantile
disorders may result from maternal adiponectin dysregulation that can be treated
by TLR2/4 inhibition.
PMID- 25590243
TI - Metformin regulates ovarian angiogenesis and follicular development in a female
polycystic ovary syndrome rat model.
AB - Polycystic ovary syndrome (PCOS) is a frequent pathology that affects more than
5% of women of reproductive age. Among other heterogeneous symptoms, PCOS is
characterized by abnormalities in angiogenesis. Metformin has been introduced in
the treatment of PCOS to manage insulin resistance and hyperglycemia. Besides its
metabolic effects, metformin has been shown to improve ovulation, pregnancy and
live birth rates in PCOS patients. In the present study, we used a
dehydroepiandrosterone-induced PCOS rat model to analyze the effect of metformin
administration on ovarian angiogenesis. We found that metformin was able to
restore the increased levels of vascular endothelial growth factor, angiopoietin
(ANGPT)1, and ANGPT1/ANGPT2 ratio and the decreased levels of platelet-derived
growth factor B and platelet-derived growth factor D observed in the
dehydroepiandrosterone-treated rats. These effects could take place, at least in
part, through a decrease in the levels of serum insulin. We also found an
improvement in follicular development, with a lower percentage of small follicles
and cysts and a higher percentage of antral follicles and corpora lutea after
metformin administration. The improvement in ovarian angiogenesis is likely to
restore the accumulation of small follicles observed in PCOS rats and to reduce
cyst formation, thus improving follicular development and the percentage of
corpora lutea. These results open new insights into the study of metformin action
not only in glucose metabolism but also in ovarian dysfunction in PCOS women.
PMID- 25590245
TI - Kisspeptin: beyond the brain.
AB - The hypothalamic-based kisspeptin-signaling system is a major positive regulator
of the neuroendocrine-reproductive axis in mammals. During the last decade, major
advances have been made in understanding how this signaling system is regulated
and how it can be manipulated clinically to achieve beneficial outcomes in
treating sex steroid-dependent disorders. Interestingly, kisspeptin was not first
identified as a regulator of fertility. Instead, approximately 7 years earlier
KISS1 was reported to be expressed in nonmetastatic melanoma cells and was
subsequently demonstrated to act as a powerful suppressor of the metastatic
potential of malignant melanoma cells. Since this discovery, numerous studies
have demonstrated the expression of the kisspeptin-signaling system at several
peripheral sites implicating it in biological processes such as the regulation of
ovarian function, embryo implantation, placentation, angiogenesis, insulin
secretion, and kidney development. Although much work remains to be done to
assess how important kisspeptin signaling is in regulating some of these
processes, for other processes recent studies have made tremendous strides toward
such an assessment. Using mice lacking either Kiss1 or Kiss1r alleles,
researchers have provided compelling evidence for kisspeptin playing a major role
in regulating breast cancer metastasis, oocyte survival, follicular maturation,
ovulation, and embryo implantation. This review critically discusses the findings
from these as well as other studies which suggest roles for kisspeptin in
regulating important physiological processes beyond the brain. It also discusses
the challenges that lie ahead in determining whether findings made with animal
models are relevant in humans.
PMID- 25590246
TI - A classification system for fat necrosis in autologous breast reconstruction.
PMID- 25590247
TI - Desferrioxamine: a practical method for improving neovascularization of
prefabricated flaps.
AB - BACKGROUND: Prefabricated flaps are an ideal alternative to repair massive and
complex tissue defects. Nevertheless, the risk of necrosis due to unpredictable
blood supplies is a major obstacle to the application of prefabricated flaps. The
survival of a prefabricated flap depends on the neovascularization between the
vascular carrier and the donor tissue. Here, we proposed that the iron chelator,
desferrioxamine (DFX), owned therapeutic effects that promoted the
neovascularization of prefabricated flaps. METHODS: An abdominal prefabricated
flap model was created in rats via a 2-stage operation. The rats were allocated
into 4 groups as follows: 2 groups of rats received DFX treatments during the
first or the second stage of the operation, respectively; 1 group of rats
received a delay procedure 1 week before the second operation; and the final
group was used as a blank control. Flap survival rates and capillary densities
were evaluated between groups. The influence of DFX on the dermal fibroblasts was
also studied in vitro. RESULTS: Desferrioxamine treatment during the first stage
of the operation greatly increased flap survival rate compared to the blank
control. The results were similar to those produced by the delay treatment. The
vessel count results were consistent with the flap survival rate findings. In
vitro, DFX treatment up-regulated the expression levels of several angiogenic
factors in the dermal fibroblasts. Nevertheless, DFX treatment during the second
stage of the operation was therapeutically detrimental. CONCLUSIONS: The
application of DFX around the time of vascular carrier implantation greatly
promoted neovascularization of prefabricated flaps, but was therapeutically
detrimental after the flaps had been elevated.
PMID- 25590244
TI - Reduced melanocortin production causes sexual dysfunction in male mice with POMC
neuronal insulin and leptin insensitivity.
AB - Proopiomelanocortin (POMC)-derived peptides like alpha-melanocyte-stimulating
hormone (MSH) substantially improve hepatic insulin sensitivity and regulate
energy expenditure. Melanocortinergic agents are also powerful inducers of sexual
arousal that are being investigated for a possible therapeutic role in erectile
dysfunction. It is currently unclear whether reduced melanocortin (MC) activity
may contribute to the sexual dysfunction accompanying obesity and type 2
diabetes. Male rodents with leptin and insulin resistance targeted to POMC
neurons (leptin receptor [LepR]/insulin receptor [IR]POMC mice) exhibit obesity,
hyperinsulinemia, hyperglycemia, and systemic insulin resistance. In this study,
we demonstrate that LepR/IRPOMC males are also subfertile due to dramatic
alterations in sexual behavior. Remarkably, these reproductive changes are
accompanied by decreased alpha-MSH production not present when a single receptor
type is deleted. Unexpectedly, behavioral sensitivity to alpha-MSH and MC
receptor expression are also reduced in LepR/IRPOMC males, a potential adaptation
of the MC system to altered alpha-MSH production. Together, these results suggest
that concurrent insulin and leptin resistance in POMC neurons in individuals with
obesity or type 2 diabetes can reduce endogenous alpha-MSH levels and impair
sexual function.
PMID- 25590248
TI - Cost-benefit analysis of outcomes from the use of fibrin sealant for fixation of
skin grafts in small-size burns compared to staples as historical controls: a
retrospective review.
AB - INTRODUCTION: Historically, split-thickness skin grafts have been fixed onto the
recipient site by suture and/or staples. Fibrin sealants have become available
for the fixation in the past 10 years. Fibrin sealants have been shown to be at
least as effective as staples, and recent reports show them to cause less pain.
However, the product is much more expensive than traditional suture and/or staple
fixation. The cost-benefit ratio of sealant has not yet been proven. METHODS: A
review of charts for 202 consecutive patients was undertaken for patients with
burns that were less than 10% total body surface area (TBSA) that underwent
excision and grafting using fibrin sealant at the regional burn center. A
historical control comprising 48 consecutive patients with burns that were less
than 10% TBSA that underwent excision and grafting using staples as the only
means of fixation was used for comparison. Demographics (such as age, weight, and
sex), personal history of tobacco use, previous diagnosis of diabetes, type and
depth of burn, TBSA, area of grafting, graft and donor locations, mesh type, rate
of hematomas, rate of graft loss, rate of complete closure at 1 month, and time
to discharge after surgery were recorded for each patient in both cohorts. The
data were compared and statistical analysis performed for graft loss
complications and number of days until the patient could be discharged home with
outpatient wound care. RESULTS: Use of fibrin sealants has resulted in
statistically significant lower rates of loss of graft at our institution.
Additionally, a decrease in the number of days until discharge to outpatient
wound care of nearly 2 days produced a lower cost of care in patients with less
than 10% TBSA undergoing excision and grafting. CONCLUSIONS: The use of fibrin
sealants allows for fewer graft loss complications and earlier discharge in
patients who have burns that are less than 10% TBSA. This decrease in hospital
days results in savings, although this difference is not statistically
significant.
PMID- 25590249
TI - Local administration of beta-blockers for infantile hemangiomas: a systematic
review and meta-analysis.
AB - BACKGROUND: Infantile hemangiomas (IHs) are a common pediatric lesion. Orally
administered beta-blockers have been reported as effective in treating these
lesions. However, oral administration is also associated with systemic adverse
effects. Treatment with locally administered beta-blockers may provide acceptable
efficacy with lower incidence of adverse effects. This may offer a better first
line treatment. METHODS: PubMed was searched through March 2014 for studies
reporting patient-level response of 5 or more patients treated with intralesional
propranolol, topical timolol, or topical propranolol for cutaneous IHs. Rates of
response to treatment, defined as clinically significant regression, were
combined using random-effects meta-analysis. RESULTS: Ninety-four articles were
identified. Seventeen articles met the study criteria. These studies primarily
focused on superficial IHs. Response rates for topical propranolol and topical
timolol were not significantly different, 76% [95% confidence interval (CI), 62%
86%] and 83% (95% CI, 65%-93%), respectively (P=0.45). Prospectively conducted
studies reported lower response rates compared to retrospective studies for both
topical propranolol (P=0.06) and topical timolol (P<0.01). When only
prospectively conducted studies were included, response rates for topical
propranolol and topical timolol were not significantly different, 72% (95% CI,
57%-83%) and 72% (95% CI, 53%-86%), respectively (P=0.98). Significant adverse
effects were rare. Only 1 case of sleep disturbance was reported across 554
patients from all studies. CONCLUSIONS: Topically administered beta-blockers are
an effective treatment for superficial IHs that pose few adverse effects and
should be considered for primary treatment.
PMID- 25590250
TI - Outcomes of immediate tissue expander breast reconstruction followed by
reconstruction of choice in the setting of postmastectomy radiation therapy.
PMID- 25590251
TI - The use of patient registries in breast surgery: a comparison of the tracking
operations and outcomes for plastic surgeons and national surgical quality
improvement program data sets.
AB - BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) and the
Tracking Operations and Outcomes for Plastic Surgeons (TOPS) registries gather
outcomes for plastic surgery procedures. The NSQIP collects hospital data using
trained nurses, and the TOPS relies on self-reported data. We endeavored to
compare the TOPS and NSQIP data sets with respect to cohort characteristics and
outcomes to better understand the strengths and weakness of each registry as
afforded by their distinct data collection methods. STUDY DESIGN: The 2008 to
2011 TOPS and NSQIP databases were queried for breast reductions and breast
reconstructions. Propensity score matching identified similar cohorts from the
TOPS and NSQIP databases. Shared 30-day surgical and medical complications rates
were compared across matched cohorts. RESULTS: The TOPS captured a significantly
greater number of wound dehiscence occurrences (4.77%-5.47% vs 0.69%-1.17%, all
P<0.001), as well as more reconstructive failures after prosthetic reconstruction
(2.82% vs 0.26%, P<0.001). Medical complications were greater in NSQIP (P<0.05).
Other complication rates did not differ across any procedure (all P>0.05).
CONCLUSIONS: The TOPS and NSQIP capture significantly different patient
populations, with TOPS' self-reported data allowing for the inclusion of private
practices. This self-reporting limits TOPS' ability to identify medical
complications; surgical complications and readmissions, however, were not
underreported. Many surgical complications are captured by TOPS at a higher rate
due to its broader definitions, and others are not captured by NSQIP at all. The
TOPS and NSQIP provide complementary information with different strengths and
weakness that together can guide evidence-based decision making in plastic
surgery.
PMID- 25590252
TI - The impact of conflict of interest in abdominal wall reconstruction with
acellular dermal matrix.
AB - INTRODUCTION: Conflict of interest (COI) and disclosure of financial
relationships have received increased attention recently owing in part to the
passage of the Physician Payments Sunshine Act, which requires manufacturers of
drugs, medical devices, and biological to record payments to physicians and
health care systems. The impact of financial relationships with industry
sponsorship and COI reporting on surgical outcomes of abdominal wall
reconstruction with acellular dermal matrices (ADMs) has not been previously
explored. METHODS: A systematic review of the literature for studies that
evaluated surgical outcomes in abdominal wall reconstruction using ADM was
conducted. The level of evidence of these studies was evaluated; and data
concerning the type of industry, government, or national society sponsorship,
primary outcome, complications, and statistical results were collected. The
overall favorability of the study with respect to ADM use was systematically
assessed. Comparisons between type of sponsorship and significant results were
analyzed using the Pearson chi2 test. RESULTS: A total of 204 studies were
identified, of which 124 fulfilled our inclusion criteria. Sixty-four (52%)
studies had a disclosure statement present. Conflict of interest was reported in
39 (61%) of these studies. Taken collectively, studies that report no COI are
more likely to be unfunded (P<0.001). Studies with a reported COI are more likely
to report a favorable outcome with respect to infection (P<0.01), wound
complications (P<0.01), and overall morbidity (P<0.07) and mortality (P<0.05).
CONCLUSIONS: Industry sponsorship and COI are common in abdominal wall
reconstruction studies with ADM. Studies authored by groups disclosing an
industry conflict that report clinical outcomes are significantly associated with
reporting lower postoperative complications, and consequently describing positive
research findings.
PMID- 25590253
TI - Outcomes of immediate tissue expander breast reconstruction followed by
reconstruction of choice in the setting of postmastectomy radiation therapy:
reply.
PMID- 25590254
TI - Local anesthetic use in tumescent liposuction: an American Society of Plastic
Surgeons survey.
AB - BACKGROUND: Current guidelines favor the use of lidocaine in liposuction wetting
solutions. The use of bupivacaine as an alternative remains controversial despite
reports of its use with safe and favorable outcomes suggesting faster
postoperative recovery time secondary to improved pain control. The goals of this
study were to determine the prevalence of bupivacaine use, examine liposuction
practices of bupivacaine users, and elucidate opinions regarding bupivacaine use.
METHODS: An online survey was distributed to 2500 randomly selected members of
the American Society of Plastic Surgeons. Data were collected and analyzed with
special attention toward the practice and opinions of bupivacaine use. RESULTS:
The response rate of the survey met the average American Society of Plastic
Surgeons online survey response rate at 12.8% (n=320). Respondents (7.2%; n=22)
reported using bupivacaine in their wetting solutions (bupivacaine group) and
provided a dosage range of 62.5 to 150 mg. Respondents (83.5%; n=254) reported
using either lidocaine or prilocaine (no-bupivacaine group). There were no
reports of bupivacaine toxicity in 2011. The demographic profile and liposuction
practices of both groups were comparable. Although 36% of the no-bupivacaine
group did not know or had no opinion on when it is appropriate to use bupivacaine
in liposuction wetting solutions, 85% of this group has used bupivacaine for
other clinical purposes. CONCLUSIONS: A review of 320 plastic surgeons'
experiences revealed that 7% of respondents are using bupivacaine in their
tumescent solutions with no reported cases of toxicity. Bupivacaine users
differed dramatically only in their opinion regarding the safety of bupivacaine
in tumescent liposuction. The recent studies suggesting better postoperative pain
control with bupivacaine along with the proportion of respondents reporting
bupivacaine use call for distinct guidelines on bupivacaine use in liposuction.
Further studies, including a rigorous clinical trial documenting the safety and
efficacy of bupivacaine when compared with lidocaine, would be warranted.
PMID- 25590255
TI - Blepharoptosis correction with buried suture method.
AB - BACKGROUND: Many surgical techniques have been developed to correct
blepharoptosis, including the anterior levator resection or advancement,
tarsoaponeurectomy, and Fasanella-Servat Mullerectomy. However, to minimize
surgical scarring and reduce the postoperative recovery time, the procedure has
been developed from a complete incision to a partial incision, which is appealing
to patients. To aid the procedural development, this study describes a surgical
technique in which the correction of blepharoptosis and a double eyelid fold
operation are performed using a buried suture technique during the same
operation. METHODS: A retrospective review was conducted using the medical
records and preoperative and postoperative photography of 121 patients who
underwent simultaneous correction of blepharoptosis and had a double eyelid fold
created between October 2010 and July 2011. All of the patients had mild (1-2 mm)
or moderate (3-4 mm) bilateral blepharoptosis and excellent or good levator
function (>8 mm). RESULTS: The average preoperative marginal reflex distance
(MRD1) measured 1.174 (0.3) mm. No intraoperative complications occurred. The
average postoperative MRD1 measured 3.968 (0.2) mm. There was statistical
significance improvement between preoperative MRD1 and postoperative MRD1
(P<0.05). No symptomatic dry eye and exposure keratopathy were noted.
CONCLUSIONS: Blepharoptosis correction using the buried suture technique is an
effective technique for young patients experiencing mild to moderate
blepharoptosis who want to have the double eyelid fold operation using the buried
suture technique.
PMID- 25590256
TI - Coffee, tea, and chocolate after microsurgery: why not?
PMID- 25590258
TI - Real-time pathogen monitoring during enrichment: a novel nanotechnology-based
approach to food safety testing.
AB - We describe a new approach for the real-time detection and identification of
pathogens in food and environmental samples undergoing culture. Surface Enhanced
Raman Scattering (SERS) nanoparticles are combined with a novel homogeneous
immunoassay to allow sensitive detection of pathogens in complex samples such as
stomached food without the need for wash steps or extensive sample preparation.
SERS-labeled immunoassay reagents are present in the cultural enrichment vessel,
and the signal is monitored real-time through the wall of the vessel while
culture is ongoing. This continuous monitoring of pathogen load throughout the
enrichment process enables rapid, hands-free detection of food pathogens.
Furthermore, the integration of the food pathogen immunoassay directly into the
enrichment vessel enables fully biocontained food safety testing, thereby
significantly reducing the risk of contaminating the surrounding environment with
enriched pathogens. Here, we present experimental results showing the detection
of E. coli, Salmonella, or Listeria in several matrices (raw ground beef, raw
ground poultry, chocolate milk, tuna salad, spinach, brie cheese, hot dogs, deli
turkey, orange juice, cola, and swabs and sponges used to sample a stainless
steel surface) using the SERS system and demonstrate the accuracy of the approach
compared to plating results.
PMID- 25590257
TI - Surface chemistry of photoluminescent F8BT conjugated polymer nanoparticles
determines protein corona formation and internalization by phagocytic cells.
AB - Conjugated polymer nanoparticles are being developed for a variety of diagnostic
and theranostic applications. The conjugated polymer, F8BT, a polyfluorene
derivative, was used as a model system to examine the biological behavior of
conjugated polymer nanoparticle formulations stabilized with ionic (sodium
dodecyl sulfate; F8BT-SDS; ~207 nm; -31 mV) and nonionic (pegylated 12
hydroxystearate; F8BT-PEG; ~175 nm; -5 mV) surfactants, and compared with
polystyrene nanoparticles of a similar size (PS200; ~217 nm; -40 mV). F8BT
nanoparticles were as hydrophobic as PS200 (hydrophobic interaction
chromatography index value: 0.96) and showed evidence of protein corona formation
after incubation with serum-containing medium; however, unlike polystyrene, F8BT
nanoparticles did not enrich specific proteins onto the nanoparticle surface.
J774A.1 macrophage cells internalized approximately ~20% and ~60% of the F8BT-SDS
and PS200 delivered dose (calculated by the ISDD model) in serum-supplemented and
serum-free conditions, respectively, while cell association of F8BT-PEG was
minimal (<5% of the delivered dose). F8BT-PEG, however, was more cytotoxic (IC50
4.5 MUg cm(-2)) than F8BT-SDS or PS200. The study results highlight that F8BT
surface chemistry influences the composition of the protein corona, while the
properties of the conjugated polymer nanoparticle surfactant stabilizer used
determine particle internalization and biocompatibility profile.
PMID- 25590259
TI - Survival and growth of Salmonella Typhimurium, Escherichia coli O157:H7 and
Staphylococcus aureus in eggplant dip during storage.
AB - Eggplant dip is an internationally popular appetizer, prepared in some instances
under uncertain hygienic conditions with inconsistent refrigeration. This study
examined the effects of citric acid on the survival of pathogenic microorganisms
(Salmonella Typhimurium, Escherichia coli O157:H7 and Staphylococcus aureus) and
naturally present organisms (lactic acid bacteria, LAB, aerobic bacteria, APC and
yeast and mold, YM) in eggplant dip during storage. Eggplant dip with 0, 0.2,
0.4, 0.6 or 0.8% citric acid was inoculated with S. Typhimurium, E. coli O157:H7
or S. aureus and stored at 4, 10 and 21 degrees C for <=15 d. Throughout the
study, the survival of the inoculated microorganisms was monitored, and LAB, APC,
YM numbers and pH were determined. There was no significant (p>0.05) effect of
citric acid on inoculated S. Typhimurium and E. coli O157:H7. Salmonella and E.
coli O157:H7 survived >7d with little reduction in viability. Reduction of S.
aureus viability increased with citric acid concentration and reached>3.0 log10
CFU/g by 15 d at 4 degrees C. Citric acid had no effect (p>0.05) on the
background YM during storage at 4, 10 and 21 degrees C or LAB stored at 4 and 10
degrees C, while at 21 degrees C, 0.6 and 0.8% citric acid significantly
reduced LAB. Citric acid had no effect (p>0.05) on the APC in samples stored at 4
degrees C but it had significant effects on samples stored at 10 and 21 degrees
C. Work reported showed that the use of citric acid at 0.4-0.8% can inhibit the
growth of S. aureus in eggplant dip, but adequate refrigeration is essential to
minimize risk from this and other pathogens in this product.
PMID- 25590260
TI - Norovirus cross-contamination during preparation of fresh produce.
AB - Infection with human norovirus (HuNoV) is considered a common cause of foodborne
illness worldwide. Foodborne HuNoV outbreaks may result from consumption of food
contaminated by an infected food handler in the foodservice environment, in which
bare-hand contact, lack of hand washing, and inadequate cleaning and disinfection
are common contributing factors. The goal of this study was to examine cross
contamination of a HuNoV surrogate, murine norovirus (MNV-1), during common
procedures used in preparing fresh produce in a food service setting, including
turning water spigots, handling and chopping Romaine lettuce, and washing hands.
MNV-1 transfer % was log-transformed to achieve a normal distribution of the data
and enable appropriate statistical analyses to be performed. MNV-1 transfer
coefficients varied by surface type, and a greater affinity for human hands and
chopped lettuce was observed. For example, greater transfer was observed from a
contaminated stainless steel spigot to a clean hand (24% or 1.4-log transfer %)
compared to transfer from hand to spigot (0.6% or -0.2-log transfer %). During
the chopping of Romaine lettuce, MNV-1 was transferred from either a contaminated
cutting board (25% or 1.4-log transfer %) or knife (~100% or 2.0-log transfer %)
to lettuce at a significantly greater rate (p>0.05) than from contaminated
lettuce to the board (2.1% or 0.3-log transfer %) and knife (1.2% or 0.06-log
transfer %). No significant difference (p>0.05) in MNV-1 transfer coefficients
was observed between bare hands and Romaine lettuce during handling. For
handwashing trials, only one hand was inoculated with MNV-1 prior to washing. The
handwashing methods included rubbing hands under tap water for at least 5s
(average 2.8-log reduction) or washing hands for at least 20s with liquid soap
(average 2.9-log reduction) or foaming soap (average 3.0-log reduction), but no
statistical difference between these reductions was achieved (p>0.05). Despite
the reductions of MNV-1 observed, residual virions were detected on both hands
after washing in every replicate trial. This observation reveals that virions are
transferred from one hand to the other during washing with and without soap. Each
transfer scenario was repeated at least 9 times, and the data gathered indicate
that MNV-1 transfers readily between common surfaces during food preparation.
These data are important for the development of quantitative risk analyses, and
will assist in the development of appropriate intervention strategies for enteric
viruses in food preparation.
PMID- 25590261
TI - Electron beam inactivation of Tulane virus on fresh produce, and mechanism of
inactivation of human norovirus surrogates by electron beam irradiation.
AB - Ionizing radiation, whether by electron beams or gamma rays, is a non-thermal
processing technique used to improve the microbial safety and shelf-life of many
different food products. This technology is highly effective against bacterial
pathogens, but data on its effect against foodborne viruses is limited. A
mechanism of viral inactivation has been proposed with gamma irradiation, but no
published study discloses a mechanism for electron beam (e-beam). This study had
three distinct goals: 1) evaluate the sensitivity of a human norovirus surrogate,
Tulane virus (TV), to e-beam irradiation in foods, 2) compare the difference in
sensitivity of TV and murine norovirus (MNV-1) to e-beam irradiation, and 3)
determine the mechanism of inactivation of these two viruses by e-beam
irradiation. TV was reduced from 7 log10 units to undetectable levels at target
doses of 16 kGy or higher in two food matrices (strawberries and lettuce). MNV-1
was more resistant to e-beam treatment than TV. At target doses of 4 kGy, e-beam
provided a 1.6 and 1.2 log reduction of MNV-1 in phosphate buffered saline (PBS)
and Dulbecco's Modified Eagle Medium (DMEM), compared to a 1.5 and 1.8 log
reduction of TV in PBS and Opti-MEM, respectively. Transmission electron
microscopy revealed that increased e-beam doses negatively affected the structure
of both viruses. Analysis of viral proteins by SDS-PAGE found that irradiation
also degraded viral proteins. Using RT-PCR, irradiation was shown to degrade
viral genomic RNA. This suggests that the mechanism of inactivation of e-beam was
likely the same as gamma irradiation as the damage to viral constituents led to
inactivation.
PMID- 25590262
TI - CUET-ting edge research.
PMID- 25590263
TI - Selective growth of ZnO nanorods on hydrophobic Si nanorod arrays.
AB - In this paper we describe the selective growth of ZnO nanorods (NRs) on top of
hydrophobic Si NR arrays. The periodic Si NR arrays, prepared through electroless
chemical etching and HF treatment, functioned as hydrophobic substrates. Droplets
containing ZnO seeds could be positioned on the Si NR arrays, causing the ZnO
seeds to deposit selectively upon them, with n-ZnO NR/p-Si NR array
heterojunctions ultimately forming after hydrothermal growth of ZnO NRs. Because
of compensation for the difference in refractive index between air and the Si
substrate, the n-ZnO NR/p-Si NR arrays exhibited excellent absorption ability in
the visible range. Devices based on these n-ZnO NR/p-Si NR array heterojunctions
displayed not only rectifying behavior but also photovoltaic effects when
illuminated with UV light. The low temperature and low cost of this fabrication
process suggest that the selective growth of n-ZnO NRs on p-Si NR arrays might
allow such structures to have diverse applications in optoelectronics.
PMID- 25590264
TI - Simultaneous recovery of organic and inorganic content of paper deinking residue
through low-temperature microwave-assisted pyrolysis.
AB - Significant amounts of paper deinking residue (DIR) has been and is still being
generated from paper deinking processes, representing both an economic and
environmental burden for recycled paper mills. Our research on low-temperature
(<200 degrees C) microwave-assisted (MW-assisted) pyrolysis of DIR allows for
simultaneously efficient fast separation and recovery of the organic and
inorganic content of DIR at relatively low temperature and within 15 min. Our
study is the first highly detailed account of the use low-temperature MW-assisted
pyrolysis to effect this change. The obtained liquid and solid products were
characterized by a variety of analytical techniques (e.g., attenuated total
reflection infrared, gas chromatography-mass spectrometry, liquid-state nuclear
magnetic resonance (NMR), X-ray diffraction, solid-state cross-polarization/magic
angle spinning (13)C NMR, and Bloch-decay (13)C NMR). The results reveal that the
process efficiently separates the inorganic minerals as microwave residue (mainly
calcite and kaolinite) from organic matter, and hence the microwave residue could
be reused to produce new paper/cardboard products. The organic fraction bio-oil
generated is energy-densified and rich in carbohydrates and is a potential source
for valuable aromatic compounds.
PMID- 25590265
TI - The Trajectory of Long-Term Psychosocial Development 16 Years following Childhood
Traumatic Brain Injury.
AB - Childhood traumatic brain injury (CTBI) is one of the most common causes of
impairment in children and adolescents, with psychosocial difficulties found to
be the most persisting. Given that the transition into adolescence and adulthood
can be a stressful period, it is likely that young people who have sustained a
CTBI will be more vulnerable to developing psychosocial problems. To date, most
research has focused on psychosocial development up to five years following a
CTBI and it is unclear how survivors develop in the long-term as young adults.
The aim of this research was to track the long-term psychosocial outcomes of
children with CTBI and compare them with healthy controls over a period of 16
years. Seventy-five participants with a CTBI and 29 control participants were
followed up at five time-points over a period of 16 years. To measure
psychosocial functioning (social skills, internalizing, and externalizing
symptoms), questionnaires were completed by the primary caregiver acutely (pre
injury baseline), then six months, five years, 10 years, and 16 years post
injury. No significant group differences were found regarding the developmental
trajectory of social skills, or internalizing and externalizing symptoms between
the CTBI and control groups. The severe CTBI group demonstrated a trend of lower
social skills, while the mild CTBI group showed a trend of higher internalizing
and externalizing skills at six months, five years, and ten years post-CTBI
event, compared with other groups. The mild CTBI group scored in the borderline
range for externalizing symptoms six months post-CTBI; however, all other mean
scores were within the normal range. Over a period of 16 years, young adults with
CTBI showed similar developmental trajectories regarding psychosocial outcomes,
compared with healthy controls. This study confirmed previous literature that
CTBI is associated with increased levels of psychosocial problems.
PMID- 25590266
TI - CD11c+CD123Low dendritic cell subset and the triad TNF-alpha/IL-17A/IFN-gamma
integrate mucosal and peripheral cellular responses in HIV patients with high
grade anal intraepithelial neoplasia: a systems biology approach.
AB - BACKGROUND: The incidence of anal cancer has increased over the past 25 years,
and HIV/HPV coinfection is the most important risk factor for anal squamous cell
carcinoma. In this study, we demonstrated that the evaluation of systemic and
compartmentalized anal mucosa immune response is relevant to differentiating
HIV(+) patients at risk of anal intraepithelial neoplasia (AIN). METHODS: A
systems biology approach was used to integrate different immunological parameters
from anal mucosal tissue and peripheral blood assessed by phenotypic and
intracytoplasmic analysis of lymphocytes and dendritic cell subsets. RESULTS: Our
data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients
showed a robust capacity in producing proinflammatory/regulatory cytokines,
mainly mTNF-alpha > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-alpha/IFN-gamma/IL
17A are selective high-grade squamous intraepithelial lesion (HSIL)-related
biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along
with elevated levels of IFN-gammaCD4 T cells are major features associated with
HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients
presented a complex biomarker network, rich in negative connections. Among those
patients, however, HSIL+ patients displayed stronger positive links between
peripheral blood and anal mucosa environments, exemplified by the subnet of IL
17A/TNF-alpha/CD4IFN-gamma/CD11cCD123 cells. CONCLUSIONS: The significant
association between HSIL and the levels of TNF-alpha/IL-17A/IFN-gamma along with
the different subsets of DCs present in the anal mucosa milieu should be studied
in more detail as a way to identify and categorize HIV(+) patients vis a vis the
high risk of anal cancer outcome.
PMID- 25590267
TI - HIV through the looking glass: insights derived from Hepatitis B.
AB - BACKGROUND: Although higher levels of hepatitis B virus (HBV) replication in HIV
HBV co-infection may relate to liver disease progression, this has not been
completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in
liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a
marker for HBV replication, and related these findings to clinical and
histological parameters. METHODS: Data from 244 HBV patients were compared with
34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis,
HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were
performed. RESULTS: HBcAg, but not hepatitis B surface antigen, staining was
stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono
infected had similar alanine aminotransferase, inflammatory and fibrosis scores,
and hepatitis B e antigen status. HBcAg staining correlated with HIV after
correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level
did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in
HIV co-infected and correlated with HBcAg staining. CONCLUSIONS: By looking at
HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled
HIV, our findings suggest that these patients may have subtle immune function
defects, which could lead to adverse liver disease outcomes.
PMID- 25590268
TI - Diagnostic utility of quantitative plasma cytomegalovirus DNA PCR for
cytomegalovirus end-organ diseases in patients with HIV-1 infection.
AB - OBJECTIVE: To investigate the diagnostic value of quantitative plasma
cytomegalovirus (CMV)-DNA polymerase chain reaction (PCR) for CMV end-organ
diseases (CMV-EOD) in patients with HIV-1 infection. DESIGN: Single-center cross
sectional study. METHODS: The study subjects were HIV-1-infected patients with
CD4 <=200 per microliter, who had undergone ophthalmologic examination with
plasma CMV-DNA PCR measured within 7 days. CMV retinitis and other CMV-EOD were
diagnosed according to the ACTG criteria. PCR value was converted into the WHO
international standard. RESULTS: CMV retinitis and all CMV-EOD were diagnosed in
23 (5%) and 37 (8%) of the 461 study patients, respectively. CMV-DNA was
undetectable (<185 IU/mL) in 2 patients with CMV retinitis and 1 with
encephalitis. The area under the receiver operating characteristic curve of CMV
DNA for CMV retinitis and all CMV-EOD were 0.80 [95% confidence interval (CI):
0.71 to 0.89] and 0.82 (0.75 to 0.89), respectively. The sensitivity,
specificity, positive predictive value, and negative predictive value for each
cutoff value of CMV-DNA were as follows: for CMV retinitis, >=10,086 IU/mL:
26.1%, 94.1%, 18.8%, 96%; >=2946 IU/mL; 56.5%, 86.8%, 18.3%, 97.4%; >=959 IU/mL;
60.9%, 78.1%, 12.7%, 97.4%; detectable CMV-DNA (>=185 IU/mL): 91.3%, 48.2%, 8.5%,
99.1%; for all CMV-EOD: >=10,086 IU/mL: 32.4%, 95.3%, 37.5%, 94.2%; >=2946 IU/mL;
54.1%, 88%, 28.2%, 95.6%; >=959 IU/mL; 62.2%, 79.5%, 20.9%, 96%; detectable CMV
DNA; 91.9%, 49.5%, 13.7%, 98.6%. CONCLUSIONS: Plasma CMV-DNA PCR has a high
diagnostic value for both CMV retinitis and all CMV-EOD in patients with advanced
HIV-1 infection. A cutoff value of CMV-DNA >=10,086 IU/mL and >=2946 IU/mL yields
high specificity, whereas undetectable CMV-DNA load (<185 IU/mL) likely rules out
CMV-EOD.
PMID- 25590269
TI - Stimulant use patterns and HIV transmission risk among HIV-serodiscordant male
couples.
AB - BACKGROUND: Substance use is strongly linked to HIV risk, and members of couples
can have a powerful influence on each other's health behaviors. We examined
whether couple-level patterns of stimulant use were differentially associated
with engaging in condomless anal intercourse with primary partners and outside
partners. METHODS: Members of HIV serodiscordant male couples (N = 117 couples,
232 men) completed surveys, and HIV-positive men had blood drawn for viral load.
RESULTS: Results revealed that stimulant use by only one partner in the couple
was associated with a decrease in the odds of engaging in condomless anal sex
with one's primary partner (AOR = 0.09, 95% CI: 0.01, 0.89). When both partners
reported stimulant use, the HIV-negative partner had an increase in the odds of
condomless sex with outside partners (AOR = 6.68, 95% CI: 1.09, 8.01).
CONCLUSIONS: Understanding the role of couples' stimulant use patterns in HIV
transmission risk is an important area for future research and intervention.
PMID- 25590270
TI - Rates and correlates of antiretroviral therapy use and virologic suppression
among perinatally and behaviorally HIV-infected youth linked to care in the
United States.
AB - OBJECTIVE: To measure rates of antiretroviral therapy (ART) use and virologic
suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV
infected youth (BIY) linked to care in the United States and examine the effects
of demographic, biomedical, and psychosocial factors on those rates. METHODS:
Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials
Network for HIV/AIDS Interventions sites completed cross-sectional surveys
through audio computer-assisted self-interviews. Viral load data were collected
from chart abstraction or blood draw. RESULTS: Overall 82.4% of PIY and 49.1% of
BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were
virologically suppressed. Virologic suppression rates did not vary as a function
of time since HIV diagnosis in either group. Consistent HIV care and no current
substance abuse were significant correlates of ART use among PIY. These variables
and non-African American race were some factors associated with virologic
suppression for PIY [odds ratios (ORs) P < 0.05]. Among BIY, older age,
heterosexuals, employment, and education were significantly related to ART use
(ORs: P < 0.05); suppression was related to ART use >=6 months, >=90% ART
adherence, and consistent HIV care (ORs: P < 0.05). Nearly 75% (n = 498) of
nonsuppressed youth reported unprotected sex in the past 3 months. CONCLUSIONS:
There are continued challenges with successfully treating youth even once
diagnosed and linked to HIV care. Strategies targeting barriers to ART access,
use, and virologic suppression are needed to optimize the impact of the
"Treatment as Prevention" paradigm among PIY and BIY.
PMID- 25590271
TI - Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS
in Asia: results from the TREAT Asia HIV observational database.
AB - BACKGROUND: Roughly 4% of the 1.25 million patients on antiretroviral therapy
(ART) in Asia are using second-line therapy. To maximize patient benefit and
regional resources, it is important to optimize the timing of second-line ART
initiation and use the most effective compounds available. METHODS: HIV-positive
patients enrolled in the TREAT Asia HIV Observational Database who had used
second-line ART for >=6 months were included. ART use and rates and predictors of
second-line treatment failure were evaluated. RESULTS: There were 302 eligible
patients. Most were male (76.5%) and exposed to HIV via heterosexual contact
(71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell
count was 146 cells per cubic millimeter, and median HIV viral load was 16,224
copies per milliliter. Patients started second-line ART before 2007 (n = 105),
2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and
atazanavir accounted for the majority of protease inhibitor use after 2006.
Median follow-up time on second-line therapy was 2.3 years. The rates of
treatment failure and mortality per 100 patient/years were 8.8 (95% confidence
interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9),
respectively. Older age, high baseline viral load, and use of a protease
inhibitor other than lopinavir or atazanavir were associated with a significantly
shorter time to second-line failure. CONCLUSIONS: Increased access to viral load
monitoring to facilitate early detection of first-line ART failure and subsequent
treatment switch is important for maximizing the durability of second-line
therapy in Asia. Although second-line ART is highly effective in the region, the
reported rate of failure emphasizes the need for third-line ART in a small
portion of patients.
PMID- 25590272
TI - Pregnancy and contraceptive use among women participating in the FEM-PrEP trial.
AB - BACKGROUND: Pregnancy among study participants remains a challenge for trials of
new HIV prevention agents despite promotion and provision of contraception. We
evaluated contraceptive use, pregnancy incidence, and study drug adherence by
contraceptive method among women enrolled in the FEM-PrEP trial of once-daily
oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV
prevention. METHODS: We required women to be using effective non-barrier
contraception at enrollment. At each monthly follow-up visit, women were
counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was
determined by measuring plasma drug concentrations at 4-week intervals. We used
Cox proportional hazards models to assess factors associated with incident
pregnancy and multivariate logistic regression to examine the relationship
between contraceptive method used at enrollment and TDF-FTC adherence. RESULTS:
More than half of women were not using effective contraception before enrollment.
Ninety-eight percent of these women adopted either injectable (55%) or oral (43%)
contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among
injectable users and new users of combined oral contraceptives (COCs), the rates
were 1.6 and 35.1, respectively. New users of injectables had significantly
greater odds of adhering to TDF-FTC than new COC users [odds ratio (95%
confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3
to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04].
CONCLUSIONS: Women using COCs during FEM-PrEP, particularly new adopters, were
more likely to become pregnant and less likely to adhere to study product than
injectable users. HIV prevention trials should consider requiring long-acting
methods, including injectables, for study participation.
PMID- 25590273
TI - Viremia copy-years as a predictive marker of all-cause mortality in HIV-1
infected patients initiating a protease inhibitor-containing antiretroviral
treatment.
AB - BACKGROUND: Viremia copy-years (VCY) has been reported as a short-term predictor
of mortality. We evaluated the association of this parameter with 10-year outcome
within the APROCO-COPILOTE cohort. METHODS: Prospective data from 1281 HIV-1
infected patients who started a first protease inhibitor-containing regimen in
1997-1999 were analyzed. Patients with baseline plasma viral load (pVL) > 500
copies per milliliter and at least 2 pVL measures from the eighth month of follow
up were selected. VCY was calculated individually over the follow-up as the area
under the pVL curve. Multivariate Cox models analyzed the relation between all
cause mortality and the following variables: age, sex, geographical origin,
transmission group, HIV infection duration, ART-naive, pVL at baseline, time
dependent CD4 count, and VCY. RESULTS: Nine hundred seventy-nine patients were
followed up for a median of 10 years (interquartile range: 5-11.5). At baseline,
median (interquartile range) values for duration of HIV infection, pVL, and CD4
cell count were 43 (4-95) months, 4.6 (3.9-5.2) log10 copies per milliliter, and
278 (125-416) cells per cubic millimeter, respectively. At censoring date, 77
patients (8%) had died. VCY >1.4 log10 copies * yrs/mL was an independent
predictor of death (hazard ratio: 2.0; 95% confidence interval: 1.2 to 3.5),
which was no longer the case after adjustment for the latest pVL value [risk
ratio (RR): 1.2 for 1 additional log10 copies per milliliter; 95% confidence
interval: 1.1 to 1.4]. CONCLUSIONS: VCY was associated with mortality in HIV
infected patients under combined antiretroviral therapy but did not overweigh the
predictive value of the latest pVL. VCY might be more useful as a marker of
persistent viral replication than for routine clinical care.
PMID- 25590274
TI - Dynamics of HIV DNA and residual viremia in patients treated with a raltegravir
containing regimen.
PMID- 25590275
TI - A run-in period is needed in randomized controlled trials of directly observed
antiretroviral therapy for HIV infection.
PMID- 25590276
TI - Nephroprotective role of resveratrol and ursolic Acid in aristolochic Acid
intoxicated zebrafish.
AB - The nephrotoxicity of aristolochic acid (AA) is well known, but information
regarding the attenuation of AA-induced toxicity is limited. The aim of the
present study was to study the nephroprotective effects of resveratrol (Resv) and
ursolic acid (UA) in a zebrafish model. We used two transgenic lines,
Tg(wt1b:EGFP) and Tg(gata1:DsRed), to evaluate the nephroprotective effects of
Resv and UA by recording subtle changes in the kidney and red blood cell
circulation. Our results demonstrated that both Resv and UA treatment can
attenuate AA-induced kidney malformations and improve blood circulation.
Glomerular filtration rate assays revealed that both Resv and UA treatment can
restore renal function (100% for Mock; 56.1% +/- 17.3% for AA-treated; 80.2% +/-
11.3% for Resv+AA; and 83.1% +/- 8.1% for UA+AA, n = 15). Furthermore, real-time
RT-PCR experiments showed that pre-treatment with either Resv or UA suppresses
expression of pro-inflammatory genes. In conclusion, our findings reveal that AA
induced nephrotoxicities can be attenuated by pre-treatment with either Resv or
UA. Therefore, we believe that zebrafish represent an efficient model for
screening AA-protective natural compounds.
PMID- 25590277
TI - The cytolytic activity of vaginolysin strictly depends on cholesterol and is
potentiated by human CD59.
AB - Gardnerella vaginalis produces cytolysin vaginolysin (VLY), which has been
suggested to be a contributor to bacterial vaginosis pathogenesis. VLY along with
intermedilysin (ILY) from Streptococcus intermedius have been attributed to a
group of cholesterol-dependent cytolysins (CDCs) whose pore-forming activity
depends on human CD59 (hCD59). Here, we show that different types of cells
lacking hCD59 are susceptible to VLY-mediated lysis, albeit to different extents.
We analyze the effects of both hCD59 and cholesterol on VLY cytolytic activity.
We show that VLY binds to cholesterol-rich membranes of non-human cells, while
VLY with an impaired cholesterol recognition site retains binding to the hCD59
containing cells. We further demonstrate that cholesterol binding by VLY is
sufficient to trigger the formation of oligomeric complexes on cholesterol rich
liposomes lacking hCD59. Thus, VLY may induce cell lysis following two
alternative pathways. One requires only cholesterol and does not depend on hCD59.
The second pathway involves hCD59 contribution similarly to ILY. Apparently,
under physiological conditions VLY acts in the most effective way by accepting
the assistance of hCD59.
PMID- 25590279
TI - Minimally invasive management of urological fistulas.
AB - PURPOSE OF REVIEW: Urological fistulas are an underestimated problem worldwide
and have devastating consequences for patients. Many urological fistulas result
from surgical complications and/or inadequate perinatal obstetric healthcare.
Surgical correction is the standard treatment. This article reviews minimally
invasive surgical approaches to manage urological fistulas with a particular
emphasis on the robotic techniques of fistula correction. RECENT FINDINGS: In
recent years, many surgeons have explored a minimally invasive approach for the
management of urological fistulas. Several studies have demonstrated the
feasibility of laparoscopic surgery and the reproducibility of reconstructive
surgery techniques. Introduction of the robotic platform has provided significant
advantages given the improved dexterity and exceptional vision that it confers.
SUMMARY: Fistulas are a concern worldwide. Laparoscopic surgery correction has
been developed through the efforts of several authors, and difficulties such as
the increased learning curve have been overcome with innovations, including the
robotic platform. Although minimally invasive surgery offers numerous advantages,
the most successful approach remains the one with the surgeon is most familiar.
PMID- 25590278
TI - Increased circulating levels of vitamin D binding protein in MS patients.
AB - Vitamin D (vitD) low status is currently considered a main environmental factor
in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites
are highly hydrophobic and circulate mostly bound to the vitamin D binding
protein (DBP) and with lower affinity to albumin, while less than 1% are in a
free form. The aim of this study was to investigate whether the circulating
levels of either of the two vitD plasma carriers and/or their relationship are
altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24
healthy controls. MS patients were found to have higher DBP levels than healthy
subjects. Concomitant interferon beta therapy did not influence DBP
concentration, and the difference with the control group was significant in both
females and males. No significant correlation between DBP and albumin levels was
observed either in healthy controls or in patients. These observations suggest
the involvement of DBP in the patho-physiology of MS.
PMID- 25590280
TI - Anatomic partial nephrectomy: technique evolution.
AB - PURPOSE OF REVIEW: Partial nephrectomy provides equivalent long-term oncologic
and superior functional outcomes as radical nephrectomy for T1a renal masses.
Herein, we review the various vascular clamping techniques employed during
minimally invasive partial nephrectomy, describe the evolution of our partial
nephrectomy technique and provide an update on contemporary thinking about the
impact of ischemia on renal function. RECENT FINDINGS: Recently, partial
nephrectomy surgical technique has shifted away from main artery clamping and
towards minimizing/eliminating global renal ischemia during partial nephrectomy.
Supported by high-fidelity three-dimensional imaging, novel anatomic-based
partial nephrectomy techniques have recently been developed, wherein partial
nephrectomy can now be performed with segmental, minimal or zero global ischemia
to the renal remnant. Sequential innovations have included early unclamping,
segmental clamping, super-selective clamping and now culminating in anatomic zero
ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for
the surgeon, these techniques allow an unhurried, tightly contoured tumour
excision with point-specific sutured haemostasis. Recent data indicate that zero
ischemia partial nephrectomy may provide better functional outcomes by
minimizing/eliminating global ischemia and preserving greater vascularized kidney
volume. SUMMARY: Contemporary partial nephrectomy includes a spectrum of surgical
techniques ranging from conventional-clamped to novel zero-ischemia approaches.
Technique selection should be tailored to each individual case on the basis of
tumour characteristics, surgical feasibility, surgeon experience, patient
demographics and baseline renal function.
PMID- 25590281
TI - Enhanced functionality and stabilization of a cold active laccase using
nanotechnology based activation-immobilization.
AB - A simple nanotechnology based immobilization technique for imparting
psychrostability and enhanced activity to a psychrophilic laccase has been
described here. Laccase from a psychrophile was supplemented with Copper oxide
nanoparticles (NP) corresponding to copper (NP-laccase), the cationic activator
of this enzyme and entrapped in single walled nanotube (SWNT). The activity and
stability of laccase was enhanced both at temperatures as low as 4 degrees C and
as high as 80 degrees C in presence of NP and SWNT. The enzyme could be released
and re-trapped (in SWNT) multiple times while retaining significant activity.
Laccase, immobilized in SWNT, retained its activity after repeated freezing and
thawing. This unique capability of SWNT to activate and stabilize cold active
enzymes at temperatures much lower or higher than their optimal range may be
utilized for processes that require bio-conversion at low temperatures while
allowing for shifts to higher temperature if so required.
PMID- 25590282
TI - Focus formation: a cell-based assay to determine the oncogenic potential of a
gene.
AB - Malignant transformation of cells is typically associated with increased
proliferation, loss of contact inhibition, acquisition of anchorage-independent
growth potential, and the ability to form tumors in experimental animals(1). In
NIH 3T3 cells, the Ras signal transduction pathway is known to trigger many of
these events, what is known as Ras transformation. The introduction of an
overexpressed gene in NIH 3T3 cells may promote morphological transformation and
loss of contact inhibition, which can help determine the oncogenic potential of
that gene of interest. An assay that provides a straightforward method to assess
one aspect of the transforming potential of an oncogene is the Focus Formation
Assay (FFA)(2). When NIH 3T3 cells divide normally in culture, they do so until
they reach a confluent monolayer. However, in the presence of an overexpressed
oncogene, these cells can begin to grow in dense, multilayered foci(1) that can
be visualized and quantified by crystal violet or Hema 3 staining. In this
article we describe the FFA protocol with retroviral transduction of the gene of
interest into NIH 3T3 cells, and how to quantify the number of foci through
staining. Retroviral transduction offers a more efficient method of gene delivery
than transfection, and the use of an ecotropic murine retrovirus provides a
biosafety control when working with potential human oncogenes.
PMID- 25590283
TI - Flexible ferroelectric polymer devices based on inkjet-printed electrodes from
nanosilver ink.
AB - High-quality silver (Ag) patterns were inkjet-printed with nanosilver ink on a
flexible polyethylene terephthalate (PET) substrate. All-solution-processed
flexible ferroelectric polymer devices that use inkjet-printed Ag to create their
bottom and top electrodes were demonstrated. The active layer, a poly (vinylidene
fluoride-trifluoroethylene) (PVDF-TrFE) thin film, was spin-coated from solution.
The devices have a remanent polarization of 8.03 MUC cm(-2) and a coercive field
of 68.5 MV m(-1), which is comparable to the device with evaporated-Ti electrodes
on a silicon substrate. Based on the results presented in this paper, mass
production of flexible ferroelectric devices is predictable.
PMID- 25590285
TI - Long-ranged and soft interactions between charged colloidal particles induced by
multivalent coions.
AB - Forces between charged particles in aqueous solutions containing multivalent
coions and monovalent counterions are studied by the colloidal probe technique.
Here, the multivalent ions have the same charge as the particles, which must be
contrasted to the frequently studied case where multivalent ions have the
opposite sign as the substrate. In the present case, the forces remain repulsive
and are dominated by the interactions of the double layers. The valence of the
multivalent coion is found to have a profound influence on the shape of the force
curve. While for monovalent coions the force profile is exponential down to
separations of a few nanometers, the interaction is much softer and longer-ranged
in the presence of multivalent coions. The force profiles in the presence of
multivalent coions and in the mixtures of monovalent and multivalent coions can
be accurately described by Poisson-Boltzmann theory. These results are accurate
for different surfaces and even in the case of highly charged particles. This
behavior can be explained by the fact that the force profile follows the near
field limit to much larger distances for multivalent coions than for monovalent
ones. This limit corresponds to the conditions with no salt, where the coions are
expelled between the two surfaces.
PMID- 25590284
TI - A novel vertebral stabilization method for producing contusive spinal cord
injury.
AB - Clinically-relevant animal cervical spinal cord injury (SCI) models are essential
for developing and testing potential therapies; however, producing reliable
cervical SCI is difficult due to lack of satisfactory methods of vertebral
stabilization. The conventional method to stabilize the spine is to suspend the
rostral and caudal cervical spine via clamps attached to cervical spinous
processes. However, this method of stabilization fails to prevent tissue
yielding during the contusion as the cervical spinal processes are too short to
be effectively secured by the clamps (Figure 1). Here we introduce a new method
to completely stabilize the cervical vertebra at the same level of the impact
injury. This method effectively minimizes movement of the spinal column at the
site of impact, which greatly improves the production of consistent SCIs. We
provide visual description of the equipment (Figure 2-4), methods, and a step-by
step protocol for the stabilization of the cervical 5 vertebra (C5) of adult
rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter.
Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS
impactor device, this vertebral stabilization technique can be applied to other
regions of the spinal cord, or be adapted to other SCI devices. Improving spinal
cord exposure and fixation through vertebral stabilization may be valuable for
producing consistent and reliable injuries to the spinal cord. This vertebral
stabilization method can also be used for stereotactic injections of cells and
tracers, and for imaging using two-photon microscopy in various neurobiological
studies.
PMID- 25590286
TI - Applicability of an anti-trichophyton monoclonal antibody for the
immunohistochemical diagnosis of human fungal skin infections (dermatophytosis)
in tissue sections.
PMID- 25590287
TI - Metastatic atypical fibroxanthoma: a series of 11 cases including with minimal
and no subcutaneous involvement.
AB - Atypical fibroxanthoma (AFX) is a dermal mesenchymal neoplasm arising in sun
damaged skin, primarily of the head and neck region of older men. Conservative
excision cures most. However, varying degrees of subcutaneous involvement can
lead to a more aggressive course and rare metastases. Thus, AFX involving the
subcutis are termed pleomorphic dermal sarcomas or other monikers by some to
recognize the more threatening natural history. We reviewed cases of "metastatic
AFX" from our institution and from the files of a consultative dermatopathology
practice. Nine of 152 patients with AFX were identified at a single institution
(2000-2011). Two additional patients were identified from the files of a
consultative practice. Clinical, radiological, and pathological features were
reviewed and cases with histologically verified metastases identified. Median age
was 67 (range, 45-91) years, all male, and involving the head and neck region.
Two cases had no documented involvement of the subcutis, and 2 cases had only
superficial subcutis involvement. Median time to metastases was 13 (range, 8-49)
months. Three patients developed solitary regional lymph node metastases while 8
had widespread metastases. Five patients developed local recurrence within 8
months, and all 5 developed widespread metastasis. With median follow-up of 26
(range, 10-145) months, 6 died of disease (median, 19 months; range, 10-35
months), 4 were alive and well, and 1 was alive with disease. AFX has very rare
metastatic potential, even those without or with minimal subcutis involvement,
and can lead to mortality. Most metastasis and local recurrence occurred within 1
year of presentation. Solitary regional metastases were associated with better
outcomes than those with multiple distant metastases. Patients with repeated
local recurrences portended more aggressive disease including development of
distant metastases.
PMID- 25590288
TI - Primary cutaneous marginal IgG4 lymphoma and Rosai-Dorfman's disease coexisting
in several lesions of the same patient.
AB - We report the unique association of primary cutaneous marginal zone B-cell
lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving
the same lesions. The patient was an 82-year-old woman with 3 long-standing, well
circumscribed firm erythematous to brownish plaques on her left arm, right
scapular area, and lumbosacral area. Histopathologic examination disclosed a
dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of
germinal center colonization and light-chain restriction and sheets of S-100 CD68
positive histiocytes with ample pale cytoplasm and occasional emperipolesis of
lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A
review of 14 examples of cutaneous RDD showed a substantial number of IgG4
positive cells in only 3 of them, and a review of 8 primary cutaneous marginal
zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The
coexistence of lymphomas and RDD has been rarely reported in the literature but
only seldom involving the same lymph node and-to the best of our knowledge-never
in the skin.
PMID- 25590289
TI - Ketoconazole-induced Sweet syndrome: a new association.
AB - Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that can be
associated with malignancy and medications. A 60-year-old man presented with
erythematous, edematous, and ulcerated plaques in the extensor surface of the
upper extremities, after a ketoconazole course due to pityrosporum folliculitis.
Skin biopsy showed a dense dermal neutrophilic infiltrate, associated with marked
papillary dermal edema. Blood count showed leukocytosis and neutrophilia. Skin
lesions resolved spontaneously with discoloration after 2 weeks of
discontinuation of ketoconazole. Although most cases of drug-induced SS are
associated with granulocyte colony-stimulating factor, other medications need to
be considered. This is the first reported case of ketoconazole-induced SS despite
its widespread use.
PMID- 25590291
TI - Sleep: soothing and restorative.
PMID- 25590290
TI - Homocysteine-lowering interventions for preventing cardiovascular events.
AB - BACKGROUND: Cardiovascular disease, which includes coronary artery disease,
stroke and congestive heart failure, is a leading cause of death worldwide.
Homocysteine is an amino acid with biological functions in methionine metabolism.
A postulated risk factor is an elevated circulating total homocysteine level,
which is associated with cardiovascular events. The impact of homocysteine
lowering interventions, given to patients in the form of vitamins B6, B9 or B12
supplements, on cardiovascular events. This is an update of a review previously
published in 2009 and 2013. OBJECTIVES: To determine whether homocysteine
lowering interventions, provided in patients with and without pre-existing
cardiovascular disease are effective in preventing cardiovascular events, as well
as all-cause mortality and evaluate their safety. SEARCH METHODS: We searched the
Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 1), MEDLINE
(1950 to January week 5 2014), EMBASE (1980 to 2014 week 6) and LILACS (1986 to
February 2014). We also searched Web of Science (1970 to 7 February 2014). We
handsearched the reference lists of included papers. We also contacted
researchers in the field. There was no language restriction in the search.
SELECTION CRITERIA: We included randomised controlled trials assessing the
effects of homocysteine-lowering interventions for preventing cardiovascular
events with a follow-up period of one year or longer. We considered myocardial
infarction and stroke as the primary outcomes. We excluded studies in patients
with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We performed study
selection, 'Risk of bias' assessment and data extraction in duplicate. We
estimated risk ratios (RR) for dichotomous outcomes. We measured statistical
heterogeneity using the I(2) statistic. We used a random-effects model. MAIN
RESULTS: In this second updated Cochrane Review, we identified no new randomised
controlled trials. Therefore, this new version includes 12 randomised controlled
trials involving 47,429 participants. In general terms, 75% (9/12) trials had a
low risk of bias. Homocysteine-lowering interventions compared with placebo did
not significantly affect non-fatal or fatal myocardial infarction (1743/23,590
(7.38%) versus 1247/20,190 (6.17%); RR 1.02, 95% confidence interval (CI) 0.95 to
1.10, I(2) = 0%, high quality evidence), stroke (968/22,348 (4.33%) versus
974/18,957 (5.13%); RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%, high quality
evidence) or death from any cause (2784/22,648 (12.29%) versus 2502/19,250
(10.64%); RR 1.01, 95% CI 0.96 to 1.07, I(2) = 6%, high quality evidence).
Homocysteine-lowering interventions compared with placebo did not significantly
affect serious adverse events (cancer) (1558/18,130 (8.59%) versus 1334/14,739
(9.05%); RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%, high quality evidence).
AUTHORS' CONCLUSIONS: This second update of this Cochrane Review found no
evidence to suggest that homocysteine-lowering interventions in the form of
supplements of vitamins B6, B9 or B12 given alone or in combination should be
used for preventing cardiovascular events. Furthermore, there is no evidence to
suggest that homocysteine-lowering interventions are associated with an increased
risk of cancer.
PMID- 25590292
TI - The effects of simultaneous exercise and psychotherapy on depressive symptoms in
inpatient, psychiatric older adults.
AB - CONTEXT: Depression is the leading cause of early death, affecting 15% of
Americans older than 65 y and costing $43 billion each year. The current mental
health service system for seniors, particularly for the population hospitalized
in acute inpatient psychiatric units, is fragmented because of poor funding and a
shift to a transitory health care paradigm, leading to inadequate treatment
modalities, questionable quality of care, and lack of research demonstrating the
superiority of a particular treatment. These issues are likely to lead to a
public health crisis in the coming years. OBJECTIVE: To investigate the
effectiveness of combining exercise and psychotherapy in improving acute
depressive symptoms among older adults who were receiving treatment in an
inpatient psychiatric unit. DESIGN: Based on rolling admissions, inpatients were
randomly assigned to 1 of 3 treatment groups. The study was blinded and
controlled. SETTING: This study took place in inpatient psychiatric units at the
Loma Linda University's Behavioral Medicine Center (LLUBMC) in Redlands,
California. PARTICIPANTS: Participants were 78 inpatients, aged 50-89 y.
INTERVENTION: Participants in the simultaneous exercise and psychotherapy (STEP)
group (n = 26) took part in exercise and received psychotherapy for 30 min per
session, whereas those in the TALK group (n = 26) received individual
psychotherapy for 30 min per session. Participants in the control group (n = 26)
served as a comparison group, receiving standard therapy. OUTCOME MEASURES: The
effects of the interventions were determined by assessing differences from
baseline to postintervention in the symptomatology of all 3 groups. The research
team also administered the Behavioral and Symptom Identification Scale (BASIS-32)
and the Geriatric Depression Scale (GDS) pre- and postintervention. RESULTS: At
posttest, the STEP group (M = 4.24, SE = 0.62) had a better response than the
TALK group (M = 11.34, SE = 0.62, P < .001), which in turn showed greater
improvement than the control group (M = 14.84, SE = 0.62, P < .001). Overall,
these results indicate that patients' posttreatment depression scores were
significantly lower in those receiving the STEP treatment compared with those
receiving individual psychotherapy only or standard care. CONCLUSION: A short
term exercise program consisting of 30 min of walking in conjunction with
individual psychotherapy was an effective intervention for depression among older
adults in inpatient psychiatric units.
PMID- 25590293
TI - Toward an operational model of decision making, emotional regulation, and mental
health impact.
AB - Current brain research increasingly reveals the underlying mechanisms and
processes of human behavior, cognition, and emotion. In addition to being of
interest to a wide range of scientists, educators, and professionals, as well as
laypeople, brain-based models are of particular value in a clinical setting.
Psychiatrists, psychologists, counselors, and other mental health professionals
are in need of operational models that integrate recent findings in the physical,
cognitive, and emotional domains, and offer a common language for
interdisciplinary understanding and communication. Based on individual traits,
predispositions, and responses to stimuli, we can begin to identify emotional and
behavioral pathways and mental processing patterns. The purpose of this article
is to present a brain-path activation model to understand individual differences
in decision making and psychopathology. The first section discusses the role of
frontal lobe electroencephalography (EEG) asymmetry, summarizes state- and trait
based models of decision making, and provides a more complex analysis that
supplements the traditional simple left-right brain model. Key components of the
new model are the introduction of right hemisphere parallel and left hemisphere
serial scanning in rendering decisions, and the proposition of pathways that
incorporate both past experiences as well as future implications into the
decision process. Main attributes of each decision-making mechanism are provided.
The second section applies the model within the realm of clinical mental health
as a tool to understand specific human behavior and pathology. Applications
include general and chronic anxiety, depression, paranoia, risk taking, and the
pathways employed when well-functioning operational integration is observed.
Finally, specific applications such as meditation and mindfulness are offered to
facilitate positive functioning.
PMID- 25590297
TI - The potential of minor ginsenosides isolated from the leaves of Panax ginseng as
inhibitors of melanogenesis.
AB - Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2)
and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax
ginseng. The chemical structures were determined based on spectroscopic methods,
including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic
resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic
inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%,
respectively, at a concentration of 80 uM. Likewise, the three compounds showed
inhibitory activity on body pigmentation on a zebrafish model, which is commonly
used as a model for biomedical or cosmetic research. These results from in vitro
and in vivo systems suggest that the three aforementioned compounds isolated from
Panax ginseng may have potential as new skin whitening compounds.
PMID- 25590299
TI - Synthesis and degradation of Schiff bases containing heterocyclic pharmacophore.
AB - This paper reports on the synthesis and characterization of two Schiff bases
bearing 1,2,4-triazolic moieties, namely 4H-4-(2-hydroxy-benzylidene-amino)-5
benzyl-3-mercapto-1,2,4-triazole and 4H-4-(4-nitro-benzylidene-amino)-5-benzyl-3
mercapto-1,2,4-triazole using thin layer chromatography, melting interval,
elemental analysis, spectroscopy and thermal stability studies.
PMID- 25590300
TI - The cluster [Re6Se8I6]3- induces low hemolysis of human erythrocytes in vitro:
protective effect of albumin.
AB - The cluster Re6Se8I63- has been shown to induce preferential cell death of a
hepatic carcinoma cell line, thus becoming a promising anti-cancer drug. Whether
this cluster induces acute hemolysis or if it interacts with albumin remains
unclear. The effect of acute exposure of human red blood cells to different
concentrations of the cluster with and without albumin is described. Red blood
cells from healthy donors were isolated, diluted at 1% hematocrit and exposed to
the cluster (25-150 uM) at 37 degrees C, under agitation. Hemolysis and
morphology were analyzed at 1 and 24 h. The potential protection of 0.1% albumin
was also evaluated. Exposition to therapeutic doses of the cluster did not induce
acute hemolysis. Similar results were observed following 24 h of exposition, and
albumin slightly reduced hemolysis levels. Furthermore, the cluster induced
alteration in the morphology of red blood cells, and this was prevented by
albumin. Together, these results indicate that the cluster Re6Se8I63- is not a
hemolytic component and induces moderate morphological alterations of red blood
cells at high doses, which are prevented by co-incubation with albumin. In
conclusion, the cluster Re6Se8I63- could be intravenously administered in animals
at therapeutic doses for in vivo studies.
PMID- 25590298
TI - Mechanisms and applications of interleukins in cancer immunotherapy.
AB - Over the past years, advances in cancer immunotherapy have resulted in innovative
and novel approaches in molecular cancer diagnostics and cancer therapeutic
procedures. However, due to tumor heterogeneity and inter-tumoral discrepancy in
tumor immunity, the clinical benefits are quite restricted. The goal of this
review is to evaluate the major cytokines-interleukins involved in cancer
immunotherapy and project their basic biochemical and clinical applications.
Emphasis will be given to new cytokines in pre-clinical development, and
potential directions for future investigation using cytokines. Furthermore,
current interleukin-based approaches and clinical trial data from combination
cancer immunotherapies will also be discussed. It appears that continuously
increasing comprehension of cytokine-induced effects, cancer stemness,
immunoediting, immune-surveillance as well as understanding of molecular
interactions emerging in the tumor microenvironment and involving microRNAs,
autophagy, epithelial-mesenchymal transition (EMT), inflammation, and DNA
methylation processes may hold much promise in improving anti-tumor immunity. To
this end, the emerging in-depth knowledge supports further studies on optimal
synergistic combinations and additional adjuvant therapies to realize the full
potential of cytokines as immunotherapeutic agents.
PMID- 25590301
TI - Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of
oxidative enzyme expression and protein activation through inhibition of MAPK
phosphorylation.
AB - Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid
that is currently prescribed to treat inflammatory diseases such as upper
respiratory infections. Recently, several studies have shown that its anti
inflammatory activities have been strongly linked to the inhibition of secretion
of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and
cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-kappaB
(NF-kappaB) and mitogen-activated protein kinases (MAPK) pathways. Additionally,
inflammation, which can decrease the activities of antioxidative enzymes (AOEs)
is also observed in these studies. At the same time, flavonoids are reported to
promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose
of this study was to assess these theories in a series of experiments on the
suppressive effects of AP7Glu based on LPS-induced nitric oxide production in
RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six
hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological,
myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells,
cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and
changed. Meanwhile, our data revealed that AP7Glu not only did significantly
inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti
inflammatory effect through the MAPK and inhibitor NF-kappaB (IkappaB) pathways.
PMID- 25590302
TI - Novel transcription factor variants through RNA-sequencing: the importance of
being "alternative".
AB - Alternative splicing is a pervasive mechanism of RNA maturation in higher
eukaryotes, which increases proteomic diversity and biological complexity. It has
a key regulatory role in several physiological and pathological states. The
diffusion of Next Generation Sequencing, particularly of RNA-Sequencing, has
exponentially empowered the identification of novel transcripts revealing that
more than 95% of human genes undergo alternative splicing. The highest rate of
alternative splicing occurs in transcription factors encoding genes, mostly in
Kruppel-associated box domains of zinc finger proteins. Since these molecules are
responsible for gene expression, alternative splicing is a crucial mechanism to
"regulate the regulators". Indeed, different transcription factors isoforms may
have different or even opposite functions. In this work, through a targeted re
analysis of our previously published RNA-Sequencing datasets, we identified nine
novel transcripts in seven transcription factors genes. In silico analysis,
combined with RT-PCR, cloning and Sanger sequencing, allowed us to experimentally
validate these new variants. Through computational approaches we also predicted
their novel structural and functional properties. Our findings indicate that
alternative splicing is a major determinant of transcription factor diversity,
confirming that accurate analysis of RNA-Sequencing data can reliably lead to the
identification of novel transcripts, with potentially new functions.
PMID- 25590304
TI - Serum level of interleukin-21 is elevated in chronic rhinosinusitis.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease of the
sinuses and mucosa with unclear pathogenesis. Interleukin (IL)-21 is mainly
expressed in activated cluster of differentiation (CD)4(+) T cells and has potent
regulatory effects on the immune system. OBJECTIVE: This study is to determine
whether IL-21 in the blood is correlated with CRS. METHODS: The blood samples
from CRS patients and normal controls were analyzed in correlation with clinical
features. The eosinophil percentage was counted, and serum levels of total
immunoglobulin E (IgE) and IL-21 were analyzed by enzyme-linked immunosorbent
assay (ELISA). In addition, IL-21 and interferon (IFN)-gamma secreted from
stimulated peripheral blood mononuclear cells (PBMCs) were measured by ELISA, and
their mRNA expression levels were analyzed by real-time quantitative polymerase
chain reaction (RT-qPCR). Disease severity was scored based on computed
tomography (CT) scan, nasal endoscopy, and global osteitis scoring scale (GOSS).
RESULTS: A total of 55 CRS and 37 healthy subjects were recruited. The average
levels of serum total IgE were 20 kU/L in normal group, 290 kU/L in CRS with
nasal polys (CRSwNP), and 187 kU/L in CRS without nasal polys (CRSsNP). IL-21
levels were 28 pg/mL in normal group, 54 pg/mL in CRSwNP, and 71 pg/mL in CRSsNP.
Both IgE and IL-21 were significantly elevated in both CRS patient subgroups.
However, no significant difference was found between these two patient subgroups.
The serum IL-21 levels correlated well with the disease severity in the patients.
In addition, the secreted IL-21 was enhanced significantly in the patient's PBMCs
stimulated by phytohemagglutin (PHA). CONCLUSION: IL-21 could be a target for
diagnosis and treatment of CRS.
PMID- 25590305
TI - Editorial: Advances in the diagnosis and treatment of patients with chronic
rhinosinusitis and allergy.
PMID- 25590303
TI - Mechanisms and implications of dual-acting methotrexate in folate-targeted
nanotherapeutic delivery.
AB - The rational design of a nanoplatform in drug delivery plays a crucial role in
determining its targeting specificity and efficacy in vivo. A conventional
approach relies on the surface conjugation of a nanometer-sized particle with two
functionally distinct types of molecules, one as a targeting ligand, and the
other as a therapeutic agent to be delivered to the diseased cell. However, an
alternative simplified approach can be used, in which a single type of molecule
displaying dual function as both a targeting ligand and therapeutic agent is
conjugated to the nanoparticle. In this review, we evaluate the validity of this
new strategy by using methotrexate, which displays multifunctional mechanisms of
action. Methotrexate binds to the folate receptor, a surface biomarker frequently
overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an
enzyme critical for cell survival and division. Thus we describe a series of
fifth generation poly(amido amine) dendrimers conjugated with methotrexate, and
discuss several lines of evidence supporting the efficacy of this new platform
strategy based on surface plasmon resonance spectroscopy, enzyme activity assays,
and cell-based studies with folate receptor (+) KB cancer cells.
PMID- 25590306
TI - Intranasal steroids and the myth of mucosal atrophy: a systematic review of
original histological assessments.
AB - BACKGROUND: Intranasal corticosteroids (INCSs) are well established in the
treatment of allergic rhinitis, chronic rhinosinusitis, and nasal polyposis.
Although reversible atrophy of keratinized skin is seen with corticosteroids, the
respiratory mucosa is histologically very different and but concerns remain among
patients and some health-care professionals over local side effects on nasal
respiratory mucosa. A systematic review and meta-analysis were performed of the
available evidence for nasal mucosal atrophy as an adverse effect of INCSs in
patients with sinonasal disease. METHODS: A systematic search of Embase (1974-)
and Medline (1946-) databases to September 27, 2013 was performed. Inclusion
criteria selected any study where the histopathology of nasal mucosa was assessed
in patients with sinonasal disease using intranasally administered
corticosteroids with or without a control group. RESULTS: Twenty-three hundred
sixty-four publications were retrieved with a subsequent full text review of 149
publications for 34 articles that met the selection criteria. These articles
included 11 randomized controlled trials, 5 cohorts, and 20 case series. Duration
of treatment varied from 5 days to 5.5 years. "Mucosal atrophy" as an outcome was
reported in 17 studies. The definition of "mucosal atrophy" was highly variable
with a definition given in only 10 studies. One hundred thirty-six patients were
represented in controlled studies of atrophy with only one study reporting the
event in both groups with an odds ratio of "mucosal atrophy" at 0.51 (95% CI,
0.09-3.11; p = 0.47). CONCLUSION: The concept of nasal mucosal atrophy is poorly
defined and there is no histological evidence for deleterious effects from INCS
use on human nasal mucosa.
PMID- 25590307
TI - Septic cavernous sinus thrombosis secondary to acute bacterial sinusitis: a
retrospective study of seven cases.
AB - BACKGROUND: Septic cavernous sinus thrombosis (SCST) is a rare but severe
complication of acute bacterial sinusitis. Evaluations of advances in imaging
techniques as well as in medical and surgical treatment are hampered by the lack
of recent studies. OBJECTIVE: We aim to report our experience in the management
of SCST in patients with acute bacterial sphenoid sinusitis over the past 10
years and to discuss the initial work-up and treatment strategies. METHODS: We
performed a retrospective study of patients admitted for SCST related to acute
sinusitis at a tertiary care center between 2003 and 2013. Clinical charts were
reviewed for demographics, clinical presentations, imaging and microbiologic
findings, medical and surgical treatments, and outcomes. RESULTS: Seven patients
were treated for SCST. Sphenoid sinus was involved in all cases. The most
frequent presenting signs included headache (100%), cranial nerve impairment
(86%), fever (71%), and orbital symptoms (71%). Diagnosis was confirmed by a
cerebral contrast-enhanced CT scan in all cases. Four patients (57%) had an
additional intracranial complication. The average time between clinical onset and
diagnosis was 13.7 days. All patients were treated by high-dose i.v. antibiotics,
anticoagulation therapy, and surgical endoscopic drainage of the infected
sinuses. This treatment strategy resulted in a mortality rate of 0%, but four out
of the seven patients developed transient or permanent neurologic deficits,
including one with permanent unilateral visual loss. CONCLUSION: The combination
of high-dose i.v. antibiotics, anticoagulation therapy, and endoscopic drainage
of the infected paranasal sinus is an effective strategy for the treatment of
SCST, but long-term sequelae remain frequent.
PMID- 25590308
TI - Squeeze bottle versus saline spray after endoscopic sinus surgery for chronic
rhinosinusitis: a pilot multicentre trial.
AB - BACKGROUND: There is a need for controlled trials to guide the perioperative
management of patients undergoing endoscopic sinus surgery (ESS). The authors
performed a pilot multicenter trial to compare two types of saline delivery
devices in this population. METHODS: Patients were randomized to high volume
saline irrigation with a squeeze bottle and low volume saline spray after ESS in
patients with chronic rhinosinusitis (CRS). Surgeons were blinded to treatment,
and one-month postoperative scores for sinonasal outcomes [Sinonasal Outcome Test
22 (SNOT-22)] scale, nasal and sinus symptom score (NSS), and perioperative sinus
endoscopy (POSE) scale were compared with preoperative scores. RESULTS: Nine
centers provided data for 86 patients. All three outcomes measures improved
significantly for both groups. Saline spray: SNOT-22 48.8 versus. 23.7, treatment
effect 25.1 (95% confidence interval [CI], 17.9-32.2), POSE 21.1 versus. 8.4,
treatment effect 12.7 (95% CI, 9.2-16.1), and NSS 8.2 versus 5.0, treatment
effect 3.1 (95% CI, 1.4-4.9) pre- and postoperatively, respectively (all p <
0.0001). Squeeze bottle: SNOT-22 49.5 versus 23.6, treatment effect 25.9 (95% CI,
20.3-31.6), POSE 18.6 versus 9.2, treatment effect 9.3, (95% CI 6.7-12.0), and
NSS 9.0 versus 5.7, treatment effect 3.3 (95% CI, 2.3-4.3) pre- and
postoperatively, respectively (all p < 0.0001). Analysis of variance did not
identify a difference between the two treatment groups. Subgroup analysis based
on preoperative disease severity did not change the nonassociation of saline
bottle with outcome measures. Post hoc sample size calculation determined that
176 patients is required to detect an 8.9-point difference in SNOT-22 scores.
CONCLUSION: In this pilot multicenter trial examining patients with chronic
rhinosinusitis undergoing ESS, both squeeze bottle and saline spray showed
significant improvement in SNOT-22, POSE, and NSS scores at one-month
postoperatively. Because the study was nonpowered, we cannot rule out a potential
difference between the two treatment groups.
PMID- 25590309
TI - Expression and regulation of interleukin-9 in chronic rhinosinusitis.
AB - BACKGROUND: The pathogenesis of human chronic rhinosinusitis (CRS) remains
controversial. Recent evidence has suggested that interleukin (IL)-9 is vital in
eliciting inflammatory response, stimulating cell proliferation and preventing
apoptosis, through binding to the IL-9 receptor (IL-9R). However, little is known
about the roles of both molecules in the etiology of CRS. Therefore, this study
aimed to assess IL-9 and IL-9R expression and determine their roles in the
pathophysiology of CRS. METHODS: Immunohistochemistry was used to assess IL-9 and
IL-9R immunolabeling. In addition, Western blotting and real-time polymerase
chain reaction (PCR) were used for IL-9 and IL-9R protein and mRNA level
quantitation, respectively, in CRS and control subjects. Furthermore, the effects
of various stimulators at different concentrations and time on IL-9 were
evaluated using nasal explant cultures. RESULTS: IL-9 and IL-9R were
overexpressed in CRS, especially in CRS with nasal polyps. Interestingly, IL-9
expression was closely related to that of IL-9R. In addition, IL-9 mRNA levels
were increased by treatment with IL-4, IL-17A, IL-1beta, and the IL-4 and
transforming growth factor (TGF) beta1 combination, but suppressed by interferon
gamma and IL-27. CONCLUSION: IL-9 and IL-9R were overexpressed in CRS at both
protein and mRNA levels. In addition, IL-4, IL-17A, IL-1beta, and the IL-4 and
TGF-beta1 combination contributed to increased IL-9 levels. Our findings indicate
that IL-9 may play a proinflammatory role after IL-9R binding to induce mucosal
epithelial cell growth, gland epithelial cell proliferation, and inflammatory
cell infiltration in CRS. Future studies are required to further define the role
of IL-9 in CRS etiology.
PMID- 25590310
TI - The seasonality of respiratory viruses in patients with chronic rhinosinusitis.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a common illness, yet little is known
about its pathogenesis, including the role played by respiratory viruses.
METHODS: A transversal prospective study was conducted to analyze the seasonality
of CRS using real-time polymerase chain reaction to detect respiratory virus
genomes in secretions and tissue samples from patients with CRS with and without
nasal polyps. RESULTS: The frequency of viral detection was 41% (31/75). The
respiratory virus most frequently detected was human rhinovirus, found in 18
patients (24%), followed by human metapneumovirus, human enterovirus, human
respiratory sincicial virus, human adenovirus, human bocavirus, human
coronavirus, and human influenza virus, detected in 12 (16%), five (6.6%), four
(5.3%), four (5.3%), two (2.6%), two (2.6%), and one (1.3%) patient(s),
respectively. Although none of the patients presented symptoms when the samples
were collected, there was a peak in detection of the most prevalent virus in the
autumn and winter seasons of both years, similar to the pattern that occurs in
acute conditions. CONCLUSIONS: The pattern of respiratory virus seasonality found
in nasal mucosa, polyps, and paranasal sinus samples in patients with CRS
reinforces the possibility of asymptomatic respiratory viral infections.
PMID- 25590311
TI - Staphylococcus aureus biofilms induce apoptosis and expression of interferon
gamma, interleukin-10, and interleukin-17A on human sinonasal explants.
AB - BACKGROUND: Staphylococcus aureus is one of the most common bacteria associated
with chronic rhinosinusitis (CRS). Although S. aureus biofilms have been
correlated with disease severity in CRS, little is known about the initial immune
response that biofilms induce in the sinonasal mucosa. OBJECTIVE: The aim of this
study was to evaluate the innate immune response (in terms of cytokines) of
nondiseased human sinonasal tissue to S. aureus biofilms. METHODS: Full-thickness
sinonasal explant cultures (n = 7 donors) were challenged with established S.
aureus biofilms for 24 hours. The expression profiles of 17 cytokines were
measured using multiplex analysis, real-time quantitative reverse transcription
polymerase chain reaction, and immunohistochemistry. Differences in expression
were evaluated using Student's t-test. RESULTS: Interleukin (IL)-1beta, IL-10,
TNF, IL-17A, and interferon (IFN)-gamma were up-regulated at the RNA and protein
levels in biofilm-treated tissues compared with controls. Elevation of caspase-3
in biofilm-treated samples indicates S. aureus biofilms induce apoptosis on the
sinonasal mucosa. CONCLUSION: S. aureus biofilms induced apoptosis and a
predominant proinflammatory immune response on normal sinonasal mucosal explants.
This immune response appeared to be triggered by intrinsic bacterial elements but
also by components of the biofilm matrix. Live biofilms were present on the
mucosa at the end of the challenge, suggesting an inability of the induced immune
response to eliminate the S. aureus biofilms.
PMID- 25590312
TI - Prevalence of nasal polyps and its risk factors: Korean National Health and
Nutrition Examination Survey 2009-2011.
AB - BACKGROUND: Although nasal polyps (NPs) are thought to be a common
otorhinolaryngologic disease, there have been few population-based epidemiologic
studies on the prevalence of NPs. The aim of this study is to evaluate the
prevalence of NPs and the risk factors in the general Korean population. METHODS:
The data were obtained from the Korea National Health and Nutrition Examination
Survey (KNHANES) (2009-2011), which was a cross-sectional survey of
noninstitutionalized populations all around the country (n = 28,009). Among them,
19,152 participants (age more than or equal to 20 years) completed medical
interviews, physical examinations and endoscopic examination. Analyses were
performed using a complex sample design to identify the prevalence and its risk
factors. RESULTS: The weighted prevalence of NPs was 2.5%. The increased
prevalence was associated with increasing age. In the multivariate analyses, male
sex [adjusted odds ratio (OR) = 1.68, 95% confidence interval (CI) = 1.25-2.26],
low education level (adjusted OR = 1.57, CI = 1.16-2.13), obesity (adjusted OR =
1.49, CI = 1.19-1.87), asthma (adjusted OR = 1.80, CI = 1.24-2.62), and thyroid
cancer (adjusted OR = 2.98, CI = 1.26-7.09) were associated with NPs. Among those
with NPs, the proportion of symptomatic NPs was 34.4% and asthma was the only
significant associated risk factor. CONCLUSION: The prevalence of NPs in the
Korean general population was not low despite advances in medical and surgical
treatment and two thirds of the subjects with NPs were asymptomatic. Further
investigation is needed to exhibit the causal relationship between the associated
risk factors identified and NPs.
PMID- 25590313
TI - Initial investigation of small colony variants of Staphylococcus aureus in
chronic rhinosinusitis.
AB - BACKGROUND: Small colony variants (SCVs) are a metabolically inactive form of
bacteria that can be difficult to eradicate. To examine whether SCVs contribute
to Staphylococcus aureus persistence in chronic rhinosinusitis (CRS), we compared
the prevalence of S. aureus SCVs in CRS patients and healthy controls. METHODS:
Endoscopically guided middle meatus samples were collected from 23 CRS patients
and 12 controls. Samples were cultured and screened for the presence of
phenotypically small colonies. Candidate SCV isolates were classified by 16S rRNA
gene sequencing. To further characterize the capacity of S. aureus isolates to
form SCVs when stressed, colonies underwent a gentamicin exposure assay. RESULTS:
Among CRS patient samples, 15 were culture positive for S. aureus (65.2%), and of
those, two grew putative SCVs on selective media (8.7%). However, neither was
genetically confirmed to be S. aureus upon sequencing. In healthy controls, eight
specimens were culture positive for S. aureus (66.7%), and of these, two grew
putative S. aureus SCVs on selective media (16.7%); but again, neither was
confirmed to be S. aureus by 16S analysis. None of the four patients colonized
with SCVs had evidence of sinonasal disease at a mean follow-up of eight months.
S. aureus isolates from CRS patients and controls were equally likely to form
SCVs with gentamicin exposure. CONCLUSION: S. aureus SCVs were not associated
with CRS in the current study. Their role in refractory CRS remains theoretical,
and further research is warranted to determine whether S. aureus SCVs may reside
in the intracellular compartment.
PMID- 25590314
TI - Therapeutic effects of intranasal cyclosporine for eosinophilic rhinosinusitis
with nasal polyps in a mouse model.
AB - BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a
principally type 2 T helper cell (Th2)-mediated inflammatory disease. Systemic
corticosteroids currently represent the most effective treatment for CRSwNP, but
their long-term use is constrained due to their detrimental side effects. Long
term use of topical steroids is safe, but their efficacy is often limited.
Topical cyclosporine has proven to be safe and effective for Th2-mediated
diseases such as allergic conjunctivitis. OBJECTIVE: It was hypothesized that
topical cyclosporine would be an effective novel drug for the treatment of
CRSwNP; its therapeutic efficacy was assessed using a previously established
mouse model. METHODS: After induction of eosinophilic CRSwNP in four-week-old
BALB/c mice according to previous protocols, the therapeutic effects of
intranasal cyclosporine were evaluated and compared with those of triamcinolone
acetonide (TAC). Histopathologic changes were evaluated using hematoxylin and
eosin for polyp formation and Sirius red staining for eosinophilic infiltration.
The production of cytokines in sinonasal tissues, including tumor necrosis factor
(TNF), interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-5, IL-13, and IL-17A,
was measured using a cytometric bead array. RESULTS: The number of polyp-like
lesions was reduced significantly only by systemic TAC, but the degree of
eosinophilic infiltration was decreased significantly by topical cyclosporine,
the potency of which was similar to that of topical or systemic TAC. Except for
IFN-gamma, the majority of measured cytokines were reduced significantly by
topical cyclosporine, although their effects on IL-2 and IL-13 were less potent
than those of systemic TAC. CONCLUSION: Topical cyclosporine might be an
effective drug for the management of CRSwNP.
PMID- 25590315
TI - A novel method for comparison of tissue fibrosis after inferior turbinate
surgery: ultrasound elastography.
AB - BACKGROUND: Ultrasound (US) elastography has been widely used for thyroid, liver,
and lymph nodes as a research tool in the current medical practice. It has been
described in the inferior turbinates and validated as a reliable, reproducible,
noninvasive, and objective method that can detect the fibrosis-related tissue
strain. There is no previous study that investigated the amount of fibrosis
induced by radiofrequency and bipolar electrocautery in the inferior turbinates
in a noninvasive and objective manner. The aim of this study was to assess the
amount of inferior turbinate soft tissue fibrosis that was induced by
radiofrequency ablation (RFA) and submucosal bipolar diathermy (SBD) by US
elastography. METHODS: Thirty-eight inferior turbinates of 19 patients were
included. RFA was applied to 18 inferior turbinates (group 1) and SBD was applied
to 20 inferior turbinates (group 2). US elastography and visual analog scale
(VAS) assessments were performed on all patients preoperatively and 6 months
postoperatively. RESULTS: Preoperative mean US elastography scores in groups 1
and 2 were 2.55 +/- 0.78 m/s and 2.56 +/- 0.49 m/s, respectively (p < 0.05).
Postoperative mean US elastography scores in groups 1 and 2 were 2.91 +/- 1.03
m/s and 3.41 +/- 0.86 m/s, respectively (p < 0.05). Preoperative mean VAS scores
in groups 1 and 2 were 2.78 +/- 0.94 and 2.50 +/- 1.15, respectively.
Postoperative mean VAS scores in groups 1 and 2 were 6.61 +/- 1.61 and 6.10 +/-
1.4, respectively (p < 0.05). Correlation of US elastography and VAS scores was
insignificant (p > 0.05). CONCLUSION: Both RFA and SBD of the inferior turbinates
were effective in inducing scar tissue and, eventually, fibrosis in the soft
tissue of inferior turbinates. Cauterization has been found to cause
significantly higher amounts of fibrosis than radiofrequency; however, it did not
reflect the comparable clinical outcome. This is the first study that objectively
and noninvasively evaluates the targeted tissue fibrosis of the inferior
turbinate surgeries by the novel inferior turbinate US elastography.
PMID- 25590317
TI - Management of sinonasal mucosal melanomas and comparison of classification
staging systems.
AB - OBJECTIVE: The aim of this study was to describe treatment results in patients
with sinonasal mucosal melanomas (SMMs) and to compare three different
classification staging systems. MATERIALS AND METHODS: From 1988 to 2013, we
performed a retrospective study of 20 patients with primary sinonasal melanomas.
The median age at diagnosis was 71 years. There were 10 males and 10 females.
RESULTS: Nine SMMs (45%) were originated in the ethmoidal sinus complex, four
(20%) in the inferior turbinate, three (15%) in the nasal septum, two (10%) in
the maxillary sinus, and two (10%) in the nasal vestibule. Local recurrence was
diagnosed in eight patients (40%), and six out of 20 patients (30%) developed
distant metastasis during the course of their disease. The adjusted survival
rates at three and five years were 47% and 34%, respectively. The adjusted three
year survival rate according to the sinonasal staging system 7th edition for SMM
(TNM-SMM) was 60% in T3 stage, 50% in T4a stage, and 34% in T4b stage (p = 0.05).
According to Thompson's staging system, survival was 33% for group one, 58% for
group two, and 0% for group three (p = 0.006). With the sinonasal staging system
7th edition for carcinoma (TNM-CAR) survival was 33% in T1, 100% in T2 and T3, 0%
in T4a, and 34% in T4b (p = 0.006). CONCLUSIONS: Our experience confirms the
distribution of patients according to survival rates was better with the TNM-SMM
than with Thompson's or the TNM-CAR systems.
PMID- 25590318
TI - State of the Art: Medical treatment of aspirin exacerbated respiratory disease
(AERD).
AB - Aspirin exacerbated respiratory disease (AERD) is characterized as adult onset
asthma, nasal polyps, chronic rhinosinusitis, and hypersensitivity to a
cyclooxygenase-1 (COX-1) inhibitor, viz aspirin or nonsteroidal antiinflammatory
drugs (NSAIDs). The method for diagnosing AERD is with aspirin challenge, and
treatment includes aspirin desensitization followed by continued daily aspirin.
Although oral challenge has been the mainstay in the United States, lysyl-aspirin
has been validated as a diagnostic tool for aspirin-sensitive asthma and will be
discussed further in this article. The challenges with aspirin therapy
surrounding endoscopy and perioperative aspirin therapy will be discussed.
Additionally, daily aspirin therapy is not for everyone. Aspirin is relatively
contraindicated in those with a history of gastrointestinal bleed and an absolute
contraindication in pregnancy. Aspirin desensitization and subsequent treatment
has been shown to be highly effective for AERD.
PMID- 25590319
TI - Dementia is associated with chronic rhinosinusitis: a population-based case
controlled study.
AB - BACKGROUND: Cardiovascular diseases are reported to be associated with both
chronic rhinosinusitis (CRS) and dementia. Nevertheless, whether dementia is
associated with CRS is still unknown. In the present study, we explored the
association between dementia with prior CRS using a population-based data set.
METHODS: This study used the Taiwan Longitudinal Health Insurance Database 2000
as the source of data for a case-control study. We included 8768 subjects with
dementia as cases and 8768 age- and sex-matched subjects as controls. We
identified cases who had received a diagnosis of CRS before having received a
diagnosis of dementia. Conditional logistic regression analyses were performed to
examine the association of dementia with previously diagnosed CRS. RESULTS:
Results showed that of all sampled subjects, 875 (5.0%) had been previously
diagnosed with CRS. A chi-squared test showed that there was a significant
difference in the prevalences of prior CRS between cases and controls (6.0%
versus 4.0%; p < 0.001). The adjusted odds ratio (OR) of prior CRS for subjects
with dementia was 1.44 (95% CI, 1.25~1.66) compared with controls. Furthermore,
compared with controls, the OR of prior CRS was similar for subjects with
dementia for both sexes (the OR for male subjects was 1.48 and OR for female
subjects was 1.41). CONCLUSION: We concluded that subjects with dementia had a
higher odds of having had prior CRS than controls. This study implies a potential
association between CRS and dementia.
PMID- 25590316
TI - Factors driving the aspirin exacerbated respiratory disease phenotype.
AB - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is explained in part
by overexpression of 5-lipoxygenase and leukotriene C4 synthase (LTC4S),
resulting in constitutive overproduction of cysteinyl leukotrienes (CysLTs) and
driving the surge in CysLT production that occurs with aspirin ingestion.
Similarly, AERD is characterized by the overexpression of CysLT receptors.
Increased levels of both interleukin (IL)-4 and interferon (IFN)-gamma are
present in the tissue of AERD subjects. Previous studies demonstrated that IL-4
is primarily responsible for the up-regulation of LTC4S by mast cells. METHODS:
Literature review. RESULTS: Our previous studies demonstrated that IFN-gamma, but
not IL-4, drives this process in eosinophils. These published studies also extend
to both IL-4 and IFN-gamma the ability to up-regulate CysLT receptors.
Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell
and eosinophil activation. PGE2 concentrations are reduced in AERD, and our
published studies confirm that this reflects diminished expression of
cyclooxygenase (COX)-2. A process again that is driven by IL-4. Thus, IL-4 and
IFN-gamma together play an important pathogenic role in generating the phenotype
of AERD. Finally, induction of LTC4S and CysLT1 receptors by IL-4 reflects in
part the IL-4-mediated activation of signal transducer and activator of
transcription 6 (STAT6). Our previous studies demonstrated that aspirin blocks
trafficking of STAT6 into the nucleus and thereby prevents IL-4-mediated
induction of these transcripts, thereby suggesting a modality by which aspirin
desensitization could provide therapeutic benefit for AERD patients. CONCLUSION:
This review will examine the evidence supporting this model.
PMID- 25590320
TI - Prognostic factors for survival in patients with acute invasive fungal
rhinosinusitis.
AB - BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is an aggressive
opportunistic infection with a high mortality rate. There are few reports that
demonstrate an improvement in the overall prognosis. Furthermore, definite
prognostic factors related to patient survival remain unclear. OBJECTIVE: The
objective of this study was to evaluate the various clinical factors related to
survival of patients with AIFR. METHODS: This is a retrospective case series with
patients treated for AIFR between 1997 and 2013. A total of 45 patients with AIFR
were enrolled for analysis. We evaluated demographics, clinical characteristics,
and disease course. RESULTS: Mean age of patients was 59.6 years. AIFR developed
most commonly in patients with immunocompromised host, such as diabetes (n = 23)
or hematologic malignancy (n = 17). There were two main genera of fungus,
Aspergillus (n = 30) and Mucor (n = 14). Headache, cranial neuropathy, visual
loss, and orbital pain were the most common presenting symptoms. Overall survival
was 53%. Underlying hematologic malignancy and diabetes were significantly
associated with overall survival, and accompanying severe neutropenia and
elevated C-reactive protein (CRP) were also related to poor prognosis. Initial
presentation with facial swelling, involvement of nasal septum, or shorter
symptom duration was also associated with survival reduction. Multivariate
analysis revealed that CRP more than 5.50 mg/dL (Hazard ratio [HR], 9.04; p =
.003) was an independent prognostic factor in patients with AIFR. CONCLUSIONS:
Overall survival rate remained approximately 50% in patients with AIFR. The
prognosis of AIFR is significantly influenced by underlying diseases,
accompanying neutropenia, CRP levels, symptom duration, involvement of septum,
and the presence of facial swelling. Elevation of CRP, in particular, was an
independent predictor of poor outcomes and should be monitored appropriately.
PMID- 25590321
TI - Does atopy influence the effectiveness of treatment of adenoid hypertrophy with
mometasone furoate?
AB - BACKGROUND: The effect of topical mometasone for adenoid hypertrophy treatment is
well established. Nevertheless, the influence of atopy on this treatment remains
ill defined. OBJECTIVE: This study aims to compare the effects of topical
mometasone furoate treatment on the adenoid tissue between atopic and nonatopic
children. METHODS: Fifty-one children with obstructive respiratory complaints
underwent a semistructured clinical questionnaire on nasal symptoms, prick test,
and nasoendoscopy. Nasoendoscopic images were digitalized, and both adenoid and
nasopharyngeal areas were measured in pixels; the relative adenoid/nasopharyngeal
area was calculated. Patients were initially treated for 40 days with nasal
saline solution. In a subsequent 40-day period, topical mometasone furoate (total
dose, 100 MUg/day) was used. RESULTS: Topical mometasone significantly improved
nasal obstruction, snoring, and apnea and also significantly reduced the adenoid
tissue area related to the nasopharynx (p < 0.0001). Treatment with this
glucocorticoid was not influenced by atopy, neither for symptoms nor for adenoid
area. CONCLUSION: Topical mometasone furoate significantly reduced the adenoid
tissue area and led to a supplementary improvement of nasal symptoms. This
improvement was similar for atopic and nonatopic patients.
PMID- 25590322
TI - Acupuncture for the treatment of allergic rhinitis: a systematic review and meta
analysis.
AB - BACKGROUND: Because acupuncture may modulate the immune system, it has been
proposed as a useful treatment for patients with allergic rhinitis (AR). Here, we
assessed the evidence for the clinical efficacy of acupuncture for the management
of AR patients by performing a systematic review and meta-analysis of the
published literatures. METHODS: By searching PubMed, EMBASE, the Cochrane
clinical trials database, and the China National Knowledge Infrastructure from
1980 through July 11, 2013, we collected and analyzed the randomized controlled
trials (RCTs) of acupuncture for the treatment of AR patients to assess its
efficacy and safety. RESULTS: Thirteen full papers that met our inclusion
criteria were included, and a total of 2365 participants, including 1126 as
treatment group and 1239 as control group, were enrolled. Compared with control
group, acupuncture treatment group exerted a significant reduction in nasal
symptom scores (weighted mean difference [WMD]: -4.42, 95% confidence interval
[CI]: -8.42 to -0.43, p = 0.03), medication scores (WMD: 1.39, 95% CI: -2.18 to
0.61, p = .0005), and serum IgE (WMD: -75.00, 95% CI: -91.17 to -58.83, p <
0.00001). Data relating to Rhinitis Quality of Life Questionnaire (RQLQ) and 36
Item Short-Form (SF-36) component score in included studies were analyzed, which
ultimately point to the efficacy of acupuncture treatment in improving quality of
life in AR patients. No fatal events were reported in any of the included
studies, and no serious systemic reaction, which needed treatment in the
hospital, was related to the acupuncture treatment. CONCLUSION: Our meta-analysis
suggests that that acupuncture could be a safe and valid treatment option for AR
patients.
PMID- 25590323
TI - Endoscopic dacryocystorhinostomy with silicone, polypropylene, and T-tube stents;
randomized controlled trial of efficacy and safety.
AB - OBJECTIVE: To compare the efficacy and safety of endoscopic dacryocystorhinostomy
(En-DCR) with different stent materials for lacrimal sac intubation in primary
nasolacrimal ductal obstructions. STUDY DESIGN: Randomized controlled study with
three parallel groups. Level of evidence is 1b. METHODS: A total of 91 patients
(five bilateral) with primary nasolacrimal duct obstruction (NLDO) at a tertiary
referral center scheduled for En-DCR were to allocated into three stent groups
with a sealed envelope and were randomized into three treatments: silicone,
Prolene (polypropylene), and otologic T-tube. Ophthalmology and otolaryngology
clinics evaluated the patients preoperatively and postoperatively with
endoscopes, lacrimal system syringing, and dacryocystography. The success of the
stents was evaluated 12 months after surgery with symptom relief and ostial
patency. Complications were also noted. RESULTS: The overall success rate of the
En-DCR in the stent groups was 78.1% (75/96); specifically, 87.5% (28/32) with
silicone, 84.4% (27/32) with Prolene, and 62.5% (20/32) with T-tube. The efficacy
of the procedures with the T-tube was significantly lower than that of the
Prolene and silicone (p = .031, chi(2) test). There were no significant
differences between the silicone and Prolene (p = .718, chi(2) test). Prolene was
found to be related with orbital complications. Spontaneous loss is a particular
complication of otologic T-tube and highly portends to failure. CONCLUSIONS: The
results of our study suggest that efficacy, defined as anatomic and functional
success, is equally high for silicone and Prolene stents and lower for otologic T
tube in En-DCR.
PMID- 25590324
TI - Do sinus computed tomography findings predict olfactory dysfunction and its
postoperative recovery in chronic rhinosinusitis patients?
AB - BACKGROUND: Olfactory dysfunction secondary to chronic rhinosinusitis (CRS) is a
mixed disorder of conductive and sensorineural olfactory impairment. Although
endoscopic sinus surgery has some beneficial effects on olfaction, the outcomes
are challenging to predict. The aim of this study was to assess the olfactory
outcomes after surgery, to investigate the correlation between the severity of
regional computed tomography (CT) findings and olfactory performance, and to
identify the predictors of postoperative outcomes based on unilateral olfactory
threshold analysis. METHODS: This study included 167 CRS nostrils of 97 patients
with/without polyps (68/99 nostrils) undergoing sinus surgery between January
2007 and December 2011. Olfactory function was evaluated using the butanol
threshold test (BTT) before and 6 months after surgery. Clinical and nasal
factors from sinus CT scan (sinuses, ostiomeatal complex, olfactory cleft [OC],
nasal polyps, and unilateral Lund-Mackay CT score) were analyzed to correlate
them with pre- and postoperative olfactory performances. RESULTS: Eighty-two
percent of the CRS nostrils had anosmia or hyposmia. After surgery, 42% of them
showed an improvement in BTT score. Despite improvement, most of the subjects
remained with residual hyposmia. The BTT scores deteriorated after surgery in 23%
of the total subjects. The disease severity of the OC, posterior ethmoid, and
frontal sinus were the significant risk factors for CRS-related anosmia. The
strongest risk factor for anosmia was totally obstructed OC (odds ratio [OR],
16.56; 95% CI, 4.31-63.71; p = 0.000). The nostrils with anosmia or partly
opacified anterior ethmoid benefited from surgery with respect to olfaction.
CONCLUSION: Our results can give support to the combined use of the butanol
threshold and sinonasal CT findings in the evaluation of olfaction in CRS
patients and help us counsel the patients about the likelihood of postoperative
olfactory recovery.
PMID- 25590325
TI - Spontaneous CSF rhinorrhea: prevalence of multiple simultaneous skull base
defects.
AB - BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks are caused by
intracranial hypertension. Given this underlying etiology, patients may be at
risk for developing multiple skull base defects. OBJECTIVE: The purpose of our
study is to present the prevalence of multiple simultaneous skull base defects in
patients with spontaneous CSF rhinorrhea. METHODS: We performed a retrospective
chart review in a tertiary care practice of 44 consecutive patients with
spontaneous CSF rhinorrhea who underwent endoscopic repair by the senior author
(R.R.C.) to determine the prevalence of having multiple simultaneous skull base
defects identified at the time of surgery. We defined this as two or more bony
defects identified endoscopically with intact intervening bone with or without
soft tissue prolapse into the nasal cavity or paranasal sinus cavity. RESULTS:
Eight of 44 patients (18.2%) were found to have multiple simultaneous skull base
defects. The average body mass index (BMI) of the study population was 34.5
(range, 22.7-59). CONCLUSION: A significant number of patients with spontaneous
CSF rhinorrhea may have more than one skull base defect present at the time of
presentation. The clinical significance of this finding in surgical and medical
decision making is not clear at this time.
PMID- 25590326
TI - American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF)
will publish its latest "Clinical practice guideline: allergic rhinitis (AR) in
February, 2015".
PMID- 25590328
TI - Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various
branched alkyl side chains and their applications in thin-film transistors and
polymer solar cells.
AB - New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing pi
extended conjugated polymers with various branched alkyl side-chains were
successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2
tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were
selected as the side-chain moieties and were anchored to the N-positions of the
thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found
to be soluble owing to the bulkiness of the side chains. The thin-film transistor
based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole
mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest pi-pi stacking
distance between the polymer chains, which was determined by grazing incidence X
ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]
phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8
diiodooctane (1 vol %) were also constructed from the synthesized polymers
without thermal annealing; the device containing the 2-octyldodecyl-substituted
polymer exhibited the highest power conversion efficiency of 5.8%. Although all
the polymers showed similar physical properties, their device performance was
clearly influenced by the sizes of the branched alkyl side-chain groups.
PMID- 25590329
TI - Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in
insect muscle.
AB - This paper proposes a remarkably facile staining protocol to visually investigate
dynamic physiological events in insect tissues. We attempted to monitor Ca2+
dynamics during contraction of electrically stimulated living muscle. Advances in
circuit miniaturization and insect neuromuscular physiology have enabled the
hybridization of living insects and man-made electronic components, such as
microcomputers, the result of which has been often referred as a Living Machine,
Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use,
electrical stimulation parameters need to be optimized to induce desired muscle
response (motor action) and minimize the damage in the muscle due to the
electrical stimuli. Staining tissues and organs as well as measuring the dynamics
of chemicals of interest in muscle should be conducted to quantitatively and
systematically evaluate the effect of various stimulation parameters on the
muscle response. However, existing staining processes require invasive surgery
and/or arduous procedures using genetically encoded sensors. In this study, we
developed a non-invasive and remarkably facile method for staining, in which
chemical indicators can be orally administered (oral dosing). A chemical Ca2+
indicator was orally introduced into an insect of interest via food containing
the chemical indicator and the indicator diffused from the insect digestion
system to the target muscle tissue. We found that there was a positive
relationship between the fluorescence intensity of the indicator and the
frequency of electrical stimulation which indicates the orally dosed indicator
successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing
method has a potential to globally stain tissues including neurons, and
investigating various physiological events in insects.
PMID- 25590330
TI - The formation of multi-synaptic connections by the interaction of synaptic and
structural plasticity and their functional consequences.
AB - Cortical connectivity emerges from the permanent interaction between neuronal
activity and synaptic as well as structural plasticity. An important
experimentally observed feature of this connectivity is the distribution of the
number of synapses from one neuron to another, which has been measured in several
cortical layers. All of these distributions are bimodal with one peak at zero and
a second one at a small number (3-8) of synapses. In this study, using a
probabilistic model of structural plasticity, which depends on the synaptic
weights, we explore how these distributions can emerge and which functional
consequences they have. We find that bimodal distributions arise generically from
the interaction of structural plasticity with synaptic plasticity rules that
fulfill the following biological realistic constraints: First, the synaptic
weights have to grow with the postsynaptic activity. Second, this growth curve
and/or the input-output relation of the postsynaptic neuron have to change sub
linearly (negative curvature). As most neurons show such input-output-relations,
these constraints can be fulfilled by many biological reasonable systems. Given
such a system, we show that the different activities, which can explain the layer
specific distributions, correspond to experimentally observed activities.
Considering these activities as working point of the system and varying the pre-
or postsynaptic stimulation reveals a hysteresis in the number of synapses. As a
consequence of this, the connectivity between two neurons can be controlled by
activity but is also safeguarded against overly fast changes. These results
indicate that the complex dynamics between activity and plasticity will, already
between a pair of neurons, induce a variety of possible stable synaptic
distributions, which could support memory mechanisms.
PMID- 25590331
TI - Uptake and population-level impact of expedited partner therapy (EPT) on
Chlamydia trachomatis and Neisseria gonorrhoeae: the Washington State community
level randomized trial of EPT.
AB - BACKGROUND: Expedited partner therapy (EPT), the practice of treating the sex
partners of persons with sexually transmitted infections without their medical
evaluation, increases partner treatment and decreases gonorrhea and chlamydia
reinfection rates. We conducted a stepped-wedge, community-level randomized trial
to determine whether a public health intervention promoting EPT could increase
its use and decrease chlamydia test positivity and gonorrhea incidence in women.
METHODS AND FINDINGS: The trial randomly assigned local health jurisdictions
(LHJs) in Washington State, US, into four study waves. Waves instituted the
intervention in randomly assigned order at intervals of 6-8 mo. Of the state's 25
LHJs, 24 were eligible and 23 participated. Heterosexual individuals with
gonorrhea or chlamydial infection were eligible for the intervention. The study
made free patient-delivered partner therapy (PDPT) available to clinicians, and
provided public health partner services based on clinician referral. The main
study outcomes were chlamydia test positivity among women ages 14-25 y in 219
sentinel clinics, and incidence of reported gonorrhea in women, both measured at
the community level. Receipt of PDPT from clinicians was evaluated among randomly
selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia
outcomes, respectively. The intervention increased the percentage of persons
receiving PDPT from clinicians (from 18% to 34%, p < 0.001) and the percentage
receiving partner services (from 25% to 45%, p < 0.001). Chlamydia test
positivity and gonorrhea incidence in women decreased over the study period, from
8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for
temporal trends, the intervention was associated with an approximately 10%
reduction in both chlamydia positivity and gonorrhea incidence, though the
confidence bounds on these outcomes both crossed one (chlamydia positivity
prevalence ratio = 0.89, 95% CI 0.77-1.04, p = 0.15; gonorrhea incidence rate
ratio = 0.91, 95% CI .71-1.16, p = 0.45). Study findings were potentially limited
by inadequate statistical power, by the institution of some aspects of the study
intervention outside of the research randomization sequence, and by the fact that
LHJs did not constitute truly isolated sexual networks. CONCLUSIONS: A public
health intervention promoting the use of free PDPT substantially increased its
use and may have resulted in decreased chlamydial and gonococcal infections at
the population level. TRIAL REGISTRATION: ClinicalTrials.gov NCT01665690.
PMID- 25590332
TI - Antiarrhythmic agents and the risk of malignant neoplasm of liver and
intrahepatic bile ducts.
AB - BACKGROUND: The objective of this study was to determine the association between
the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and
intrahepatic bile ducts (MNLIHD). METHODS: We used the research database of the
Taiwan National Health Insurance Program to conduct a population-based, case
control study. We identified 9944 patients with antiarrhythmic history who were
first diagnosed as having MNLIHD between 2005 and 2010. We identified an
additional 19,497 patients with antiarrhythmic history in the same period who did
not develop MNLIHD and were frequency-matched using age, sex, and index year to
form a control group. Five commercially available antiarrhythmic agents,
amiodarone, mexiletine, propafenone, quinidine, and procainamide, were analyzed.
RESULTS: The adjusted odds ratio (OR) of MNLIHD was 1.60 (95% confidence interval
[CI], 1.45-1.77) for amiodarone users versus nonamiodarone users. In subgroup
analysis, amiodarone use was significantly associated with an increased risk of
MNLIHD with an adjusted OR of 18.0 (95% CI, 15.7-20.5) for patients with
comorbidities compared to an OR of 2.43 (95% CI, 1.92-3.06) for those without
comorbidities. After adjustment for age, sex, statins, anti-diabetes medications,
non-steroidal antiinflammatory drugs, propafenone use, quinidine use, and
comorbidities, the ORs were 1.49, 1.66, and 1.79 for MNLIHD associated with
annual mean defined daily doses of <= 30, 31-145, and >145, respectively.
CONCLUSIONS: The results of the present study indicated that amiodarone might be
associated with the development of MNLIHD in a dose-dependent manner,
particularly among patients with comorbidities.
PMID- 25590334
TI - Real-time continuous glucose monitoring reduces the duration of hypoglycemia
episodes: a randomized trial in very low birth weight neonates.
AB - OBJECTIVES: Hypoglycemia is frequent in very low birth weight (VLBW) neonates and
compromises their neurological outcome. The aim of this study was to compare real
time continuous glucose monitoring system (RT-CGMS) to standard methods by
intermittent capillary blood glucose testing in detecting and managing
hypoglycemia. STUDY DESIGN: Forty-eight VLBW neonates were enrolled in this
prospective study. During their 3 first days of life, their glucose level was
monitored either by RT-CGMS (CGM-group), or by intermittent capillary glucose
testing (IGM-group) associated with a blind-CGMS to detect retrospectively missed
hypoglycemia. Outcomes were the number and duration of hypoglycemic (<= 50 mg/dl)
episodes per patient detected by CGMS. RESULTS: Forty-three monitorings were
analyzed (IGM n = 21, CGM n = 22), with a median recording time of 72 hours. In
the IGM group, blind-CGMS revealed a significantly higher number of hypoglycemia
episodes than capillary blood glucose testing (1.2 +/- 0.4 vs 0.4 +/- 0.2
episode/patient, p<0.01). In the CGM-group, the use of RT-CGMS made it possible
(i) to detect the same number of hypoglycemia episodes as blind-CGMS (1.2 +/- 0.4
episode/patient), (ii) to adapt the glucose supply in neonates with hypoglycemia
(increased supply during days 1 and 2), and (iii) to significantly reduce the
duration of hypoglycemia episodes per patient (CGM 44[10-140] min versus IGM
95[15-520] min, p<0.05). Furthermore, it reduced the number of blood samples (CGM
16.9 +/- 1.0 vs IGM 21.9 +/- 1.0 blood sample/patient, p<0.001). CONCLUSION: RT
CGMS played a beneficial role in managing hypoglycemia in VLBW neonates by
adjusting the carbohydrate supply to the individual needs and by reducing the
duration of hypoglycemia episodes. The clinical significance of the biological
differences observed in our study need to be explored.
PMID- 25590333
TI - Transcriptome analysis and systemic RNAi response in the African sweetpotato
weevil (Cylas puncticollis, Coleoptera, Brentidae).
AB - The African sweetpotato weevil (SPW) Cylas puncticollis Boheman is one of the
most important constraints of sweetpotato production in Sub-Saharan Africa and
yet is largely an uncharacterized insect pest. Here, we report on the
transcriptome analysis of SPW generated using an Illumina platform. More than 213
million sequencing reads were obtained and assembled into 89,599 contigs. This
assembly was followed by a gene ontology annotation. Subsequently, a
transcriptome search showed that the necessary RNAi components relevant to the
three major RNAi pathways, were found to be expressed in SPW. To address the
functionality of the RNAi mechanism in this species, dsRNA was injected into
second instar larvae targeting laccase2, a gene which encodes an enzyme involved
in the sclerotization of insect exoskeleton. The body of treated insects showed
inhibition of sclerotization, leading eventually to death. Quantitative Real Time
PCR (qPCR) confirmed this phenotype to be the result of gene silencing. Together,
our results provide valuable sequence data on this important insect pest and
demonstrate that a functional RNAi pathway with a strong and systemic effect is
present in SPW and can further be explored as a new strategy for controlling this
important pest.
PMID- 25590335
TI - Green fluorescent protein-based expression screening of membrane proteins in
Escherichia coli.
AB - The production of recombinant membrane proteins for structural and functional
studies remains technically challenging due to low levels of expression and the
inherent instability of many membrane proteins once solubilized in detergents. A
protocol is described that combines ligation independent cloning of membrane
proteins as GFP fusions with expression in Escherichia coli detected by GFP
fluorescence. This enables the construction and expression screening of multiple
membrane protein/variants to identify candidates suitable for further investment
of time and effort. The GFP reporter is used in a primary screen of expression by
visualizing GFP fluorescence following SDS polyacrylamide gel electrophoresis
(SDS-PAGE). Membrane proteins that show both a high expression level with minimum
degradation as indicated by the absence of free GFP, are selected for a secondary
screen. These constructs are scaled and a total membrane fraction prepared and
solubilized in four different detergents. Following ultracentrifugation to remove
detergent-insoluble material, lysates are analyzed by fluorescence detection size
exclusion chromatography (FSEC). Monitoring the size exclusion profile by GFP
fluorescence provides information about the mono-dispersity and integrity of the
membrane proteins in different detergents. Protein: detergent combinations that
elute with a symmetrical peak with little or no free GFP and minimum aggregation
are candidates for subsequent purification. Using the above methodology, the
heterologous expression in E. coli of SED (shape, elongation, division, and
sporulation) proteins from 47 different species of bacteria was analyzed. These
proteins typically have ten transmembrane domains and are essential for cell
division. The results show that the production of the SEDs orthologues in E. coli
was highly variable with respect to the expression levels and integrity of the
GFP fusion proteins. The experiment identified a subset for further
investigation.
PMID- 25590336
TI - Log in and breathe out: internet-based recovery training for sleepless employees
with work-related strain - results of a randomized controlled trial.
AB - OBJECTIVES: The primary purpose of this randomized controlled trial (RCT) was to
evaluate the efficacy of a guided internet-based recovery training for employees
who suffer from both work-related strain and sleep problems (GET.ON Recovery).
The recovery training consisted of six lessons, employing well-established
methods from cognitive behavioral therapy for insomnia (CBT-I) such as sleep
restriction, stimulus control, and hygiene interventions as well as techniques
targeted at reducing rumination and promoting recreational activities. METHODS:
In a two-arm RCT (N=128), the effects of GET.ON Recovery were compared to a
waitlist-control condition (WLC) on the basis of intention-to-treat analyses.
German teachers with clinical insomnia complaints (Insomnia Severity Index >=15)
and work-related rumination (Irritation Scale, cognitive irritation subscale
>=15) were included. The primary outcome measure was insomnia severity. RESULTS:
Analyses of covariance (ANCOVA) revealed that, compared to the WLC, insomnia
severity of the intervention group decreased significantly stronger (F=74.11,
P<0.001) with a d=1.45 [95% confidence interval (95% CI) 1.06-1.84] The number
needed to treat (NNT) was <2 for reliable change and NNT <4 for reduction in
expert-rated diagnosis of primary insomnia. CONCLUSION: The training
significantly reduces sleep problems and fosters mental detachment from work and
recreational behavior among adult stressed employees at post-test and 6-months
follow up. Given the low threshold access this training could reach out to a
large group of stressed employees when results are replicated in other studies.
PMID- 25590337
TI - Effect of antenatal parasitic infections on anti-vaccine IgG levels in children:
a prospective birth cohort study in Kenya.
AB - BACKGROUND: Parasitic infections are prevalent among pregnant women in sub
Saharan Africa. We investigated whether prenatal exposure to malaria and/or
helminths affects the pattern of infant immune responses to standard vaccinations
against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and
tetanus toxoid (TT). METHODS AND FINDINGS: 450 Kenyan women were tested for
malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths
during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their
newborns were followed biannually to age 36 months and tested for absolute levels
of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood
(CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma
haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed.
Three immunophenotype categories were compared: i) tolerant (those having
Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective
Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii)
sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB
recall response to respective parasite antigen); or iii) unexposed (no evidence
of maternal infection or CB recall response). Overall, 78.9% of mothers were
infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm
(33.8%). Antenatal maternal malaria, LF, and hookworm were independently
associated with significantly lower Hib-specific IgG. Presence of multiple
maternal infections was associated with lower infant IgG levels against Hib and
DT antigens post-vaccination. Post-vaccination IgG levels were also significantly
associated with immunophenotype: malaria-tolerized infants had reduced response
to DT, whereas filaria-tolerized infants showed reduced response to Hib.
CONCLUSIONS: There is an impaired ability to develop IgG antibody responses to
key protective antigens of Hib and diphtheria in infants of mothers infected with
malaria and/or helminths during pregnancy. These findings highlight the
importance of control and prevention of parasitic infections among pregnant
women.
PMID- 25590340
TI - The myth of the angry atheist.
AB - Atheists are often portrayed in the media and elsewhere as angry individuals.
Although atheists disagree with the pillar of many religions, namely the
existence of a God, it may not necessarily be the case that they are angry
individuals. The prevalence and accuracy of angry-atheist perceptions were
examined in 7 studies with 1,677 participants from multiple institutions and
locations in the United States. Studies 1-3 revealed that people believe atheists
are angrier than believers, people in general, and other minority groups, both
explicitly and implicitly. Studies 4-7 then examined the accuracy of these
beliefs. Belief in God, state anger, and trait anger were assessed in multiple
ways and contexts. None of these studies supported the idea that atheists are
particularly angry individuals. Rather, these results support the idea that
people believe atheists are angry individuals, but they do not appear to be
angrier than other individuals in reality.
PMID- 25590341
TI - Potential job facilitation benefits of "water cooler" conversations: the
importance of social interactions in the workplace.
AB - This study looked at the extent to which personality and cultural factors
predicted participants' perceptions of the importance private interactions played
in the workplace. The 134 participants read a vignette (where a new employee
socially interacted at low or high levels with co-workers) and completed the Big
Five Inventory, Social Axioms Survey, and questions concerning expected workplace
experiences. Results indicated employees who engaged in high levels of private
interaction with co-workers were expected to be better liked, to receive better
performance evaluations, were more likely to receive co-worker assistance, and
were thought to be more likely chosen for future projects. However, the
personality and social axiom variables studied did not significantly interact
with social interaction to influence expectations of workplace outcomes.
PMID- 25590338
TI - Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors
in breast cancer cells.
AB - Approximately 25% of breast cancers overexpress and depend on the receptor
tyrosine kinase ERBB2, one of 4 ERBB family members. Targeted therapies directed
against ERBB2 have been developed and used clinically, but many patients continue
to develop resistance to such therapies. Although much effort has been focused on
elucidating the mechanisms of acquired resistance to ERBB2-targeted therapies,
the involvement of ERBB4 remains elusive and controversial. We demonstrate that
genetic ablation of ERBB4, but not ERBB1-3, led to apoptosis in lapatinib
resistant cells, suggesting that the efficacy of pan-ERBB inhibitors was, at
least in part, mediated by the inhibition of ERBB4. Moreover, ERBB4 was
upregulated at the protein level in ERBB2+ breast cancer cell lines selected for
acquired lapatinib resistance in vitro and in MMTV-Neu mice following prolonged
lapatinib treatment. Knockdown of ERBB4 caused a decrease in AKT phosphorylation
in resistant cells but not in sensitive cells, suggesting that ERBB4 activated
the PI3K/AKT pathway in lapatinib-resistant cells. Importantly, ERBB4 knockdown
triggered apoptosis not only in lapatinib-resistant cells but also in trastuzumab
resistant cells. Our results suggest that although ERBB4 is dispensable for naive
ERBB2+ breast cancer cells, it may play a key role in the survival of ERBB2+
cancer cells after they develop resistance to ERBB2 inhibitors, lapatinib and
trastuzumab.
PMID- 25590342
TI - Engaged, committed and helpful employees: the role of psychological empowerment.
AB - Although previous research has been focused on the relationship among
personality, empowerment, and outcomes, little is known about the incremental
effect of empowerment on positive work outcomes. This article aims at exploring
the relation between personality factors (i.e., extraversion and
conscientiousness) and positive work outcomes (i.e., work engagement, affective
organizational commitment, and organizational citizenship behavior), and at
determining the incremental effect of psychological empowerment on these
outcomes. A convenience sample from three organizations has been used for data
collection (N = 258; 52% women, mean age 38.55 years, SD = 10.21). Hierarchical
multiple regressions indicate that personality and psychological empowerment
explain a significant amount of the variance in the positive organizational
outcomes, and that psychological empowerment has a significant incremental value
over demographics and personality for the studied outcomes.
PMID- 25590343
TI - Professional self-efficacy as a predictor of burnout and engagement: the role of
challenge and hindrance demands.
AB - The objective of the current study is to analyze the role of professional self
efficacy as a predictor of psychosocial well-being (i.e., burnout and engagement)
following the Social Cognitive Theory of Albert Bandura (1997). Structural
Equation Modeling was performed in a sample of secondary school teachers (n =
460) and users of Information and Communication Technology (n = 596). Results
show empirical support for the predicting role that professional self-efficacy
plays in the perception of challenge (i.e., mental overload) and hindrance
demands (i.e., role conflict, lack of control, and lack of social support), which
are in turn related to burnout (i.e., erosion process) and engagement (i.e.,
motivational process). Specifically, employees with more professional self
efficacy will perceive more challenge demands and fewer hindrance demands, and
this will in turn relate to more engagement and less burnout. A multi-group
analysis showed that the research model was invariant across both samples.
Theoretical and practical implications are discussed.
PMID- 25590344
TI - Assessment of anger terms in Hebrew: a gender comparison.
AB - ABSTRACT Appraisal of anger terms is based on past experience recollections,
social norms, and gender roles. The objectives of this study were to find
combinations of emotional components presented by a new composite variable that
will exhibit differences between genders and differentiate between anger terms in
Hebrew. The sample was comprised of forty students, Hebrew native speakers who
participated in a web based study. Participants were asked to rate eight anger
terms in Hebrew on a number of features that comprised five emotional components:
subjective feelings states body reactions, expressions, action tendencies, and
cognitive evaluations. A two-factor between-subjects multivariate analysis of
variance (MANOVA) was conducted. A simplified multivariate composite, defined as
subjective experience minus regulation, explained 10% of the gender difference.
Another simplified composite, which combines the additive effect of the
subjective experience and the actions that accompany this emotional state,
explained 14% of difference between the anger terms. The findings are discussed
with respect to appraisal theory and social constructivist conceptualization.
PMID- 25590339
TI - RNA-guided isomerization of uridine to pseudouridine--pseudouridylation.
AB - Box H/ACA ribonucleoproteins (RNPs), each consisting of one unique guide RNA and
4 common core proteins, constitute a family of complex enzymes that catalyze, in
an RNA-guided manner, the isomerization of uridines to pseudouridines (Psis) in
RNAs, a reaction known as pseudouridylation. Over the years, box H/ACA RNPs have
been extensively studied revealing many important aspects of these RNA modifying
machines. In this review, we focus on the composition, structure, and biogenesis
of H/ACA RNPs. We explain the mechanism of how this enzyme family recognizes and
specifies its target uridine in a substrate RNA. We discuss the substrates of box
H/ACA RNPs, focusing on rRNA (rRNA) and spliceosomal small nuclear RNA (snRNA).
We describe the modification product Psi and its contribution to RNA function.
Finally, we consider possible mechanisms of the bone marrow failure syndrome
dyskeratosis congenita and of prostate and other cancers linked to mutations in
H/ACA RNPs.
PMID- 25590346
TI - Developmental pathways to attention-deficit/hyperactivity disorder and disruptive
behavior disorders: Investigating the impact of the stress response on executive
functioning.
AB - A current theory suggests multiple pathways to the onset of attention
deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder
or conduct disorder, proposing that heterogeneous factors lead to various
patterns of behavior, cognitive impairments, and even physiological signs which
are categorized as ADHD and comorbid disorders. This review focused on one
proposed pathway to the onset of ADHD and ODD/CD in order to examine how low
physiological arousal, as indicated by atypical hypothalamic-pituitary-adrenal
axis and sympathetic adrenomedullary functioning, might be associated with
cognitive impairment. First, the cognitive deficits associated with ADHD and
disruptive behavior disorders were reviewed. In order to understand the atypical
response, studies of the typical stress response and its relationship to
cognition, particularly executive functioning, were then examined. Finally, this
review summarized findings of an atypical stress response among children with
ADHD and ODD/CD. Review of the literature led to the conclusion that the
theorized pathway may be improved by taking into account the effects of stress on
executive functioning given that an atypical stress response would likely be
associated with impairment in this area. Future research directions needed to
advance our understanding of the relationship between low arousal, ADHD, and
ODD/CD were highlighted.
PMID- 25590345
TI - The use of the puzzle box as a means of assessing the efficacy of environmental
enrichment.
AB - Environmental enrichment can dramatically influence the development and function
of neural circuits. Further, enrichment has been shown to successfully delay the
onset of symptoms in models of Huntington's disease (1-4), suggesting
environmental factors can evoke a neuroprotective effect against the progressive,
cellular level damage observed in neurodegenerative disorders. The ways in which
an animal can be environmentally enriched, however, can vary considerably.
Further, there is no straightforward manner in which the effects of environmental
enrichment can be assessed: most methods require either fairly complicated
behavioral paradigms and/or postmortem anatomical/physiological analyses. This
protocol describes the use of a simple and inexpensive behavioral assay, the
Puzzle Box (5-7) as a robust means of determining the efficacy of increased
social, sensory and motor stimulation on mice compared to cohorts raised in
standard laboratory conditions. This simple problem solving task takes advantage
of a rodent's innate desire to avoid open enclosures by seeking shelter.
Cognitive ability is assessed by adding increasingly complex impediments to the
shelter's entrance. The time a given subject takes to successfully remove the
obstructions and enter the shelter serves as the primary metric for task
performance. This method could provide a reliable means of rapidly assessing the
efficacy of different enrichment protocols on cognitive function, thus paving the
way for systematically determining the role specific environmental factors play
in delaying the onset of neurodevelopmental and neurodegenerative disease.
PMID- 25590347
TI - Quantitative residue-specific protein backbone torsion angle dynamics from
concerted measurement of 3J couplings.
AB - Three-bond (3)J(C'C') and (3)J(HNHalpha) couplings in peptides and proteins are
functions of the intervening backbone torsion angle phi. In well-ordered regions,
(3)J(HNHalpha) is tightly correlated with (3)J(C'C'), but the presence of large
phi angle fluctuations differentially affects the two types of couplings.
Assuming the phi angles follow a Gaussian distribution, the width of this
distribution can be extracted from (3)J(C'C') and (3)J(HNHalpha), as demonstrated
for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins,
slow transverse relaxation permits measurement of (3)J(C'C') and (3)J(HNH)
couplings at very high precision, and impact of factors other than the
intervening torsion angle on (3)J will be minimal, making these couplings
exceptionally valuable structural reporters. Analysis of alpha-synuclein yields
rather homogeneous widths of 69 +/- 6 degrees for the phi angle distributions
and (3)J(C'C') values that agree well with those of a recent maximum entropy
analysis of chemical shifts, J couplings, and (1)H-(1)H NOEs. Data are consistent
with a modest (<=30%) population of the polyproline II region.
PMID- 25590349
TI - T538 phosphorylation, Pin-ing p63-Itch stability.
PMID- 25590348
TI - Centrosomal nucleolin is required for microtubule network organization.
AB - Nucleolin is a pleiotropic protein involved in a variety of cellular processes.
Although multipolar spindle formation has been observed after nucleolin
depletion, the roles of nucleolin in centrosome regulation and functions have not
been addressed. Here we report using immunofluorescence and biochemically
purified centrosomes that nucleolin co-localized only with one of the centrioles
during interphase which was further identified as the mature centriole. Upon
nucleolin depletion, cells exhibited an amplification of immature centriole
markers surrounded by irregular pericentrin staining; these structures were
exempt from maturation markers and unable to nucleate microtubules. Furthermore,
the microtubule network was disorganized in these cells, exhibiting frequent non
centrosomal microtubules. At the mature centriole a reduced kinetics in the
centrosomal microtubule nucleation phase was observed in live silenced cells, as
well as a perturbation of microtubule anchoring. Immunoprecipitation experiments
showed that nucleolin belongs to protein complexes containing 2 key centrosomal
proteins, gamma-tubulin and ninein, involved in microtubule nucleation and
anchoring steps. Altogether, our study uncovered a new role for nucleolin in
restricting microtubule nucleation and anchoring at centrosomes in interphase
cells.
PMID- 25590351
TI - Cancer research in Brazil - stuck in second gear?
AB - This article describes the main issues regarding clinical cancer research in
Brazil, including both the opportunities and the hurdles. Scientists and
clinicians in this field had the opportunity to talk to regulatory agencies and
to the Health Ministry representative at a meeting held in the State of Rio de
Janeiro, Brazil, in April 2014. Our conclusions are that we do indeed have
opportunities; however, we need to move forward regarding partnerships between
academia and industry, increase the availability of funding, and provide easier
navigation through the regulatory processes.
PMID- 25590350
TI - Bilateral repetitive transcranial magnetic stimulation for treatment-resistant
depression: a systematic review and meta-analysis of randomized controlled
trials.
AB - There has been concern regarding the use of controversial paradigms for
repetitive transcranial magnetic stimulation (rTMS) to manage treatment-resistant
depression (TRD). This meta-analysis assessed the efficacy of bilateral rTMS
compared with unilateral and sham rTMS in patients with TRD. PubMed, Embase,
CENTRAL, PsycINFO, Web of Science, EAGLE and NTIS databases were searched to
identify relevant studies, and randomized controlled trials (RCTs) on bilateral
rTMS for TRD patients were included. The response was defined as the primary
outcome, and remission was the secondary outcome. Ten RCTs that included 634
patients met the eligibility criteria. The risk ratio (RRs) of both the primary
and secondary outcomes of bilateral rTMS showed non-significant increases
compared to unilateral rTMS (RR=1.01, P=0.93; odds ratio [OR]=0.77, P=0.22).
Notably, the RR of the primary bilateral rTMS outcome was significantly increased
compared to that for sham rTMS (RR=3.43, P=0.0004). The results of our analysis
demonstrated that bilateral rTMS was significantly more effective than sham rTMS
but not unilateral rTMS in patients with TRD. Thus, bilateral rTMS may not be a
useful paradigm for patients with TRD.
PMID- 25590354
TI - Fluence inhomogeneities due to a ripple filter induced Moire effect.
AB - At particle therapy facilities with pencil beam scanning, the implementation of a
ripple filter (RiFi) broadens the Bragg peak, so fewer energy steps from the
accelerator are required for a homogeneous dose coverage of the planning target
volume (PTV). However, sharply focusing the scanned pencil beams at the RiFi
plane by ion optical settings can lead to a Moire effect, causing fluence
inhomogeneities at the isocenter. This has been experimentally proven at the
Heidelberg Ionenstrahl-Therapiezentrum (HIT), Universitatsklinikum Heidelberg,
Germany. 150 MeV u(-1) carbon-12 ions are used for irradiation with a 3 mm thick
RiFi. The beam is focused in front of and as close to the RiFi plane as possible.
The pencil beam width is estimated to be 0.78 mm at a 93 mm distance from the
RiFi. Radiographic films are used to obtain the fluence profile 30 mm in front of
the isocenter, 930 mm from the RiFi. The Monte Carlo (MC) code SHIELD-HIT12A is
used to determine the RiFi-induced inhomogeneities in the fluence distribution at
the isocenter for a similar setup, pencil beam widths at the RiFi plane ranging
from sigmachi(RiFi to 1.2 mm and for scanning step sizes ranging from 1.5 to 3.7
mm. The beam application and monitoring system (BAMS) used at HIT is modelled and
simulated. When the width of the pencil beams at the RiFi plane is much smaller
than the scanning step size, the resulting inhomogeneous fluence distribution at
the RiFi plane interfers with the inhomogeneous RiFi mass distribution and
fluence inhomogeneity can be observed at the isocenter as large as an 8%
deviation from the mean fluence. The inverse of the fluence ripple period at the
isocenter is found to be the difference between the inverse of the RiFi period
and the inverse of the scanning step size. We have been able to use MC
simulations to reproduce the spacing of the ripple stripes seen in films
irradiated at HIT. Our findings clearly indicate that pencil beams sharply
focused near the RiFi plane result in fluence inhomogeneity at the isocenter. In
the normal clinical application, such a setting should generally be avoided.
PMID- 25590352
TI - Epilepsy-induced electrocardiographic alterations following cardiac ischemia and
reperfusion in rats.
AB - The present study evaluated electrocardiographic alterations in rats with
epilepsy submitted to an acute myocardial infarction (AMI) model induced by
cardiac ischemia and reperfusion. Rats were randomly divided into two groups:
control (n=12) and epilepsy (n=14). It was found that rats with epilepsy
presented a significant reduction in atrioventricular block incidence following
the ischemia and reperfusion procedure. In addition, significant alterations were
observed in electrocardiogram intervals during the stabilization, ischemia, and
reperfusion periods of rats with epilepsy compared to control rats. It was noted
that rats with epilepsy presented a significant increase in the QRS interval
during the stabilization period in relation to control rats (P<0.01). During the
ischemia period, there was an increase in the QRS interval (P<0.05) and a
reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy
compared to control rats. During the reperfusion period, a significant reduction
in the QT interval (P<0.01) was verified in the epilepsy group in relation to the
control group. Our results indicate that rats submitted to an epilepsy model
induced by pilocarpine presented electrical conductivity alterations of cardiac
tissue, mainly during an AMI episode.
PMID- 25590353
TI - PPARgamma induces growth inhibition and apoptosis through upregulation of insulin
like growth factor-binding protein-3 in gastric cancer cells.
AB - Peroxisome proliferator activator receptor-gamma (PPARgamma) is a ligand
activated transcriptional factor involved in the carcinogenesis of various
cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor
suppressor gene that has anti-apoptotic activity. The purpose of this study was
to investigate the anticancer mechanism of PPARgamma with respect to IGFBP-3.
PPARgamma was overexpressed in SNU-668 gastric cancer cells using an adenovirus
gene transfer system. The cells in which PPARgamma was overexpressed exhibited
growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3
expression. We investigated the underlying molecular mechanisms of PPARgamma in
SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase
activity was increased up to 15-fold in PPARgamma transfected cells, suggesting
that PPARgamma may directly interact with IGFBP-3 promoter to induce its
expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase
activity was markedly reduced in cells without putative p53-binding sites (
Delta1755, -Delta1795). This suggests that the critical PPARgamma-response region
is located within the p53-binding region of the IGFBP-3 promoter. We further
demonstrated an increase in PPARgamma-induced luciferase activity even in cells
treated with siRNA to silence p53 expression. Taken together, these data suggest
that PPARgamma exhibits its anticancer effect by increasing IGFBP-3 expression,
and that IGFBP-3 is a significant tumor suppressor.
PMID- 25590356
TI - Effects of H 2SO4 and O 2 on Hg0 uptake capacity and reversibility of sulfur
impregnated activated carbon under dynamic conditions.
AB - Powder activated carbon (AC) injection is widely considered as the most viable
technology for removing gaseous elemental mercury (Hg(0)) in flue gases of coal
fired power plants. However, sulfuric acid (H2SO4) can form on the external and
internal surfaces of AC particles due to the presence of sulfur oxides, nitrogen
oxides, oxygen, and moisture in flue gases. This work focuses on the effects of
H2SO4 and O2 on the Hg(0) uptake capacity and reversibility of sulfur impregnated
activated carbon (SIAC) under dynamic conditions. Experiments were conducted with
25 MUg-Hg(0)/m(3) of nitrogen or air, using a semicontinuous flow fixed-bed
reactor kept at 120 or 180 degrees C. H2SO4 had a profound hindering effect on
Hg(0) uptake due to pore blockage. O2 significantly enhanced Hg(0) uptake and its
reversibility, via the oxidation of Hg(0) which facilitated chemisorption and the
subsequent physisorption onto chemically adsorbed Hg. Absorption of Hg in H2SO4
was unlikely a significant contributor, when Hg(0) concentrations were at levels
of typical power plants (tens of ppb). The reversibility of and relative
contributions of physisorption and chemisorption to Hg(0) uptake would change
with Hg(0) concentrations in flue gases. These findings could be significant in
developing a complete solution for Hg capture where the handling of spent sorbent
materials and the possible secondary pollution need to be considered.
PMID- 25590358
TI - A Medical Food Formulation of Griffonia simplicifolia/Magnesium for Childhood
Periodic Syndrome Therapy: An Open-Label Study on Motion Sickness.
AB - Motion sickness (MS) is a disabling condition dominated by disagreement between
visually perceived movement and the vestibular system's sense of movement, with
symptoms like dizziness, fatigue, and nausea, and other autonomic disabling
symptoms. Preparations of Griffonia simplicifolia, containing high concentrations
of 5-HTP, might be effective for serotonin-related disorders, including MS.
Therefore, the aim of the present study is to assess the efficacy and safety of
the G. simplicifolia/magnesium complex in a pediatric population with MS. The
Griffonia/magnesium complex (50 and 200 mg, respectively) was orally administered
as a prophylactic therapy for MS twice a day for 3 months to group A, and no
therapy for MS was administered to group B. The MS clinical signs were recorded
by parents or, where possible, directly from children by a specific module, which
included validated questions for the diagnoses that were administered to all
subjects and parents of both groups. Two study groups were matched for age
(P=.224), sex (P=.801), and z-score body-mass index (P=.173). At T0, all
recruited subjects in both groups complained about MS. After 3 months (T1), group
A showed an MS prevalence of 36%, significantly lower than MS prevalence in group
B (73%) (P<.001). The findings of the present study suggest the role of the
Griffonia/magnesium complex as a potential treatment with middle-term efficacy
even for MS.
PMID- 25590359
TI - Epigenetic changes and functional study of HOXA11 in human gastric cancer.
AB - AIM: To examine epigenetic changes and the function of HOXA11 in human gastric
cancer (GC). MATERIALS & METHODS: Seven GC cell lines, five cases of normal
gastric mucosa and 112 cases primary GC samples were used in this study. RESULTS:
Expression of HOXA11 and lack of promoter region methylation were found in NCI
N87, MKN45, BGC823 and HGC27 cells. Loss of expression and complete methylation
were found in AGS gastric cancer cells. Reduced expression and partial
methylation were found in MGC803 and SGC7901 cells. Restoration of HOXA11
expression was induced by 5-aza-2'-deoxycytidine. HOXA11 was methylated in 81.25%
(91/112) of primary GCs. The presence of methylation was associated with male
gender, tumor size, tumor differentiation and lymph node metastasis (all p <
0.05). Restoration of HOXA11 expression reduced cell proliferation, invasion,
migration and induced apoptosis and G2/M phase arrest. HOXA11 was found to
inhibit Wnt signaling by upregulating NKD1 expression. CONCLUSION: Epigenetic
silencing of HOXA11 promotes GC proliferation, migration and invasion through
activation of Wnt signaling.
PMID- 25590357
TI - Perfluoroalkylfullerenes.
PMID- 25590361
TI - Pathway toward large two-dimensional hexagonally patterned colloidal nanosheets
in solution.
AB - We report the solution self-assembly of an ABC block terpolymer consisting of a
polystyrene-block-poly(ethylene oxide) (PS-b-PEO) diblock copolymer tail tethered
to a fluorinated polyhedral oligomeric silsesquioxane (FPOSS) cage in 1,4
dioxane/water. With increasing water content, abundant unconventional
morphologies, including circular cylinders, two-dimensional hexagonally patterned
colloidal nanosheets, and laterally patterned vesicles, are sequentially
observed. The formation of toroids is dominated by two competing free energies:
the end-cap energy of cylinders and the bending energy to form the circular
structures. Incorporating the superhydrophobic FPOSS cages enhances the end-cap
energy and promotes toroid formation. Lateral aggregation and fusion of the
cylinders results in primitive nanosheets that are stabilized by the thicker rims
to partially release the rim-cap energy. Rearrangement of the parallel-aligned
FPOSS cylindrical cores generates hexagonally patterned nanosheets. Further
increasing the water content induces the formation of vesicles with nanopatterned
walls.
PMID- 25590360
TI - Stemistry: the control of stem cells in situ using chemistry.
AB - A new paradigm for drug research has emerged, namely the deliberate search for
molecules able to selectively affect the proliferation, differentiation, and
migration of adult stem cells within the tissues in which they exist. Recently,
there has been significant interest in medicinal chemistry toward the discovery
and design of low molecular weight molecules that affect stem cells and thus have
novel therapeutic activity. We believe that a successful agent from such a
discover program would have profound effects on the treatment of many long-term
degenerative disorders. Among these conditions are examples such as
cardiovascular decay, neurological disorders including Alzheimer's disease, and
macular degeneration, all of which have significant unmet medical needs. This
perspective will review evidence from the literature that indicates that
discovery of such agents is achievable and represents a worthwhile pursuit for
the skills of the medicinal chemist.
PMID- 25590362
TI - Association of decreased rate of influenza vaccination with increased subjective
olfactory dysfunction.
AB - IMPORTANCE: Seasonal influenza causes significant morbidity and mortality, with
cardiovascular and respiratory complications the most common among susceptible
individuals. Upper respiratory tract infections (URIs) are known to precede
olfactory dysfunction in some patients. To our knowledge, there has been no study
assessing the possible relationship between influenza vaccination status and
olfactory dysfunction. OBJECTIVE: To compare vaccination status of a group of
patients with subjective olfactory dysfunction with that of a group of controls.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review and
telephone survey in a matched case-control study. Forty-two patients were
identified via diagnosis codes who presented to a tertiary care academic
rhinologic center with subjective smell dysfunction over the course of 1 year.
Only post-URI and idiopathic etiologies were included. Forty-two age-, sex-, and
race/ethnicity-matched control patients were also selected. MAIN OUTCOMES AND
MEASURES: Demographic data, influenza vaccination status, and smoking status were
reviewed. chi2 Testing was used. RESULTS: We were able to obtain vaccination data
for 36 of 42 patients in the olfactory dysfunction group and 38 of 42 in the
control group. Seven of the 36 (19%) in the olfactory dysfunction group had
received the vaccine in the year prior to presentation compared with 16 of 38
(42%) in the control group (P = .04). CONCLUSIONS AND RELEVANCE: Influenza
vaccination seems to be associated with a decreased rate of subjective olfactory
dysfunction. This is a preliminary finding, and further studies would be needed
to elucidate the exact role of influenza and influenza vaccination in patients
with olfactory loss.
PMID- 25590363
TI - Hemodynamic Monitoring During Heated Intraoperative Intraperitoneal Chemotherapy
Using the FloTrac/Vigileo System.
AB - Cytoreductive surgery with HIPEC has provided a chance for long-term survival in
selected patients. However, perioperative management remains a challenge for the
anesthesiology team. The aim of this study was to evaluate the changes in
hemodynamic parameters during hyperthermic intraperitoneal chemotherapy (HIPEC)
using the FloTrac/Vigileo system. Forty-one consecutive patients undergoing
cytoreductive surgery and HIPEC were enrolled. Heart rate (HR), esophageal
temperature, and cardiac output (CO) steadily increased until the end of HIPEC.
In the first half of HIPEC, systolic blood pressure (SBP) and central venous
pressure (CVP) increased whereas systemic vascular resistance (SVR) decreased;
SVR stabilized in the second half. Diastolic blood pressure (DBP), mean arterial
pressure (MAP), and stroke volume (SV) showed no significant variation. Male
gender was related to increased CVP, CO, and SV, and decreased SVR; age >55 years
was related to increased SBP, and peritoneal cancer index (PCI) was correlated
with HR, DBP, and SV. PCI >14 was associated with increased HR and decreased DBP
and MAP. American Society of Anesthesiologists score >1 was related to decreased
CO and SV. Patients undergoing HIPEC develop a hyperdynamic circulatory state
because of the increased temperature, characterized by a steady decrease in SVR
and continuous increase in HR and CO. FloTrac/Vigileo system may provide an easy
to-handle, noninvasive monitoring tool.
PMID- 25590364
TI - Eriocitrin and Apigenin as New Carbonic Anhydrase VA Inhibitors from a Virtual
Screening of Calabrian Natural Products.
AB - In this work, we performed a structure-based virtual screening against five
carbonic anhydrase isoforms using, as a ligand library, natural components of
Citrus bergamia (Bergamot) and Allium cepa var. Tropea (red onion) sources, which
are some typical Calabrian products. The most relevant Bergamot and red onion
components, identified as potentially new hits by means of the computational
work, were submitted to in vitro tests in order to confirm the ability to exert
the predicted biological activity. Apigenin and eriocitrin were identified as new
potent inhibitors of human carbonic anhydrase VA isozyme.
PMID- 25590365
TI - Identification of angiotensin-converting enzyme inhibitory proteins from mycelium
of Pleurotus pulmonarius (oyster mushroom).
AB - Pleurotus pulmonarius (grey oyster mushroom) has been acknowledged as a
recuperative agent for many diseases in addition to its recognition as a
nutritious provision. We performed a study on P. pulmonarius mycelium for an
antihypertensive effect via the angiotensin-converting enzyme inhibitory
activity. The preliminary assay on the mycelial water extract demonstrated that
the angiotensin-converting enzyme inhibitory activity had an IC50 value of 720
ug/mL. Further protein purifications via ammonium sulphate precipitation and RP
HPLC resulted in 60* stronger angiotensin-converting enzyme inhibitory activity
than that of the mycelial water extract (IC50 = 12 ug/mL). Protein identification
and characterisation by MALDI-TOF/TOF, later corroborated by LC-MS/MS, indicated
three proteins that are responsible for the blood pressure lowering effects via
different mechanisms: serine proteinase inhibitor-like protein, nitrite reductase
like protein, and DEAD/DEAH box RNA helicase-like protein.
PMID- 25590366
TI - Polysaccharides of Dendrobium officinale induce aquaporin 5 translocation by
activating M3 muscarinic receptors.
AB - Dendrobium officinale is an herbal medicine that has been clinically used to
promote body fluid production. Previous works demonstrated that D. officinale
polysaccharides could ameliorate symptoms of salivary secretion of patients with
Sjogren's syndrome and in a respective mice model. In the present study, we
investigated the underlying mechanism by which D. officinale polysaccharides
activate M3 muscarinic receptors and induce extracellular calcium influx, leading
to the translocation of aquaporin 5, a water channel protein, to the apical
membrane of human submandibular gland epithelial cells. Enzymatic treatment of D.
officinale polysaccharides suggested that they are hydrolyzed but do not permeate
cell membranes. This finding supports the pharmacological activity of D.
officinale polysaccharides to promote salivary secretion.
PMID- 25590367
TI - Essential oil of Syzygium aromaticum reverses the deficits of stress-induced
behaviors and hippocampal p-ERK/p-CREB/brain-derived neurotrophic factor
expression.
AB - Syzygium aromaticum has been widely used in traditional medicine. Our study
investigated the safety and antidepressant-like effects of the essential oil of
S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight
volatile constituents were identified in the essential oil of S. aromaticum. The
single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity
study. In a long-term repeated toxicity study of this essential oil (100, 200,
and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body
weight. In addition, no significant changes in relative organ weights and
histopathological analysis were observed in all doses of essential oil-treated
mice compared with the control group. Furthermore, acute S. aromaticum essential
oil administration by gavage exerted antidepressant-like effects in the forced
swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg,
p < 0.05). Long-term S. aromaticum essential oil treatment via gavage
significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200
mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p
CREB, and brain-derived neurotrophic factor in mice exposed to chronic
unpredictable mild stress. These results confirmed the safety of the essential
oil of S. aromaticum and suggested that its potent antidepressant-like property
might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF
pathway in rats exposed to chronic unpredictable mild stress.
PMID- 25590368
TI - Aceroside VIII is a new natural selective HDAC6 inhibitor that synergistically
enhances the anticancer activity of HDAC inhibitor in HT29 cells.
AB - The identification of new isoform-specific histone deacetylase inhibitors is
important for revealing the biological functions of individual histone
deacetylase and for determining their potential use as therapeutic agents. Among
the 11 zinc-dependent histone deacetylases that have been identified in humans,
histone deacetylase 6 is a structurally and functionally unique enzyme. Here, we
tested the inhibitory activity of diarylheptanoids isolated from Betula
platyphylla against histone deacetylase 6. Aceroside VIII selectively inhibited
histone deacetylase 6 catalytic activity and the combined treatment of aceroside
VIII or (-)-centrolobol with A452, another selective histone deacetylase 6
inhibitor, led to a synergistic increase in levels of acetylated alpha-tubulin.
Aceroside VIII, paltyphyllone, and (-)-centrolobol synergistically enhanced the
induction of apoptosis and growth inhibition by A452. Consistent with these
results, A452 in combination with aceroside VIII, paltyphyllone, or (-)
centrolobol was more potent than either drug alone for the induction of
apoptosis. Together, these findings indicate that aceroside VIII is a specific
histone deacetylase 6 inhibitor and points to a mechanism by which natural
histone deacetylase 6-selective inhibitors may enhance the efficacy of other
histone deacetylase 6 inhibitors in colon cancer cells.
PMID- 25590369
TI - Blockade of emodin on amyloid-beta 25-35-induced neurotoxicity in AbetaPP/PS1
mice and PC12 cells through activation of the class III phosphatidylinositol 3
kinase/Beclin-1/B-cell lymphoma 2 pathway.
AB - Autophagy plays an important role in the pathogenesis of Alzheimer's disease. In
the present study, the blockade mechanism of emodin on amyloid-beta 25-35-induced
neurotoxicity was explored. Cell viability of PC12 cells was evaluated by the MTT
assay and neuro damage by the lactate dehydrogenase leakage assay. Gene silencing
by small interfering RNA, cDNA constructs and transfection, as well as Western
blot were performed to assess protein expression levels. AbetaPP/PS1 mice were
administered orally with emodin (50 mg/kg/day), and LC3-II positive cells in
their brain cortex sections were detected by immunohistochemical staining. Emodin
could significantly inhibit the LC3-I/LC3-II conversion ratio and cell viability
while decreasing the lactate dehydrogenase level in AbetaPP/PS1 mice and PC12
cells. LC3II positive cells in the cortex were decreased significantly by the
treatment with both emodin and 3-methyladenine. Furthermore, emodin and 3
methyladenine could increase B-cell lymphoma 2 while decreasing Beclin-1 and
hVps34 expressions, which were induced by amyloid-beta 25-35. Small interfering
gene silencing Beclin-1 and B-cell lymphoma 2 confirmed this signaling pathway.
We also found that the phosphatidylinositol 3-kinase inhibitor LY294002 could
block LC3-I/LC3-II conversion and increase B-cell lymphoma 2 while decreasing
hVps34 and Beclin-1 expressions. The results suggest that the blockade of emodin
on amyloid-beta 25-35-induced autophagy may occur via the activation of the class
III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway. Our results
provide confirmatory evidence for the application of emodin in the prevention and
treatment of Alzheimer's disease.
PMID- 25590370
TI - Antispasmodic effects of myrrh due to calcium antagonistic effects in inflamed
rat small intestinal preparations.
AB - Myrrh is the oleo-gum resin of mainly Commiphora molmol and as a powdered
substance, one compound in the traditional medicinal product Myrrhinil-Intest(r),
which has been used for the treatment of unspecific, inflammatory intestinal
disorders. The aim of the present study was to evaluate the antispasmodic effect
of myrrh under healthy and inflamed conditions, and to evaluate a calcium
antagonistic effect as a possible mode of action. Therefore, an ethanolic myrrh
extract was tested for its effects on muscle tone and acetylcholine-induced
contractions in untreated and inflamed rat ileum/jejunum preparations.
Inflammation was experimentally induced by 2,4,6-trinitrobenzene sulfonic acid
(10 mM, 30 min). Additionally, the effect of the calcium channel agonist Bay
K8644 in the presence of varying myrrh extract concentrations was examined. Myrrh
extract (0.99 mg/mL) suppressed the acetylcholine-induced contraction down to
25.8 % in untreated and 15.2 % in inflamed preparations. Myrrh extract (0.15;
0.25 and 0.35 mg/mL) induced a concentration-dependent rightward shift of the Bay
K8644 concentration-response curve in untreated and inflamed preparations with a
significant EC50 shift. Schild analysis resulted in a pA2 value of 0.93 for
untreated preparations. Increasing myrrh extract concentrations induced a
concentration-dependent decrease of the agonistic maximum effect in untreated and
inflamed preparations down to 15.8 % and 25.8 %, respectively, for the highest
concentration leading to a pD2 value of 0.58. Myrrh extract reduced intestinal
muscle tone and acetylcholine-induced contraction of untreated and inflamed
ileum/jejunum preparations based on dual calcium antagonism characterized by a
right shift of the agonistic dose-response curve and a depression of the maximum
effect. The resulting reduction of intestinal motility and spasmolytic effects
provide a rationale for the symptom treatment of intestinal disorders such as
irritable bowel syndrome.
PMID- 25590371
TI - Antiviral butyrolactones from the endophytic fungus Aspergillus versicolor.
AB - Versicolactones A-D (1-4), four new butyrolactones, along with four known
butyrolactones (5-8) were isolated from the fermentation products of the
endophytic fungus Aspergillus versicolor. The structures of compounds 1-4,
including absolute configuration, were elucidated by interpretation of the NMR
and CD data. Compound 2 was further confirmed by single-crystal X-ray diffraction
analysis. In particular, compound 1 is the first naturally occurring
butyrolactone possessing an unusual 2-oxopropyl group. More importantly,
compounds 1 and 8 displayed significant antitobacco mosaic virus activities with
inhibition rates of 46.4 % and 35.4 %, even more potent than the positive control
ningnanmycin (30.8 %). Compound 1 also showed moderate cytotoxicity against A549
and MCF7 cells with IC50 values of 3.2 and 2.5 uM, respectively.
PMID- 25590372
TI - Symphonia globulifera, a widespread source of complex metabolites with potent
biological activities.
AB - Symphonia globulifera has been widely used in traditional medicine and has
therefore been subjected to several phytochemical studies in the American and
African continents. Interestingly, some disparities have been observed concerning
its metabolic profile. Several phytochemical studies of S. globulifera have led
to the identification of more than 40 compounds, including several polycyclic
polyprenylated acylphloroglucinols. Biological evaluations have pointed out the
promising biological activities of these secondary metabolites, mostly as
antiparasitic or antimicrobial, confirming the traditional use of this plant. The
purpose of this review is to describe the natural occurrence, botanical aspects,
ethnomedicinal use, structure, and biogenesis, as well as biological activities
of compounds isolated from this species according to their provenance.
PMID- 25590374
TI - Hupehenols A-E, selective 11beta-hydroxysteroid dehydrogenase type 1 (11beta
HSD1) inhibitors from Viburnum hupehense.
AB - Five selective 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
competitive inhibitors, hupehenols A-E (1-5), were isolated from Viburnum
hupehense. The structure elucidation indicated that compounds 1-5 are new
20,21,22,23,24,25,26,27-octanordammarane triterpenoids. Their structures were
established on the basis of NMR spectroscopic and mass spectrometric analysis.
Hupehenols A-E (1-5) showed inhibition against human 11beta-HSD1, with hupehenols
B (2) and E (5) having IC50 values of 15.3 and 34.0 nM, respectively. Moreover,
hupehenols C (3) and D (4) are highly selective inhibitors of human 11beta-HSD1
when compared to murine 11beta-HSD1.
PMID- 25590373
TI - Activation of autophagy via Ca(2+)-dependent AMPK/mTOR pathway in rat notochordal
cells is a cellular adaptation under hyperosmotic stress.
AB - Nucleus pulposus (NP) cells experience hyperosmotic stress in spinal discs;
however, how these cells can survive in the hostile microenvironment remains
unclear. Autophagy has been suggested to maintain cellular homeostasis under
different stresses by degrading the cytoplasmic proteins and organelles. Here, we
explored whether autophagy is a cellular adaptation in rat notochordal cells
under hyperosmotic stress. Hyperosmotic stress was found to activate autophagy in
a dose- and time-dependent manner. SQSTM1/P62 expression was decreased as the
autophagy level increased. Transient Ca(2+) influx from intracellular stores and
extracellular space was stimulated by hyperosmotic stress. Activation of AMPK and
inhibition of p70S6K were observed under hyperosmotic conditions. However,
intercellular Ca(2+) chelation inhibited the increase of LC3-II and partly
reversed the decrease of p70S6K. Hyperosmotic stress decreased cell viability and
promoted apoptosis. Inhibition of autophagy led to SQSTM1/P62 accumulation,
reduced cell viability, and accelerated apoptosis in notochordal cells under this
condition. These evidences suggest that autophagy induction via the Ca(2+)
dependent AMPK/mTOR pathway might occur as an adaptation mechanism for
notochordal cells under hyperosmotic stress. Thus, activating autophagy might be
a promising approach to improve viability of notochordal cells in intervertebral
discs.
PMID- 25590375
TI - Genetically encoding lysine modifications on histone H4.
AB - Post-translational modifications of proteins are important modulators of protein
function. In order to identify the specific consequences of individual
modifications, general methods are required for homogeneous production of
modified proteins. The direct installation of modified amino acids by genetic
code expansion facilitates the production of such proteins independent of the
knowledge and availability of the enzymes naturally responsible for the
modification. The production of recombinant histone H4 with genetically encoded
modifications has proven notoriously difficult in the past. Here, we present a
general strategy to produce histone H4 with acetylation, propionylation,
butyrylation, and crotonylation on lysine residues. We produce homogeneous
histone H4 containing up to four simultaneous acetylations to analyze the impact
of the modifications on chromatin array compaction. Furthermore, we explore the
ability of antibodies to discriminate between alternative lysine acylations by
incorporating these modifications in recombinant histone H4.
PMID- 25590376
TI - Perspectives on oral pulmonary hypertension therapies recently approved by the
U.S. Food and Drug Administration.
AB - In the past 18 months, the U.S. Food and Drug Administration approved macitentan,
riociguat, and treprostinil as oral agents for the treatment of pulmonary
arterial hypertension (PAH); riociguat also became the first agent approved for
the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). These new
agents are welcome additional therapeutic options for PAH and CTEPH. However,
their use can be complicated by potential drug interactions, adverse effects,
dosing complexity, and cost. Macitentan, the newest endothelin receptor
antagonist, showed significant benefits in a long-term event-driven trial of
morbidity and mortality. Dosed once daily and with minimal liver toxicity, it has
potential drug interactions with potent CYP 3A4 inhibitors and inducers, and can
decrease hemoglobin levels. Riociguat is approved for PAH and clinically
inoperable CTEPH to improve exercise capacity and functional status. Riociguat
requires dose titration beginning with 1 mg up to 2.5 mg three times a day, as
tolerated, and should be used with caution in patients with underlying risk
factors for systemic hypotension. Oral treprostinil, approved to improve exercise
capacity in PAH, is associated with gastrointestinal side effects and headaches
that are often dose limiting. Doses can begin with 0.125 mg or 0.25 mg twice a
day with gradual increases on up to a weekly basis, as tolerated. Thrice daily
dosing and administration with a meal can improve tolerance. These newer agents
represent advances, but their specific roles in relation to pre-existing
therapies are undergoing further evaluation. Therefore, close collaboration with
clinicians at centers with therapeutic expertise is highly recommended to
optimize patient outcomes.
PMID- 25590377
TI - Unraveling the role of hydrogen peroxide in alpha-synuclein aggregation using an
ultrasensitive nanoplasmonic probe.
AB - Aggregation of alpha-Synuclein (alpha-Syn) in Lewy bodies is largely responsible
for the demise and death of dopamine neurons. Oxidative stress associated with
the aggregation-induced oxidative damage is considered as a possible origin of
the toxicity. However, the cellular mechanism of H2O2 in the aggregation of alpha
Syn remains a debate, i.e., whether the aggregation is caused by endogenously
secreted or exogenous H2O2 from upstream. Here, we report on the development of
an ultrasensitive plasmonic assay with a designed nanoplasmonic probe to unravel
the role of H2O2 in the aggregation of alpha-Syn. The nanoplasmonic probe is
composed of a Au nanoparticle with surface-attached double-stranded DNA and
horseradish peroxidase (HRP). In the presence of H2O2, HRP initiates the
polymerization of aniline, which in turn results in the in situ formation of a
layer of conducting polymer on the nanoplasmonic probe. By monitoring the
associated plasmonic response, we can sensitively detect H2O2 with a remarkably
low detection limit of 8 nM. With this ultrasensitive plasmonic assay, we find
that exogenous H2O2 plays a dominant role for the aggregation of alpha-Syn in
vitro, whereas the contribution from endogenously secreted H2O2 is negligible.
PMID- 25590378
TI - The functional implications of common genetic variation in CYP3A5 and ABCB1 in
human proximal tubule cells.
AB - BACKGROUND: Calcineurin inhibitors (CNIs) are the primary immunosuppressive drugs
used in solid organ transplantation but are associated with the development of
histological lesions leading to kidney failure. CNIs are metabolized by CYP3A and
excreted by not only P-glycoprotein (P-gp) (ABCB1) in the gut and liver, but also
by proximal tubule cells (PTCs) in the kidney. Multiple studies have demonstrated
the importance of genetic variation in CYP3A5 and ABCB1 for CNI disposition and
nephrotoxicity. The present study was designed to study the functional
implication of variation in these two genes in human PTCs. METHODS: A technique
was developed to culture cells from renal tissue obtained from renal graft
recipients by routine kidney biopsy. Primary cells were immortalized, subcloned,
and then characterized for specific PTC markers (AQP1, CD13, brush border
morphology) and donor CYP3A5(rs776746)/ABCB1(rs1045642) genotype. We then
selected specific sets of confirmed conditionally immortalized PTCs (ciPTC)
according to different combinations of the aforementioned genetic variants.
Quantitative real-time polymerase chain reaction, Western blot, and
immunohistochemistry were performed for studying CYP3A5 and ABCB1 expression.
CYP3A5 activity was assessed by differential midazolam (MDZ) hydroxylation and P
gp (ABCB1 product) activity by a calcein efflux assay. Differential drug
metabolism between cell lines was assessed by tacrolimus disappearance over 24 h.
RESULTS: Cell lines were generated from 27 out of 38 tissue samples. On the basis
of genotype and PTC biomarkers, 11 subclones were selected. In vitro PTC
morphology with brush border microvilli was confirmed. CYP3A5*1 carriers had
increased 1-OH/4-OH MDZ formation versus homozygous *3 carriers (mean: 2.36 (95%
CI:1.11-3.40) vs 0.88 (95% CI:0.48-1.27); p < 0.05). P-gp activity was confirmed
by calcein accumulation (mean 38.6%; 95% CI:32.8-44.4%), which was higher in cell
lines with the ABCB1 3435TT than the 3435CC/CT genotype (46.2% vs 35.5%; 95%
CI:28.7-42.2%). Tacrolimus disappearance was about two-fold higher in cell lines
with the combined CYP3A5*1/ABCB1 3435TT genotype versus other genotype
combinations. CONCLUSION: Biopsy-derived and immortalized human PTC cell lines
demonstrate functional expression of genes involved in CNI metabolism.
Differences in functional expression were detected according to common genetic
variants in CYP3A5 and ABCB1. The studied genetic variants had a significant
impact on in vitro tacrolimus metabolism. In particular, ciPTC with the combined
CYP3A5*1/ABCB1 3435TT genotype demonstrated higher tacrolimus disappearance
versus ciPTCs with a different pharmacogenetic profile. This in vitro model
stresses the importance of the incorporation of pharmacogenetic variation in
studies involved in (renal) drug disposition.
PMID- 25590379
TI - Genotoxic and biochemical changes in Baccharis trimera induced by coal
contamination.
AB - The processing and combustion of coal in thermal power plants release
anthropogenic chemicals into the environment. Baccharis trimera is a common plant
used in folk medicine that grows readily in soils degraded by coal mining
activities. This shrub bioaccumulates metals released into the environment, and
thus its consumption may be harmful to health. The purpose of this study was to
investigate the phytochemical profile, antioxidant capacity (DPPH), genotoxic
(comet assay) and mutagenic potential (CBMN-cyt) in V79 cells of B. trimera
aqueous extracts in the coal-mining region of Candiota (Bt-AEC), and in Bage, a
city that does not experience the effects of exposure to coal (Bt-AEB, a
reference site). In the comet assay, only Bt-AEC was genotoxic at the highest
doses (0.8mg/mL and 1.6mg/mL), compared to the control. For extracts from both
areas, mutagenic effects were observed at higher concentrations compared to the
control. The cell damage parameters were significantly high in both extracts;
however, more striking values were observed for Bt-AEC, up to the dose of
0.8mg/mL. In chemical analysis, no variation was observed in the contents of
flavonoids and phenolic compounds, neither the antioxidant activity, which may
suggest that DNA damage observed in V79 cells was induced by the presence of coal
contaminants absorbed by the plant.
PMID- 25590380
TI - Stereological and flow cytometry characterization of leukocyte subpopulations in
models of transient or permanent cerebral ischemia.
AB - Microglia activation, as well as extravasation of haematogenous macrophages and
neutrophils, is believed to play a pivotal role in brain injury after stroke.
These myeloid cell subpopulations can display different phenotypes and functions
and need to be distinguished and characterized to study their regulation and
contribution to tissue damage. This protocol provides two different methodologies
for brain immune cell characterization: a precise stereological approach and a
flow cytometric analysis. The stereological approach is based on the optical
fractionator method, which calculates the total number of cells in an area of
interest (infarcted brain) estimated by a systematic random sampling. The second
characterization approach provides a simple way to isolate brain leukocyte
suspensions and to characterize them by flow cytometry, allowing for the
characterization of microglia, infiltrated monocytes and neutrophils of the
ischemic tissue. In addition, it also details a cerebral ischemia model in mice
that exclusively affects brain cortex, generating highly reproducible infarcts
with a low rate of mortality, and the procedure for histological brain processing
to characterize infarct volume by the Cavalieri method.
PMID- 25590382
TI - NMR crystallography for structural characterization of oxovanadium(V) complexes:
deriving coordination geometry and detecting weakly coordinated ligands at atomic
resolution in the solid state.
AB - NMR crystallography is an emerging method for atomic-resolution structural
analysis of ubiquitous vanadium(V) sites in inorganic and bioinorganic complexes
as well as vanadium-containing proteins. NMR crystallography allows for
characterization of vanadium(V) containing solids, based on the simultaneous
measurement of (51)V-(15)N internuclear distances and anisotropic spin
interactions, described by (13)C, (15)N, and (51)V chemical shift anisotropy and
(51)V electric field gradient tensors. We show that the experimental (51)V,
(13)C, and (15)N NMR parameters are essential for inferring correct coordination
numbers and deriving correct geometries in density functional theory (DFT)
calculations, particularly in the absence of single-crystal X-ray structures. We
first validate this approach on a structurally known vanadium(V) complex, ((15)N
salicylideneglycinate)-(benzhydroxamate)oxovanadium(V), VO(15)NGlySalbz. We then
apply this approach to derive the three-dimensional structure of (methoxo)((15)N
salicylidene-glycinato)oxovanadium(V) with solvated methanol,
[VO((15)NGlySal)(OCH3)].(CH3OH). This is a representative complex with
potentially variable coordination geometry depending on the solvation level of
the solid. The solid material containing molecules of CH3OH, formally expressed
as [VO((15)NGlySal)(OCH3)].(CH3OH), is found to have one molecule of CH3OH weakly
coordinated to the vanadium. The material is therefore best described as
[VO((15)NGlySal)(OCH3)(CH3OH)] as deduced by the combination of multinuclear
solid-state NMR experiments and DFT calculations. The approach reported here can
be used for structural analysis of systems that are not amenable to single
crystal X-ray diffraction characterization and which can contain weakly
associated solvents.
PMID- 25590381
TI - Synthesis, molecular docking and anti-inflammatory screening of novel quinoline
incorporated pyrazole derivatives using the Pfitzinger reaction II.
AB - In continuation of our study of novel quinolines with anti-inflammatory activity
using the Pfitzinger reaction, several new quinoline derivatives were synthesized
and tested for their anti-inflammatory and ulcerogenic effect. A docking study on
the COX-2 binding pocket was carried out for the target compounds to rationalize
the possible selectivity of them against COX-2 enzyme. The most active compounds
(5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a
demonstrated the highest anti-inflammatory activity as well as the best binding
profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a
were devoid of ulcerogenic activity.
PMID- 25590384
TI - Radiographic findings after treatment with balloon brachytherapy accelerated
partial breast irradiation.
AB - The use of accelerated partial breast irradiation (APBI) following breast
conserving surgery is rapidly gaining popularity as an alternative to whole
breast irradiation (WBI) in selected patients with early-stage breast cancer.
Although data on the long-term effectiveness and safety of APBI accelerated
partial breast irradiation are still being gathered, the shorter treatment course
and narrowed radiation target of APBI accelerated partial breast irradiation
provide an attractive alternative for carefully selected patients. These patients
include those with relatively small tumors (<=3 cm), negative or close margins,
and negative sentinel lymph nodes. Possible long-term complications include
telangiectasia and the development of a palpable mass at the lumpectomy site.
Mammographic findings in patients who have undergone APBI accelerated partial
breast irradiation are distinct from those in patients who have undergone
conventional WBI whole-breast irradiation . The most common post-APBI accelerated
partial breast irradiation radiographic findings include formation of seromas at
the lumpectomy site, focal parenchymal changes such as increased trabeculation
and parenchymal distortion, fat necrosis, and skin changes such as thickening or
retraction. Given the continued evolution of breast cancer treatment, it is
important that radiologists have a comprehensive understanding of APBI
accelerated partial breast irradiation in terms of rationale, patient selection
criteria, common postprocedural radiographic findings (and how they differ from
post-WBI whole-breast irradiation findings), and advantages and potential
complications.
PMID- 25590385
TI - The right atrium: gateway to the heart--anatomic and pathologic imaging findings.
AB - Knowledge of right atrial anatomic and pathologic imaging findings and associated
clinical symptoms is important to avoid false-positive diagnoses and missed
findings. Complete evaluation of the heart often requires a multimodality
approach that includes radiography, echocardiography, computed tomography (CT),
magnetic resonance (MR) imaging, and invasive angiography. In general, CT
provides the highest spatial resolution of these modalities at the cost of
radiation exposure to the patient. Echocardiography and MR imaging offer
complementary and detailed information for functional evaluation without added
radiation exposure. The advantages and disadvantages of each modality for the
evaluation of right atrial anatomic structure, size, and pathologic findings are
discussed. Cardiac MR imaging is the reference standard for evaluation of right
atrial size and volume but often is too time consuming and resource intensive to
perform in routine clinical practice. Therefore, established reference ranges for
two-dimensional transthoracic echocardiography are often used. Right atrial
pathologic findings can be broadly categorized into (a) congenital anomalies (cor
triatriatum dexter, Ebstein anomaly, and aneurysm), (b) disorders of volume
(tricuspid regurgitation, pathologic mimics such as a pseudoaneurysm, and atrial
septal defect), (c) disorders of pressure (tricuspid stenosis, restrictive
cardiomyopathy, and constrictive pericarditis), and (d) masses (pseudomasses,
thrombus, lipomatous hypertrophy of the interatrial septum, lipoma, myxoma,
sarcoma, and metastatic disease). Familiarity with each pathologic entity and its
treatment options is essential to ensure that appropriate imaging modalities are
selected. Online supplemental material is available for this article.
PMID- 25590386
TI - Bronchial arteries: anatomy, function, hypertrophy, and anomalies.
AB - The two main sources of blood supply to the lungs and their supporting structures
are the pulmonary and bronchial arteries. The bronchial arteries account for 1%
of the cardiac output but can be recruited to provide additional systemic
circulation to the lungs in various acquired and congenital thoracic disorders.
An understanding of bronchial artery anatomy and function is important in the
identification of bronchial artery dilatation and anomalies and the formulation
of an appropriate differential diagnosis. Visualization of dilated bronchial
arteries at imaging should alert the radiologist to obstructive disorders that
affect the pulmonary circulation and prompt the exclusion of diseases that
produce or are associated with pulmonary artery obstruction, including chronic
infectious and/or inflammatory processes, chronic thromboembolic disease, and
congenital anomalies of the thorax (eg, proximal interruption of the pulmonary
artery). Conotruncal abnormalities, such as pulmonary atresia with ventricular
septal defect, are associated with systemic pulmonary supply provided by aortic
branches known as major aortopulmonary collaterals, which originate in the region
of the bronchial arteries. Bronchial artery malformation is a rare left-to-right
or left-to-left shunt characterized by an anomalous connection between a
bronchial artery and a pulmonary artery or a pulmonary vein, respectively.
Bronchial artery interventions can be used successfully in the treatment of
hemoptysis, with a low risk of adverse events. Multidetector computed tomography
helps provide a vascular road map for the interventional radiologist before
bronchial artery embolization.
PMID- 25590387
TI - US of gastrointestinal tract disease.
AB - The potential use of ultrasonography (US) in evaluating gut disease has been
underappreciated in most diagnostic imaging departments in North America. The
impression that US has a questionable role in bowel assessment is related to the
operator-dependent nature of the modality, the technical challenges of performing
bowel US examinations, and the lack of familiarity of radiologists and
technologists with the US appearances of normal and abnormal bowel. However, with
development of technical experience by the sonographer and integration of a
clinical focus at patient evaluation, US can become a powerful tool for bowel
assessment. Unlike computed tomography and magnetic resonance imaging, it
provides a widely available, noninvasive, inexpensive method for evaluating the
gut without the use of ionizing radiation. These factors are of particular
importance in young patients and those who require recurrent follow-up imaging.
Because US is performed with real-time imaging, the modality also allows the
sonographer to view and assess the motility properties of the bowel, a feature
that has not been previously used to its full potential. Color Doppler US can
yield useful information about mural vascularity in bowel disease when used in
conjunction with gray-scale findings and clinical symptoms. Radiologists should
be familiar with the static and dynamic US appearances of the normal and abnormal
bowel, recognize features of various pathologic conditions, and understand
potential errors at imaging interpretation. Online supplemental material is
available for this article.
PMID- 25590388
TI - Invited commentary on "US of gastrointestinal tract disease".
PMID- 25590389
TI - Hematologic malignancies of the liver: spectrum of disease.
AB - The incidence of hematologic malignancies and their extranodal manifestations is
continuously increasing. Previously unsuspected hepatic involvement in
hematologic malignancies such as Hodgkin disease and non-Hodgkin lymphoma,
posttransplant lymphoproliferative disorder, myeloid sarcoma (chloroma), multiple
myeloma, Castleman disease, and lymphohistiocytosis may be seen by radiologists.
Although the imaging features of more common hepatic diseases such as
hepatocellular carcinoma, metastases, and infection may overlap with those of
hepatic hematologic malignancies, combining the imaging features with clinical
manifestations and laboratory findings can facilitate correct diagnosis. Clinical
features that suggest a hematologic neoplasm as the cause of liver lesions
include a young patient (<40 years of age), no known history of cancer, abnormal
bone marrow biopsy results, fever of unknown origin, and night sweats. Imaging
features that suggest hematologic malignancy include hepatosplenomegaly or
splenic lesions, vascular encasement by a tumor without occlusion or thrombosis,
an infiltrating mass at the hepatic hilum with no biliary obstruction, and
widespread adenopathy above and below the diaphragm. Familiarity with the imaging
features of hepatic hematologic malignancies permits correct provisional
diagnosis and may influence therapeutic management. For example, when biopsy is
performed, core biopsy may be needed in addition to fine-needle aspiration so
that the tissue architecture of the neoplasm can be discerned. The predominant
treatment of hematologic malignancies is chemotherapy or radiation therapy rather
than surgery. Online supplemental material is available for this article.
PMID- 25590390
TI - Nonvascular post-liver transplantation complications: from US screening to cross
sectional and interventional imaging.
AB - Orthotopic liver transplantation is becoming an increasingly routine procedure
for a variety of benign and malignant diseases of the liver and biliary system.
Continued improvements in surgical techniques and post-transplantation
immunosuppression regimens have resulted in better graft and patient survival. A
number of potentially treatable nonvascular complications of liver
transplantation are visible at imaging, and accurate diagnosis of these
complications allows patients to benefit from potential treatment options.
Biliary complications include stricture (anastomotic and nonanastomotic), leak,
biloma formation, and development of intraductal stones. Pathologic conditions,
including hepatitis C infection, hepatocellular carcinoma, hepatic steatosis, and
primary sclerosing cholangitis, may recur after liver transplantation. Transplant
patients are at increased risk for developing de novo malignancy, including post
transplantation lymphoproliferative disorder, which results from
immunosuppression. Patients are also at increased risk for systemic infection
from immunosuppression, and patients with hepatic artery and biliary
complications are at increased risk for liver abscess. Transplant recipients are
typically followed with serial liver function testing; abnormal serum liver
function test results may be the first indication that there is a problem with
the transplanted liver. Ultrasonography is typically the first imaging test
performed to try to identify the cause of abnormal liver function test results.
Computed tomography, magnetic resonance imaging, angiography, and/or
cholangiography may be necessary for further evaluation. Accurately diagnosing
nonvascular complications of liver transplantation that are visible at imaging is
critically important for patients to benefit from appropriate treatment.
PMID- 25590391
TI - Dysphagia revisited: common and unusual causes.
AB - Dysphagia is a common clinical problem whose prevalence is increasing with the
aging population in the United States. The term dysphagia is commonly used to
describe subjective awareness of swallowing difficulty during the passage of a
bolus from the mouth to the stomach or the perception of obstruction during
swallowing. Dysphagia may be further classified as oropharyngeal or substernal,
depending on the location of this sensation. It can be due to benign or malignant
structural lesions, esophageal motility abnormalities, oropharyngeal dysfunction
(including aspiration), neuromuscular disorders, or postsurgical changes and is
also associated with gastroesophageal reflux disease. Pathologic conditions of
the oral cavity, pharynx, esophagus, and proximal stomach can manifest with
dysphagia. Imaging remains the preferred method for evaluating patients with
dysphagia, and dysphagia is an increasingly encountered indication for radiologic
evaluation. Fluoroscopic studies, including the modified barium swallow and
esophagography in particular, are often used in the assessment of patients with
dysphagia, and the techniques used for these studies should be tailored to the
patient's needs. Fluoroscopic studies can be used to evaluate the esophagus for
structural abnormalities (eg, webs, diverticula, strictures, masses) and to
assess function (eg, the swallowing mechanism and esophageal motility). Knowledge
of the imaging spectrum of disease entities that may cause dysphagia and thorough
radiologic assessment with a tailored approach may help avoid misdiagnosis.
PMID- 25590392
TI - Appendicitis: atypical and challenging CT appearances.
PMID- 25590393
TI - CT and MR imaging for evaluation of cystic renal lesions and diseases.
AB - Cystic renal lesions are commonly encountered in abdominal imaging. Although most
cystic renal lesions are benign simple cysts, complex renal cysts, infectious
cystic renal disease, and multifocal cystic renal disease are also common
phenomena. The Bosniak classification system provides a useful means of
categorizing cystic renal lesions but places less emphasis on their underlying
pathophysiology. Cystic renal diseases can be categorized as focal, multifocal,
or infectious lesions. Diseases that manifest with focal lesions, such as cystic
renal cell carcinoma, mixed epithelial and stromal tumor, and cystic nephroma,
are often difficult to differentiate but have differing implications for follow
up after resection. Multifocal cystic renal lesions can be categorized as
acquired or heritable. Acquired entities, such as glomerulocystic kidney disease,
lithium-induced nephrotoxicity, acquired cystic kidney disease, multicystic
dysplastic kidney, and localized cystic renal disease, often have distinct
imaging and clinical features that allow definitive diagnosis. Heritable
diseases, such as autosomal dominant polycystic kidney disease, von Hippel-Lindau
disease, and tuberous sclerosis, are usually easily identified and have various
implications for patient management. Infectious diseases have varied imaging
appearances, and the possibility of infection must not be overlooked when
assessing a cystic renal lesion. A thorough understanding of the spectrum of
cystic renal disease will allow the radiologist to make a more specific diagnosis
and provide the clinician with optimal recommendations for further diagnostic
testing and follow-up imaging.
PMID- 25590395
TI - Extrapulmonary small cell carcinoma: imaging features with radiologic-pathologic
correlation.
AB - Extrapulmonary small cell carcinoma (EPSCC) refers to small cell carcinoma
arising outside of the lungs. EPSCC extrapulmonary small cell carcinoma is a rare
aggressive neoplasm, representing a minority of all small cell carcinomas.
Despite its uncommon occurrence, EPSCC extrapulmonary small cell carcinoma has
been described in nearly every organ, most commonly in the gastrointestinal and
genitourinary systems. As such, it is important for radiologists to be aware of
the entity. Although imaging is neither sensitive nor specific for EPSCC
extrapulmonary small cell carcinoma , it plays an important role by helping
exclude metastases from a primary pulmonary tumor, establish tumor staging, and
assess response to therapy. EPSCC extrapulmonary small cell carcinoma is
diagnosed by demonstrating pathologic features of small cell carcinoma in an
extrapulmonary site. There are two ways to stage EPSCC extrapulmonary small cell
carcinoma . One method uses the Veterans Administration Lung Study Group system
developed for small cell lung cancer that allocates patients into limited or
extensive disease categories. The second approach is the American Joint Committee
on Cancer tumor-node-metastasis system applied to other tumor subtypes arising
from the same organ. Because of its rare and varied manifestations, the most
effective treatment for EPSCC extrapulmonary small cell carcinoma has not been
established. Current management recommendations are derived from retrospective
studies and single-institution experiences or are extrapolated from small cell
lung cancer data. Regardless of therapy, overall survival rates are poor, with 5
year survival rates around 13%. To help radiologists increase their familiarity
with EPSCC extrapulmonary small cell carcinoma , this article provides (a) a
background for EPSCC extrapulmonary small cell carcinoma based on the literature
and (b) a pictorial review of EPSCC extrapulmonary small cell carcinoma in
multiple organs, with radiologic-pathologic correlation.
PMID- 25590396
TI - Dynamic high-resolution US of ankle and midfoot ligaments: normal anatomic
structure and imaging technique.
AB - The ankle is the most frequently injured major joint in the body, and ankle
sprains are frequently encountered in individuals playing football, basketball,
and other team sports, in addition to occurring in the general population.
Imaging plays a crucial role in the evaluation of ankle ligaments. Magnetic
resonance imaging has been proven to provide excellent evaluation of ligaments
around the ankle, with the ability to show associated intraarticular
abnormalities, joint effusion, and bone marrow edema. Ultrasonography (US)
performed with high-resolution broadband linear-array probes has become
increasingly important in the assessment of ligaments around the ankle because it
is low cost, fast, readily available, and free of ionizing radiation. US can
provide a detailed depiction of normal anatomic structures and is effective for
evaluating ligament integrity. In addition, US allows the performance of dynamic
maneuvers, which may contribute to increased visibility of normal ligaments and
improved detection of tears. In this article, the authors describe the US
techniques for evaluation of the ankle and midfoot ligaments and include a brief
review of the literature related to their basic anatomic structures and US of
these structures. Short video clips showing dynamic maneuvers and dynamic real
time US of ankle and midfoot structures and their principal pathologic patterns
are included as supplemental material. Use of a standardized imaging technique
may help reduce the intrinsic operator dependence of US. Online supplemental
material is available for this article.
PMID- 25590397
TI - High-resolution US and MR imaging of peroneal tendon injuries.
AB - Injuries of the peroneal tendon complex are common and should be considered in
every patient who presents with chronic lateral ankle pain. These injuries occur
as a result of trauma (including ankle sprains), in tendons with preexisting
tendonopathy, and with repetitive microtrauma due to instability. The peroneus
brevis and peroneus longus tendons are rarely torn simultaneously. Several
anatomic variants, including a flat or convex fibular retromalleolar groove,
hypertrophy of the peroneal tubercle at the lateral aspect of the calcaneus, an
accessory peroneus quartus muscle, a low-lying peroneus brevis muscle belly, and
an os peroneum, may predispose to peroneal tendon injuries. High-resolution 1.5-T
and 3-T magnetic resonance (MR) imaging with use of dedicated extremity coils and
high-resolution ultrasonography (US) with high-frequency linear transducers and
dynamic imaging are proved to adequately depict the peroneal tendons for
evaluation and can aid the orthopedic surgeon in injury management. An
understanding of current treatment approaches for partial- and full-thickness
peroneal tendon tears, subluxation and dislocation of these tendons with superior
peroneal retinaculum (SPR) injuries, intrasheath subluxations, and peroneal
tendonopathy and tenosynovitis can help physicians achieve a favorable outcome.
Patients with low functional demands do well with conservative treatment, while
those with high functional demands may benefit from surgery if nonsurgical
treatment is unsuccessful. Radiologists should recognize the normal anatomy and
specific pathologic conditions of the peroneal tendons at US and MR imaging and
understand the various treatment options for peroneal tendon and SPR superior
peroneal retinaculum injuries. Online supplemental material is available for this
article.
PMID- 25590394
TI - Ontology-based image navigation: exploring 3.0-T MR neurography of the brachial
plexus using AIM and RadLex.
AB - Disorders of the peripheral nervous system have traditionally been evaluated
using clinical history, physical examination, and electrodiagnostic testing. In
selected cases, imaging modalities such as magnetic resonance (MR) neurography
may help further localize or characterize abnormalities associated with
peripheral neuropathies, and the clinical importance of such techniques is
increasing. However, MR image interpretation with respect to peripheral nerve
anatomy and disease often presents a diagnostic challenge because the relevant
knowledge base remains relatively specialized. Using the radiology knowledge
resource RadLex(r), a series of RadLex queries, the Annotation and Image Markup
standard for image annotation, and a Web services-based software architecture,
the authors developed an application that allows ontology-assisted image
navigation. The application provides an image browsing interface, allowing users
to visually inspect the imaging appearance of anatomic structures. By interacting
directly with the images, users can access additional structure-related
information that is derived from RadLex (eg, muscle innervation, muscle
attachment sites). These data also serve as conceptual links to navigate from one
portion of the imaging atlas to another. With 3.0-T MR neurography of the
brachial plexus as the initial area of interest, the resulting application
provides support to radiologists in the image interpretation process by allowing
efficient exploration of the MR imaging appearance of relevant nerve segments,
muscles, bone structures, vascular landmarks, anatomic spaces, and entrapment
sites, and the investigation of neuromuscular relationships.
PMID- 25590398
TI - Congenital abnormalities of the posterior fossa.
AB - The frequency and importance of the evaluation of the posterior fossa have
increased significantly over the past 20 years owing to advances in neuroimaging.
Nowadays, conventional and advanced neuroimaging techniques allow detailed
evaluation of the complex anatomic structures within the posterior fossa. A wide
spectrum of congenital abnormalities has been demonstrated, including
malformations (anomalies due to an alteration of the primary developmental
program caused by a genetic defect) and disruptions (anomalies due to the
breakdown of a structure that had a normal developmental potential). Familiarity
with the spectrum of congenital posterior fossa anomalies and their well-defined
diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and
correct genetic counseling. The authors discuss the spectrum of posterior fossa
malformations and disruptions, with emphasis on neuroimaging findings (including
diagnostic criteria), neurologic presentation, systemic involvement, prognosis,
and risk of recurrence.
PMID- 25590399
TI - Postoperative imaging of the orbital contents.
AB - Ophthalmologists perform a wide array of interventions on the orbital contents.
The surgical treatment of glaucoma, cataracts, retinal detachment, and ocular
trauma or malignancy results in alteration of the standard anatomy, which is
often readily evident at radiologic examinations. The ability to accurately
recognize the various imaging manifestations after orbital surgery is critical
for radiologists to avoid misdiagnosis. Of particular importance is familiarity
with the numerous types of implanted devices, such as glaucoma drainage devices,
orbital implants, and eyelid weights. Although knowledge of patients' surgical
history is helpful, this information is often not available at the time of
interpretation. Fortunately, there are characteristic posttreatment findings that
enable diagnosis. The imaging features of the most commonly performed
ophthalmologic procedures are highlighted, with emphasis on computed tomography
and magnetic resonance (MR) imaging, because they are currently the primary
modalities involved in evaluating the orbits. Glaucoma drainage devices and
orbital implants after enucleation are two of the more pertinent implanted
devices because their composition has substantially evolved over the past 2
decades, which affects their imaging appearance. Some devices, such as the
Baerveldt Glaucoma Implant and platinum-weighted eyelid implants, may distort
radiologic images. The MR imaging safety profiles of numerous implanted devices
are also reported.
PMID- 25590401
TI - Strategic planning and radiology practice management in the new health care
environment.
AB - Current comprehensive health care reform in the United States demands that policy
makers, insurers, providers, and patients work in reshaping the health care
system to deliver care that is both more affordable and of higher quality. A
tectonic shift is under way that runs contrary to the traditional goal of
radiology groups to perform and interpret large numbers of imaging examinations.
In fact, radiology service requisitions now must be evaluated for their
appropriateness, possibly resulting in a reduction in the number of imaging
studies performed. To be successful, radiology groups will have to restructure
their business practices and strategies to align with the emerging health care
paradigm. This article outlines a four-stage strategic framework that has aided
corporations in achieving their goals and that can be readily adapted and applied
by radiologists. The four stages are (a) definition and articulation of a
purpose, (b) clear definition of strategic goals, (c) prioritization of specific
strategic enablers, and (d) implementation of processes for tracking progress and
enabling continuous adaptation. The authors provide practical guidance for
applying specific tools such as analyses of strengths, weaknesses, opportunities,
and threats (so-called SWOT analyses), prioritization matrices, and balanced
scorecards to accomplish each stage. By adopting and applying these tools within
the strategic framework outlined, radiology groups can position themselves to
succeed in the evolving health care environment.
PMID- 25590400
TI - Rabies encephalitis.
PMID- 25590402
TI - Abdominal aortic aneurysms revisited: MDCT with multiplanar reconstructions for
identifying indicators of instability in the pre- and postoperative patient.
AB - Rupture of an abdominal aortic aneurysm is commonly a fatal event. Multidetector
computed tomographic (CT) signs of frank aortic rupture are usually readily
apparent and widely understood. However, diagnosing an impending aortic rupture
on the basis of imaging findings can prove more difficult. CT is the primary
modality used for serial imaging in patients with aortic aneurysm and may show
findings indicative of aortic instability. Therefore, it is critical that
radiologists be familiar with the CT findings of aortic instability to avert the
potential complications of hemorrhage, end organ or limb ischemia, and death.
Various preoperative CT indicators have been previously described in both
research investigations and review articles. A large baseline aneurysm size and a
rapid increase in size over time are associated with a higher risk for rupture.
The importance of obtaining accurate measurements with multiplanar
reconstructions and the role of new semiautomated tools for obtaining accurate,
reproducible measurements are discussed. Additional CT findings that reflect
aortic aneurysm instability include luminal expansion with lysis of thrombus,
intramural hemorrhage (ie, the crescent sign), periaortic hemorrhage, a
penetrating atherosclerotic ulcer, and contained rupture (ie, the draped aorta
sign). After open or endovascular aneurysm repair, CT is routinely used to
monitor for graft complications. In this setting, radiologists should understand
that the presence of an endoluminal stent or surgical graft does not preclude
aortic rupture. Online supplemental material is available for this article.
PMID- 25590403
TI - Pleomorphic liposarcoma of the inferior vena cava.
PMID- 25590404
TI - Holoprosencephaly: a survey of the entity, with embryology and fetal imaging.
AB - Structural malformations of the brain are an important cause of childhood
mortality and morbidity, with the latter having long-term financial and
psychosocial implications for the affected child and family. Holoprosencephaly
(HPE) is a severe brain malformation characterized by abnormal cleavage of the
prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly
occur earlier because of failure in the formation of the prosencephalon and
telencephalon, respectively. The HPE holoprosencephaly spectrum classically
includes alobar, semilobar, and lobar forms, although there are no clear-cut
defining features. The middle interhemispheric variant (MIH), also known as
syntelencephaly, is classified as a variant of HPE holoprosencephaly with midline
interhemispheric fusion. Other conditions sometimes included in the spectrum of
HPE holoprosencephaly include septo-optic dysplasia (SOD); "minimal" HPE
holoprosencephaly , which is associated with subtle craniofacial malformations
and mild developmental delay; and microform HPE holoprosencephaly , which by
definition excludes brain involvement. The focus of this article will be on the
spectrum of findings visible in fetal manifestation of the HPE holoprosencephaly
spectrum. Brain embryology; the imaging characteristics, epidemiology, and
embryology of HPE; and the more common associated anomalies, particularly those
of the face ("the face predicts the brain") are reviewed. Recognition of these
anomalies is important for accurate parental counseling, since the prognosis is
poor but not invariably lethal; children with the milder forms may live well into
their teens with severe developmental delays, endocrine dysfunction, and
disrupted homeostasis. Available data on outcome in surviving children are
summarized. Illustrative fetal ultrasonographic and magnetic resonance images are
presented with clinical, autopsy, and postnatal imaging correlation.
PMID- 25590405
TI - Give and take in the radiology workplace.
PMID- 25590407
TI - Carney complex: one more entity with skin and bone manifestations.
PMID- 25590408
TI - Dorsal thoracic arachnoid web: another intradural entity with ventral cord
displacement.
PMID- 25590409
TI - Preprocedural CT Evaluation of Transcatheter Aortic Valve Replacement: What the
Radiologist Needs to Know-Erratum.
PMID- 25590410
TI - Techniques for creating video content for radiology education-erratum.
PMID- 25590411
TI - Designer germanium quantum dot phototransistor for near infrared optical
detection and amplification.
AB - We demonstrated a unique CMOS approach for the production of a high-performance
germanium (Ge) quantum dot (QD) metal-oxide-semiconductor phototransistor. In the
darkness, low off-state leakage (Ioff ~ 0.27 pA MUm(-2)), a high on-off current
ratio (Ion/Ioff ~ 10(6)), and good switching behaviors (subthreshold swing of 175
mV/dec) were measured on our Ge-QD phototransistor at 300 K, indicating good
hetero-interfacial quality of the Ge-on-Si. Illumination makes a significant
enhancement in the drain current of Ge QD phototransistors when biased at both
the on- and off-states, which is a great benefit from Ge QD-mediated
photoconductive and photovoltaic effects. The measured photocurrent-to-dark
current ratio (Iphoto/Idark) and the photoresponsivities from the Ge QD
phototransistor are as high as 4.1 * 10(6) and 1.7 A W(-1), respectively, under
an incident power of 0.9 mW at 850 nm illumination. A superior external quantum
efficiency of 240% and a very fast temporal response time of 1.4 ns suggest that
our Ge QD MOS phototransistor offers great promise as optical switches and
transducers for Si-based optical interconnects.
PMID- 25590412
TI - An ex vivo model to study hormone action in the human breast.
AB - The study of hormone action in the human breast has been hampered by lack of
adequate model systems. Upon in vitro culture, primary mammary epithelial cells
tend to lose hormone receptor expression. Widely used hormone receptor positive
breast cancer cell lines are of limited relevance to the in vivo situation. Here,
we describe an ex vivo model to study hormone action in the human breast. Fresh
human breast tissue specimens from surgical discard material such as reduction
mammoplasties or mammectomies are mechanically and enzymatically digested to
obtain tissue fragments containing ducts and lobules and multiple stromal cell
types. These tissue microstructures kept in basal medium without growth factors
preserve their intercellular contacts, the tissue architecture, and remain
hormone responsive for several days. They are readily processed for RNA and
protein extraction, histological analysis or stored in freezing medium.
Fluorescence activated cell sorting (FACS) can be used to enrich for specific
cell populations. This protocol provides a straightforward, standard approach for
translational studies with highly complex, varied human specimens.
PMID- 25590414
TI - Conductance switching and organization of two structurally related molecular
wires on gold.
AB - The self-assembly and electron transfer properties of adsorbed organic molecules
are of interest for the construction of miniaturized molecular circuitries. We
have investigated with scanning probe microscopy the self-organization of two
structurally related molecular wires embedded within a supportive alkanethiol
matrix. Our results evidence heterogeneous adsorption patterns of the molecular
wires on gold with either incommensurate unit cells driven into assembly by
lateral interactions or a dynamic, commensurate distribution on gold, along with
formation of distinct 2D phases. We also observed diffusion-based conductance
switching for one of the molecular wires, due to its propensity toward weaker
lateral interactions and Au-S adatom formation. We have further demonstrated
through the use of scanning tunneling spectroscopy differential current-voltage
response for each molecular wire, despite their close structural similarity. Such
molecular wires embedded in alkanethiol matrix and exhibiting conductance
switching phenomena have the potential to be used for the functionalization of
electrodes in bioelectronic devices.
PMID- 25590413
TI - Wnt pathway activation and ABCB1 expression account for attenuation of proteasome
inhibitor-mediated apoptosis in multidrug-resistant cancer cells.
AB - Multiple drug resistance (MDR) is a major obstacle to attenuating the
effectiveness of chemotherapy to many human malignancies. Proteasome inhibition
induces apoptosis in a variety of cancer cells and is recognized as a novel
anticancer therapy approach. Despite its success, some multiple myeloma patients
are resistant or become refractory to ongoing treatment by bortezomib suggesting
that chemoresistant cancer cells may have developed a novel mechanism directed
against the proteasome inhibitor. The present study aimed to investigate
potential mechanism(s) of attenuation in a MDR cell line, MES-SA/Dx5. We found
that compared to the parental human uterus sarcoma cell line MES-SA cells, MES
SA/Dx5 cells highly expressed the ABCB1 was more resistant to MG132 and
bortezomib, escaping the proteasome inhibitor-induced apoptosis pathway. The
resistance was reversed by co-treatment of MG132 and the ABCB1 inhibitor
verapamil. The data indicated that ABCB1 might play a role in the efflux of MG132
from the MES-SA/Dx5 cells to reduce MG132-induced apoptosis. Furthermore, the
canonical Wnt pathway was found activated only in the MES-SA/Dx5 cells through
active beta-catenin and related transactivation activities. Western blot analysis
demonstrated that Wnt-targeting genes, including c-Myc and cyclin D1, were
upregulated and were relevant in inhibiting the expression of p21 in MES-SA/Dx5
cells. On the other hand, MES-SA cells expressed high levels of p21 and
downregulated cyclin D1 and caused cell cycle arrest. Together, our study
demonstrated the existence and participation of ABCB1 and the Wnt pathway in an
MDR cell line that attenuated proteasome inhibitor-induced apoptosis.
PMID- 25590415
TI - Cannabinoid receptors in mantle cell lymphoma.
PMID- 25590416
TI - Phenotyping mouse pulmonary function in vivo with the lung diffusing capacity.
AB - The mouse is now the primary animal used to model a variety of lung diseases. To
study the mechanisms that underlie such pathologies, phenotypic methods are
needed that can quantify the pathologic changes. Furthermore, to provide
translational relevance to the mouse models, such measurements should be tests
that can easily be done in both humans and mice. Unfortunately, in the present
literature few phenotypic measurements of lung function have direct application
to humans. One exception is the diffusing capacity for carbon monoxide, which is
a measurement that is routinely done in humans. In the present report, we
describe a means to quickly and simply measure this diffusing capacity in mice.
The procedure involves brief lung inflation with tracer gases in an anesthetized
mouse, followed by a 1 min gas analysis time. We have tested the ability of this
method to detect several lung pathologies, including emphysema, fibrosis, acute
lung injury, and influenza and fungal lung infections, as well as monitoring lung
maturation in young pups. Results show significant decreases in all the lung
pathologies, as well as an increase in the diffusing capacity with lung
maturation. This measurement of lung diffusing capacity thus provides a pulmonary
function test that has broad application with its ability to detect phenotypic
structural changes with most of the existing pathologic lung models.
PMID- 25590417
TI - An accurate and portable eye movement detector for studying sleep in small
animals.
AB - Although eye movements are a highly valuable variable in attempts to precisely
identify different periods of the sleep-wake cycle, their indirect measurement by
electrooculography is not good enough. The present article describes an accurate
and portable scleral search coil that allows the detection of tonic and phasic
characteristics of eye movements in free-moving animals. Six adult Wistar rats
were prepared for chronic recording of electroencephalography, electromyography
and eye movements using the scleral search coil technique. We developed a
miniature magnetic field generator made with two coils, consisting of 35 turns
and 15 mm diameter of insulated 0.2 mm cooper wire, mounted in a frame of carbon
fibre. This portable scleral search coil was fixed on the head of the animal,
with each magnetic coil parallel to the eye coil and at 5 mm from each eye. Eye
movements detected by the portable scleral search coil were compared with those
measured by a commercial scleral search coil requiring immobilizing the head of
the animal. No qualitative differences were found between the two scleral search
coil systems in their capabilities to detect eye movements. This innovative
portable scleral search coil system is an essential tool to detect slow changes
in eye position and miniature rapid eye movements during sleep. The portable
scleral search coil is much more suitable for detecting eye movements than any
previously available system because of its precision and simplicity, and because
it does not require immobilization of the animal's head.
PMID- 25590419
TI - Catalytic kinetics of single gold nanoparticles observed via optical microwell
arrays.
AB - Catalytic activities and kinetics are measured at the single-particle level for
gold nanoparticles catalyzing a fluorogenic oxidation reaction. This measurement
is accomplished by confining the reactions in optically addressable microwell
arrays. Citrate-capped gold nanoparticles are isolated in sealed ~70 fL
microwells along with a substrate, and the accumulation of a fluorescent product
over time is observed. Thousands of reactions are measured in parallel. Catalytic
activities are calculated for each nanoparticle and the activity distribution is
analyzed.
PMID- 25590418
TI - In vitro aggregation assays using hyperphosphorylated tau protein.
AB - Alzheimer's disease is one of a large group of neurodegenerative disorders known
as tauopathies that are manifested by the neuronal deposits of
hyperphosphorylated tau protein in the form of neurofibrillary tangles (NFTs).
The density of NFT correlates well with cognitive impairment and other
neurodegenerative symptoms, thus prompting the endeavor of developing tau
aggregation-based therapeutics. Thus far, however, tau aggregation assays use
recombinant or synthetic tau that is devoid of the pathology-related
phosphorylation marks. Here we describe two assays using recombinant,
hyperphosphorylated tau as the subject. These assays can be scaled up for high
throughput screens for compounds that can modulate the kinetics or stability of
hyperphosphorylated tau aggregates. Novel therapeutics for Alzheimer's disease
and other tauopathies can potentially be discovered using hyperphosphorylated tau
isoforms.
PMID- 25590420
TI - Cadmium toxicity to Microcystis aeruginosa PCC 7806 and its microcystin-lacking
mutant.
AB - The adverse effects of microcystin (MC) produced by cyanobacteria have drawn
considerable attention from the public. Yet it remains unclear whether MC confers
any benefits to the cyanobacteria themselves. One suggested function of MC is
complexation, which may influence the bioaccumulation and toxicity of trace
metals. To test this hypothesis, we examined Cd toxicity to wild-type Microcystis
aeruginosa PCC 7806 (WT) and its MC-lacking mutant (MT) under nutrient-enriched
(+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The
accumulation of Cd and the biochemical parameters associated with its
detoxification [total phosphorus (TP), inorganic polyphosphate (Poly-P), and
glutathione (GSH) in the cells as well as intra- and extra-cellular
carbohydrates] were quantified. Although the -P cyanobacteria accumulated less Cd
than their +NP and -N counterparts, the different nutrient-conditioned
cyanobacteria were similarly inhibited by similar free ion concentration of Cd in
the medium ([Cd2+]F). Such good toxicity predictability of [Cd2+]F was ascribed
to the synchronous decrease in the intracellular concentrations of Cd and TP.
Nevertheless, Cd toxicity was still determined by the intracellular Cd to
phosphorus ratio (Cd/P), in accordance with what has been reported in the
literature. On the other hand, the concentrations of TP, Poly-P, and
carbohydrates went up, but GSH concentration dropped down with the enhancement of
[Cd2+]F, indicating their association with Cd detoxification. Although the
inactivation of MC peptide synthetase gene had some nutrient and Cd concentration
dependent effects on the parameters above, both cyanobacterial strains showed the
same Cd accumulation ability and displayed similar Cd sensitivity. These results
suggest that MC cannot affect metal toxicity either by regulating metal
accumulation or by altering the detoxification ability of the cyanobacteria.
Other possible functions of MC need to be further investigated.
PMID- 25590421
TI - Biohydrogen production from food waste hydrolysate using continuous mixed
immobilized sludge reactors.
AB - A continuous mixed immobilized sludge reactor (CMISR) using activated carbon as
support carrier for dark fermentative hydrogen production from enzymatic
hydrolyzed food waste was developed. The effects of immobilized sludge packing
ratio (10-20%, v/v) and substrate loading rate (OLR) (8-40kg/m(3)/d) on
biohydrogen production were examined, respectively. The hydrogen production rates
(HPRs) with packing ratio of 15% were significantly higher than the results
obtained from packing ratio of 10% and 20%. The best HPR of 353.9ml/h/L was
obtained at the condition of packing ratio=15% and OLR=40kg/m(3)/d. The Minitab
was used to elicit the effects of OLR and packing ratio on HPR (Y) which could be
expressed as Y=5.31 OLR+296 packing ratio+40.3 (p=0.003). However, the highest
hydrogen yield (85.6ml/g food waste) was happened at OLR of 16kg/m(3)/d because
of H2 partial pressure and oxidization/reduction of NADH.
PMID- 25590422
TI - Sufficient utilization of natural fluctuating light intensity is an effective
approach of promoting lipid productivity in oleaginous microalgal cultivation
outdoors.
AB - The effects of fluctuating intensity of solar radiation on biomass and lipid in
oleaginous microalgae are important. However, this topic has not been the subject
of studies for a long time. In this study, four oleaginous microalgae from semi
arid areas were screened and cultivated outdoors under different fluctuating
intensities. Results showed that the highest lipid productivities and neutral
lipid (NL) contents occurred under high fluctuating intensity (HFI), in which 13
20% of the increased NL came from glycolipid transformation without phospholipid
conversion. Chlorella sp. L1 and Monoraphidium dybowskii Y2 obtained from
biological soil crusts in desert had the largest biomass (137.13, 106.61mgL(-1)d(
1)) and lipid yields (35.06, 32.45mgL(-1)d(-1)) under HFI. The highest areal
lipid productivities of 9.06 and 8.95gm(-2)d(-1) and better biodiesel quality
were observed under HFI. Accordingly, sufficiently adopting fluctuating light
intensity outdoors to culture microalgae was an economic and effective approach.
PMID- 25590423
TI - A kinetic study on microwave-assisted conversion of cellulose and lignocellulosic
waste into hydroxymethylfurfural/furfural.
AB - Native cellulose, lignocellulosic materials from Brazil (carnauba palm leaves and
macauba pulp and shell) and pine nut shell from Spain have been studied as
substrates for the production of HMF and furfural in a conventional microwave
oven. In order to promote the dissolution of native cellulose, several ionic
liquids, catalysts, organic solvents and water doses have been assessed. The most
suitable mixture (5mL of choline chloride/oxalic acid, 2mL of sulfolane, 2mL of
water, 0.02g of TiO2 and 0.1g of substrate) has been chosen to conduct kinetic
studies at different reaction times (5-60min) and various temperatures (120-200
degrees C) and to evaluate the best conditions for HMF+furfural production
according to Seaman's model. The best production yields of HMF+furfural have been
attained for native cellulose, with a yield of 53.24% when an ultrasonic
pretreatment was used prior to a microwave treatment with stirring.
PMID- 25590424
TI - Improving performance of microbial fuel cell while controlling methanogenesis by
Chaetoceros pretreatment of anodic inoculum.
AB - Loss of substrate due to methanogenesis reduces Coulombic efficiency (CE) of the
microbial fuel cell (MFC) significantly. Hexadecatrienoic acid present in the
marine algae Chaetoceros inhibits the growth of methanogenic archaea. Influence
of Chaetoceros pre-treated mixed anaerobic sludge on the electrogenic activity of
MFC was evaluated. A MFC inoculated with Chaetoceros pre-treated mixed anaerobic
sludge demonstrated maximum CE of 45.18%, with volumetric power density of
21.43W/m(3) and current density of 93A/m(3). Cyclic voltammetry indicated higher
electron discharge on the anode surface due to suppression of methanogenesis.
Tafel analysis also showed a higher exchange current density and a lower Tafel
slope and charge transfer resistance, indicating advantage of this pre-treatment
method in reducing the cell internal losses. A 60% reduction in specific
methanogenic activity was observed in anaerobic sludge pre-treated with
Chaetoceros; emphasizing significance of this pretreatment for suppressing
methanogenesis and its utility for enhancing electricity generation in MFC.
PMID- 25590425
TI - Scaling-up of membraneless microbial electrolysis cells (MECs) for domestic
wastewater treatment: Bottlenecks and limitations.
AB - Microbial electrolysis cells (MECs) have the potential to become a sustainable
domestic wastewater (dWW) treatment system. However, new scale-up experiences are
required to gain knowledge of critical issues in MEC designs. In this study we
assess the ability of two twin membraneless MEC units (that are part of a modular
pilot-scale MEC) to treat dWW. Batch tests yielded COD removal efficiencies as
high as 92%, with most of the hydrogen (>80% of the total production) being
produced during the first 48h. During the continuous tests, MECs performance
deteriorated significantly (energy consumption was relatively high and COD
removal efficiencies fell below 10% in many cases), which was attributed to an
inadequate configuration of the anodic chamber, insufficient mixing inside this
chamber, inefficient hydrogen management on the cathode side and finally to dWW
in itself. Some alternatives to the current design are suggested.
PMID- 25590426
TI - Production of fermentable sugars from sugarcane bagasse by enzymatic hydrolysis
after autohydrolysis and mechanical refining.
AB - The autohydrolysis process has been considered a simple, low-cost and
environmental friendly technology for generation of sugars from biomass. In order
to improve accessibility of enzymes during enzymatic hydrolysis as well as to
allow the recovery of hemicellulose in the filtrate, the sugarcane bagasse was
pretreated using autohydrolysis followed by a mechanical refining process. The
autohydrolysis was carried out in three different conditions. Autohydrolysis at
190 degrees C for 10min provided the highest overall sugar (19.2/100g raw
bagasse) in prehydrolyzate. The enzymatic hydrolysis step was performed for all
the post-treated solids with and without refining at enzyme loadings of 5 and
10FPU/g for 96h. A total of 84.4% of sugar can be recovered from sugarcane
bagasse at 180 degrees C for 20min with 5 FPU/g enzyme charge. The economic
analysis for the proposed method showed that the bioethanol production can have a
financial return larger than 12%.
PMID- 25590427
TI - Synaptic plasticity enables adaptive self-tuning critical networks.
AB - During rest, the mammalian cortex displays spontaneous neural activity. Spiking
of single neurons during rest has been described as irregular and asynchronous.
In contrast, recent in vivo and in vitro population measures of spontaneous
activity, using the LFP, EEG, MEG or fMRI suggest that the default state of the
cortex is critical, manifested by spontaneous, scale-invariant, cascades of
activity known as neuronal avalanches. Criticality keeps a network poised for
optimal information processing, but this view seems to be difficult to reconcile
with apparently irregular single neuron spiking. Here, we simulate a 10,000
neuron, deterministic, plastic network of spiking neurons. We show that a
combination of short- and long-term synaptic plasticity enables these networks to
exhibit criticality in the face of intrinsic, i.e. self-sustained, asynchronous
spiking. Brief external perturbations lead to adaptive, long-term modification of
intrinsic network connectivity through long-term excitatory plasticity, whereas
long-term inhibitory plasticity enables rapid self-tuning of the network back to
a critical state. The critical state is characterized by a branching parameter
oscillating around unity, a critical exponent close to -3/2 and a long tail
distribution of a self-similarity parameter between 0.5 and 1.
PMID- 25590428
TI - Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the
dynamics of epigenetic modifications from stem cells to differentiated cells.
AB - The intestinal epithelium is a particularly attractive biological adult model to
study epigenetic mechanisms driving adult stem cell renewal and cell
differentiation. Since epigenetic modifications are dynamic, we have developed an
original ex vivo approach to study the expression and epigenetic profiles of key
genes associated with either intestinal cell pluripotency or differentiation by
isolating cryosections of the intestinal crypt-villus axis. Gene expression, DNA
methylation and histone modifications were studied by qRT-PCR, methylation
specific PCR and micro-chromatin immunoprecipitation, respectively. Using this
approach, it was possible to identify segment-specific methylation and chromatin
profiles. We show that (i) expression of intestinal stem cell markers (Lgr5,
Ascl2) exclusively in the crypt is associated with active histone marks, (ii)
promoters of all pluripotency genes studied and transcription factors involved in
intestinal cell fate (Cdx2) harbour a bivalent chromatin pattern in the crypts
and (iii) expression of differentiation markers (Muc2, Sox9) along the crypt
villus axis is associated with DNA methylation. Hence, using an original model of
cryosectioning along the crypt-villus axis that allows in situ detection of
dynamic epigenetic modifications, we demonstrate that regulation of pluripotency
and differentiation markers in healthy intestinal mucosa involves different and
specific epigenetic mechanisms.
PMID- 25590429
TI - Preparation and friction force microscopy measurements of immiscible, opposing
polymer brushes.
AB - Solvated polymer brushes are well known to lubricate high-pressure contacts,
because they can sustain a positive normal load while maintaining low friction at
the interface. Nevertheless, these systems can be sensitive to wear due to
interdigitation of the opposing brushes. In a recent publication, we have shown
via molecular dynamics simulations and atomic force microscopy experiments, that
using an immiscible polymer brush system terminating the substrate and the slider
surfaces, respectively, can eliminate such interdigitation. As a consequence,
wear in the contacts is reduced. Moreover, the friction force is two orders of
magnitude lower compared to traditional miscible polymer brush systems. This
newly proposed system therefore holds great potential for application in
industry. Here, the methodology to construct an immiscible polymer brush system
of two different brushes each solvated by their own preferred solvent is
presented. The procedure how to graft poly(N-isopropylacrylamide) (PNIPAM) from a
flat surface and poly(methyl methacrylate) (PMMA) from an atomic force microscopy
(AFM) colloidal probe is described. PNIPAM is solvated in water and PMMA in
acetophenone. Via friction force AFM measurements, it is shown that the friction
for this system is indeed reduced by two orders of magnitude compared to the
miscible system of PMMA on PMMA solvated in acetophenone.
PMID- 25590431
TI - Poly(vinyl alcohol)/gelatin Hydrogels Cultured with HepG2 Cells as a 3D Model of
Hepatocellular Carcinoma: A Morphological Study.
AB - It has been demonstrated that three-dimensional (3D) cell culture models
represent fundamental tools for the comprehension of cellular phenomena both for
normal and cancerous tissues. Indeed, the microenvironment affects the cellular
behavior as well as the response to drugs. In this study, we performed a
morphological analysis on a hepatocarcinoma cell line, HepG2, grown for 24 days
inside a bioartificial hydrogel composed of poly(vinyl alcohol) (PVA) and gelatin
(G) to model a hepatocellular carcinoma (HCC) in 3D. Morphological features of
PVA/G hydrogels were investigated, resulting to mimic the trabecular structure of
liver parenchyma. A histologic analysis comparing the 3D models with HepG2 cell
monolayers and tumor specimens was performed. In the 3D setting, HepG2 cells were
viable and formed large cellular aggregates showing different morphotypes with
zonal distribution. Furthermore, beta-actin and alpha5beta1 integrin revealed a
morphotype-related expression; in particular, the frontline cells were
characterized by a strong immunopositivity on a side border of their membrane,
thus suggesting the formation of lamellipodia-like structures apt for migration.
Based on these results, we propose PVA/G hydrogels as valuable substrates to
develop a long term 3D HCC model that can be used to investigate important
aspects of tumor biology related to migration phenomena.
PMID- 25590433
TI - Green approach for photocatalytic Cu(II)-EDTA degradation over TiO2: toward
environmental sustainability.
AB - A green approach was successfully developed to reap three environmental benefits
simultaneously: (1) clean water production, (2) hydrogen (H2) generation, and (3)
well-dispersed in situ Cu(2+) recovery for direct TiO2-CuO composite reclamation,
by exploiting the synergistic integration of photocatalytic reaction of Cu-EDTA
and one-dimensional (1D) ultralong and ultrathin TiO2 nanofibers. In this light
initiated system, Cu-EDTA was oxidized by TiO2 thus releasing Cu(2+) which was
reduced and recovered through uniform adsorption onto the long and porous TiO2
surface. A win-win platform was thus attained, on which Cu was recovered while
providing active sites for H2 generation via photoreduction of H2O and enhancing
photo-oxidation of remaining intermediate oxidation byproducts. Experimental
results showed a H2 generation rate of 251 MUmol/h concomitantly with TOC
reduction. The used TiO2 nanofibers deposited with Cu were reclaimed directly as
the TiO2-CuO composite after a facile heat treatment without additional chemicals
and subsequently reusable for photocatalytic treatment of other wastewater
(glycerol) to cogenerate H2 and clean water under both UV-visible and visible
light. This study expounds a significant advancement through an ingenious
integration which enhances the environmental sustainability of Cu-EDTA treatment
via TiO2 photocatalysis. It also represents a promising and adoptable approach to
synthesize other functional composite nanomaterials in a green manner thus
broadening its environmental application spectrum, as it promotes industrial
environmental management via waste segregation and motivates research to recover
more resources from wastewater.
PMID- 25590430
TI - Bacterial flagella: twist and stick, or dodge across the kingdoms.
AB - The flagellum organelle is an intricate multiprotein assembly best known for its
rotational propulsion of bacteria. However, recent studies have expanded our
knowledge of other functions in pathogenic contexts, particularly adherence and
immune modulation, e.g., for Salmonella enterica, Campylobacter jejuni,
Pseudomonas aeruginosa, and Escherichia coli. Flagella-mediated adherence is
important in host colonisation for several plant and animal pathogens, but the
specific interactions that promote flagella binding to such diverse host tissues
has remained elusive. Recent work has shown that the organelles act like probes
that find favourable surface topologies to initiate binding. An emerging theme is
that more general properties, such as ionic charge of repetitive binding epitopes
and rotational force, allow interactions with plasma membrane components. At the
same time, flagellin monomers are important inducers of plant and animal innate
immunity: variation in their recognition impacts the course and outcome of
infections in hosts from both kingdoms. Bacteria have evolved different
strategies to evade or even promote this specific recognition, with some
important differences shown for phytopathogens. These studies have provided a
wider appreciation of the functions of bacterial flagella in the context of both
plant and animal reservoirs.
PMID- 25590432
TI - The human otubain2-ubiquitin structure provides insights into the cleavage
specificity of poly-ubiquitin-linkages.
AB - Ovarian tumor domain containing proteases cleave ubiquitin (Ub) and ubiquitin
like polypeptides from proteins. Here we report the crystal structure of human
otubain 2 (OTUB2) in complex with a ubiquitin-based covalent inhibitor, Ub-Br2.
The ubiquitin binding mode is oriented differently to how viral otubains (vOTUs)
bind ubiquitin/ISG15, and more similar to yeast and mammalian OTUs. In contrast
to OTUB1 which has exclusive specificity towards Lys48 poly-ubiquitin chains,
OTUB2 cleaves different poly-Ub linked chains. N-terminal tail swapping
experiments between OTUB1 and OTUB2 revealed how the N-terminal structural motifs
in OTUB1 contribute to modulating enzyme activity and Ub-chain selectivity, a
trait not observed in OTUB2, supporting the notion that OTUB2 may affect a
different spectrum of substrates in Ub-dependent pathways.
PMID- 25590434
TI - Superhydrophobic cuprous oxide nanostructures on phosphor-copper meshes and their
oil-water separation and oil spill cleanup.
AB - A simple aqueous solution-immersion process was established to fabricate highly
dense ordered Cu2O nanorods on commercial phosphor-copper mesh, with which the
preparation was accomplished in distilled water. The present method, with the
advantages of simple operation, low cost, short reaction time, and environmental
friendliness, can be well adopted to fabricate desired Cu2O nanostructures on the
phosphor-copper mesh under mild conditions. After surface modification with 1
dodecanethiol, the Cu2O nanostructure obtained on the phosphor-copper mesh
exhibits excellent superhydrophobicity and superoleophilicity. Besides, a "mini
boat" made from the as-prepared superhydrophobic phosphor-copper mesh can float
freely on water surface and in situ collect oil from water surface. This
demonstrates that the present approach, being facile, inexpensive, and
environmentally friendly, could find promising application in oil-water
separation and off shore oil spill cleanup.
PMID- 25590436
TI - Comparison of nephrotoxicity associated to different lipid formulations of
amphotericin B: a real-life study.
AB - Amphotericin B (AmB) use is limited by the occurrence of kidney toxicity. Here,
we evaluated the incidence and impact of nephrotoxicity in a large series of
patients receiving therapy with amphotericin B deoxycholate (d-AmB), liposomal
AmB (L-AmB), or AmB lipid complex (ABLC), in a clinical practice scenario. In a
retrospective cohort study, patients treated with different AmB formulations
between 2003 and 2012 were evaluated. Medical records and laboratory data were
reviewed. Nephrotoxicity was determined according to modified RIFLE criteria.
Predictors of nephrotoxicity and mortality were determined and treatment groups
were compared. About 431 patients were studied (d-AmB, n = 236; L-AmB, n = 105;
ABLC, n = 90). Frequency of severe nephrotoxicity (RIFLE 'Failure') was 11.5%,
2.4% and 7.2% for d-AmB, L-AmB and ABLC, respectively (P = 0.046). Use of L-AmB
was found to be an independent protective factor (OR: 0.18; 95% CI: 0.03-0.64; P
= 0.006) for severe nephrotoxicity, considering d-AmB as a reference. L-AmB was
also a protective factor for mortality (OR: 0.56; 95% CI: 0.32-0.99; P = 0.046).
In addition, in-hospital overall mortality was associated with cancer, previous
dialysis, evolution to dialysis, and stay in the intensive care unit. Patients
treated with ABLC showed similar frequency of severe kidney toxicity than those
treated with d-AmB. L-AmB was associated with better outcomes than other
formulations, including severe nephrotoxicity and overall mortality.
PMID- 25590438
TI - Anomalous rapid defect annihilation in self-assembled nanopatterns by defect
melting.
AB - Molecular self-assembly commonly suffers from dense structural defect formation.
Spontaneous defect annihilation in block copolymer (BCP) self-assembly is
particularly retarded due to significant energy barrier for polymer chain
diffusion and structural reorganization. Here we present localized defect melting
induced by blending short neutral random copolymer chain as an unusual method to
promote the defect annihilation in BCP self-assembled nanopatterns. Chemically
neutral short random copolymer chains blended with BCPs are specifically
localized and induce local disordered states at structural defect sites in the
self-assembled nanopatterns. Such localized "defect melting" relieves the energy
penalty for polymer diffusion and morphology reorganization such that spontaneous
defect annihilation by mutual coupling is anomalously accelerated upon thermal
annealing. Interestingly, neutral random copolymer chain blending also causes
morphology-healing self-assembly behavior that can generate large-area highly
ordered 10 nm scale nanopattern even upon poorly defined defective prepatterns.
Underlying mechanisms of the unusual experimental findings are thoroughly
investigated by three-dimensional self-consistent field theory calculation.
PMID- 25590435
TI - Bartonella spp. bacteremia in blood donors from Campinas, Brazil.
AB - Bartonella species are blood-borne, re-emerging organisms, capable of causing
prolonged infection with diverse disease manifestations, from asymptomatic
bacteremia to chronic debilitating disease and death. This pathogen can survive
for over a month in stored blood. However, its prevalence among blood donors is
unknown, and screening of blood supplies for this pathogen is not routinely
performed. We investigated Bartonella spp. prevalence in 500 blood donors from
Campinas, Brazil, based on a cross-sectional design. Blood samples were
inoculated into an enrichment liquid growth medium and sub-inoculated onto blood
agar. Liquid culture samples and Gram-negative isolates were tested using a genus
specific ITS PCR with amplicons sequenced for species identification. Bartonella
henselae and Bartonella quintana antibodies were assayed by indirect
immunofluorescence. B. henselae was isolated from six donors (1.2%). Sixteen
donors (3.2%) were Bartonella-PCR positive after culture in liquid or on solid
media, with 15 donors infected with B. henselae and one donor infected with
Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found
in 16% and 32% of 500 blood donors, respectively. Serology was not associated
with infection, with only three of 16 Bartonella-infected subjects seropositive
for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of
approximately one out of 30 donors from a major blood bank in South America.
Negative serology does not rule out Bartonella spp. infection in healthy
subjects. Using a combination of liquid and solid cultures, PCR, and DNA
sequencing, this study documents for the first time that Bartonella spp.
bacteremia occurs in asymptomatic blood donors. Our findings support further
evaluation of Bartonella spp. transmission which can occur through blood
transfusions.
PMID- 25590437
TI - S-phase-dependent p50/NF-kB1 phosphorylation in response to ATR and replication
stress acts to maintain genomic stability.
AB - The apical damage kinase, ATR, is activated by replication stress (RS) both in
response to DNA damage and during normal S-phase. Loss of function studies
indicates that ATR acts to stabilize replication forks, block cell cycle
progression and promote replication restart. Although checkpoint failure and
replication fork collapse can result in cell death, no direct cytotoxic pathway
downstream of ATR has previously been described. Here, we show that ATR directly
reduces survival by inducing phosphorylation of the p50 (NF-kappaB1, p105)
subunit of NF-kB and moreover, that this response is necessary for genome
maintenance independent of checkpoint activity. Cell free and in vivo studies
demonstrate that RS induces phosphorylation of p50 in an ATR-dependent but DNA
damage-independent manner that acts to modulate NF-kB activity without affecting
p50/p65 nuclear translocation. This response, evident in human and murine cells,
occurs not only in response to exogenous RS but also during the unperturbed S
phase. Functionally, the p50 response results in inhibition of anti-apoptotic
gene expression that acts to sensitize cells to DNA strand breaks independent of
damage repair. Ultimately, loss of this pathway causes genomic instability due to
the accumulation of chromosomal breaks. Together, the data indicate that during S
phase ATR acts via p50 to ensure that cells with elevated levels of replication
associated DNA damage are eliminated.
PMID- 25590439
TI - PCTAIRE1/PCTK1/CDK16: a new oncotarget?
PMID- 25590440
TI - Tutorial for writing systematic reviews for the Brazilian Journal of Physical
Therapy (BJPT).
AB - Systematic reviews aim to summarize all evidence using very rigorous methods in
order to address a specific research question with less bias as possible.
Systematic reviews are widely used in the field of physical therapy, however not
all reviews have good quality. This tutorial aims to guide authors of the
Brazilian Journal of Physical Therapy on how systematic reviews should be
conducted and reported in order to be accepted for publication. It is expected
that this tutorial will help authors of systematic reviews as well as journal
editors and reviewers on how to conduct, report, critically appraise and
interpret this type of study design.
PMID- 25590441
TI - Static body postural misalignment in individuals with temporomandibular
disorders: a systematic review.
AB - BACKGROUND: The association between body postural changes and temporomandibular
disorders (TMD) has been widely discussed in the literature, however, there is
little evidence to support this association. OBJECTIVES: The aim of the present
study was to conduct a systematic review to assess the evidence concerning the
association between static body postural misalignment and TMD. METHOD: A search
was conducted in the PubMed/Medline, Embase, Lilacs, Scielo, Cochrane, and Scopus
databases including studies published in English between 1950 and March 2012.
Cross-sectional, cohort, case control, and survey studies that assessed body
posture in TMD patients were selected. Two reviewers performed each step
independently. A methodological checklist was used to evaluate the quality of the
selected articles. RESULTS: Twenty studies were analyzed for their methodological
quality. Only one study was classified as a moderate quality study and two were
classified as strong quality studies. Among all studies considered, only 12
included craniocervical postural assessment, 2 included assessment of
craniocervical and shoulder postures,, and 6 included global assessment of body
posture. CONCLUSION: There is strong evidence of craniocervical postural changes
in myogenous TMD, moderate evidence of cervical postural misalignment in
arthrogenous TMD, and no evidence of absence of craniocervical postural
misalignment in mixed TMD patients or of global body postural misalignment in
patients with TMD. It is important to note the poor methodological quality of the
studies, particularly those regarding global body postural misalignment in TMD
patients.
PMID- 25590442
TI - Walking training associated with virtual reality-based training increases walking
speed of individuals with chronic stroke: systematic review with meta-analysis.
AB - OBJECTIVE: To systematically review the available evidence on the efficacy of
walking training associated with virtual reality-based training in patients with
stroke. The specific questions were: Is walking training associated with virtual
reality-based training effective in increasing walking speed after stroke? Is
this type of intervention more effective in increasing walking speed, than non
virtual reality-based walking interventions? METHOD: A systematic review with
meta-analysis of randomized clinical trials was conducted. Participants were
adults with chronic stroke and the experimental intervention was walking training
associated with virtual reality-based training to increase walking speed. The
outcome data regarding walking speed were extracted from the eligible trials and
were combined using a meta-analysis approach. RESULTS: Seven trials representing
eight comparisons were included in this systematic review. Overall, the virtual
reality-based training increased walking speed by 0.17 m/s (IC 95% 0.08 to 0.26),
compared with placebo/nothing or non-walking interventions. In addition, the
virtual reality-based training increased walking speed by 0.15 m/s (IC 95% 0.05
to 0.24), compared with non-virtual reality walking interventions. CONCLUSIONS:
This review provided evidence that walking training associated with virtual
reality-based training was effective in increasing walking speed after stroke,
and resulted in better results than non-virtual reality interventions.
PMID- 25590443
TI - Relationship between the climbing up and climbing down stairs domain scores on
the FES-DMD, the score on the Vignos Scale, age and timed performance of
functional activities in boys with Duchenne muscular dystrophy.
AB - BACKGROUND: Knowing the potential for and limitations of information generated
using different evaluation instruments favors the development of more accurate
functional diagnoses and therapeutic decision-making. OBJECTIVE: To investigate
the relationship between the number of compensatory movements when climbing up
and going down stairs, age, functional classification and time taken to perform a
tested activity (TA) of going up and down stairs in boys with Duchenne muscular
dystrophy (DMD). METHOD: A bank of movies featuring 30 boys with DMD performing
functional activities was evaluated. Compensatory movements were assessed using
the climbing up and going down stairs domain of the Functional Evaluation Scale
for Duchenne Muscular Dystrophy (FES-DMD); age in years; functional
classification using the Vignos Scale (VS), and TA using a timer. Statistical
analyses were performed using the Spearman correlation test. RESULTS: There is a
moderate relationship between the climbing up stairs domain of the FES-DMD and
age (r=0.53, p=0.004) and strong relationships with VS (r=0.72, p=0.001) and TA
for this task (r=0.83, p<0.001). There were weak relationships between the going
down stairs domain of the FES-DMD-going down stairs with age (r=0.40, p=0.032),
VS (r=0.65, p=0.002) and TA for this task (r=0.40, p=0.034). CONCLUSION: These
findings indicate that the evaluation of compensatory movements used when
climbing up stairs can provide more relevant information about the evolution of
the disease, although the activity of going down stairs should be investigated,
with the aim of enriching guidance and strengthening accident prevention. Data
from the FES-DMD, age, VS and TA can be used in a complementary way to formulate
functional diagnoses. Longitudinal studies and with broader age groups may
supplement this information.
PMID- 25590444
TI - Muscular performance characterization in athletes: a new perspective on
isokinetic variables.
AB - BACKGROUND: Isokinetic dynamometry allows the measurement of several variables
related to muscular performance, many of which are seldom used, while others are
redundantly applied to the characterization of muscle function. OBJECTIVES: The
present study aimed to establish the particular features of muscle function that
are captured by the variables currently included in isokinetic assessment and to
determine which variables best represent these features in order to achieve a
more objective interpretation of muscular performance. METHOD: This study
included 235 male athletes. They performed isokinetic tests of concentric knee
flexion and extension of the dominant leg at a velocity of 60o/s. An exploratory
factor analysis was performed. RESULTS: The findings demonstrated that isokinetic
variables can characterize more than muscle torque production and pointed to the
presence of 5 factors that enabled the characterization of muscular performance
according to 5 different domains or constructs. CONCLUSIONS: The constructs can
be described by torque generation capacity; variation of the torque generation
capacity along repetitions; movement deceleration capacity;
mechanical/physiological factors of torque generation; and acceleration capacity
(torque development). Fewer than eight out of sixteen variables are enough to
characterize these five constructs. Our results suggest that these variables and
these 5 domains may lead to a more systematic and optimized interpretation of
isokinetic assessments.
PMID- 25590445
TI - Characteristics and associated factors with sports injuries among children and
adolescents.
AB - BACKGROUND: The participation of children and adolescents in sports is becoming
increasingly common, and this increased involvement raises concerns about the
occurrence of sports injuries. OBJECTIVES: To characterize the sports injuries
and verify the associated factors with injuries in children and adolescents.
METHOD: Retrospective, epidemiological study. One thousand three hundred and
eleven children and adolescents up to 18 years of age enrolled in a sports
initiation school in the city of Presidente Prudente, State of Sao Paulo, Brazil.
A reported condition inquiry in interview form was used to obtain personal data
and information on training and sports injuries in the last 12 months. Injury was
considered any physical complaint resulting from training and/or competition that
limited the participation of the individual for at least one day, regardless of
the need for medical care. RESULTS: The injury rate per 1000 hours of exposure
was 1.20 among the children and 1.30 among the adolescents. Age, anthropometric
data, and training characteristics only differed with regard to the presence or
absence of injuries among the adolescents. The most commonly reported
characteristics involving injuries in both the children and adolescents were the
lower limbs, training, non-contact mechanism, mild injury, asymptomatic return to
activities, and absence of recurrence. CONCLUSIONS: The injury rate per 1000
hours of exposure was similar among children and adolescents. Nevertheless, some
peculiarities among adolescents were observed with greater values for weight,
height, duration of training, and weekly hours of practice.
PMID- 25590446
TI - Can the adapted arcometer be used to assess the vertebral column in children?
AB - BACKGROUND: The adapted arcometer has been validated for use in adults. However,
its suitability for use in children can be questioned given the structural
differences present in these populations. OBJECTIVE: To verify the concurrent
validity, repeatability, and intra- and inter-reproducibility of the adapted
arcometer for the measurement of the angles of thoracic kyphosis and lumbar
lordosis in children. METHOD: Forty children were evaluated using both sagittal
radiography of the spine and the adapted arcometer. The evaluations using the
arcometer were carried out by two trained evaluators on two different days. In
the statistical treatment, the intraclass correlation coefficient (ICC),
Pearson's product moment correlation, Spearman's rho, the paired t test, and
Wilcoxon's test were used (alpha=.05). RESULTS: A moderate and significant
correlation was found between the x-ray and the adapted arcometer regarding
thoracic kyphosis, but no correlation was found regarding lumbar lordosis.
Repeatability and intra-evaluator reproducibility of the thoracic kyphosis and
lumbar lordosis were confirmed, which was not the case of inter-evaluator
reproducibility. CONCLUSION: The adapted arcometer can be used to accompany
postural alterations in children made by the same evaluator, while its use for
diagnostic purposes and continued evaluation by different evaluators cannot be
recommended. Further studies with the aim of adapting this instrument for use in
children are recommended.
PMID- 25590447
TI - Breathing exercises: influence on breathing patterns and thoracoabdominal motion
in healthy subjects.
AB - BACKGROUND: The mechanisms underlying breathing exercises have not been fully
elucidated. OBJECTIVES: To evaluate the impact of four on breathing exercises
(diaphragmatic breathing, inspiratory sighs, sustained maximal inspiration and
intercostal exercise) the on breathing pattern and thoracoabdominal motion in
healthy subjects. METHOD: Fifteen subjects of both sexes, aged 23 +/- 1.5 years
old and with normal pulmonary function tests, participated in the study. The
subjects were evaluated using the optoelectronic plethysmography system in a
supine position with a trunk inclination of 45 degrees during quiet breathing
and the breathing exercises. The order of the breathing exercises was randomized.
Statistical analysis was performed by the Friedman test and an ANOVA for repeated
measures with one factor (breathing exercises), followed by preplanned contrasts
and Bonferroni correction. A p<0.005 value was considered significant. RESULTS:
All breathing exercises significantly increased the tidal volume of the chest
wall (V(cw)) and reduced the respiratory rate (RR) in comparison to quiet
breathing. The diaphragmatic breathing exercise was responsible for the lowest
V(cw), the lowest contribution of the rib cage, and the highest contribution of
the abdomen. The sustained maximal inspiration exercise promoted greater
reduction in RR compared to the diaphragmatic and intercostal exercises.
Inspiratory sighs and intercostal exercises were responsible for the highest
values of minute ventilation. Thoracoabdominal asynchrony variables increased
significantly during diaphragmatic breathing. CONCLUSIONS: The results showed
that the breathing exercises investigated in this study produced modifications in
the breathing pattern (e.g., increase in tidal volume and decrease in RR) as well
as in thoracoabdominal motion (e.g., increase in abdominal contribution during
diaphragmatic breathing), among others.
PMID- 25590448
TI - Application of positive airway pressure in restoring pulmonary function and
thoracic mobility in the postoperative period of bariatric surgery: a randomized
clinical trial.
AB - OBJECTIVE: To evaluate whether the application of bilevel positive airway
pressure in the postoperative period of bariatric surgery might be more effective
in restoring lung volume and capacity and thoracic mobility than the separate
application of expiratory and inspiratory positive pressure. METHOD: Sixty
morbidly obese adult subjects who were hospitalized for bariatric surgery and met
the predefined inclusion criteria were evaluated. The pulmonary function and
thoracic mobility were preoperatively assessed by spirometry and cirtometry and
reevaluated on the 1st postoperative day. After preoperative evaluation, the
subjects were randomized and allocated into groups: EPAP Group (n=20), IPPB Group
(n=20) and BIPAP Group (n=20), then received the corresponding intervention:
positive expiratory pressure (EPAP), inspiratory positive pressure breathing
(IPPB) or bilevel inspiratory positive airway pressure (BIPAP), in 6 sets of 15
breaths or 30 minutes twice a day in the immediate postoperative period and on
the 1st postoperative day, in addition to conventional physical therapy. RESULTS:
There was a significant postoperative reduction in spirometric variables
(p<0.05), regardless of the technique used, with no significant difference among
the techniques (p>0.05). Thoracic mobility was preserved only in group BIPAP
(p>0.05), but no significant difference was found in the comparison among groups
(p>0.05). CONCLUSION: The application of positive pressure does not seem to be
effective in restoring lung function after bariatric surgery, but the use of
bilevel positive pressure can preserve thoracic mobility, although this technique
was not superior to the other techniques.
PMID- 25590449
TI - Functional priorities reported by parents of children with cerebral palsy:
contribution to the pediatric rehabilitation process.
AB - BACKGROUND: Collaborative actions between family and therapist are essential to
the rehabilitation process, and they can be a catalyst mechanism to the positive
outcomes in children with cerebral palsy (CP). OBJECTIVES: To describe functional
priorities established by caregivers of CP children by level of severity and age,
and to assess changes on performance and satisfaction on functional priorities
reported by caregivers, in 6-month interval. METHOD: 75 CP children, weekly
assisted at Associacao Mineira de Reabilitacao, on physical and occupational
therapy services. The following information was collected: gross motor function
(Gross Motor Function Classification System-GMFCS) and functional priorities
established by caregivers (Canadian Occupational Performance Measure-COPM). Data
were collected in two moments, with a 6-month interval. RESULTS: The main
functional demands presented by caregivers were related to self-care activities
(48.2%). Parents of children with severe motor impairment (GMFCS V) pointed
higher number of demands related to play (p=0.0036), compared to the other
severity levels. Parents of younger children reported higher number of demands in
mobility (p=0.025) and play (p=0.007), compared to other age groups. After 6
months, there were significant increase on COPM performance (p=0.0001) and
satisfaction scores (p=0.0001). CONCLUSIONS: Parents of CP children identified
functional priorities in similar performance domains, by level of severity and
age. Orienting the pediatric rehabilitation process to promote changes in
functional priorities indentified by caregivers can contribute to the
reinforcement of the parent-therapist collaboration.
PMID- 25590453
TI - Happy birthday, Rolf Mulhaupt!
PMID- 25590450
TI - Ground reaction forces during level ground walking with body weight unloading.
AB - BACKGROUND: Partial body weight support (BWS) systems have been broadly used with
treadmills as a strategy for gait training of individuals with gait impairments.
Considering that we usually walk on level ground and that BWS is achieved by
altering the load on the plantar surface of the foot, it would be important to
investigate some ground reaction force (GRF) parameters in healthy individuals
walking on level ground with BWS to better implement rehabilitation protocols for
individuals with gait impairments. OBJECTIVE: To describe the effects of body
weight unloading on GRF parameters as healthy young adults walked with BWS on
level ground. METHOD: Eighteen healthy young adults (27 +/- 4 years old) walked
on a walkway, with two force plates embedded in the middle of it, wearing a
harness connected to a BWS system, with 0%, 15%, and 30% BWS. Vertical and
horizontal peaks and vertical valley of GRF, weight acceptance and push-off
rates, and impulse were calculated and compared across the three experimental
conditions. RESULTS: Overall, participants walked more slowly with the BWS system
on level ground compared to their normal walking speed. As body weight unloading
increased, the magnitude of the GRF forces decreased. Conversely, weight
acceptance rate was similar among conditions. CONCLUSIONS: Different amounts of
body weight unloading promote different outputs of GRF parameters, even with the
same mean walk speed. The only parameter that was similar among the three
experimental conditions was the weight acceptance rate.
PMID- 25590458
TI - Screening for cognitive impairment after stroke: A systematic review of
psychometric properties and clinical utility.
AB - OBJECTIVE: To systematically review the psychometric properties and clinical
utility of cognitive screening tools post-stroke. DATA SOURCES: EMBASE, CINAHL,
MEDLINE, PsychInfo. STUDY SELECTION: Studies testing the accuracy of screening
tools for cognitive impairment after stroke. DATA EXTRACTION: Data regarding the
participants, selection criteria, criterion/reference measure, cut-off score,
sensitivity, specificity and positive and negative predicted values for the
selected tools were extracted. Tools with sensitivity >= 80% and specificity >=
60% were selected. Clinical utility was assessed using a previously validated
tool and those scoring <6 were excluded. DATA SYNTHESIS: Twenty-one papers
regarding 12 screening tools were selected. Only the Montreal Cognitive
Assessment (MoCA) and Mini Mental State Examination (MMSE) met all psychometric
and clinical utility criteria for any levels of cognitive impairment. However,
the MMSE is most accurate to screen for dementia (cut-off score 23/24) and should
only be used for this purpose. In addition, the following can be used to detect:
* Any impairment: Addenbrooke's Cognitive Examination-Revised (ACE-R), Barrow
Neurological Institute Screen for Higher Cerebral Functions (BNIS) and Cognistat.
* Multiple-domain impairments: ACE-R, Telephone-MoCA or modified Telephone
Interview for Cognitive Status (TICS). * Dementia: TICS; Cambridge Cognitive
Examination; Rotterdam-Cambridge Cognitive Examination; Informant Questionnaire
for Cognitive Decline in the Elderly (IQCODE) and short-IQCODE. The IQCODE and
short-IQCODE are useful when the patient is unable to respond and an informant's
view is required. CONCLUSION: The MoCA is the most valid and clinically feasible
screening tool to identify stroke survivors with a wide range of cognitive
impairments who warrant further assessment.
PMID- 25590459
TI - A dual-responsive supra-amphiphilic polypseudorotaxane constructed from a water
soluble pillar[7]arene and an azobenzene-containing random copolymer.
AB - Macromolecular supra-amphiphiles refer to a kind of macromolecular amphiphiles
whose hydrophlic and hydrophobic parts are connected by noncovalent forces. They
have applications in various fields, such as drug delivery, sensor systems, and
biomedical materials. Here we report a novel molecular recognition motif between
a new thermoresponsive water-soluble pillar[7]arene (WP7) and an azobenzene
derivative. Furthermore, we utilized this recognition motif to construct the
first pillararene-based supra-amphiphilic polypseudorotaxane which can self
assemble to form vesicles in water. Due to the dual-responsiveness of the
molecular recognition motif (the thermoresponsiveness of WP7 and
photoresponsiveness of azobenzene), the reversible transformations between solid
nanospheres based on the self-assembly of the polymer backbone and vesicles based
on the self-assembly of the supra-amphiphilic polypseudorotaxane were achieved by
adjusting the solution temperature or UV-visible light irradiation. These dual
responsive aggregation behaviors were further used in the controlled release of
water-soluble dye calcein molecules.
PMID- 25590460
TI - Bilateral conjunctivitis in a returned traveller.
PMID- 25590461
TI - "A Shrinking Kind of Life": Gay Men's Experience of Aging With HIV.
AB - More people are living with HIV into midlife and older age. Although increased
longevity brings new hope, it also raises unanticipated challenges--especially
for gay men who never thought they would live into middle and older age. Middle
aged and older people are more likely to face multiple comorbidities, yet many
lack the necessary supports to help them adapt to the challenges of aging with
HIV. This article presents the findings of a qualitative study developed to
explore gay men's experience of aging with HIV. Multiple in-depth exploratory
interviews were conducted with 15 gay-identified men living with HIV/AIDS over an
18-month period. A systematic strategy data analysis consistent with grounded
theory revealed a pattern of subtle adjustments to living with HIV that resulted
in diminishing circles of social support and social involvement. This dynamic is
referred to as "a shrinking kind of life," an in-vivo code built from the
participant's own words. Four themes from the research (physical challenges, a
magnitude of loss, internal changes, & stigma) are discussed. Conclusions include
recommendations for future research and implications for practice in the field.
Practitioners knowledgeable of the factors that impact their social involvement
can empower gay men through individual and group interventions to confront a
shrinking kind of life and define for themselves what it means to optimally age
with HIV.
PMID- 25590462
TI - Symptoms, quality of life and level of functioning of traumatized refugees at
psychiatric trauma clinic in Copenhagen.
AB - OBJECTIVE: To characterize physical and mental health in trauma exposed refugees
by describing a population of patients with regard to background, mental health
history and current health problems; and to identify pre- and post-migratory
predictors of mental health. METHOD: All patients receiving treatment at the
Psychiatric Trauma Clinic for Refugees in Copenhagen from April 2008 to February
2010 completed self-rating inventories on symptoms of PTSD, depression and
anxiety as well as level of functioning and quality of life before treatment.
Then, associations of pre and post migratory factors with mental health were
explored using linear and logistic regression and Pearson's correlation
coefficients. RESULTS: Among the patients, the prevalence of depression, somatic
disease, pain, psychotic symptoms co-existing with PTSD and very low level of
functioning was high. Persecution, being an ex-combatant and living currently in
social isolation were significantly associated with PTSD arousal symptoms and
self-reported pain. CONCLUSIONS: New treatment modalities should seek to address
all of the symptoms and challenges of the patients including psychotic and
somatic symptoms and social isolation, and studies of treatment effect should
clarify all co-morbidities so that comparable populations can be included in
treatment evaluation studies.
PMID- 25590463
TI - Psychotherapy with traumatised refugees--the design of a randomised clinical
trial.
AB - There is little evidence as to which kind of psychotherapy is the most effective
in the treatment of traumatised refugees. At the Competence Center for
Transcultural Psychiatry, a series of clinical trials have been conducted since
2008. The first results are pending publication. The aim of this paper is to
discuss some of the challenges in adapting Cognitive Behavioural Therapy (CBT) to
the treatment of traumatised refugees, as well as describe a randomised clinical
trial designed to test two such adaptations. In the described trial one group
receives CBT with a focus on cognitive restructuring while the other group
receives CBT focusing on Stress Management. A main goal of this setup is to test
whether some, perhaps even most, of the traumatised refugees referred to
treatment, may benefit from a more direct focus on current stress, and its
alleviation through simple, repetitive exercises, compared to a focus on
analysing and changing thought patterns.
PMID- 25590464
TI - Activity of daily living performance amongst Danish asylum seekers: a cross
sectional study.
AB - OBJECTIVE: The aim of this study was to evaluate the extent of Activities of
Daily Living (ADL) ability impairment in newly arrived Danish asylum seekers. It
was hypothesized that exposure to trauma and torture would negatively influence
ADL performance and that measures of ADL ability would be lower in individuals
exposed to torture as compared to the non-tortured. SUBJECTS: Forty-three newly
arrived asylum seekers aged 20-50 years, from Iran, Afghanistan and Syria, were
consecutively included in the study. METHOD: ADL ability was assessed with the
observation-based test Assessment of Motor and Process Skills (AMPS). Interviews
were based on questionnaires about torture exposure, WHO-5 Wellbeing Index, Major
Depression Inventory and Pain Detect Questionnaire. All participants were
interviewed and tested using a linguistic interpreter. RESULTS: Thirty three
(77%) participants reported exposure to torture. The tortured did not differ
significantly from the nontortured on measures of ADL ability (two-sample t
tests: Motor, p= 0.36; Process, p= 0.82). ADL performance impairment was observed
in the overall study sample. Twelve had motor and 15 process ability measures
below age norms and 2 below both AMPS motor and process cut-offs for effortless
and efficient ADL performance. There were statistically significant - weak to
moderate - correlations between self-reported psychological distress, VAS average
pain, pain distribution and the AMPS measures. CONCLUSION: The study results
supported significant ADL ability impairment in tortured as well as non-tortured
newly arrived asylum seekers. Implementation of performance-based evaluation of
ADL ability as part of the initial medical screening of this particular
population should be considered.
PMID- 25590465
TI - Hospitalizations for patients aged 85 and over in the United States, 2000-2010.
AB - KEY FINDINGS: Data from the National Hospital Discharge Survey. In 2010, adults
aged 85 and over accounted for only 2% of the U.S. population but 9% of hospital
discharges. From 2000 through 2010, the rate of hospitalizations for adults aged
85 and over declined from 605 to 553 hospitalizations per 1,000 population, a 9%
decrease. The rate of fractures and other injuries was higher for adults aged 85
and over (51 per 1,000 population) than for adults aged 65-74 (9 per 1,000
population) and 75-84 (23 per 1,000 population). Adults aged 85 and over were
less likely than those aged 65-74 and 75-84 to be discharged home and more likely
to die in the hospital. From 2000 through 2010, the number of adults aged 85 and
over in the United States rose 31%, from 4.2 million to 5.5 million, and in 2010,
this age group represented almost 14% of the population aged 65 and over (1). It
is estimated that by 2050, more than 21% of adults over age 65 will be aged 85
and over (2). Given this increase, adults aged 85 and over are likely to account
for an increasing share of hospital utilization and costs in the coming years
(3). This report describes hospitalizations for adults aged 85 and over with
comparisons to adults aged 65-74 and 75-84.
PMID- 25590466
TI - The diagnostic value of clinical symptoms in women and men presenting with chest
pain at the emergency department, a prospective cohort study.
AB - BACKGROUND: Previous studies suggested that diagnosing coronary artery disease
(CAD) is more difficult in women than in men. Studies investigating the
predictive value of clinical signs and symptoms and compare its combined
diagnostic value between women and men are lacking. METHODOLOGY: Data from a
large multicenter prospective study was used. Patients admitted to the emergency
department (ED) with chest pain but without ST-elevation were eligible. The
endpoint was proven CAD, defined as a significant stenosis at angiography or the
diagnosis of a non-ST-elevation myocardial infarction or cardiovascular death
within six weeks after presentation at the ED. Twelve clinical symptoms and seven
cardiovascular risk factors were collected. Potential predictors of CAD with a p
value <0.15 in the univariable analysis were included in a multivariable model.
The diagnostic value of clinical symptoms and cardiovascular risk factors was
quantified in women and men separately and areas under the curve (AUC) were
compared between sexes. RESULTS: A total of 2433 patients were included. We
excluded 102 patients (4%) with either an incomplete follow up or ST-elevation.
Of the remaining 2331 patients 43% (1003) were women. CAD was present in 111
(11%) women and 278 (21%) men. In women 11 out of 12 and in men 10 out of 12
clinical symptoms were univariably associated with CAD. The AUC of symptoms alone
was 0.74 (95%CI: 0.69-0.79) in women and 0.71 (95%CI: 0.68-0.75) in men and
increased to respectively 0.79 (95%CI: 0.74-0.83) in women versus 0.75 (95%CI:
0.72-0.78) in men after adding cardiovascular risk factors. The AUCs of women and
men were not significantly different (p-value symptoms alone: 0.45, after adding
cardiovascular risk factors: 0.11). CONCLUSION: The diagnostic value of clinical
symptoms and cardiovascular risk factors for the diagnosis of CAD in chest pain
patients presenting on the ED was high in women and men. No significant
differences were found between sexes.
PMID- 25590468
TI - Impact of xylomethazoline on eustachian tube function in healthy participants.
AB - INTRODUCTION: The use of decongestants is common in otitis media eustachian tube
(ET) dysfunction. However, the underlying mechanism and the type of action on the
complex middle ear pressure equalization system are poorly understood. Here, by
use of the pressure chamber, we investigated the impact of intranasal
decongestive therapy (xylomethazoline) on ET function. MATERIALS AND METHODS:
Thirty healthy participants (60 ears) were exposed to a predetermined profile of
phases of compression and decompression in a hypobaric and hyperbaric pressure
chamber. ET opening pressure, ET opening duration, ET opening frequency, and ET
closing pressure were determined before and after intranasal application of
xylomethazoline. RESULTS: A significantly higher number of ET openings (ET
opening frequency) in passive equalization condition could be measured after
application of decongestants than before. No significant difference could be
found in the values of ET opening pressure, ET opening duration, and ET closing
pressure parameters before in comparison with the values after application of
xylomethazoline. CONCLUSION: We conclude that xylomethazoline might only have a
minor effect during active and passive middle ear pressure equalization. Larger
cohorts and targeted application of decongestants should be tested to confirm
these preliminary data and to find new evidence on the effects of decongestants.
PMID- 25590469
TI - A 3-mm margin completely removes dermatofibromas: a study of 151 cases.
PMID- 25590470
TI - Reconstruction of a large defect of the glabella and forehead.
PMID- 25590467
TI - The coagulopathy of acute sepsis.
AB - PURPOSE OF REVIEW: Sepsis, defined by the presence of infection and host
inflammation, is a lethal clinical syndrome with an increasing mortality rate
worldwide. In severe disease, the coagulation system becomes diffusely activated,
with consumption of multiple clotting factors resulting in disseminated
intravascular coagulation (DIC). When present, DIC portends a higher mortality
rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis
will allow therapeutic interventions to be developed. The coagulopathy of acute
sepsis is a dynamic process that is time and disease burden specific. Whole-blood
testing of coagulation may provide more clinically useful information than the
classical tests. Natural anticoagulants that regulate thrombosis are
downregulated in sepsis. Patients may benefit from the modulation of the
coagulation system when systemic inflammation and hypercoagulopathy exist. Proper
timing of anticoagulant therapy may ultimately lead to decreased incidence of
multisystem organ dysfunction. RECENT FINDINGS: The pathogenesis of coagulopathy
in sepsis is driven by an upregulation of procoagulant mechanisms and
simultaneous downregulation of natural anticoagulants. Inflammation caused by the
invading organism is a natural host defense that cannot be eliminated during
treatment. Successful strategies to prevent multisystem organ dysfunction center
on stratifying patients at high risk for DIC and restoring the balance of
inflammation and coagulation. SUMMARY: The prevention of DIC in septic patients
is a key therapeutic target in preventing death from multisystem organ failure.
Stratifying patients for therapy using thromboelastometry, specific markers for
DIC, and composite scoring systems is an area of growing research.
PMID- 25590471
TI - Analysis of incidence of bulla formation after tattoo treatment using the
combination of the picosecond Alexandrite laser and fractionated CO2 ablation.
AB - BACKGROUND: The picosecond Alexandrite laser has shown increased efficacy in
tattoo removal in comparison to Q-switched lasers. However, bulla formation is a
well-known and expected side effect of this novel treatment and causes patient
discomfort. OBJECTIVE: To analyze the incidence of bulla formation after tattoo
treatment using the combination of the picosecond Alexandrite laser and
fractionated CO2 ablation. MATERIALS AND METHODS: This is a retrospective chart
review to determine the incidence of bulla formation after laser tattoo removal
in 95 patients who were treated with either with the picosecond Alexandrite laser
alone or in combination with fractional CO2 ablation. RESULTS: Twenty-six
patients (32%) treated with the picosecond laser alone experienced blistering,
whereas none of the patients treated with the combination of the picosecond laser
and fractionated CO2 ablation experienced blistering. The difference in incidence
of bulla formation between the 2 groups was found to be statistically significant
(p < .05). CONCLUSION: This study shows a significant decrease in bulla formation
associated with tattoo treatment when fractionated CO2 ablation is added to the
picosecond Alexandrite laser, which is consistent with observations from a
previous case series. This is important because decreasing extensive blistering
likely results in increased patient satisfaction and willingness to return for
future treatments.
PMID- 25590473
TI - Five-year outcomes of wide excision and Mohs micrographic surgery for primary
lentigo maligna in an academic practice cohort.
AB - BACKGROUND: Wide local excision with 5-mm margins is the standard of care for
lentigo maligna (LM). Mohs micrographic surgery (MMS) is used increasingly to
treat this tumor. OBJECTIVE: To study the authors' experience with these 2
approaches. MATERIALS AND METHODS: Primary LM cases treated at the authors'
institution from January 1, 1995, through December 31, 2005, were studied
retrospectively. Main outcome measures were recurrence and outcomes after
treatment for recurrence. RESULTS: In total, 423 LM lesions were treated in 407
patients: 269 (64%) with wide excision and 154 (36%) with MMS. In the MMS group
(primarily larger head and neck lesions with indistinct clinical margins),
recurrence rates were 3 of 154 (1.9%). In the wide excision group (primarily
smaller, nonhead and neck, or more distinct lesions), recurrence rates were 16 of
269 (5.9%). Each of the 16 recurrences was biopsy proven and treated surgically:
6 by standard excision and 10 by MMS. CONCLUSION: This follow-up study of LM
surgical treatments shows excellent outcomes for wide excision and MMS. Because
this is a nonrandomized retrospective study, no direct comparisons between the 2
treatments can be made. When recurrences occurred, repeat surgery, either
standard excision or MMS, was usually sufficient to provide definitive cure.
PMID- 25590472
TI - Improved upper blepharoplasty outcome using an internal intradermal suture
technique: a prospective randomized study.
AB - OBJECTIVE: To assess whether a suture technique in upper blepharoplasty may be
the cause of differences in the occurrence of suture abscess formation and focal
inflammation. MATERIALS AND METHODS: A Level I, randomized controlled trial. The
upper blepharoplasty wound was closed with a running intradermal suture. External
intradermal suturing implied that this suture was started by initially passing it
through the intact skin adjacent to the wound. In contrast, internal intradermal
suturing meant the intradermal suture was not started in the adjacent skin but
simply within the wound itself. One week and 6 weeks after surgery, the presence
of suture abscesses and focal inflammation was assessed at the entrance and exit
of the sutures. RESULTS: After 1 week, 12 abscesses (40.0%) were found at the
medial side of the externally sutured upper eyelids and 4 abscesses (13.3%) in
the internally sutured upper eyelids (p = .02). The presence of erythema and
edema after 1 week was also significantly lower in internally sutured upper
eyelids (p = .02). CONCLUSION: In this series, the method of starting the suture
(internal vs external) at the medial side of an upper blepharoplasty wound was
associated with a statistically significant reduction in the incidence of medial
wound inflammation and suture abscess formation at a 1-week follow-up.
PMID- 25590474
TI - The effects of IL-2 and Treg cells on dendritic cell homeostasis are mediated
indirectly via activation of conventional T cells.
AB - DC homeostasis is influenced by multiple factors, including the availability of
GM-CSF and Flt3L, both of which exert positive effects on DC differentiation and
survival. IL-2 and Treg cells have recently been proposed as negative regulators
of DC numbers. It remains unclear whether their effects in immunosufficient mice
are direct, or are mediated via activation of conventional T cells in response to
deficiencies of IL-2 and/or Treg cells. Using a number of in vivo models, we have
assessed the role of IL-2 and Treg-cell number on conventional splenic and LN
DCs. We have found no evidence for a direct role of IL-2 or Treg cells in
negatively regulating DC number. Our data indicate that the expansion of DCs in
the absence of either IL-2 or Treg cells is an indirect effect secondary to the
activation and proliferation of conventional T cells.
PMID- 25590475
TI - Slide over chest x-ray.
PMID- 25590476
TI - To sleep or not to sleep: that is the question.
PMID- 25590477
TI - The effect of general anesthesia versus intravenous sedation on diagnostic yield
and success in electromagnetic navigation bronchoscopy.
AB - BACKGROUND: Navigational bronchoscopy is utilized to guide biopsies of peripheral
lung nodules and place fiducial markers for treatment of limited stage lung
cancer with stereotactic body radiotherapy. The type of sedation used for this
procedure remains controversial. We performed a retrospective chart review to
evaluate the differences of diagnostic yield and overall success of the procedure
based on anesthesia type. METHODS: Electromagnetic navigational bronchoscopy was
performed using the superDimension software system. Once the targeted lesion was
within reach, multiple tissue samples were obtained. Statistical analysis was
used to correlate the yield with the type of sedation among other factors. A
successful procedure was defined if a diagnosis was made or a fiducial marker was
adequately placed. RESULTS: Navigational bronchoscopy was performed on a total of
120 targeted lesions. The overall complication rate of the procedure was 4.1%.
The diagnostic yield and success of the procedure was 74% and 87%, respectively.
Duration of the procedure was the only significant difference between the general
anesthesia and IV sedation groups (mean, 58 vs. 43 min, P=0.0005). A larger tumor
size was associated with a higher diagnostic yield (P=0.032). All other variables
in terms of effect on diagnostic yield and an unsuccessful procedure did not meet
statistical significance. CONCLUSIONS: Navigational bronchoscopy is a safe and
effective pulmonary diagnostic tool with relatively low complication rate. The
diagnostic yield and overall success of the procedure does not seem to be
affected by the type of sedation used.
PMID- 25590478
TI - Role of ultrasonography in the diagnosis and management of pneumothorax following
transbronchial lung biopsy.
AB - BACKGROUND: Pneumothorax (PTX) following flexible bronchoscopy (FB) and
transbronchial lung biopsy (TBLB) occurs in 1% to 6% of cases. Chest radiography
(CXR) is therefore routinely requested to detect PTX following TBLB. The
objective of this study was to prospectively evaluate the accuracy of ultrasound
(US) in the detection of post-TBLB PTX. METHODS: Consecutive patients undergoing
elective FB at a tertiary care hospital were included in the study. A real-time
US was used to rule out PTX immediately after FB. PTX was defined by the absence
of lung sliding and the presence of "lung point" and "stratosphere" sign. In
cases of PTX, US was repeated at 2-hour intervals, and the resolution or
progression of PTX was assessed based on dynamic shifts of the "lung points."
RESULTS: A total of 379 FB procedures and 113 TBLB were performed during the
study period. PTX occurred in 8 (2.1%) patients. US detected all cases of PTX,
whereas CXR missed 1 PTX. The sensitivity, specificity, and overall accuracy for
US were 100% as compared with sensitivity of 87.5% and accuracy of 99.6% for the
CXR group. Shift of the "lung point" below the mid-thoracic line implied the
progression of PTX and hence favored intervention (performed in 3 cases), whereas
conservative management was done in cases where "lung point" shifted above mid
thoracic line. CONCLUSIONS: This study demonstrates a good sensitivity of US in
detecting PTX following TBBL. Bedside US may become the method of choice for
diagnosing, monitoring, and managing PTX after TBLB.
PMID- 25590479
TI - Assessment of the new thin convex probe endobronchial ultrasound bronchoscope and
the dedicated aspiration needle: a preliminary study in the porcine lung.
AB - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
(EBUS-TBNA) allows for accurate minimally invasive mediastinal lymph node staging
of lung cancer. The current convex probe EBUS (CP-EBUS) has limitations in the
access to certain N1 lymph nodes (lobar and segmental) because of its size. The
aim of this study was to assess the new thin CP-EBUS (TCP-EBUS) and an aspiration
needle for sampling of N1 lymph nodes in a porcine model. METHODS: The prototype
TCP-EBUS (BF-Y0046, Olympus Medical Systems Corp.) with a thinner tip (5.9 mm)
and larger bending angle (170 degrees upward) was used. Accessibility,
operability, and TBNA capability of the TCP-EBUS were assessed and compared with
the current CP-EBUS using porcine lungs. The endoscopic visibility range and the
maximum reach were evaluated at the left upper lobe bronchus, tracheobronchus,
and right lower lobe bronchus. The prototype aspiration needle (Olympus Medical
Systems Corp.) was used for EBUS-TBNA. RESULTS: In all of the evaluated bronchi
(n=9), the TCP-EBUS had a greater reach (14.7 mm in the endoscopic visibility
range, 16.0 mm in the maximum reach) than the current CP-EBUS. The TCP-EBUS was
able to visualize 1 to 3 distal bifurcations farther compared with the current CP
EBUS. Adequate lymph node sampling from lobar and segmental lymph nodes was
possible using the aspiration needle. CONCLUSIONS: The TCP-EBUS has improved
accessibility to peripheral bronchi with excellent operability and is capable of
sampling lobar and segmental lymph nodes using the dedicated aspiration needle.
PMID- 25590480
TI - Use of endobronchial ultrasound to evaluate nonthrombotic endovascular lesions in
pulmonary arteries: a systematic review.
AB - BACKGROUND: The finding of a filling defect in a pulmonary artery (PA) sometimes
raises the possibility of cancer. Endobronchial ultrasound (EBUS)-guided
transbronchial needle aspiration (TBNA) may confirm the underlying nature of the
endovascular lesion. However, little is known about the use of this procedure for
this purpose. METHODS: We searched PubMed and abstracts of major international
conferences. RESULTS: There was a total of 12 cases: 8 female, 3 male, and 1
unknown. The median (range) age was 60 (51 to 79) years. EBUS was performed to
evaluate mass-like lesion involving the PA (n=5), persistent or progressive
filling defects in the PA despite anticoagulation (n=3), filling defect in the PA
with multiple areas of consolidation, air-fluid levels in the lung (n=1), and
hilar density (n=1). Moreover, an endovascular lesion was incidentally noted in
the PA during EBUS for evaluating lymph nodes (n=2). EBUS-TBNA was diagnostic in
9 of the 10 cases in which it was performed. The final diagnoses were: sarcoma
(n=6), lung cancer (n=2), thyroid cancer (n=1), renal cell cancer (n=1), melanoma
(n=1), and pulmonary embolism (n=1). The cancer was a recurrence in 6 of the 7
cases with a known history of cancer. CONCLUSIONS: EBUS should be considered as a
possible method for evaluating endovascular lesions when PA sarcoma or tumor
macroembolism is suspected.
PMID- 25590481
TI - Confocal laser endomicroscopy for diagnosis and monitoring of pulmonary alveolar
proteinosis.
AB - BACKGROUND: The diagnosis of pulmonary alveolar proteinosis (PAP) is based on
computed tomography, histology, and antibodies to granulocyte-macrophage colony
stimulating factor. The role of a novel technique for imaging cells and elastin
during endoscopy, probe-based confocal laser endomicroscopy (pCLE), has not yet
been investigated in PAP patients. The aim of the present study was to estimate
the value of pCLE in the PAP diagnosis and treatment in comparison with the
findings of high-resolution computed tomography (HRCT) before and after whole
lung lavage. METHODS: In vivo pCLE was performed during bronchoscopy in 6 male
patients with PAP before and after whole-lung lavage. In certain lung segments,
pCLE was followed by HRCT. RESULTS: During the in vivo pCLE, we found
characteristic signs of PAP: a fluorescent floating amorphous substance in the
alveoli lumen sticking to conglomerates along with alveolar macrophages. These
features were present to a lesser extent after a whole-lung lavage. pCLE revealed
specific PAP features not only in segments with crazy-paving and ground-glass
opacity, but also in segments without HRCT findings. CONCLUSIONS: The alveolar
imaging in PAP patients is able to reveal characteristic changes, both in the
presence and in the absence of HRCT findings. Therefore, pCLE may be a helpful
tool for the diagnosis and whole-lung lavage therapy. Our data prove that
accumulation of lipoproteinaceous substances within the alveoli at PAP is a
diffuse but not a patchy process.
PMID- 25590482
TI - Critical airway obstruction: challenges in airway management and ventilation
during therapeutic bronchoscopy.
AB - BACKGROUND: Endobronchial interventions are used to alleviate symptoms of airway
stenosis. The ventilatory management may be challenging during these procedures,
and may influence the choice of airway device. We report our experiences from 902
procedures. METHODS: Patients undergoing interventional bronchoscopy procedures
were consecutively registered from 1999 to 2012. Critical airway obstruction
(CAO) was defined as stridor, tracheal diameter <5 mm, stenosis of both the main
bronchi, or clots/tumor fragments occluding the trachea or both main bronchi.
Choice of airway, ventilation strategy, and survival are reported. Results are
presented as median (interquartile range), and P<=0.05 was considered
significant. RESULTS: A total of 561 patients underwent 902 interventional
bronchoscopy procedures (mechanical debulking, laser resection, balloon
dilatation, and stent placement). The procedures were performed using flexible
bronchoscope through an endotracheal tube (68.2%) or laryngeal mask airway
(10.4%), or by rigid bronchoscopy (9.3%). All patients were primarily ventilated
by volume-controlled ventilation. CAO was classified in 60 procedures, with more
frequent use of laryngeal mask airway (21.7%), and change of airway device in
20/60 procedures. The survival for patients with malignant disease with or
without CAO was 100 and 182 days, respectively, with 90 days survival probability
of 0.65 and 0.51 (P=0.14). CONCLUSIONS: Bronchoscopic treatment in patients with
CAO may require a change of ventilatory and airway strategy during the procedure.
Despite various challenges in the management of patients with CAO, the short-term
survival in these patients is comparable to that in patients without CAO.
PMID- 25590483
TI - Effectiveness of thoracoscopic talc pleurodesis in the management of complicated
spontaneous pneumothorax.
AB - BACKGROUND: Complicated (recurring or persistent) spontaneous pneumothorax
requires intervention either by surgical or nonsurgical pleurodesis or other
interventions. As for high-risk patients, aggressive interventions may be
associated with morbidity, the safety and effectiveness of less aggressive
alternative interventions like thoracoscopic talc pleurodesis (TTP) should be
evaluated. METHODS: Data were extracted on patients who had undergone TTP for
complicated spontaneous pneumothorax at Interventional Clinic, University
Hospital, Brussels, Belgium. The complications, length of hospital stay, and
success rate over a 24-month period were studied. RESULTS: A total of 41 TTP
procedures were performed for 25 (61%) cases of primary spontaneous pneumothorax
and for 16 (39%) cases of secondary spontaneous pneumothorax. Twenty-four cases
were first episodes, whereas it was a recurrence in 17. Of 4 patients with
blebs/bullae, 2 had recurrence after TTP.No patient had acute respiratory
distress syndrome or any other serious complication after TTP. Recurrence rates
after TTP in primary and secondary spontaneous pneumothorax were 9.5% and 25% at
24 months, respectively. The mean length of hospital stay after TTP was 3+/-3.2
days. CONCLUSIONS: TTP is a safe and effective intervention in complicated
spontaneous pneumothorax.
PMID- 25590484
TI - Tracheal fibroepithelial polyp.
PMID- 25590485
TI - Thoracic metastasis from renal cell carcinoma: bronchoscopic and EBUS images.
PMID- 25590486
TI - Inflammatory myofibroblastic tumor of the trachea in the pediatric age group:
case report and systematic review of the literature.
AB - Inflammatory myofibroblastic tumors are uncommon tumors, which present as
solitary masses in the pulmonary parenchyma. Tracheal involvement by these tumors
is extremely rare and can be misdiagnosed as asthma. The closest histologic
differential diagnoses are IgG4-related sclerosing pseudotumors, which are
differentiated by IgG4 positivity. Fifty percent of inflammatory myofibroblastic
tumors are positive for anaplastic lymphoma kinase gene rearrangements. The
treatment modality of choice is surgical resection with therapeutic bronchoscopy
reserved for patients presenting with acute airway obstruction or in those
unwilling for surgery. New and upcoming treatments include anaplastic lymphoma
kinase inhibitors like crizotinib.
PMID- 25590487
TI - Endobronchial glomus tumor.
AB - We report a case of a 52-year-old patient who had undergone a bladder resection
and an ileal conduit for a transitional cell carcinoma. He then presented with a
short history of hemoptysis 3 months later. Rigid bronchoscopy was performed
revealing an endobronchial lesion, which was removed via laser and debulking
method without complications. Histopathologic examination confirmed it to be a
benign endobronchial glomus tumor. On the basis of our literature search, this is
the 34th reported case of glomus tumor arising from the respiratory tract,
seventh reported case of an endobronchial glomus tumor treated bronchoscopically,
and the first possibly coincidental finding in relation to a patient with primary
transitional bladder cell carcinoma.
PMID- 25590488
TI - Tension bulla: a cause of reversible pulmonary hypertension.
AB - A tension pneumothorax represents a medical emergency warranting urgent diagnosis
and treatment. A rapidly expanding bulla may resemble the same clinical
presentation but requires an entirely different treatment. A 53-year-old woman
presented with increasing shortness of breath and her physical examination and
chest x-ray were interpreted as showing a tension pneumothorax. A chest tube was
placed which did not resolve the process. Placement of a second chest tube was
likewise unsuccessful. A chest CT was then performed and was interpreted as
showing an unresolved tension pneumothorax, despite seemingly adequate placement
of the 2 chest tubes. Further review of the CT showed the border of a giant bulla
and a tentative diagnosis was made of a rapidly expanding bulla with tension
physiology. Echocardiogram revealed significant pulmonary hypertension. The bulla
was surgically excised, the patient had marked improvement in her clinical
symptoms and signs, and echocardiographic follow-up showed complete resolution of
the pulmonary hypertension.
PMID- 25590489
TI - Incidental tracheal diverticulum discovered 30 years after tracheo-esophageal
fistula repair.
AB - Tracheo-esophageal fistula is a well-described congenital abnormality treated
surgically upon diagnosis. Although respiratory-related and reflux-related
complications are frequent, recurrent fistula and diverticulum can occur. This
case report describes the rare occurrence of a gross type B fistula repaired at
birth, which was then asymptomatic for nearly 30 years until presentation with
chest pain. Upon workup, the patient was found to have an isolated tracheal
diverticulum without recurrent fistula. We highlight the need for a focused
workup despite the length of time since fistula repair and the varied treatment
modalities described in the literature.
PMID- 25590490
TI - Cryotechnology in diagnosing and treating lung diseases.
AB - Cryotechnology has been used in treating lung cancer for many years, now it is
emerging to have a new indication in diagnosing lung diseases. Cryoprobe
transbronchial lung biopsy has been introduced into clinical practice as a new
technique, providing a larger biopsy specimen, potentially improving the
diagnostic yield of transbronchial biopsies in parenchymal lung diseases.
Although recent small pilot studies suggest that cryotransbronchial lung biopsies
are comparable to conventional transbronchial biopsies in terms of diagnostic
yield and safety profile in lung transplant patients, cryoprobe transbronchial
lung biopsy is still being evaluated and its role in clinical practice is not
well defined. Cryotherapy has been proven as a safe and effective method to
debulk endobronchial lesions, providing palliation for advanced central
obstructive tumors. Its use and efficacy is also studied in direct cryosurgery
and percutaneous application in lung cancer. Cryoprobes can also be used to
extract foreign bodies from the airways by causing cryoadhesion. We aim to
summarize the therapeutic and diagnostic application of cryotechnology in
pulmonary diseases.
PMID- 25590491
TI - Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation
plus bevacizumab: management with a Y-silicone stent inside a metallic covered
stent.
AB - Tracheal or bronchial-mediastinal fistulas are a rare entity associated to high
mortality. We report a case of a 58-year-old man with an unresectable non-small
cell carcinoma of the lung, treated with chemoradiation followed by bevacizumab.
Approximately, 6 weeks after starting bevacizumab he developed a severe cough
with copious secretions He could not lie supine due to the feeling of drowning.
Investigations revealed a large tracheo-mediastinal-parenchymal-pleural fistula.
Palliative management was offered with interventional bronchoscopic techniques.
He was found to have a large central airway defect that obliterated almost 40% of
the trachea. Under general anesthesia and positive pressure ventilation, a unique
approach was used to rebuild an eroded tracheal and right main stem bronchial
wall. A self-expanding metallic stent (SEMS) was placed to provide a scaffold of
support, whereas a Dumon Y-stent was placed inside the SEMS. This combination
allowed for a patent, stable airway; recreating the normal anatomy in a minimally
invasive manner walling off the fistula. The patient was discharged 2 days after
the bronchoscopic intervention, with significant palliation of his
symptomatology. Eighteen months later, the upper lobe cavity persists with a
stable airway and stents perfectly positioned with clinically insignificant
evidence of stent related granulation in the upper trachea.
PMID- 25590492
TI - Tracheal leiomyoma resected with endobronchial electrocautery snare.
AB - Tracheobronchial leiomyoma is a rare benign tumor, which comprises about 2% of
benign tumors of the lower respiratory tract. Bronchoscopic intervention is a
minimally invasive treatment, but incomplete resection or recurrence has been
reported. We report a case of a 76-year-old woman with a tracheal tumor of 14 mm
in diameter incidentally detected on chest computed tomography. Bronchoscopic
examination revealed a smooth polypoid tumor which pedunculated from the left
side of the cartilaginous tracheal wall. An endobronchial electrocautery snare
with flexible bronchoscope was successfully used under general anesthesia and
with intubation. The resected specimen was pathologically consistent with
leiomyoma. Bronchoscopic intervention can yield successful treatment of
pedunculated tracheobronchial leiomyomas, although surgical resection should also
be considered in cases of broad-based or iceberg-type leiomyomas because of the
risk of incomplete resection or recurrence.
PMID- 25590493
TI - The value of endobronchial ultrasound transbronchial needle aspiration in normal
positron emission tomography in lung cancer.
PMID- 25590494
TI - Difficult Removal of Montgomery T-tube.
PMID- 25590495
TI - Anti-tumor activity of miR-17 in melanoma.
PMID- 25590496
TI - Nonnatural deaths among users of illicit drugs: pathological findings and illicit
drug abuse stigmata.
AB - The aim of the study was to provide information on illicit drug abuse stigmata
and general pathological findings among an adult narcotic drug-using population
aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal
autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin,
amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP
(phencyclidine), and high levels of GHB (gamma-hydroxybutyric acid) in addition
to methadone and buprenorphine were investigated. Reported findings of hepatitis,
portal lymphadenopathy, recent injection marks, drug user's equipment, and
numbers of significant pathological conditions were registered and analyzed
according to cases positive for opiates, opioids (OPs), and central nervous
system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305
were positive for one or more opiate or OP. Cases positive for OPs had
significantly more findings of noninfectious pathological conditions. Hepatitis,
portal lymphadenopathy, recent injections marks findings of drug user's equipment
were all findings found more frequently among the opiate OP-positive individuals.
Portal lymphadenopathy was significantly more often found in cases with hepatitis
than in cases with other or no infection. In the population positive for CNS
stimulants, hepatitis recent injection marks were more frequent findings than in
the CNS stimulant-negative group, irrespective of whether they were opiate OP
positive or negative.
PMID- 25590498
TI - Reply to Letter: "Poorer Survival for Stage IIa Patients After Minimally Invasive
Esophagectomy".
PMID- 25590497
TI - Ninety-day Postoperative Mortality Is a Legitimate Measure of
Hepatopancreatobiliary Surgical Quality.
AB - OBJECTIVE: To investigate the legitimacy of 90-day mortality as a measure of
hepatopancreatobiliary quality. BACKGROUND: The 90-day mortality rate has been
increasingly but not universally reported after hepatopancreatobiliary surgery.
The legitimacy of this definition as a measure of surgical quality has not been
evaluated. METHODS: We retrospectively reviewed the causes of all deaths that
occurred within 365 postoperative days in patients undergoing hepatectomy (n =
2811) and/or pancreatectomy (n = 1092) from January 1997 to December 2012. The
rates of surgery-related, disease-related, and overall mortality within 30 days,
within 30 days or during the index hospitalization, within 90 days, and within
180 days after surgery were calculated. RESULTS: Seventy-nine (3%) surgery
related deaths and 92 (3%) disease-related deaths occurred within 365 days after
hepatectomy. Twenty (2%) surgery-related deaths and 112 (10%) disease-related
deaths occurred within 365 days after pancreatectomy. The overall mortality rates
at 99 and 118 days optimally reflected surgery-related mortality after
hepatobiliary and pancreatic operations, respectively. The 90-day overall
mortality rate was a less sensitive but equivalently specific measure of surgery
related death. CONCLUSIONS AND RELEVANCE: The 99- and 118-day definitions of
postoperative mortality optimally reflected surgery-related mortality after
hepatobiliary and pancreatic operations, respectively. However, among commonly
reported metrics, the 90-day overall mortality rate represents a legitimate
measure of surgical quality.
PMID- 25590499
TI - Trans-venous occlusion of incompetent pelvic veins for chronic pelvic pain in
women: a systematic review.
AB - Chronic pelvic pain (CPP) affects 24% of women worldwide; the cause cannot be
identified in 40% despite invasive investigations. Dilated, refluxing pelvic
veins may be a cause of CPP and treatment by trans-venous occlusion is
increasingly performed when gynecological causes are excluded, but is it
effective? A systematic review of the literature published between 1966 and July
2014 was conducted. Two authors independently reviewed potential studies
according to a set of eligibility criteria, with a third assessor available as an
arbiter. Thirteen studies including 866 women undergoing trans-venous occlusion
of pelvic veins for CPP were identified (Level of evidence: one study grade 2b,
12 studies grade four). Statistical significant improvements in pelvic pain were
reported in nine of the 13 studies. Technical success was reported in 865 of 866
(99.8%) with low complication rates: coil migration in 14 women (1.6%), abdominal
pain in ten women (1.2%) and vein perforation in five (0.6%). In a study on
varicose veins of the legs, recurrence was seen in 13% of 179 women 5-years
following coil embolization. Subjective improvements in pain were seen in all 13
studies after treatment by trans-venous occlusion. All 13 studies were of poor
methodological quality. Complication rates were low and no fatalities occurred.
Well-designed studies are essential to determine whether pelvic vein incompetence
(PVI) is associated with CPP, and to explore whether trans-venous occlusion of
PVI improves quality of life for these women.
PMID- 25590500
TI - Achieving an early pregnancy following allogeneic uterine transplantation in a
rabbit model.
AB - OBJECTIVE: Uterine transplantation (UTx) has been proposed as a treatment option
for women diagnosed with absolute uterine factor infertility (AUFI). The goal of
UTx remains achieving pregnancy and live birth of a healthy neonate following
allogeneic UTx. Our aim was to assess whether fertility was possible following
allogeneic uterine transplantation (UTx), when the recipient had demonstrated
long-term survival and had been administered immunosuppression. STUDY DESIGN:
Nine allogeneic UTx in New Zealand White rabbits were performed using a pre
determined protocol. Tacrolimus was the immunosuppressant selected. Embryos were
transferred into both cornua of the sole living recipient via a mini-midline
laparotomy. The pregnancy was monitored with regular reproductive profiles and
serial trans-abdominal ultrasound to measure conceptus growth (gestation sac and
crown rump length (CRL)). RESULTS: In the sole surviving doe a gestation sac was
visualised on ultrasound from Day 9 (D9) after embryo transfer. Gestation sac
diameter and CRL increased from D9 to D16 but by D18 the gestation sac had
reduced in size. The fetus was no longer visible, suggesting fetal resorption had
occurred. Subsequent scans on D22 and D25 did not demonstrate a gestation sac.
Scheduled necropsy on D27 and histopathology confirmed evidence of a gravid
uterus and presence of a gestational sac. A single episode of acute rejection
occurred on D13. CONCLUSION: Pregnancy was achieved after rabbit allogeneic UTx
but serial ultrasound suggested that fetal demise occurred prior to scheduled
necropsy. The study represents only the third example of conception and pregnancy
following an animal allogeneic UTx.
PMID- 25590501
TI - Effect of maternal death reviews and training on maternal mortality among
cesarean delivery: post-hoc analysis of a cluster-randomized controlled trial.
AB - OBJECTIVES: To explore the differential effect of a multifaceted intervention on
hospital-based maternal mortality between patients with cesarean and vaginal
delivery in low-resource settings. STUDY DESIGN: We reanalyzed the data from a
major cluster-randomized controlled trial, QUARITE (Quality of care, Risk
management and technology in obstetrics). These subgroup analyses were not pre
specified and were treated as exploratory. The intervention consisted of an
initial interactive workshop and quarterly educational clinically oriented and
evidence-based outreach visits focused on maternal death reviews (MDR) and best
practices implementation. The trial originally recruited 191,167 patients who
delivered in each of the 46 participating hospitals in Mali and Senegal, between
2007 and 2011. The primary endpoint was hospital-based maternal mortality.
Subgroup-specific Odds Ratios (ORs) of maternal mortality were computed and
tested for differential intervention effect using generalized linear mixed model
between two subgroups (cesarean: 40,975; and vaginal delivery: 150,192). RESULTS:
The test for homogeneity of intervention effects on hospital-based maternal
mortality among the two delivery mode subgroups was statistically significant (p
value: 0.0201). Compared to the control, the adjusted OR of maternal mortality
was 0.71 (95% CI: 0.58-0.82, p=0.0034) among women with cesarean delivery. The
intervention had no significant effect among women with vaginal delivery
(adjusted OR 0.87, 95% CI 0.69-1.11, p=0.6213). This differential effect was
particularly marked for district hospitals. CONCLUSION: Maternal deaths reviews
and on-site training on emergency obstetric care may be more effective in
reducing maternal mortality among high-risk women who need a cesarean section
than among low-risk women with vaginal delivery.
PMID- 25590502
TI - Distribution of sagittal occlusal relationships in different stages of dentition.
AB - The aim of this study was to assess the distribution of sagittal occlusal
relationships in different dentition periods in a Turkish sample group. In total,
1,110 patients (561 females, 549 males) aged 4.6-23 years were randomly chosen
after intraoral clinical examination. The subjects were classified according to
their sagittal occlusal relationships and four dentition stages -deciduous, early
mixed, late mixed, and permanent dentition. The statistical significance of the
occurrence of malocclusion types in dentition stages was evaluated by Chi-square
and Fischer's exact tests. Class I malocclusion was observed at the highest rate
in all dentition stages. Class III malocclusion was observed at the highest rate
in the permanent dentition, whereas Class II malocclusion was observed at the
highest rate in the late mixed dentition. The rates of Class I, II, and III
malocclusions were similar in males and females. Our study reveals that the
prevalence of malocclusion and need for orthodontic treatment has increased in
the population towards the permanent dentition.
PMID- 25590503
TI - Dental fluorosis and its influence on children's life.
AB - This study verified the prevalence of dental fluorosis in 12-year-old children
and its association with different fluoride levels in the public water supply,
and evaluated the level of perception of dental fluorosis by the studied
children. To assess fluorosis prevalence, clinical examinations were performed
and a structured instrument was used to evaluate the self-perception of
fluorosis. The water supply source in the children's area of residence since
birth was used as the study criterion. In total, 496 children were included in
the study. Fluorosis was diagnosed in 292 (58.9%) children; from these, 220
(44.4%) children were diagnosed with very mild fluorosis, 59 (11.9%) with mild
fluorosis, 12 (2.4%) with moderate fluorosis, and 1 (0.2%) child with severe
fluorosis. A significant association (p = 0.0004) was observed between the
presence of fluorosis and areas with excessive fluoride in the water supply.
Among the 292 children that showed fluorosis, 40% perceived the presence of spots
in their teeth. The prevalence of fluorosis was slightly high, and the mildest
levels were the most frequently observed. Although most of the children showed
fluorosis to various degrees, the majority did not perceive these spots,
suggesting that this alteration did not affect their quality of life.
PMID- 25590504
TI - Dental age estimation in a Brazilian adult population using Cameriere's method.
AB - The objectives of this study were to develop a specific formula to estimate age
in a Brazilian adult population and to compare the original formula from
Cameriere to this Brazilian formula. The sample comprised 1,772 periapical
radiographs from 443 subjects (219 men, 224 women) that were organized into 12
groups according to sex (men or women) and age (20-29, 30-39, 40-49, 50-59, 60
69, and 70 years and older). The films were analyzed using the criteria described
by Cameriere et al. (2004) and Adobe Photoshop(r). We obtained a mean error of
8.56 (SD = 5.80) years for tooth 13, 7.99 (SD = 5.78) years for tooth 23, 8.38
(SD = 6.26) years for tooth 33, and 8.20 (SD = 6.54) years for tooth 43. When
teeth were combined in the analysis, we observed lower mean errors. The Brazilian
formula developed from this sample group was more accurate than Cameriere's
formula. However, other factors must be considered to improve age estimates in
adults.
PMID- 25590505
TI - Chronicity factors of temporomandibular disorders: a critical review of the
literature.
AB - Facial pain often persists long after any identifiable organic pathology has
healed. Moreover, in a subgroup of patients with temporomandibular disorder
(TMD), no treatment is effective. Knowledge of factors associated with persistent
pain in TMD could help identify personalized treatment approaches. Therefore, we
conducted a critical review of the literature for the period from January 2000 to
December 2013 to identify factors related to TMD development and persistence. The
literature findings showed that chronic TMD is marked by psychological distress
(somatization and depression, affective distress, fear of pain, fear of movement,
and catastrophizing) and characteristics of pain amplification (hyperalgesia and
allodynia). Furthermore, these factors seem to interact in TMD development. In
addition, our review demonstrates that upregulation of the serotonergic pathway,
sleep problems, and gene polymorphisms influence the chronicity of TMD. We
conclude that psychological distress and pain amplification contribute to chronic
TMD development, and that interactions among these factors complicate pain
management. These findings emphasize the importance of multidisciplinary
assistance in TMD treatment.
PMID- 25590506
TI - CBCT-based evaluation of integrity of cortical sinus close to periapical lesions.
AB - The purpose of the present study was to test the applicability of cone beam
computed tomography (CBCT) to evaluate the integrity of the cortical sinus close
to periapical lesions. Two observers analyzed samples of 64 alveoli of first
molar roots in macerated swine maxillas prepared with perchloric acid to simulate
periapical lesions. The specimens were evaluated using CBCT (55-mm high and 100
mm diameter cylinder at 0.2-mm voxel resolution) for the presence of oroantral
communication (OAC) caused by the simulated lesions. Sensitivity, specificity,
and accuracy were calculated. Fair values were obtained for accuracy (66%-78%)
and good values for specificity (70%-98%), whereas the values for sensibility
showed relevant variation (41%-78%). For this reason, the interobserver agreement
score was weak. CBCT proved capable of evaluating the integrity of the cortical
sinus (absence of oroantral communication) when it lies close to an apical
periodontitis lesion. However, the low interobserver agreement reflects the
difficulty in performing diagnoses when OAC is adjacent to a periapical lesion,
using the acquisition protocol adopted in this research. This could be attributed
to the high level of image noise.
PMID- 25590507
TI - Genotoxic potential of 10% and 16% carbamide peroxide in dental bleaching.
AB - Dental bleaching has become one of the most frequently requested esthetic
treatments in dental offices. Despite the high clinical success observed with
this procedure, some adverse effects have been reported, including a potential
for developing premalignant lesions, root resorption and tooth sensitivity,
especially when misused. The aim of this study was to evaluate the genotoxic
response using a micronucleus (MN) assay, after the application of two
concentrations of carbamide peroxide. Thirty-seven patients were divided into two
groups and randomly received either a 10% carbamide peroxide (CP) (19) or a 16%
carbamide peroxide (18) concentration for 21 days in individual dental trays.
Gingival margin cells were collected immediately before the first use (baseline),
and then 15 and 45 days after baseline. The cells were placed on a histological
slide, stained by the Feulgen technique, and evaluated by an experienced blinded
examiner. One thousand cells per slide were counted, and the MN rate was
determined. The two groups were analyzed by the Wilcoxon rank-sum test and the
Kruskal-Wallis equality-of-populations rank test. A slight increase in MN was
observed for both groups, in comparison with the baseline, at 15 days. However,
no difference was observed between the two groups (10% and 16%), at either 15 or
45 days (p = 0.90). When bleaching is not prolonged or not performed very
frequently, bleaching agents containing carbamide peroxide alone will not cause
mutagenic stress on gingival epithelial cells.
PMID- 25590508
TI - Comparison surface characteristics and chemical composition of conventional
metallic and nickel-free brackets.
AB - This study aims at comparing conventional and nickel-free metal bracket surface
characteristics with elemental composition by scanning electron microscopy (SEM),
using energy dispersive spectroscopy (EDS). The sample consisted of 40 lower
incisor brackets divided into four groups: ABZ = conventional brackets, Kirium
Abzil 3M(r) (n = 10); RL = conventional brackets, Roth Light Morelli(r) (n = 10);
NF = nickel-free brackets, Nickel-Free Morelli(r) (n = 10); and RM = nickel-free
brackets, Roth Max Morelli(r) (n = 10). Qualitative evaluation of the bracket
surface was performed using SEM, whereby surface features were described and
compared. The elemental composition was analyzed by EDS. According to surface
analysis, groups ABZ and RL showed a homogeneous surface, with better finishing,
whereas the surfaces in groups NF and RM were rougher. The chemical components
with the highest percentage were Fe, Cr and C. Groups NF and MR showed no nickel
in their composition. In conclusion, the bracket surface of the ABZ and RL groups
was more homogeneous, with grooves and pores, whereas the surfaces in groups NF
and RM showed numerous flaws, cracks, pores and grooves. The chemical composition
analysis confirmed that the nickel-free brackets had no Ni in their composition,
as confirmed by the manufacturer's specifications, and were therefore safe to use
in patients with a medical history of allergy to this metal.
PMID- 25590509
TI - Presumptive intramuscular hemangioma of the masseter muscle.
AB - BACKGROUND: Hemangioma is a benign vascular proliferation. Intramuscular
hemangiomas are rare, accounting for less than 1% of all hemangiomas, and occur
normally in the trunk and extremities. Approximately 10-20% of intramuscular
hemangiomas are found in the head and neck region, most often in the masseter
muscles. The typical clinical characteristic is a painful soft tissue mass
without cutaneous changes. Currently, MRI is the standard imaging technique for
diagnosing soft-tissue hemangioma. The optimal management is the surgical
resection. CASE REPORT: We report a case of 34-year-old male patient consulted
for a swelling of 1 year evolution, around the parotid region. On physical
examination, a soft, well-contoured lesion of about 2 cm on its long axis was
found. MRI showed a space-occupying lesion in the left masseter muscle, with
intermediate signal intensity on T1-weighted images and hyperignal intensity on
T2-weighted images, containing nodular hypointense foci corresponding to
calcification. The presumptive diagnosis of an intramasseteric hemangioma with
phlebolith was made based on these findings. The patient was informed about her
condition, and treatment options were discussed; however, the patient elected to
forgo treatment at that time. CONCLUSIONS: The possibility of an IMH should be
included in the differential diagnosis of any intra-masseteric lesion. The
appropriate radiologic examinations especially MRI can enhance accurate
preoperative diagnosis; the treatment of choice should be individualized in view
of the clinical status of the patient.
PMID- 25590510
TI - Changes in physicochemical and transport properties of a reverse osmosis membrane
exposed to chloraminated seawater.
AB - This study contributed to improving our understanding of how disinfectants,
applied to control biofouling of reverse osmosis (RO) membranes, result in
membrane performance degradation. We investigated changes in physicochemical
properties and permeation performance of a RO membrane with fully aromatic
polyamide (PA) active layer. Membrane samples were exposed to varying
concentrations of monochloramine, bromide, and iodide in both synthetic and
natural seawater. Elemental analysis of the membrane active layer by Rutherford
backscattering spectrometry (RBS) revealed the incorporation of bromine and
iodine into the polyamide. The kinetics of polyamide bromination were first order
with respect to the concentration of the secondary oxidizing agent Br2 for the
conditions investigated. Halogenated membranes were characterized after treatment
with a reducing agent and heavy ion probes to reveal the occurrence of
irreversible ring halogenation and an increase in carboxylic groups, the latter
produced as a result of amide bond cleavage. Finally, permeation experiments
revealed increases in both water permeability and salt passage as a result of
oxidative damage.
PMID- 25590511
TI - Completeness and accuracy of the wisconsin immunization registry: an evaluation
coinciding with the beginning of meaningful use.
AB - CONTEXT: Vaccination coverage rates can be improved through the application of
complete and accurate immunization information systems (IISs). OBJECTIVE:
Evaluate the completeness and accuracy of Wisconsin's IIS, the Wisconsin
Immunization Registry (WIR). DESIGN: Cross-sectional evaluation, comparing
vaccination medical records (MRs) from provider clinics with WIR records.
PARTICIPANTS: Medical records of patients born during 2009 were randomly selected
from 251 Wisconsin clinics associated with the Vaccines for Children Program.
MAIN OUTCOME MEASURES: Completeness: percentage of patients with client records
in the WIR, percentage of patients up-to-date (%UTD) with the 4:3:1:3:3:1:4
vaccination series, and percentage of patients' MR vaccinations matched by
administration date (+/-10 days) and type to vaccinations documented in the WIR.
Accuracy: percentages of matched vaccinations with the same administration date,
same trade name (TN), and same lot number. RESULTS: Of the 1863 selected patient
MRs, 98% (n = 1833) had WIR client records and 97% of their 30 899 vaccinations
were documented in the WIR. The %UTD was 49.3% using the MR only, 76.5% using the
WIR only, and 75.2% as estimated by the National Immunization Survey. Among
matched vaccinations, 99% had the same administration date, 96% had the same TN,
and 95% had the same lot number. Compared with patients from clinics that entered
data into the WIR using data exchange from electronic health records, patients
from clinics that entered data using the Web-based user interface were less
likely to have client records in the WIR (odds ratio: 0.3; 95% confidence
interval: 0.1-0.9) and less likely to have accurate TNs (odds ratio: 0.3; 95%
confidence interval: 0.1-0.5). CONCLUSIONS: The WIR was complete and accurate
among this sample of children born during 2009 and provided a vaccination
coverage assessment similar to the National Immunization Survey. Our results
provide support for the expectation that meaningful use and other initiatives
that increase data exchange from electronic health records to IISs will improve
IIS data quality.
PMID- 25590512
TI - Humic acid and glucan: protection against liver injury induced by carbon
tetrachloride.
AB - Humic acids (HAs) have a rather pleiotropic presence, however, their biological
effects are still unclear. In this study, we focused on possible hepatoprotective
effects of either HA alone or in combination with beta-glucan. Using a model of
experimental hepatotoxicity caused by carbon tetrachloride (CCL4), we showed that
both HA and the glucan-HA combination offered significant protection against
hepatotoxicity, with the combination offering superior effects. Our biochemical
observations were confirmed by histological evaluation. Based on the experimental
data, we conclude that whereas HA has significant effects, the synergy with
glucan offers superior effects.
PMID- 25590513
TI - Generation of Reactive Oxygen Species Mediated by 1-Hydroxyphenazine, a
Virulence Factor of Pseudomonas aeruginosa.
AB - 1-Hydroxyphenazine (1-HP) is a virulence factor produced by Pseudomonas
aeruginosa. In this study,supercoiled plasmid DNA was employed as an analytical
tool for the detection of ROS generation mediated by 1-HP. These assays provided
evidence that 1-HP, in conjunction with NADPH alone or NADPH and the enzyme
NADPH:cytochrome P450 reductase, mediated the production of superoxide radical
under physiological conditions. Experiments with murine macrophage RAW264.7 cells
and profluorescent ROS probes dichlorodihydrofluorescein or dihydroethidine
provided preliminary evidence that 1-HP mediates the generation of intracellular
oxidants. Generation of reactive oxygen species may contribute to the virulence
properties of 1-HP in P. aeruginosa infections.
PMID- 25590514
TI - State laws, syringe exchange, and HIV among persons who inject drugs in the
United States: History and effectiveness.
AB - In 1981, when acquired immune deficiency syndrome (AIDS) was first observed among
persons who inject drugs, almost all US states had laws criminalizing the
possession and distribution of needles and syringes for injecting illicit drugs.
We reviewed changes to these laws to permit 'syringe exchanges' and the provision
of public funding for such programs. Most of the changes in law occurred during
the 1990s, 5-10 years later than in many other countries. Public funding of
syringe exchanges is associated with lower rates of human immunodeficiency virus
(HIV) infection, greater numbers of syringes distributed (a possible causal
mechanism), and greater numbers of health and social services provided.
Experience in the United states may prove useful in other countries: state,
provincial, and local governments may need to move ahead of central governments
in addressing HIV infection among persons who inject drugs.
PMID- 25590516
TI - Targeting cell death pathways with small molecules: playing with life and death
at the cellular level to treat diseases.
PMID- 25590515
TI - Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as
potential therapeutic agents for the treatment of Huntington's disease.
AB - We report on the development of a series of pyrimidine carboxylic acids that are
potent and selective inhibitors of kynurenine monooxygenase and competitive for
kynurenine. We describe the SAR for this novel series and report on their
inhibition of KMO activity in biochemical and cellular assays and their
selectivity against other kynurenine pathway enzymes. We describe the
optimization process that led to the identification of a program lead compound
with a suitable ADME/PK profile for therapeutic development. We demonstrate that
systemic inhibition of KMO in vivo with this lead compound provides
pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in
the periphery and in the central nervous system.
PMID- 25590517
TI - Laryngeal electromyography-guided hyaluronic acid vocal fold injection for
unilateral vocal fold paralysis: a prospective long-term follow-up outcome
report.
AB - IMPORTANCE: Unilateral vocal fold paralysis (UVFP) is a common voice disorder
that may cause glottal closure insufficiency with hoarseness of voice. Laryngeal
electromyography (LEMG)-guided hyaluronic acid vocal fold (VF) injection has been
proposed as a treatment option to improve glottal closure with a satisfactory
short-term effect. To our knowledge, this study reports the first long-term
follow-up result of this treatment modality. OBJECTIVE: To present the long-term
treatment results of LEMG-guided hyaluronic acid VF injection for UVFP. DESIGN,
SETTING, AND PARTICIPANTS: Prospective study of the treatment results of 74
patients who received LEMG-guided hyaluronic acid VF injection for UVFP at a
tertiary referral medical center from March 2010 to February 2013. INTERVENTIONS:
In the office-based procedure, 1.0 mL of hyaluronic acid was injected via a 26
gauge monopolar injectable needle electrode into paralyzed thyroarytenoid muscles
by LEMG guidance. MAIN OUTCOMES AND MEASURES: Various glottal closure evaluations
such as normalized glottal gap area, maximal phonation time, phonation quotient,
mean airflow rate, perceptual GRBAS (grade, roughness, breathiness, asthenia,
strain) scale, and Voice Handicap Index were compared before and after injection
using the nonparametric Wilcoxon signed rank test within 1 month, at 6 months,
and at the last follow-up examination. RESULTS: Sixty patients had been followed
up for at least 6 months. Forty-four patients received only 1 injection, and 16
patients received repeated injections (2 injections for 13 patients and 3 for 3
patients). All the glottal closure parameters improved significantly (P < .001)
within 1 month, at 6 months, and at the last follow-up examination, with a mean
(SD) of 17.4 (8.9) months. At the last follow-up examination, the mean (SD)
normalized glottal gap area was significantly reduced from 7.9 (5.7) to 0.6
(1.6). Mean (SD) maximal phonation time was significantly prolonged from 4.6
(3.8) seconds to 12.1 (7.4) seconds. Mean (SD) phonation quotient was
significantly reduced from 647 (508) mL/s to 277 (212) mL/s. Mean (SD) airflow
rate was significantly reduced from 445 (338) mL/s to 175 (145) mL/s. When all
the GRBAS scale parameters improved, the mean (SD) Voice Handicap Index score was
significantly reduced from 76 (22) to 38 (30) (all P < .001). CONCLUSIONS AND
RELEVANCE: Of the 74 patients in this study, 44 (60%) who received a single
injection and 16 (22%) who received repeated injections did not require another
treatment after long-term follow-up. Laryngeal electromyography-guided hyaluronic
acid VF injection is an option for treating UVFP with satisfactory results.
PMID- 25590518
TI - Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis,
Management, and Controversies.
AB - In this article, we aimed to review the literature on the clinics and management
of nonfunctional pancreatic neuroendocrine tumors (NPNET). Pancreatic
neuroendocrine tumors (PNET) are rare tumors with a <1/100,000 incidence and
constitute approximately 2 to 10% of all pancreatic tumors. Nonfunctional PNETs
are difficult to detect at early stages since they have no symptoms. Except those
detected accidentally during different diagnoses, the majority of PNETs are
detected in the advanced stages, with symptoms related to tumor size or liver
metastasis. We reviewed the studies published in the English medical literature
through PubMed and summarized the clinical features and current approaches to the
treatment and follow-up of the NPNET. The common imaging techniques used for the
detection of tumor localization, size, locoregional, and metastatic involvement
are contrasted computed tomography, magnetic resonance imaging, endoscopic
ultrasonography, and somatostatin receptor scintigraphy. Surgical resection is
the only curative treatment. However, in advanced locoregional disease and liver
metastasis, interventive ablative therapies such as palliative reductive surgery,
selective hepatic arterial embolization, radiofrequency ablation; and systemic
therapies, such as peptide receptor radionuclide therapy, chemotherapy,
somatostatin analogous therapy, interferon, VEGF inhibitor, and mTOR inhibitor
may be used as symptom relieving or may improve progression-free survival and
total survival. Current knowledge on NPNET shows that the treatment should be
personalized considering the prognostic features and life expectancy of the
patient.
PMID- 25590519
TI - Differences in the location of guest molecules within zeolite pores as revealed
by multilaser excitation confocal fluorescence microscopy: which molecule is
where?
AB - A detailed and systematic polarized confocal fluorescence microscopy
investigation is presented on three batches of large coffin-shaped ZSM-5 crystals
(i.e., parent, steamed at 500 degrees C, and steamed at 700 degrees C). In
total, six laser lines of different wavelength in the visible region are employed
on two crystal positions and three orientations with respect to the polarization
plane of the excitation laser light. A fluorescent probe molecule is generated
inside the zeolite pores, originating from the acid-catalyzed oligomerization of
4-fluorostyrene. A thorough analysis of the polarization plane of emitting
fluorescent light reveals insight into the orientation of the fluorescent probe
molecule restricted by the highly ordered zeolite channel framework, thereby
visualizing pore accessibility and clearly distinguishing the occupation of
straight and sinusoidal channels by the probe molecule. Spectral features are,
furthermore, observed to tell apart molecules situated in one or the other pore.
Special focus was given on the rim and tip regions of the zeolite ZSM-5 crystals.
On the basis of the confocal approach of the investigation, the aforementioned
features are evaluated in three dimensions, while the degradation of the zeolite
framework upon postsynthesis steam treatment could be visualized by occupation of
the sinusoidal pores.
PMID- 25590521
TI - Hemostasis and thrombosis in major liver resection.
AB - The liver plays an important role in the balance between hemostasis and
thrombosis. Hepatic resection, particularly when performed in the presence of
underlying parenchymal liver disease, can cause perturbation of this balance.
This review summarizes the changes that occur in normal hemostasis and thrombosis
before, during, and after nontransplant hepatic resection and, wherever possible,
provides strategies for the perioperative management of bleeding and thrombosis.
PMID- 25590520
TI - Evolutionarily conserved pressure for the existence of distinct G2/M cell cycle
arrest and A3H inactivation functions in HIV-1 Vif.
AB - HIV-1 Vif assembles the Cul5-EloB/C E3 ubiquitin ligase to induce proteasomal
degradation of the cellular antiviral APOBEC3 proteins. Detailed structural
studies have confirmed critical functional domains in Vif that we have previously
identified as important for the interaction of EloB/C, Cul5, and CBFbeta.
However, the mechanism by which Vif recognizes substrates remains poorly
understood. Specific regions of Vif have been identified as being responsible for
binding and depleting APOBEC3G and APOBEC3F. Interestingly, we have now
identified distinct yet overlapping domains that are required for HIV-1 Vif
mediated G2/M-phase cell cycle arrest and APOBEC3H degradation, but not for the
inactivation of APOBEC3G or APOBEC3F. Surprisingly, Vif molecules from primary
HIV-1 variants that caused G2/M arrest were unable to inactivate APOBEC3H; on the
other hand, HIV-1 Vif variants that could inactivate APOBEC3H were unable to
induce G2/M arrest. All of these Vif variants still maintained the ability to
inactivate APOBEC3G/F. Thus, primary HIV-1 variants have evolved to possess
distinct functional activities that allow them to suppress APOBEC3H or cause G2
cell cycle arrest, using mutually exclusive interface domains. APOBEC3H depletion
and G2 arrest are apparently evolutionary selected features that cannot co-exist
on a single Vif molecule. The existence and persistence of both types of HIV-1
Vif variant suggests the importance of APOBEC3H suppression and cell cycle
regulation for HIV-1's survival in vivo.
PMID- 25590522
TI - Fibrinogen level deteriorates before other routine coagulation parameters and
massive transfusion in the early phase of severe trauma: a retrospective
observational study.
AB - In trauma, hemostatic functions should be maintained appropriately to prevent
massive bleeding. This study elucidated the time-dependent changes in platelet
count and coagulation variables, and the effects of disseminated intravascular
coagulation (DIC) on these changes during the early phase of trauma. Trauma
patients with an injury severity score >=16 were enrolled. The critical levels of
platelet count and coagulation variables were defined according to recent trauma
guidelines. Massive transfusion was defined as >10 units red cell concentrate.
The time from arrival at the emergency department to reaching the critical levels
and meeting the criteria for massive transfusion were evaluated. Eighty trauma
patients were enrolled; 35 were diagnosed with DIC on arrival. Among all
patients, fibrinogen levels reached the critical level earliest among routine
coagulation parameters; other routine coagulation parameters deteriorated after
the patients met the criteria for massive transfusion. Routine coagulation
parameters reached their critical levels earlier in DIC patients than patients
without DIC. Massive transfusion was performed more frequently in DIC patients,
who met the criteria earlier. During the early phase of trauma, fibrinogen levels
deteriorate earlier than other routine coagulation parameters, especially in DIC
patients.
PMID- 25590524
TI - Coagulation in patients with severe sepsis.
AB - In the majority of patients with severe sepsis, systemic activation of
coagulation is present. Increasing evidence points to an extensive cross-talk
between coagulation and inflammation that may play an important role in the
pathogenesis of sepsis. Inflammation not only leads to activation of coagulation,
but coagulation also considerably affects inflammatory activity. Molecular
pathways that contribute to inflammation-induced activation of coagulation have
been precisely identified. Proinflammatory cytokines and other mediators are
capable of activating the coagulation system and downregulating important
physiological anticoagulant pathways. Activation of the coagulation system and
ensuing thrombin generation is dependent on expression of tissue factor on
activated mononuclear cells and endothelial cells, and is insufficiently
counteracted by TFPI. Simultaneously, endothelial-bound anticoagulant mechanism,
in particular the protein C system, is shutoff by proinflammatory cytokines. In
addition, fibrin removal is severely inhibited, because of inactivation of the
fibrinolytic system, caused by an upregulation of its main inhibitor, plasminogen
activator inhibitor type 1 (PAI-1). Increased fibrin formation and impaired
removal lead to (micro)vascular thrombosis, which may result in tissue ischemia
and subsequent organ damage. The cornerstone of the management of coagulation in
sepsis is the specific and vigorous treatment of the underlying disorder.
Strategies aimed at the inhibition of coagulation activation may theoretically be
justified and have been found beneficial in experimental and initial clinical
studies. Heparin may be an effective anticoagulant approach and alternative
strategies comprise restoration of physiological anticoagulant pathways.
PMID- 25590525
TI - Hypercoagulability and venous thromboembolism in burn patients.
AB - To our knowledge, this is the first comprehensive review on the subject of venous
thromboembolism (VTE) and hypercoagulability in burn patients. Specific changes
in coagulability are reviewed using data from thromboelastography and other
techniques. Disseminated intravascular coagulation in burn patients is discussed.
The incidence and risk factors associated with VTE in burn patients are then
examined, followed by the use of low-molecular-weight heparin thromboprophylaxis
and monitoring techniques using antifactor Xa levels. The need for large,
prospective trials in burn patients is highlighted, especially in the areas of
VTE incidence and safe, effective thromboprophylaxis.
PMID- 25590526
TI - Hemostasis and thrombosis in continuous renal replacement treatment.
AB - During continuous renal replacement therapy, the delicate equilibrium of
hemostasis is disturbed. Owing to a complex interaction of critical illness,
uremia, use of an extracorporeal circuit and anticoagulation, patients exhibit
both hypercoagulability and an increased risk of bleeding. Contact of blood with
foreign material initiates coagulation by triggering the contact activation
coagulation pathway, the tissue factor-factor VIIa pathway and activation of
platelets and monocytes, which adhere to the membrane. The interaction with
critical illness induced alterations further enhances coagulation and
inflammation. Classical markers of coagulation, prothrombin and activated
thromboplastin time, and platelet count do not detect the procoagulant state.
Critically ill patients also have in increased risk of bleeding and
anticoagulation used for circuit clotting enhances this risk. Heparin is most
commonly used. Heparin increases the risk of bleeding. Its efficacy and safety
are further compromised by antithrombin deficiency, heparin binding to acute
phase proteins and apoptotic and necrotic cells, and by its unpredictable effects
on inflammation. Its interference with anticoagulation is therefore unreliable
during critical illness. Citrate provides regional anticoagulation and increases
biocompatibility. It is better tolerated than heparin and confers less bleeding,
less transfusion, and longer circuit life.
PMID- 25590523
TI - Profound endothelial damage predicts impending organ failure and death in sepsis.
AB - Endothelial damage contributes to organ failure and mortality in sepsis, but the
extent of the contribution remains poorly quantified. Here, we examine the
association between biomarkers of superficial and profound endothelial damage
(syndecan-1 and soluble thrombomodulin [sTM], respectively), organ failure, and
death in sepsis. The data from a clinical trial, including critically ill
patients predominantly suffering sepsis (Clinicaltrials.gov: NCT00271752) were
studied. Syndecan-1 and sTM levels at the time of study enrollment were
determined. The predictive ability of biomarker levels on death and organ
failures during follow-up were assessed in Cox models adjusted for potential
confounders including key organ dysfunction measures assessed at enrollment. Of
the 1,103 included patients, 418 died. sTM levels at the time of enrollment
independently predicted risk of death in adjusted models (hazard ratio [HR]
[highest quartile > 14 ng/mL vs. lowest quartile < 7 ng/mL] 2.2 [95% confidence
interval [CI]: 1.2-4.0], p = 0.02, respectively). Conversely, syndecan-1 levels
failed to predict death (adjusted HR [> 240 vs. < 70 ng/mL] 1.0 [95% CI: 0.6
1.5], p = 0.67). sTM but not syndecan-1 levels at enrollment predicted risk of
multiple organ failure during follow-up (HR [> 14 ng/mL vs. < 7 ng/mL] 3.5 [95%
CI: 1.5-8.3], p = 0.005 and 2.0 [95% CI: 0.8-5.0], p = 0.1321, respectively).
Profound damage to the endothelium independently predicts risk of multiple organ
failure and death in septic patients. Our findings also suggest that the
detrimental effect of profound endothelial damage on risk of death operates via
mechanisms other than causing organ failures per se. Therefore, damage to the
endothelium appears centrally involved in the pathogenesis of death in sepsis and
could be a target for intervention.
PMID- 25590527
TI - Hemostatic and thrombotic issues in cardiac surgery.
AB - Cardiac surgery with cardiopulmonary bypass determines a serious imbalance of the
hemostatic system. The clinical pattern is multifactorial, involving patient
related, drug-related, and surgery-related factors. As a result, the patient is
prone to both hemorrhagic and thrombotic complications. To address the clinical
management of a bleeding patient after cardiac surgery, avoiding empirical
administration of drugs and blood derivates, it is mandatory to correctly
identify the factor(s) responsible for bleeding. Bleeding after cardiac
operations can be ascribed to seven basic mechanisms: residual heparin effect;
reduced thrombin generation; fibrinogen deficiency; thrombocytopenia; platelet
dysfunction; hyperfibrinolysis; and surgical sources. These factors may interact
together, creating a complex coagulopathy. Point-of-care coagulation tests are
useful to orienteer the clinician in this complex scenario. Viscoelastic
coagulation tests find their greater usefulness in the diagnosis of the bleeding
mechanism(s), whereas platelet function tests appear more useful for the
preoperative assessment of patients under the effects of antiplatelet agents.
Thromboembolic complications are the other side of the coin, and their prevention
is still a matter of debate. Consumption of natural anticoagulants and
endothelial disturbance are important mechanisms underlying this condition.
Strategies to limit antithrombin (AT) consumption or to correct low postoperative
levels of AT are still a matter of discussion.
PMID- 25590528
TI - Heparin-induced thrombocytopenia in critically ill patients.
AB - Many critically ill patients receive heparin, either before intensive care unit
(ICU) admission (e.g., postcardiac surgery), for prophylaxis/treatment of
thrombosis, for hemodialysis/filtration, or even incidentally (e.g., flushing of
intravascular catheters), and are therefore at risk for developing immune heparin
induced thrombocytopenia (HIT), a prothrombotic drug reaction caused by platelet
activating antiplatelet factor 4 (PF4)/heparin antibodies. However, HIT explains
at most 1 in 100 thrombocytopenic ICU patients (HIT frequency 0.3-0.5% vs. 30-50%
background frequency of ICU-associated thrombocytopenia), and most patients who
form anti-PF4/heparin antibodies do not develop HIT; hence, HIT overdiagnosis
often occurs. This review discusses HIT-related issues relevant to ICU patients,
including how to (1) distinguish HIT both clinically and serologically from non
HIT-related thrombocytopenia; (2) recognize HIT-mimicking disorders, such as the
acute disseminated intravascular coagulation (DIC)/liver necrosis-limb necrosis
syndrome; (3) prevent HIT in the ICU through use of low-molecular-weight heparin;
and (4) treat HIT, including awareness of "PTT confounding" when anticoagulating
patients with DIC.
PMID- 25590529
TI - Diterpene alkaloids with an aza-ent-kaurane skeleton from Isodon rubescens.
AB - Two compounds belonging to a new group of diterpene alkaloids, kaurines A and B
(1 and 2), and an alkaloid bearing a succinimide moiety (3) were obtained from
Isodon rubescens. Their structures and absolute configurations were determined by
spectroscopy and quantum-chemical computational (13)C NMR and ECD data analysis.
These alkaloids differ from known diterpene alkaloids and diterpenoids and are
presumably biosynthesized from ent-kaurane diterpenoids.
PMID- 25590530
TI - Composition and structural transitions of polyelectrolyte-surfactant complexes in
the presence of fatty acid studied by NMR and cryo-SEM.
AB - Insoluble complexes formed when a cationic polyelectrolyte is neutralized by the
oppositely charged surfactant sodium dodecylethersulfate (SDES) in the presence
and absence of lauric acid (LA) have been examined directly using NMR
spectroscopy and cryo-SEM. Below the SDES critical micelle concentration (CMC')
the insoluble complex contains about 10 times more water than just above CMC'.
This is related to a structural transition of the complex, where water is
contained mainly in larger compartments below CMC' and then mainly in narrower
compartments above CMC'. The structure of the complex's solid matrix was
monitored by recording two-dimensional T2-diffusion correlation spectra of the
water proton resonance, which reveal the presence of several different water
environments which correspond to different complex structures. Structural
features in the micrometer range were confirmed using cryo-SEM. When LA is
present, the larger water compartments seen below CMC' are to some extent present
in the entire SDES concentration range, which is not the case in the absence of
LA. Furthermore, the inclusion of LA into the SDES aggregates above CMC' leads to
a lamellar sheetlike organization of the polyelectrolyte-stabilized surfactant
phase. In the absence of LA, a stringy network of fibers is seen in cryo-SEM
images, indicating a spherical or rodlike SDES phase. Consequently, the complex
without LA holds about 1.7-1.9 times more water than the complex with LA above
the SDES CMC'. T1 relaxation, (13)C chemical shifts, and (1)H resonance line
widths of SDES in the system support the above observations. The combination of
MAS NMR, T2-diffusion correlation, and cryo-SEM proved to be an effective method
for studying structural transitions in the surfactant-polyelectrolyte(-LA)
insoluble complexes.
PMID- 25590531
TI - Spectroscopy and viability of Bacillus subtilis spores after ultraviolet
irradiation: implications for the detection of potential bacterial life on
Europa.
AB - One of the most habitable environments in the Solar System outside of Earth may
exist underneath the ice on Europa. In the near future, our best chance to look
for chemical signatures of a habitable environment (or life itself) will likely
be at the inhospitable icy surface. Therefore, it is important to understand the
ability of organic signatures of life and life itself to persist under simulated
europan surface conditions. Toward that end, this work examined the UV photolysis
of Bacillus subtilis spores and their chemical marker dipicolinic acid (DPA) at
temperatures and pressures relevant to Europa. In addition, inactivation curves
for the spores at 100 K, 100 K covered in one micron of ice, and 298 K were
measured to determine the probability for spore survival at the surface. Fourier
transform infrared spectra of irradiated DPA showed a loss of carboxyl groups to
CO2 as expected but unexpectedly showed significant opening of the heterocyclic
ring, even for wavelengths>200 nm. Both DPA and B. subtilis spores showed
identical unknown spectral bands of photoproducts after irradiation, further
highlighting the importance of DPA in the photochemistry of spores. Spore
survival was enhanced at 100 K by ~5* relative to 298 K, but 99.9% of spores were
still inactivated after the equivalent of ~25 h of exposure on the europan
surface.
PMID- 25590532
TI - Habitable evaporated cores: transforming mini-Neptunes into super-Earths in the
habitable zones of M dwarfs.
AB - We show that photoevaporation of small gaseous exoplanets ("mini-Neptunes") in
the habitable zones of M dwarfs can remove several Earth masses of hydrogen and
helium from these planets and transform them into potentially habitable worlds.
We couple X-ray/extreme ultraviolet (XUV)-driven escape, thermal evolution, tidal
evolution, and orbital migration to explore the types of systems that may harbor
such "habitable evaporated cores" (HECs). We find that HECs are most likely to
form from planets with ~1 M? solid cores with up to about 50% H/He by mass,
though whether or not a given mini-Neptune forms a HEC is highly dependent on the
early XUV evolution of the host star. As terrestrial planet formation around M
dwarfs by accumulation of local material is likely to form planets that are small
and dry, evaporation of small migrating mini-Neptunes could be one of the
dominant formation mechanisms for volatile-rich Earths around these stars.
PMID- 25590534
TI - Nonfaradaic nanoporous electrochemistry for conductometry at high electrolyte
concentration.
AB - Nanoporous electrified surfaces create a unique nonfaradaic electrochemical
behavior that is sensitively influenced by pore size, morphology, ionic strength,
and electric field modulation. Here, we report the contributions of ion
concentration and applied ac frequency to the electrode impedance through an
electrical double layer overlap and ion transport along the nanopores. Nanoporous
Pt with uniform pore size and geometry (L2-ePt) responded more sensitively to
conductivity changes in aqueous solutions than Pt black with poor uniformity
despite similar real surface areas and enabled the previously difficult
quantitative conductometry measurements at high electrolyte concentrations. The
nanopores of L2-ePt were more effective in reducing the electrode impedance and
exhibited superior linear responses to not only flat Pt but also Pt black,
leading to successful conductometric detection in ion chromatography without ion
suppressors and at high ionic strengths.
PMID- 25590533
TI - Identification of a fragment-like small molecule ligand for the methyl-lysine
binding protein, 53BP1.
AB - Improving our understanding of the role of chromatin regulators in the
initiation, development, and suppression of cancer and other devastating diseases
is critical, as they are integral players in regulating DNA integrity and gene
expression. Developing small molecule inhibitors for this target class with
cellular activity is a crucial step toward elucidating their specific functions.
We specifically targeted the DNA damage response protein, 53BP1, which uses its
tandem tudor domain to recognize histone H4 dimethylated on lysine 20 (H4K20me2),
a modification related to double-strand DNA breaks. Through a cross-screening
approach, we identified UNC2170 (1) as a micromolar ligand of 53BP1, which
demonstrates at least 17-fold selectivity for 53BP1 as compared to other methyl
lysine (Kme) binding proteins tested. Structural studies revealed that the tert
butyl amine of UNC2170 anchors the compound in the methyl-lysine (Kme) binding
pocket of 53BP1, making it competitive with endogenous Kme substrates. X-ray
crystallography also demonstrated that UNC2170 binds at the interface of two
tudor domains of a 53BP1 dimer. Importantly, this compound functions as a 53BP1
antagonist in cellular lysates and shows cellular activity by suppressing class
switch recombination, a process which requires a functional 53BP1 tudor domain.
These results demonstrate that UNC2170 is a functionally active, fragment-like
ligand for 53BP1.
PMID- 25590536
TI - Physiological recordings and RNA sequencing of the gustatory appendages of the
yellow-fever mosquito Aedes aegypti.
AB - Electrophysiological recording of action potentials from sensory neurons of
mosquitoes provides investigators a glimpse into the chemical perception of these
disease vectors. We have recently identified a bitter sensing neuron in the
labellum of female Aedes aegypti that responds to DEET and other repellents, as
well as bitter quinine, through direct electrophysiological investigation. These
gustatory receptor neuron responses prompted our sequencing of total mRNA from
both male and female labella and tarsi samples to elucidate the putative
chemoreception genes expressed in these contact chemoreception tissues. Samples
of tarsi were divided into pro-, meso- and metathoracic subtypes for both sexes.
We then validated our dataset by conducting qRT-PCR on the same tissue samples
and used statistical methods to compare results between the two methods. Studies
addressing molecular function may now target specific genes to determine those
involved in repellent perception by mosquitoes. These receptor pathways may be
used to screen novel repellents towards disruption of host-seeking behavior to
curb the spread of harmful viruses.
PMID- 25590535
TI - Structural characterization and in vivo evaluation of beta-Hairpin
peptidomimetics as specific CXCR4 imaging agents.
AB - The CXCR4 chemokine receptor is integral to several biological functions and
plays a pivotal role in the pathophysiology of many diseases. As such, CXCR4 is
an enticing target for the development of imaging and therapeutic agents. Here we
report the evaluation of the POL3026 peptidomimetic template for the development
of imaging agents that target CXCR4. Structural and conformational analyses of
POL3026 and two of its conjugates, DOTA (POL-D) and PEG12-DOTA (POL-PD), by
circular dichroism, two-dimensional NMR spectroscopy and molecular dynamics
calculations are reported. In silico observations were experimentally verified
with in vitro affinity assays and rationalized using crystal structure-based
molecular modeling studies. [(111)In]-labeled DOTA conjugates were assessed in
vivo for target specificity in CXCR4 expressing subcutaneous U87 tumors (U87-stb
CXCR4) through single photon emission computed tomography (SPECT/CT) imaging and
biodistribution studies. In silico and in vitro studies show that POL3026 and its
conjugates demonstrate similar interactions with different micelles that mimic
cellular membrane and that the epsilon-NH2 of lysine(7) is critical to maintain
high affinity to CXCR4. Modification of this group with DOTA or PEG12-DOTA led to
the decrease of IC50 value from 0.087 nM for POL3026 to 0.47 nM and 1.42 nM for
POL-D and POL-PD, respectively. In spite of the decreased affinity toward CXCR4,
[(111)In]POL-D and [(111)In]POL-PD demonstrated high and significant uptake in
U87-stb-CXCR4 tumors compared to the control U87 tumors at 90 min and 24 h post
injection. Uptake in U87-stb-CXCR4 tumors could be blocked by unlabeled POL3026,
indicating specificity of the agents in vivo. These results suggest POL3026 as a
promising template to develop new imaging agents that target CXCR4.
PMID- 25590537
TI - Advancing the climate data driven crop-modeling studies in the dry areas of
Northern Syria and Lebanon: an important first step for assessing impact of
future climate.
AB - Inter-annual and seasonal variability in climatic parameters, most importantly
rainfall, have potential to cause climate-induced risk in long-term crop
production. Short-term field studies do not capture the full nature of such risk
and the extent to which modifications to crop, soil and water management
recommendations may be made to mitigate the extent of such risk. Crop modeling
studies driven by long-term daily weather data can predict the impact of climate
induced risk on crop growth and yield however, the availability of long-term
daily weather data can present serious constraints to the use of crop models. To
tackle this constraint, two weather generators namely, LARS-WG and MarkSim, were
evaluated in order to assess their capabilities of reproducing frequency
distributions, means, variances, dry spell and wet chains of observed daily
precipitation, maximum and minimum temperature, and solar radiation for the eight
locations across cropping areas of Northern Syria and Lebanon. Further, the
application of generated long-term daily weather data, with both weather
generators, in simulating barley growth and yield was also evaluated. We found
that overall LARS-WG performed better than MarkSim in generating daily weather
parameters and in 50 years continuous simulation of barley growth and yield. Our
findings suggest that LARS-WG does not necessarily require long-term e.g., >30
years observed weather data for calibration as generated results proved to be
satisfactory with >10 years of observed data except in area with higher altitude.
Evaluating these weather generators and the ability of generated weather data to
perform long-term simulation of crop growth and yield is an important first step
to assess the impact of future climate on yields, and to identify promising
technologies to make agricultural systems more resilient in the given region.
PMID- 25590538
TI - Experimental warming differentially affects microbial structure and activity in
two contrasted moisture sites in a Sphagnum-dominated peatland.
AB - Several studies on the impact of climate warming have indicated that peat
decomposition/mineralization will be enhanced. Most of these studies deal with
the impact of experimental warming during summer when prevalent abiotic
conditions are favorable to decomposition. Here, we investigated the effect of
experimental air warming by open-top chambers (OTCs) on water-extractable organic
matter (WEOM), microbial biomasses and enzymatic activities in two contrasted
moisture sites named Bog and Fen sites, the latter considered as the wetter ones.
While no or few changes in peat temperature and water content appeared under the
overall effect of OTCs, we observed that air warming smoothed water content
differences and led to a decrease in mean peat temperature at the warmed Bog
sites. This thermal discrepancy between the two sites led to contrasting changes
in microbial structure and activities: a rise in hydrolytic activity at the
warmed Bog sites and a relative enhancement of bacterial biomass at the warmed
Fen sites. These features were not associated with any change in WEOM properties
namely carbon and sugar contents and aromaticity, suggesting that air warming did
not trigger any shift in OM decomposition. Using various tools, we show that the
use of single indicators of OM decomposition can lead to fallacious conclusions.
Lastly, these patterns may change seasonally as a consequence of complex
interactions between groundwater level and air warming, suggesting the need to
improve our knowledge using a high time-resolution approach.
PMID- 25590539
TI - Pooled versus separate tree-ring deltaD measurements, and implications for
reconstruction of the Arctic Oscillation in northwestern China.
AB - Stable hydrogen isotope ratios (deltaD) in tree rings are an attractive but still
rarely explored terrestrial archive of past climatic information. Because the
preparation of the cellulose nitrate for deltaD measurements requires more wood
and a longer preparation time than preparation techniques for other isotopes in
cellulose (delta18O or delta13C), it is challenging to obtain high-resolution
records, especially for slow-growing trees at high elevations and in boreal
regions. Here, we tested whether annually pooled samples of Qinghai spruce (Picea
crassifolia Kom.) trees from northwestern China provided results similar to those
derived as the mean of individual measurements of the same trees and whether the
resulting chronologies recorded useful climate information. Inter-tree
variability of deltaD was higher than that of measured ring width for the same
trees. We found higher and significant coherence between pooled and mean isotope
chronologies than that among the individual series. It showed a logarithmic
relationship between ring mass and deltaD; however, accounting for the influence
of ring mass on deltaD values only slightly improved the strength of climatic
signals in the pooled records. Tree-ring deltaD was significantly positively
correlated with the mean, maximum, and minimum temperatures during the previous
winter and with maximum temperature during the current August, and significantly
negatively correlated with precipitation in the previous November to January and
the current July. The winter climate signal seems to dominate tree-ring deltaD
through the influence of large-scale atmospheric circulation patterns, i.e. the
Arctic Oscillation. These results will facilitate reconstruction of winter
atmospheric circulation patterns over northwestern China based on a regional tree
ring deltaD networks.
PMID- 25590540
TI - A system-of-systems approach as a broad and integrated paradigm for sustainable
engineered nanomaterials.
AB - There is an urgent need for a trans-disciplinary approach for the collective
evaluation of engineered nanomaterial (ENM) benefits and risks. Currently,
research studies are mostly focused on examining effects at individual endpoints
with emphasis on ENM risk effects. Less research work is pursuing the integration
needed to advance the science of sustainable ENMs. Therefore, the primary
objective of this article is to discuss the system-of-systems (SoS) approach as a
broad and integrated paradigm to examine ENM benefits and risks to society,
environment, and economy (SEE) within a sustainability context. The aims are
focused on: (a) current approaches in the scientific literature and the need for
a broad and integrated approach, (b) documentation of ENM SoS in terms of
architecture and governing rules and practices within sustainability context, and
(c) implementation plan for the road ahead. In essence, the SoS architecture is a
communication vehicle offering the opportunity to track benefits and risks in an
integrated fashion so as to understand the implications and make decisions about
advancing the science of sustainable ENMs. In support of the SoS architecture, we
propose using an analytic-based decision support system consisting of a knowledge
base and analytic engine along the benefit and risk informatics routes in the SEE
system to build sound decisions on what constitutes sustainable and unsustainable
ENMs in spite of the existing uncertainties and knowledge gaps. The work
presented herein is neither a systematic review nor a critical appraisal of the
scientific literature. Rather, it is a position paper that largely expresses the
views of the authors based on their expert opinion drawn from industrial and
academic experience.
PMID- 25590541
TI - [In Process Citation].
PMID- 25590542
TI - [Craving as a core symptom in substance use disorders: epidemiology,
neurobiological substrates and clinical relevance].
AB - OBJECTIVE: Observed by physicians and often reported by patients, craving is a
core symptom of addiction, although not well defined nor understood completely.
In the last several years, functional imaging as well as the measurement of
different biological substrates of addiction have greatly evolved, allowing for a
better understanding of the underlying neurobiological pathways of craving.
Furthermore, with the development of the DSM-V and its inclusion as a diagnostic
criterion for substance use disorders, craving has gained a whole new level of
interest. Hence, the general objective of this article is to examine findings of
studies that have led to a better understanding of craving and its implications.
First, we address the definition of craving and its epidemiology in individuals
with substance use disorders. We then summarize the results of the research
conducted on the neurobiological substrates of craving. Finally, we present the
role of craving in the cycle of addiction and its potential as a therapeutic
target for pharmacological and non-pharmacological interventions. METHODS:
Narrative review of the literature. RESULTS: The definition of craving has
greatly evolved throughout the years, and it is commonly described as an abnormal
desire or need to take a drug. While its conscious aspect is well known, whereas
it is expressed subjectively, it is growingly also defined as an unconscious
phenomenon illustrated by a physiologic activation that is not perfectly
correlated with subjective measures. Available data on craving have also
demonstrated the presence of this symptom in all three phases of the addiction
cycle, including early and prolonged abstinence, long after the acute physical
withdrawal syndrome. Three factors have been identified as potent craving
inducers: the drug itself, drug related cues and stress. PET scan studies and
fMRI studies confirmed the implication of dopaminergic pathways in craving, and
have more recently shed light on the contribution of other neurotransmission
systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid
systems, but their roles are not yet fully understood. Furthermore, craving
related activations of specific areas of the brain involved in learned habits and
behavior as well as memory have been demonstrated by various studies; in
contrast, regions associated with regulation and control of emotion have been
demonstrated to be hypoactive during craving episodes. Finally, several studies
have demonstrated that craving is a valid predictive indicator of relapse, making
it an interesting target for pharmacological and non-pharmacological treatment.
Several anti-craving medications have been shown to decrease craving, including
varenicline for tobacco and naltrexone for alcohol dependence. Studies examining
the efficacy of other anti-craving medications for other substances are growing
in numbers. CONCLUSIONS: Available data on craving support its role as a core
symptom of addiction and allow for a better understanding of the underlying
neurobiological substrates. Studies tend to show that it is a valid indicator of
relapse during early and prolonged abstinence. Further research is needed to
truly understand the complexity of the neurobiological substrates involved in
craving as well as to develop new anti-craving interventions to facilitate long
term abstinence in individuals with substance use disorders.
PMID- 25590543
TI - [The Nature and Issues of Drug Addiction Treatment under Constraint].
AB - OBJECTIVES: This article is exploring different forms of constraint that are
exerted in the field of drug addiction treatment. The objective of this article
is to establish benchmarks and to stimulate reflection about the ethical and
clinical implications of those constraints in the field of drug addiction
treatment. METHODS: This article is presenting a critical review of different
forms of constraint that can be exerted in Canada in regard to the treatment of
drug addiction. In the first section of the article, a definition of therapeutic
intervention is proposed, that includes the dimension of power, which justifies
the importance of considering the coercive aspects of treatment. The second
section, which represents the core section of the paper, is devoted to the
presentation of different levels of constraint that can be distinguished in
regard to drug addicts who are under treatment. RESULTS: Three levels of
constraint are exposed: judicial constraint, institutional constraint and
relational constraint. The coercive aspect of treatment can then be recognized as
a combination of all tree levels of constraint. Judicial constraint refers to any
form of constraint in which the court or the judge is imposing or recommending
treatment. This particular level of constraint can take different forms, such as
therapeutic remands, conditions of a probation order, conditions of a conditional
sentence of imprisonment, and coercive treatment such as the ones provided
through drug courts. Institutional constraint refers to any form of constraint
exerted within any institutional setting, such as correctional facilities and
programs offered in community. Correctional facilities being limited by their own
specific mission, it might have a major impact on the way the objectives of
treatment are defined. Those limitations can then be considered as a form of
constraint, in which drug users don't have much space to express their personal
needs. Finally, relational constraint refers to any form of constraint in which
the drug addict might be coerced to treatment under the pressure of people from
the immediate environment, such as members of family, friends or employers. Even
if this form of constraint is not as obvious as the ones exerted by court and
correctional facilities, it has to be considered by practitioners who are
evaluating the motivation of drug addicts under treatment. CONCLUSION:
Considering the diversity of constraints that are exerted on drug addicts who are
under treatment, it appears that we should be always aware of the ethical and
clinical challenges facing practitioners every day. The recognition of those
constraints can also help to understand how important it is to consider the
institutional and social context in which treatment is being provided.
PMID- 25590544
TI - [Are there any sex/gender differences in drug use and drug addiction?].
AB - Drug use and drug addiction have been traditionally considered to be a male
problem, however the gender gap has been decreasing over the past few decades.
Thus, while the prevalence of alcohol, cannabis and nicotine dependence is still
overall greater among men than among women, sex/gender differences in the abuse
of stimulants and opiates seem to have disappeared. Moreover, women appear to be
more prone to develop drug dependence, suffer more severe physical and
psychological consequences of drug abuse, and have more difficulties quitting the
habit. Numerous psychological, socio-cultural and biological factors have been
implicated in these changing statistics. For example, while a large proportion of
men initiate drug use to induce feelings of elation, energy or focus, women
frequently start taking drugs to alleviate pre-existing mental health problems,
including high levels of stress, feelings of alienation, depression, anxiety, or
post-traumatic stress disorder. This maladaptive self-medication strategy often
results in a faster transition to a habitual drug use and eventually a more
severe dependence. In addition, the socio-cultural norms (particularly in the
Western society) have changed dramatically over the past few decades. Thus, while
there is still a more severe stigma and prejudice against women who use drugs
(especially if they are pregnant of have children), overall there is much greater
acceptance of women's drug use than it was several decades ago. Moreover, women
have much greater access to various drugs of abuse than they used to have.
Finally, over the past couple of decades new research started emerging pointing
to some neurobiological factors that could also contribute to sex differences in
drug addiction. Thus, there is now evidence that dopamine system, which for
decades has been strongly implicated in drug reinforcement, is sexually
dimorphic. The number of dopaminergic neurons, the density of the dopaminergic
terminals, as well as responsiveness of the dopaminergic system to drugs of
abuse, has been shown to differ between males and females and it has been shown
to be modulated by sex steroid hormones, especially estrogen. For example, female
rats exhibit greater motivation to self-administer cocaine than male rats and
their motivation is the highest during elevated levels of estrogen. All these
psychological, socio-cultural and biological factors that contribute to
sex/gender difference in drug use and drug dependence, should be considered while
evaluating and treating individuals with drug addiction problem.
PMID- 25590545
TI - [Psychosis and addiction: The evidence cemetery].
AB - Objectives The comorbidity between psychosis and substance use has attracted wide
attention over the years, and a vast literature is now available for meta
analytic treatment. In the field, a majority of authors assume that cannabis
smoking is a risk factor for psychosis, that substance abuse is highly prevalent
in schizophrenia, that substance abuse worsens the prognosis of schizophrenia,
and that integrated treatments have greater efficacy than treatment-as-usual for
this complex population. The objective of the current article is to review the
meta-analyses that have been published in the comorbidity field in order to
determine if the above-mentioned assumptions are substantiated by evidence or
not. Methods A search of the literature was performed using PubMed, PsycINFO and
EMBASE. The literature search retrieved a total of 25 systematic quantitative
reviews, addressing the following issues: etiology, age at onset, prevalence
rates, cognition, treatment, as well as psychiatric, neurologic and functional
outcomes. Results Evidence shows that the prevalence of tobacco smoking, cannabis
smoking and alcohol use is elevated in psychosis. However, this prevalence is
likely to be over-estimated since studies have been performed in clinical
settings rather than the general population. Reliable evidence also suggests that
cannabis smoking is a risk factor for psychosis outcomes. However, the
association is rather small and it remains difficult to draw an unequivocal
public health message from this literature. In the same vein, evidence suggests
that cannabis smoking is associated with an earlier age at onset of psychosis.
However, this observation is derived from cross-sectional studies, not
longitudinal ones; thus, no undisputable claims on causality can be made from
them. On clinical grounds, some evidence also suggests that substance use is
associated with self-harm, increased positive and depressive symptoms in
psychosis patients, but this evidence is derived from cross-sectional studies,
not longitudinal ones. Cocaine may exacerbate antipsychotic-induced
extrapyramidal symptoms in schizophrenia, but this observation is based on a
small number of studies. In the case of violence, the aggregation of studies
involving very large samples of patients has shown a strong association with
substance abuse in psychosis patients. However, this association is based on
statistics that are not adjusted for potential confounds, and the role of cluster
B personality disorders in the substance abuse-violence association has yet to be
determined from an evidence-based perspective. The effects of psychoactive
substances on cognition in psychosis patients are inconsistent and contradictory.
In terms of treatment, evidence shows that bupropion and varenicline increase
tobacco smoking cessation rates in psychosis. However, this observation is based
on a small number of studies. Finally, there is no evidence that integrated
psychosocial interventions are superior to treatment as usual in this population.
This lack of efficacy may due to a real lack of efficacy or to methodological
problems making the comparison of intervention studies difficult. Discussion The
evidence supporting the main assumptions of the comorbidity field is not as
strong as it may seem. Moreover, important gaps in our understanding of the
psychosis-addiction comorbidity remain. Due to lack of interest or lack of data,
no meta-analysis has been performed, in the dual-diagnosis population, on
injectable antipsychotics, subjective reasons for use, treatment compliance,
medical comorbidities, the social context of use, the neurobiological links
between substance use and psychosis, as well as the comparative efficacy of
nicotine replacement therapy.
PMID- 25590546
TI - [Exploration of potential mechanisms underlying substance use disorders in
individuals with personality disorders].
AB - Background Cluster-B personality disorders (DSM-V), particularly borderline and
antisocial personality disorders, are associated with high rates of substance use
disorder. However, the mechanisms underlying this relationship have yet to be
fully understood. Craving has recently been identified as an important component
of substance use disorder. The purpose of this article is therefore to review the
current literature and explore whether craving could be implicated as an
underlying mechanism of comorbid substance use disorder in antisocial and
borderline personality disorders.Method Critical review of the literature.Results
Emerging evidence indicates that there is in fact an association between craving
and personality disorders. Patients afflicted with the latter, incidentally,
respond differently to anti-craving medication when compared to normal subjects.
While a limited number of studies have directly assessed craving in patients with
personality disorders, a growing number have looked at the association between
craving and specific personality traits. The correlation between impulsivity,
negative affect and craving seems like a plausible explanation for the high
prevalence and severity of substance use disorder in subjects with antisocial or
borderline personality disorders.Conclusion These findings suggest that specific
personality traits are related to craving and could represent promising targets
for the prevention, assessment and management of comorbid substance use
disorders.
PMID- 25590547
TI - [Opioid use disorder in patients with chronic non-cancer pain].
AB - Epidemiology Canada now has the second highest number of opioid prescriptions per
capita in the world. The rate of prescriptions has increased over the last
decade, most notably in adults over 55 years of age. A recognition of the
importance of treating pain has influenced this increase, but higher rates of
opioid prescribing have produced undesirable outcomes including the misuse of
medication as well as an increased number of deaths and emergency department
visits attributable to opioids. Diverse psychiatric disorders, such as major
depression, now also occur in 40% of those with an opioid use disorder (OUD).
Neuroscience We now understand that addictive behaviors are caused by both
environmental and genetic factors. Although OUD has historically been perceived
as a weakness of character, it is now clear that it is a chronic disease, which
results from a complex interaction between a substance, such as opioid,
environmental factors, and an individual's genotype. Unfortunately, this evidence
has yet to be successfully translated into clinical practice and most physicians
are unable to diagnose and manage OUD patients appropriately.Clinical guidelines
Many clinical guidelines for the management of chronic, non-cancer pain are
available. All guidelines identify the need to assess the patient appropriately
and screen for factors associated with misuse before prescribing opioids.
Guidelines generally acknowledge that patients should not be denied appropriate
pain management, but that some patients will require close supervision and
frequent follow-up to prevent the misuse of prescription opioids.
PMID- 25590548
TI - [Methamphetamine - just another stimulant or a more complex problem?].
AB - Methamphetamine (MA) has recently become very popular in the media, due in part
to its increasing popularity as well as its psychotropic effects and the negative
consequences of its use. Is it a stimulant like any other, or does
methamphetamine use lead to specific difficulties in its users? The aim of this
article is to provide a brief review of the literature by explaining some of the
reasons for its popularity in Canada as well as the physical, dental,
psychiatric, cognitive and legal problems associated with its use. MA's
popularity: Regarding its popularity, MA has benefitted from multiple factors,
namely its low cost for users and manufacturers, its quick and intense
psychotropic effects (increased energy, sexual arousal, rapid thinking,
sleeplessness, lack of appetite), its easy access, as well as its various methods
of ingestion (nasal, oral, injection). MA abuse also results in a multitude of
negative effects, both physical and mental. MA's physical effects: In terms of
negative physical effects, cardiac problems, skin infections, sexually
transmitted (and injection-related) diseases as well as meth mouth are described.
MA's mental effects: In terms of mental consequences, two recently published
Canadian studies revealing high rates of depression symptoms and of sustained
psychotic symptoms in a subgroup of MA users are presented. Studies reporting
various cognitive deficits in MA user are also reviewed, including reports of
high prevalence of childhood attention deficit and hyperactivity disorder
diagnoses among adult MA users. Furthermore, MA abusers are documented as having
been highly exposed to trauma in their lives, with many presenting with post
traumatic stress disorder criteria. This manuscript also explores the reasons
behind the forensic profiles of individuals using MA, particularly the increased
tendency toward violent acts, the high incarceration rates of the homeless users
and the high percentage of individuals diagnosed with antisocial personality
disorder reported in studies. In terms of user profiles, various methods of
ingestion, frequency of use as well as combination with other drugs are
described, with a special focus on the frequent polysubstance abuse found in MA
users and the reality of bingers. TREATMENT: This manuscript describes specific
treatments designed for stimulant users such as MA abusers, namely the MATRIX
program, as well as modifications piloted for those with comorbid depression.
Pharmacological treatments, as well as antioxidant supplements, are also
discussed although they have not yielded positive results with humans to date.
Overall, our goal in this manuscript is to highlight the complexity of the
difficulties faced by MA users as well as the limited ability of currently
available treatments to address the multiple needs associated with this
complexity.
PMID- 25590549
TI - [Internet addiction: a descriptive clinical study of people asking for help in
rehabilitation treatment center in Quebec: exploratory study].
AB - To date, there is no consensus on the diagnostic criteria for Internet addiction
(Hinic, 2011; Tonioni & coll., 2012; Weinstein & Lejoyeux, 2010). Nonetheless,
some people consider themselves cyberdependent and request treatment services in
the addiction rehabilitation centers (ARC) of the province of Quebec. These
admissions have led the Health and Social Services Agency of Montreal to ask for
the realization of a descriptive study on Internet addiction. OBJECTIVES: 1)
Describe the socio-demographical characteristics of cyberdependent individuals
receiving treatment in the ARC; 2) Document their associated problems, such as
problems related to alcohol and drug abuse, gambling, self-esteem, and symptoms
of depression and anxiety. METHODOLOGY: The study was conducted in eight ARC's of
the province of Quebec. A convenience sample of 57 people was recruited over a
period of 24 months, from 2010 to 2012. To participate in this study, individuals
had to be 18 years or older, identify themselves as cyberdependent, and request
help for an Internet addiction problem in a public ARC. The Internet Addiction
Test (Young, 1998), in its validated French version (Khazaal & coll., 2008), was
used to assess the severity of Internet use habits. The associated problems were
assessed using the following questionnaires: the Beck Anxiety Inventory (Beck,
Epstein, Brown & Steer, 1988); the Beck Depression Inventory, in its validated
French version (Bourque & Beaudette, 1982); the DEBA-Alcool/Drogues/Jeu
(Depistage-evaluation du besoin d'aide), an instrument used to screen and assess
the need for help in problems related to alcohol, drugs, and gambling (Tremblay &
Blanchette-Martin, 2009), and the Rosenberg's Self-Esteem Scale (Rosenberg,
1965). RESULTS: Fifty-seven people agreed to participate in the study. A large
majority of these cyberdependent individuals were male (88%), the mean age was 30
years old, had low incomes and were living with their parents. They consulted
following the pressure of their entourage and reported many consequences due to
their Internet addiction problem.They spent, on average, 65.8 hours per week on
the Internet and reported having several problematic applications. Amongst these
problematic applications, the most frequently reported were the role playing game
(MMORPG) (57.8%), the streaming on entertainment sites (35.1%), and the chat
rooms (29.8%). Regarding the self-esteem scale, 66.6% of participants presented a
very low or low self-esteem, while 21.1% presented an above average self-esteem.
According to Beck Depression and Anxiety Inventories, 3.5% (n=2) of the sample
reached the clinical threshold for depression, while 7.5% (n=4) reached it for
anxiety. Almost half (45.6%) of the participants were taking psychotropic
medication for a mental health problem, and 33.3% had a chronic physical health
problem. CONCLUSION: This study highlights the characteristics of a still unknown
group in the population, that of cyberdependent people. Individuals having an
Internet addiction problem live significant consequences due to the loss of
control on their Internet use. In addition, when they are admitted into
treatment, even if the subjective psychological distress is not always high,
participants present a complex clinical profile, where comorbidity is the rule
rather than the exception. We believe that the current data show enough
similarities with other addictive disorders, to allow clinicians to work taking
into consideration their experience with other addictive behaviours.
PMID- 25590550
TI - [Noise Effects on Mental Health: a review of literature].
AB - Any human activity generates noise. It is considered as a risk factor for
people's health. The present review of literature has assessed the impact of
noise on mental health; it is summarized into four points: objective, methods,
results and conclusion. OBJECTIVE: The main objective of this study is to expose
the actual knowledge state of noise effects on mental health after overview and
critical analysis of literature to identify the acquired and shortcomings, to
reflect on research direction in terms of noise pollution in the future. METHODS:
The literature review was conducted based on: research of keys words in articles
published, research of the number of quotations of articles in Journal Citation
Reports (JCR), published in web of science, research of impact factor of
journals. One hundred articles were selected, after analyzing contents, items
were classified into: fundamental studies (25%), experimental studies (50%), and
epidemiological studies (25%). RESULTS: The fundamental studies have verified the
hypothesis according to which noise generates stress. Researchers have dosed
hormones of stress in plasma, urine and saliva in individuals exposed to noise of
different decibels. The results found were unanimous: The rates of stress
hormones found, were significantly high in three liquids. This means that noise
causes stress. For experimental studies, researchers have experienced the role of
noise on memory, attention and performance. Human subjects were exposed to
different decibels to assess level of disruption to their memory, attention, and
performance. The results revealed that noise disturbs memory, distracts attention
and decreases performance. Experimental studies are the most abundant and
constitute 50% of the current literature review.The epidemiological studies have
evaluated the intellectual performance of students in schools located in noisy
environments and residents in areas surrounding airports, railways and highways.
RESULTS have revealed that students in schools located in noisy environments have
presented cognitive impairment. CONCLUSION: This review of literature on noise
effects on mental health lead to the following conclusion. It seems to exist a
consensus in fundamental and experimental studies on the detrimental effect of
noise but results from epidemiological are not convincing and require further
studies.
PMID- 25590551
TI - [Neurocognitive insight in schizophrenia: a meta-analysis].
AB - Background Schizophrenia is well-known to be associated with a lack of insight
into symptoms. Comparatively, little is known on insight into neurocognitive
deficits in schizophrenia, despite the fact that these dysfunctions are
undoubtedly core features of the disorder. Recently, growing interest has been
paid to subjective cognition, and thus far, results have been heterogeneous. The
objectives of current meta-analysis were to determine the magnitude of subjective
complaints in schizophrenia; to examine the association between subjective
cognitive complaints and objective cognition, as well psychiatric symptoms and
insight into illness. The meta-analysis also sought to determine if results are
influenced by the choice of the scale used to measure subjective cognition.
Methods A search was performed with PubMed, PsycInfo and EMBASE, using the
following key words: schizophrenia OR psychosis AND cognition OR memory OR
attention OR "executive functions" AND insight OR "subjective cognition" OR
awareness. Studies involving patients with schizophrenia-spectrum disorders and
measuring subjective cognition with a validated self-report scale were included.
Studies using scales measuring insight into thinking processes (e.g. Beck
Cognitive Insight Scale) were excluded. Statistical analyses were performed with
the Comprehensive Meta-Analysis-2 software. Cognitive scores were grouped into 6
cognitive domains (as recommended by the MATRICS group): attention, problems
solving, speed of processing, verbal memory, visual memory and working memory.
The difference in cognitive complaints between schizophrenia patients and healthy
controls was examined using Cohen's d. The associations between subjective
cognition and objective cognition, psychiatric symptoms and insight into illness
were examined using Pearson's correlation coefficients. Results Twenty-two
studies were retrieved, including a total of 1609 patients and 294 controls.
Patients reported increased subjective cognitive complaints, compared to controls
(moderate effect size). A weak association was observed between subjective and
objective (global) cognition. The association was larger in studies using the
Subjective Scale To Investigate Cognition in Schizophrenia (SSTICS), compared to
studies using other scales. The largest association was observed between
subjective complaints and problem solving. The association between subjective
complaints and depressive symptoms was in the same range as the association
between subjective complaints (measured with the SSTICS) and objective cognition.
No association was found between subjective complaints and positive / negative
symptoms. Finally, a weak association was found between subjective complaints and
insight into illness. Discussion Taken together, these results suggest that
schizophrenia patients report significant subjective cognitive complaints.
However, patients have a poor understanding of these deficits, since subjective
complaints are as strongly associated with depressive symptoms as they are
associated with objective cognitive deficits. Schizophrenia patients may be more
aware of their problem solving deficits. However, this observation is based on a
limited number of studies and will need to be replicated in future studies. Our
results also show that insight into neurocognitive deficits is largely
independent from insight into illness. Finally, the results of the current meta
analysis may have methodological implications, since they suggest that the SSTICS
produces stronger associations between subjective and objective cognition than
other scales. In the future, greater attention will need to be paid to the
domains of subjective complaints, as well as to subjective cognitive complaints
in other psychiatric disorders.
PMID- 25590552
TI - [Early intervention in psychosis: concepts, current knowledge and future
directions].
AB - OBJECTIVES: This paper seeks to provide an overview of the motives, rationale,
theoretical underpinnings and foundational literature of the early intervention
movement for psychoses. It also seeks to review the current status of the field,
highlight its significant developments and identify its emergent trends. METHODS:
This paper begins by contextualizing the burden of psychosis. It then traces the
origins of the early intervention movement and surveys the seminal literature
that established and shapes the field. It describes the movement's characteristic
elements, types, approaches, strengths, criticisms and trajectories in select
Western nations. It closes with a presentation of how the early intervention
movement is informing broader endeavours to transform youth mental health.
RESULTS: We find that the early intervention movement is predicated on the
critical period hypothesis that emphasizes the significance of the early stages
of the illness; and on findings that the duration of untreated psychosis
influences prognoses. Early intervention redresses this situation by facilitating
access to specialized, phase-specific treatment. Access is enhanced through open
referral, fast response times, and public and practitioner education. Ideally,
the intervention, provided for the first two years after detection, features
intensive case management; low-dose antipsychotic medication; an emphasis on
social functioning; family intervention; early attention to comorbid concerns;
and due regard for the needs and priorities of youth and their families. Evidence
suggests that specialized early intervention yields better outcomes than routine
care. The cost-effectiveness of such services has not yet been definitely
investigated. Criticisms of early intervention pertain to the quality of evidence
for, the manner of implementation of, the allocation of resources to early
intervention and its utility for persons at high risk for developing psychosis.
We also identify advocacy within the field for extending early intervention to
the first five years of the course of psychosis. CONCLUSION: We conclude that the
status of the early intervention movement (in terms of availability and policy)
in Western public healthcare systems can be resolved into a spectrum. The United
Kingdom is shown to be the leader while Canada appears at the middle of the
spectrum (with the United States bringing up the rear). In the Quebec context,
the picture is found to be mixed and recommendations for further research and
investment are made. Finally, an examination is undertaken of how the early
intervention for psychosis movement has provided the impetus for and dovetails
into the larger effort to transform youth mental healthcare in general, a
development that is in its nascent stages in Canada.
PMID- 25590553
TI - [Transference in the treatment of dissociative identity disorder: A review of
literature and a case example].
AB - A literature review about transference in the treatment of dissociative identity
disorder (DID) is presented. Common transference reactions resulting from serious
traumas are explored, considering that those kind of trauma are higly present in
the pathways of DID patients. Post traumatic transference aspects specific to DID
are also presented. In addition, common transference patterns and dissociative
aspects of transference in the treatment of DID are explained. Transference is
also discussed in relationship to the possible impact of disorganized attachment,
which is a main component in the development of DID. The clinical implications of
this proposition will be discussed and supported by a case example.
PMID- 25590554
TI - [First stage in identifying traumatic profil inpatients hospitalised in
psychiatry in Martinique].
AB - The population hospitalised in psychiatry seems more exposed to traumatic events
than the French general population, with particularly more sexual aggressions.
The aim of this study is to describe the population hospitalised in psychiatry
and more precisely the traumatic history of these patients, their comorbidities
(mental diseases and addictions), and socio economical level. This descriptive,
cross sectional and retrospective study took place in the Crisis Center in the
University Hospital in Martinique (French West Indies), from February to July
2013. A socio-demographic information, the Mini International Neuropsychiatric
Interview 5.0, the Trauma History Questionnaire and the Impact Events Scale
Revised were realised with 49 of the 143 patients admitted during this period
(34.3%). In this population, we found a mean of 6.5 (standart-deviation=4.2)
different types of traumatic event, with 38.8% patients reporting a natural
disaster, and 38.8% declaring at least one sexual aggression. In the 25 patients
suffering from post-traumatic stress disorder, 66.7% underwent a sexual
aggression, significatively during childhood (before 10 years old, P=0.01), and
during adolescence (between 10 to 18 years old, P=0.01). These results underline
the importance of a systematic screening of the traumatic profile: the
characteristics of the traumatic events and its clinical impact.
PMID- 25590555
TI - Uniformly embedded silver nanomesh as highly bendable transparent conducting
electrode.
AB - Ag-nanomesh-based highly bendable conducting electrodes are developed using a
combination of metal nanotransfer printing and embossing for the 6-inch wafer
scale. Two Ag nanomeshes, including pitch sizes of 7.5 and 10 MUm, are used to
obtain highly transparent (approximately 85% transmittance at a wavelength of 550
nm) and electrically conducting properties (below 10 Omega sq(-1)). The Ag
nanomeshes are also distinguished according to the fabrication process, which is
called transferred or embedded Ag nanomesh on polyethylene terephthalate (PET)
substrate, in order to compare their stability against bending stress. Then the
enhancement of bending stability when the Ag nanomesh is embedded in the PET
substrate is confirmed.
PMID- 25590557
TI - Analyzing the effects of stromal cells on the recruitment of leukocytes from
flow.
AB - Stromal cells regulate the recruitment of circulating leukocytes during
inflammation through cross-talk with neighboring endothelial cells. Here we
describe two in vitro "vascular" models for studying the recruitment of
circulating neutrophils from flow by inflamed endothelial cells. A major
advantage of these models is the ability to analyze each step in the leukocyte
adhesion cascade in order, as would occur in vivo. We also describe how both
models can be adapted to study the role of stromal cells, in this case
mesenchymal stem cells (MSC), in regulating leukocyte recruitment. Primary
endothelial cells were cultured alone or together with human MSC in direct
contact on Ibidi microslides or on opposite sides of a Transwell filter for 24
hr. Cultures were stimulated with tumor necrosis factor alpha (TNFalpha) for 4 hr
and incorporated into a flow-based adhesion assay. A bolus of neutrophils was
perfused over the endothelium for 4 min. The capture of flowing neutrophils and
their interactions with the endothelium was visualized by phase-contrast
microscopy. In both models, cytokine-stimulation increased endothelial
recruitment of flowing neutrophils in a dose-dependent manner. Analysis of the
behavior of recruited neutrophils showed a dose-dependent decrease in rolling and
a dose-dependent increase in transmigration through the endothelium. In co
culture, MSC suppressed neutrophil adhesion to TNFalpha-stimulated endothelium.
Our flow based-adhesion models mimic the initial phases of leukocyte recruitment
from the circulation. In addition to leukocytes, they can be used to examine the
recruitment of other cell types, such as therapeutically administered MSC or
circulating tumor cells. Our multi-layered co-culture models have shown that MSC
communicate with endothelium to modify their response to pro-inflammatory
cytokines, altering the recruitment of neutrophils. Further research using such
models is required to fully understand how stromal cells from different tissues
and conditions (inflammatory disorders or cancer) influence the recruitment of
leukocytes during inflammation.
PMID- 25590558
TI - Meiotic crossover patterns: obligatory crossover, interference and homeostasis in
a single process.
AB - During meiosis, crossover recombination is tightly regulated. A spatial
patterning phenomenon known as interference ensures that crossovers are well
spaced along the chromosomes. Additionally, every pair of homologs acquires at
least one crossover. A third feature, crossover homeostasis, buffers the system
such that the number of crossovers remains steady despite decreases or increases
in the number of earlier recombinational interactions. Here we summarize recent
work from our laboratory supporting the idea that all 3 of these aspects are
intrinsic consequences of a single basic process and suggesting that the
underlying logic of this process corresponds to that embodied in a particular
(beam-film) model.
PMID- 25590560
TI - Elucidating the fundamental mechanisms of cell death triggered by photothermal
therapy.
AB - Photothermal therapy (PTT) utilizes nanoparticles embedded within tumors as
exogenous energy absorbers to convert laser light energy into heat to ablate
cancer cells. While PTT is a promising alternative to conventional cancer
therapy, under certain irradiation conditions, it can produce cellular necrosis,
and this necrosis may lead to pro-inflammatory responses that are detrimental to
treatment success. Recent studies have shown that PTT can be modulated to induce
apoptosis rather than necrosis, which is appealing since apoptosis discourages an
inflammatory response. In this issue of ACS Nano, del Pino, Pardo, de la Fuente,
and colleagues reveal the intracellular signaling cascades involved in the
apoptotic response to PTT using cells harboring photothermal transducing
nanoprisms. In this Perspective, we present an overview of nanoparticle-mediated
PTT and discuss photothermally induced apoptosis as a potential therapeutic
pathway.
PMID- 25590559
TI - Functional relationship among PLK2, PLK4 and ROCK2 to induce centrosome
amplification.
AB - The presence of more than 2 centrosomes (centrosome amplification) leads to
defective mitosis and chromosome segregation errors, is frequently found in a
variety of cancer types, and believed to be the major cause of chromosome
instability. One mechanism for generation of amplified centrosomes is over
duplication of centrosomes in a single cell cycle, which is expected to occur
when cells are temporarily arrested. There are a growing number of kinases that
are critical for induction and promotion of centrosome amplification in the cell
cycle-arrested cells, including Rho-associated kinase (ROCK2), Polo-like kinase 2
(PLK2) and PLK4. Here, we tested whether these kinases induce centrosome
amplification in a linear pathway or parallel pathways. We first confirmed that
ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the
cells arrested by exposure to DNA synthesis inhibitor. Using the centrosome
amplification rescue assay, we found that PLK2 indirectly activates ROCK2 via
phosphorylating nucleophosmin (NPM), and PLK4 functions downstream of ROCK2 to
drive centrosome amplification in the arrested cells.
PMID- 25590561
TI - Assessment of viability of human fat injection into nude mice with micro-computed
tomography.
AB - Lipotransfer is a vital tool in the surgeon's armamentarium for the treatment of
soft tissue deficits of throughout the body. Fat is the ideal soft tissue filler
as it is readily available, easily obtained, inexpensive, and inherently
biocompatible.(1) However, despite its burgeoning popularity, fat grafting is
hampered by unpredictable results and variable graft survival, with published
retention rates ranging anywhere from 10-80%. (1-3) To facilitate investigations
on fat grafting, we have therefore developed an animal model that allows for real
time analysis of injected fat volume retention. Briefly, a small cut is made in
the scalp of a CD-1 nude mouse and 200-400 ul of processed lipoaspirate is placed
over the skull. The scalp is chosen as the recipient site because of its absence
of native subcutaneous fat, and because of the excellent background contrast
provided by the calvarium, which aids in the analysis process. Micro-computed
tomography (micro-CT) is used to scan the graft at baseline and every two weeks
thereafter. The CT images are reconstructed, and an imaging software is used to
quantify graft volumes. Traditionally, techniques to assess fat graft volume have
necessitated euthanizing the study animal to provide just a single assessment of
graft weight and volume by physical measurement ex vivo. Biochemical and
histological comparisons have likewise required the study animal to be
euthanized. This described imaging technique offers the advantage of visualizing
and objectively quantifying volume at multiple time points after initial grafting
without having to sacrifice the study animal. The technique is limited by the
size of the graft able to be injected as larger grafts risk skin and fat
necrosis. This method has utility for all studies evaluating fat graft viability
and volume retention. It is particularly well-suited to providing a visual
representation of fat grafts and following changes in volume over time.
PMID- 25590562
TI - The clinical value of whole blood point-of-care biomarkers in large animal
emergency and critical care medicine.
AB - OBJECTIVE: To summarize the current medical literature and provide a clinical
perspective of whole blood point-of-care (POC) biomarkers in large animal
emergency and critical care practice. DATA SOURCES: Original studies, reviews,
and textbook chapters in the human and veterinary medical fields. SUMMARY: POC
biomarkers are tests used to monitor normal or disease processes at or near the
patient. In both human and veterinary medicine these tools are playing an
increasingly important role in the management of critical diseases. The most
important whole blood POC biomarkers available for veterinary practitioners
include l-lactate, cardiac troponin I, serum amyloid A, triglyceride, creatinine,
and glucose, although many other tests are available or on the horizon.
CONCLUSION: Whole blood POC biomarkers enable clinicians to provide improved
management of critical diseases in large animals. These tools are especially
useful for establishing a diagnosis, guiding therapy, and estimating disease risk
and prognosis.
PMID- 25590563
TI - Neural network for constrained nonsmooth optimization using Tikhonov
regularization.
AB - This paper presents a one-layer neural network to solve nonsmooth convex
optimization problems based on the Tikhonov regularization method. Firstly, it is
shown that the optimal solution of the original problem can be approximated by
the optimal solution of a strongly convex optimization problems. Then, it is
proved that for any initial point, the state of the proposed neural network
enters the equality feasible region in finite time, and is globally convergent to
the unique optimal solution of the related strongly convex optimization problems.
Compared with the existing neural networks, the proposed neural network has lower
model complexity and does not need penalty parameters. In the end, some numerical
examples and application are given to illustrate the effectiveness and
improvement of the proposed neural network.
PMID- 25590565
TI - Black titanium dioxide (TiO2) nanomaterials.
AB - In the past few decades, there has been a wide research interest in titanium
dioxide (TiO2) nanomaterials due to their applications in photocatalytic hydrogen
generation and environmental pollution removal. Improving the optical absorption
properties of TiO2 nanomaterials has been successfully demonstrated to enhance
their photocatalytic activities, especially in the report of black TiO2
nanoparticles. The recent progress in the investigation of black TiO2
nanomaterials has been reviewed here, and special emphasis has been given on
their fabrication methods along with their various chemical/physical properties
and applications.
PMID- 25590564
TI - Chemotherapy-induced vascular toxicity--real-time in vivo imaging of vessel
impairment.
AB - Certain classes of chemotherapies may exert acute vascular changes that may
progress into long-term conditions that may predispose the patient to an
increased risk of vascular morbidity. Yet, albeit the mounting clinical evidence,
there is a paucity of clear studies of vascular toxicity and therefore the
etiology of a heterogeneous group of vascular/cardiovascular disorders remains to
be elucidated. Moreover, the mechanism that may underlie vascular toxicity can
completely differ from the principles of chemotherapy-induced cardiotoxicity,
which is related to direct myocyte injury. We have established a real-time, in
vivo molecular imaging platform to evaluate the potential acute vascular toxicity
of anti-cancer therapies. We have set up a platform of in vivo, high-resolution
molecular imaging in mice, suitable for visualizing vasculature within confined
organs and reference blood vessels within the same individuals whereas each
individual serve as its own control. Blood vessel walls were impaired after
doxorubicin administration, representing a unique mechanism of vascular toxicity
that may be the early event in end-organ injury. Herein, the method of fibered
confocal fluorescent microscopy (FCFM) based imaging is described, which provides
an innovative mode to understand physiological phenomena at the cellular and sub
cellular levels in animal subjects.
PMID- 25590566
TI - Effect of focused ion beam deposition induced contamination on the transport
properties of nano devices.
AB - Focused ion beam (FIB) deposition produces unwanted particle contamination beyond
the deposition point. This is due to the FIB having a Gaussian distribution. This
work investigates the spatial extent of this contamination and its influence on
the electrical properties of nano-electronic devices. A correlation study is
performed on carbon-nanotube (CNT) devices manufactured using FIB deposition. The
devices are observed using transmission electron microscopy (TEM) and these
images are correlated with device electrical characteristics. To discover how far
Pt-nanoparticle contamination occurs along a CNT after FIB electrical contact
deposition careful TEM inspections are performed. The results show FIB deposition
efficiently improves electrical contact; however, the practice is accompanied by
serious particle contamination near deposition points. These contaminants include
metal particles and amorphous elements originating from precursor gases and
residual water molecules in the vacuum chamber. Pt-contamination extends for
approximately 2 MUm from the point of FIB contact deposition. These contaminants
cause current fluctuations and alter the transport characteristics of devices. It
is recommended that nano-device fabrication occurs at a distance greater than 2
MUm from the FIB deposition of an electrical contact.
PMID- 25590567
TI - Dry grinding effect on pyrophyllite-quartz natural mixture and its influence on
the structural alternation of pyrophyllite.
AB - Infrared spectroscopy (IR), scanning electron microscopy (SEM), X-ray diffraction
(XRD), and high-resolution transmission electron microscopy (HRTEM) with energy
dispersive X-ray analysis (EDS) were used to investigate the evolution of
mechanical destruction of the pyrophyllite structure and final ground products
upon grinding with a laboratory planetary ball mill. The raw ore used in this
present work was mainly composed of pyrophyllite and quartz. This pyrophyllite
was more resistant toward mechanical destruction, and the crystalline order of
pyrophyllite was not completely destroyed until grinding for 240 min with a 20:1
of weight ratio of the balls to powder. The existing crystalline phase in the
final ground product was found to be quartz, which served as the associated phase
in the original pyrophyllite mineral. The rate of destruction of pyrophyllite
structure depended on the types of chemical bonds. Additionally, increasing the
intensity of grinding resulted in acceleration of the mechanically induced
amorphization of the pyrophyllite structure, whereas the associated quartz grains
contributed to the deceleration of the amorphization of pyrophyllite.
PMID- 25590568
TI - Silicone oil emulsification at the fovea as a reversible cause of vision loss.
PMID- 25590569
TI - Whole mount labeling of cilia in the main olfactory system of mice.
AB - The mouse olfactory system comprises 6-10 million olfactory sensory neurons in
the epithelium lining the nasal cavity. Olfactory neurons extend a single
dendrite to the surface of the epithelium, ending in a structure called dendritic
knob. Cilia emanate from this knob into the mucus covering the epithelial
surface. The proteins of the olfactory signal transduction cascade are mainly
localized in the ciliary membrane, being in direct contact with volatile
substances in the environment. For a detailed understanding of olfactory signal
transduction, one important aspect is the exact morphological analysis of
signaling protein distribution. Using light microscopical approaches in
conventional cryosections, protein localization in olfactory cilia is difficult
to determine due to the density of ciliary structures. To overcome this problem,
we optimized an approach for whole mount labeling of cilia, leading to improved
visualization of their morphology and the distribution of signaling proteins. We
demonstrate the power of this approach by comparing whole mount and conventional
cryosection labeling of Kirrel2. This axon-guidance adhesion molecule is known to
localize in a subset of sensory neurons and their axons in an activity-dependent
manner. Whole mount cilia labeling revealed an additional and novel picture of
the localization of this protein.
PMID- 25590571
TI - Message from the Editor-in-Chief.
AB - One year after I assumed the position of Editor in Chief of Life, it is my great
pleasure to write this editorial highlighting our achievements during this
period, which were so many! As I wrote in the first editorial, my commitment was
to make the journal a success, with the launch of exciting special issues,
publication of high quality papers as well as inclusion of the journal in major
indexing and abstracting services [1]. Basically, throughout 2014, all these
commitments have been accomplished. Several eminent team leaders have joined our
editorial board [2], timely special issues have been launched [3], and the
journal already was indexed in PubMed [4]; now, it is just a matter of time to be
indexed in Web of Science. The feedback from the scientific community already has
been quite positive. With timely special issues lined up for 2015, the journal is
developing quite fast.[...].
PMID- 25590572
TI - Octahedral metal clusters as building blocks of trimetallic superexpanded
Prussian blue analogues.
AB - The self-assembly of octahedral metal clusters (diamagnetic
[Nb(6)Cl(12)(CN)(6)](4-) or paramagnetic [Ta(6)Cl(12)(CN)(6)](3-)),
[Mn(salen)](+) [salen = N,N'-ethylenebis(salicylidene)iminate] and mononuclear
{M'(CN)(x)} polycyanometallates ([Fe(CN)(6)](4-), [Cr(CN)(6)](3-),
[Fe(CN)(5)(NO)](2-), or [Ni(CN)(4)](2-)) building blocks results in the formation
of a series of six cluster-containing 3D heterotrimetallic frameworks:
[H(3)O](2)[Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)(6)].3H(2)O (1),
[H(3)O][Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Cr(CN)(6)].4H(2)O (2),
[Nb(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)(5)(NO)].5H(2)O (3),
[Nb(6)Cl(12)(CN)6[Mn(salen)](6)Ni(CN)4].7H(2)O (4),
[H(3)O][Ta(6)Cl(12)(CN)(6)[Mn(salen)](6)Fe(CN)6].4H(2)O (5), and
[Ta(6)Cl(12)(CN)(6)[Mn(salen)](6)Cr(CN)(6)].7H(2)O (6). Single-crystal X-ray
diffraction analyses show that compounds 1, 2, 5, and 6 have distorted face
centered-cubic frameworks that can be considered as superexpanded Prussian blue
analogues built of two different hexacyanometallate nodes and expanded by
insertion of the [Mn(salen)](+) complex, while 4 features a quasi-superexpanded
Prussian blue framework because the structure is based on the hexacyano metal
cluster and disordered tetracyano [Ni(CN)(4)](2-) nodes. The powder X-ray
diffraction of 3 indicates that it possesses a quasi-superexpanded Prussian blue
framework based on the hexacyano cluster and disordered pentacyano
[Fe(CN)(5)(NO)](2-) nodes. Compound 6 is the first compound containing three 3d
3d'-M6 cluster (4d) spin centers. Magnetic measurements reveal that the overall
magnetic nature can be systematically controlled by the choice of the octahedral
metal cluster and polycyanometallate nodes. H(2)/N(2) adsorption and thermal
stability of the compounds were investigated.
PMID- 25590570
TI - Emergent chemical behavior in variable-volume protocells.
AB - Artificial protocellular compartments and lipid vesicles have been used as model
systems to understand the origins and requirements for early cells, as well as to
design encapsulated reactors for biotechnology. One prominent feature of vesicles
is the semi-permeable nature of their membranes, able to support passive
diffusion of individual solute species into/out of the compartment, in addition
to an osmotic water flow in the opposite direction to the net solute
concentration gradient. Crucially, this water flow affects the internal aqueous
volume of the vesicle in response to osmotic imbalances, in particular those
created by ongoing reactions within the system. In this theoretical study, we pay
attention to this often overlooked aspect and show, via the use of a simple semi
spatial vesicle reactor model, that a changing solvent volume introduces
interesting non-linearities into an encapsulated chemistry. Focusing on
bistability, we demonstrate how a changing volume compartment can degenerate
existing bistable reactions, but also promote emergent bistability from very
simple reactions, which are not bistable in bulk conditions. One particularly
remarkable effect is that two or more chemically-independent reactions, with
mutually exclusive reaction kinetics, are able to couple their dynamics through
the variation of solvent volume inside the vesicle. Our results suggest that
other chemical innovations should be expected when more realistic and active
properties of protocellular compartments are taken into account.
PMID- 25590573
TI - Comparative study of vapor- and solution-crystallized perovskite for planar
heterojunction solar cells.
AB - Organometal halide perovskite (CH3NH3PbI3) could be crystallized by exposing PbI2
to either CH3NH3I solution or CH3NH3I vapor. Though high performance was achieved
in both approaches, it was still not clear which approach would be more desirable
for device performance in principle. Herein, we addressed this issue by
investigating the influence of crystallization condition on perovskite
morphology, and subsequently on device performances. We found that vapor
crystallized perovskite devices demonstrated smoother surface morphology, better
light absorption, lower charge recombination, and thus much higher conversion
efficiency than solution-crystallized devices, which would give some useful
enlightenment to develop high-performance planar perovskite solar cells.
PMID- 25590575
TI - Noncovalent magnetic control and reversible recovery of graphene oxide using iron
oxide and magnetic surfactants.
AB - The unique charging properties of graphene oxide (GO) are exploited in the
preparation of a range of noncovalent magnetic GO materials, using
microparticles, nanoparticles, and magnetic surfactants. Adsorption and
desorption are controlled by modification of pH within a narrow window of <2 pH
units. The benefit conferred by using charge-based adsorption is that the process
is reversible, and the GO can be captured and separated from the magnetic
nanomaterial, such that both components can be recycled. Iron oxide (Fe2O3)
microparticles form a loosely flocculated gel network with GO, which is
demonstrated to undergo magnetic compressional dewatering in the presence of an
external magnetic field. For composites formed from GO and Fe2O3 nanoparticles,
it is found that low Fe2O3:GO mass ratios (<5:1) favor flocculation of GO,
whereas higher ratios (>5:1) cause overcharging of the surfaces resulting in
restabilization. The effectiveness of the GO adsorption and magnetic capture
process is demonstrated by separating traditionally difficult-to-recover gold
nanoparticles (d ~ 10 nm) from water. The fully recyclable nature of the assembly
and capture process, combined with the vast adsorption capacity of GO, presents
obvious and appealing advantages for applications in decontamination and water
treatment.
PMID- 25590574
TI - Learning faces: similar comparator faces do not improve performance.
AB - Recent evidence indicates that comparison of two similar faces can aid subsequent
discrimination between them. However, the fact that discrimination between two
faces is facilitated by comparing them directly does not demonstrate that
comparison produces a general improvement in the processing of faces. It remains
an open question whether the opportunity to compare a "target" face to similar
faces can facilitate the discrimination of the exposed target face from other
nonexposed faces. In Experiment 1, selection of a target face from an array of
novel foils was not facilitated by intermixed exposure to the target and
comparators of the same sex. Experiment 2 also found no advantage for similar
comparators (morphed towards the target) over unmorphed same sex comparators, or
over repeated target exposure alone. But all repeated exposure conditions
produced better performance than a single brief presentation of the target.
Experiment 3 again demonstrated that repeated exposure produced equivalent
learning in same sex and different sex comparator conditions, and also showed
that increasing the number of same sex or different sex comparators failed to
improve identification. In all three experiments, exposure to a target alongside
similar comparators failed to support selection of the target from novel test
stimuli to a greater degree than exposure alongside dissimilar comparators or
repeated target exposure alone. The current results suggest that the facilitatory
effects of comparison during exposure may be limited to improving discrimination
between exposed stimuli, and thus our results do not support the idea that
providing the opportunity for comparison is a practical means for improving face
identification.
PMID- 25590576
TI - System model network for adipose tissue signatures related to weight changes in
response to calorie restriction and subsequent weight maintenance.
AB - Nutrigenomics investigates relationships between nutrients and all genome-encoded
molecular entities. This holistic approach requires systems biology to scrutinize
the effects of diet on tissue biology. To decipher the adipose tissue (AT)
response to diet induced weight changes we focused on key molecular (lipids and
transcripts) AT species during a longitudinal dietary intervention. To obtain a
systems model, a network approach was used to combine all sets of variables (bio
clinical, fatty acids and mRNA levels) and get an overview of their interactions.
AT fatty acids and mRNA levels were quantified in 135 obese women at baseline,
after an 8-week low calorie diet (LCD) and after 6 months of ad libitum weight
maintenance diet (WMD). After LCD, individuals were stratified a posteriori
according to weight change during WMD. A 3 steps approach was used to infer a
global model involving the 3 sets of variables. It consisted in inferring intra
omic networks with sparse partial correlations and inter-omic networks with
regularized canonical correlation analysis and finally combining the obtained
omic-specific network in a single global model. The resulting networks were
analyzed using node clustering, systematic important node extraction and cluster
comparisons. Overall, AT showed both constant and phase-specific biological
signatures in response to dietary intervention. AT from women regaining weight
displayed growth factors, angiogenesis and proliferation signaling signatures,
suggesting unfavorable tissue hyperplasia. By contrast, after LCD a strong
positive relationship between AT myristoleic acid (a fatty acid with low AT
level) content and de novo lipogenesis mRNAs was found. This relationship was
also observed, after WMD, in the group of women that continued to lose weight.
This original system biology approach provides novel insight in the AT response
to weight control by highlighting the central role of myristoleic acid that may
account for the beneficial effects of weight loss.
PMID- 25590577
TI - Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive
aspergillosis.
AB - Invasive aspergillosis (IA) has become increasingly common and is characterised
by high morbidity and mortality. Upcoming resistance threatens treatment with
azoles and highlights the continuous need for novel therapeutics. This laboratory
study investigated the in vitro and in vivo potential of the alkylphospholipid
oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC,
miltefosine, posaconazole and voriconazole were determined for Aspergillus
fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was
evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long
term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity
against A. fumigatus (IC50 = 1.04 MUmol l(-1)). Intraperitoneal administration of
50 mg kg(-1) day(-1) OlPC significantly reduced the fungal organ burdens at 4
days post-infection (dpi). Although 5- and 10-day OlPC treatment improved
survival, organ burdens were not affected at 10 and 15 dpi. While this study
showed excellent in vitro activity of OlPC against Aspergillus spp., its
therapeutic efficacy in an acute mouse model for IA was less convincing. Given
the limited therapeutic options in the current antifungal market for invasive
infections, OlPC activity should be assessed in a less stringent in vivo model,
potentially in combination treatment with other already marketed antifungal
drugs.
PMID- 25590578
TI - Vanadium-catalyzed regioselective oxidative coupling of 2-hydroxycarbazoles.
AB - The first regioselective oxidative coupling of 2-hydroxycarbazoles is described.
With a vanadium catalyst and oxygen as the terminal oxidant, dimers with an ortho
ortho' coupling pattern were obtained with high selectivity. Further oxidation
led to ortho'-ortho' coupling to generate a tetramer, which provided insight that
the atropisomerization barriers of the unsymmetrical biaryl bonds are much lower
than expected.
PMID- 25590579
TI - eIF2 kinases mediate beta-lapachone toxicity in yeast and human cancer cells.
AB - beta-Lapachone (beta-lap) is a novel anticancer agent that selectively induces
cell death in human cancer cells, by activation of the NQO1 NAD(P)H dehydrogenase
and radical oxygen species (ROS) generation. We characterized the gene expression
profile of budding yeast cells treated with beta-lap using cDNA microarrays.
Genes involved in tolerance to oxidative stress were differentially expressed in
beta-lap treated cells. beta-lap treatment generated reactive oxygen species
(ROS), which were efficiently blocked by dicoumarol, an inhibitor of NADH
dehydrogenases. A yeast mutant in the mitochondrial NADH dehydrogenase Nde2p was
found to be resistant to beta-lap treatment, despite inducing ROS production in a
WT manner. Most interestingly, DNA damage responses triggered by beta-lap were
abolished in the nde2Delta mutant. Amino acid biosynthesis genes were also
induced in beta-lap treated cells, suggesting that beta-lap exposure somehow
triggered the General Control of Nutrients (GCN) pathway. Accordingly, beta-lap
treatment increased phosphorylation of eIF2alpha subunit in a manner dependent on
the Gcn2p kinase. eIF2alpha phosphorylation required Gcn1p, Gcn20p and Nde2p.
Gcn2p was also required for cell survival upon exposure to beta-lap and to elicit
checkpoint responses. Remarkably, beta-lap treatment increased phosphorylation of
eIF2alpha in breast tumor cells, in a manner dependent on the Nde2p ortholog AIF,
and the eIF2 kinase PERK. These findings uncover a new target pathway of beta-lap
in yeast and human cells and highlight a previously unknown functional connection
between Nde2p, Gcn2p and DNA damage responses.
PMID- 25590580
TI - Frequent amplification of PTP1B is associated with poor survival of gastric
cancer patients.
AB - The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine
phosphatase, has been implicated in gastric pathogenesis. Several lines of recent
evidences have shown that PTP1B is highly amplified in breast and prostate
cancers. The aim of this study was to investigate PTP1B amplification in gastric
cancer and its association with poor prognosis of gastric cancer patients, and
further determine the role of PTP1B in gastric tumorigenesis. Our data
demonstrated that PTP1B was significantly up-regulated in gastric cancer tissues
as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT
PCR) assay. In addition, copy number analysis showed that PTP1B was amplified in
68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the
control subjects. Notably, PTP1B amplification was positively associated with its
protein expression, and was significantly related to poor survival of gastric
cancer patients. Knocking down PTP1B expression in gastric cancer cells
significantly inhibited cell proliferation, colony formation, migration and
invasion, and induced cell cycle arrested and apoptosis. Mechanically, PTP1B
promotes gastric cancer cell proliferation, survival and invasiveness through
modulating Src-related signaling pathways, such as Src/Ras/MAPK and
Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data
demonstrated frequent overexpression and amplification PTP1B in gastric cancer,
and further determined the oncogenic role of PTP1B in gastric carcinogenesis.
Importantly, PTP1B amplification predicts poor survival of gastric cancer
patients.
PMID- 25590582
TI - Capillary blood flow imaging within human finger cuticle using optical
microangiography.
AB - We report non-invasive 3D imaging of capillary blood flow within human finger
cuticle by the use of Doppler optical microangiography (DOMAG) and ultra-high
sensitive optical microangiography (UHS-OMAG) techniques. Wide velocity range
DOMAG method is applied to provide red blood cell (RBC) axial velocity mapping in
capillary loops with ranges of +/-0.9 mm/s and +/-0.3 mm/s. Additionally, UHS
OMAG technique is engineered to acquire high resolution image of capillary
morphology. The presented results are promising to facilitate clinical trials of
treatment and diagnosis of various diseases such as diabetes, Raynaud's
phenomenon, and connective tissue diseases by quantifying cutaneous blood flow
changes within human finger cuticle.
PMID- 25590581
TI - GITR intrinsically sustains early type 1 and late follicular helper CD4 T cell
accumulation to control a chronic viral infection.
AB - CD4 T cells are critical for control of persistent infections; however, the key
signals that regulate CD4 T help during chronic infection remain incompletely
defined. While several studies have addressed the role of inhibitory receptors
and soluble factors such as PD-1 and IL-10, significantly less work has addressed
the role of T cell co-stimulatory molecules during chronic viral infection. Here
we show that during a persistent infection with lymphocytic choriomeningitis
virus (LCMV) clone 13, mice lacking the glucocorticoid-induced tumor necrosis
factor receptor related protein (GITR) exhibit defective CD8 T cell accumulation,
increased T cell exhaustion and impaired viral control. Differences in CD8 T
cells and viral control between GITR+/+ and GITR-/- mice were lost when CD4 T
cells were depleted. Moreover, mixed bone marrow chimeric mice, as well as
transfer of LCMV epitope-specific CD4 or CD8 T cells, demonstrated that these
effects of GITR are largely CD4 T cell-intrinsic. GITR is dispensable for initial
CD4 T cell proliferation and differentiation, but supports the post-priming
accumulation of IFNgamma+IL-2+ Th1 cells, facilitating CD8 T cell expansion and
early viral control. GITR-dependent phosphorylation of the p65 subunit of NF
kappaB as well as phosphorylation of the downstream mTORC1 target, S6 ribosomal
protein, were detected at day three post-infection (p.i.), and defects in CD4 T
cell accumulation in GITR-deficient T cells were apparent starting at day five
p.i. Consistently, we pinpoint IL-2-dependent CD4 T cell help for CD8 T cells to
between days four and eight p.i. GITR also increases the ratio of T follicular
helper to T follicular regulatory cells and thereby enhances LCMV-specific IgG
production. Together, these findings identify a CD4 T cell-intrinsic role for
GITR in sustaining early CD8 and late humoral responses to collectively promote
control of chronic LCMV clone 13 infection.
PMID- 25590584
TI - Catalysts for RNA and DNA modification.
AB - To study DNAs and RNAs it is often necessary to chemically modify them. Nature's
strategy for nucleic acid modification is to use selective catalysts, and
chemists have begun to emulate this conceptual approach. In this review we
present a summary of catalytic approaches toward the construction of modified
RNAs and DNAs and outline our opinions on where new research is needed.
PMID- 25590585
TI - Dual role of Rh(III) catalyst enables regioselective halogenation of (electron
rich) heterocycles.
AB - The Rh(III)-catalyzed selective bromination and iodination of electron-rich
heterocycles is reported. Kinetic investigations show that Rh plays a dual role
in the bromination, catalyzing the directed halogenation and preventing the
inherent halogenation of these substrates. As a result, this method gives highly
selective access to valuable halogenated heterocycles with regiochemistry
complementary to those obtained using uncatalyzed approaches, which rely on the
inherent reactivity of these classes of substrates. Furans, thiophenes,
benzothiophenes, pyrazoles, quinolones, and chromones can be applied.
PMID- 25590583
TI - Breast cancer genes PSMC3IP and EPSTI1 play a role in apoptosis regulation.
AB - A key element to delineate the biology of individual tumors is the regulation of
apoptosis. In this work, we functionally characterize two breast cancer
associated genes, the proteasome 26S subunit ATPase 3 interacting protein
(PSMC3IP) and the epithelial-stromal interaction 1 (EPSTI1), to explore their
potential apoptotic role in breast cancer. We first explore the existence of
direct physical interactions with annotated BC-apoptotic genes. Based on the
generated interaction network, we examine several apoptotic markers to determine
the effect of PSMC3IP and EPSTI1 gene expression modulation in two different
human breast cancer cell lines to suggest potential molecular mechanisms to
unveil their role in the disease. Our results show that PSMC3IP and EPSTI1 are
able to modulate the extrinsic apoptotic pathway in estrogen receptor positive
and triple negative breast cancer cell lines, highlighting them as potential
therapeutic targets.
PMID- 25590586
TI - A clinical and molecular analysis of branchio-oculo-facial syndrome patients in
Russia revealed new mutations in TFAP2A.
AB - Branchio-oculo-facial syndrome (BOFS, OMIM# 113620) is a rare autosomal dominant
disorder characterised by branchial cleft sinus defects, ocular anomalies and
facial dysmorphisms, including lip or palate cleft or pseudocleft, and is
associated with mutations in the TFAP2A gene. Here, we performed clinical
analysis and mutation diagnostics in seven BOFS patients in Russia. The
phenotypic presentation of BOFS observed in three patients showed high
heterogeneity, including variation in its main clinical manifestations (linear
loci of cervical cutaneous aplasia, ocular anomalies and orofacial cleft). In
certain other cases, isolated ocular anomalies, or an orofacial cleft with
accessory BOFS symptoms, were observed. In five BOFS patients, conductive hearing
loss was diagnosed. Direct sequencing of the coding region of the TFAP2A gene
revealed missense mutations in four BOFS patients. One patient was observed to
have a previously described mutation (p.Arg251Gly), while three patients from two
families were found to have novel mutations: p.Arg213Ser and p.Val210Asp. These
novel mutations were not present in healthy members of the same family and
therefore should be classified as de novo.
PMID- 25590588
TI - Presence, species distribution, and density of Malassezia yeast in patients with
seborrhoeic dermatitis - a community-based case-control study and review of
literature.
AB - Malassezia yeast belongs to the normal cutaneous flora and under certain
conditions it causes seborrhoeic dermatitis (SD). There is no culture-based study
about the presence and density of the Malassezia in SD patients in Serbia. Aim
was to show the presence, species distribution and density of Malassezia in
patients with SD on lesional skin (LS) and non-lesional skin (NLS) and healthy
controls (HC) and to compare data between Serbia and other countries. The study
included 70 HC and 60 patients with SD in the study group (SG). Isolation,
identification and examination of density of Malassezia colony-forming units from
LS and NLS were performed. Malassezia was found more frequently in the SG than in
HC, 90% and 60%, respectively (P < 0.01). The most frequent isolates in SG on LS
were M. slooffiae (26%), followed by M. globosa (17%) and M. sympodialis (17%).
The yeast density was much higher on LS of SG than on NLS of SG or in the HC
group (P < 0.05). Higher density of Malassezia was shown on LS of SG than on NLS
of SG and HC. M. slooffiae is the most prevalent species in SD patients in
Serbia. This study demonstrated a positive relationship between severity of SD
and presence of Malassezia spp.
PMID- 25590587
TI - Characterization of Plasmodium ovale curtisi and P. ovale wallikeri in Western
Kenya utilizing a novel species-specific real-time PCR assay.
AB - BACKGROUND: Plasmodium ovale is comprised of two genetically distinct subspecies,
P. ovale curtisi and P. ovale wallikeri. Although P. ovale subspecies are similar
based on morphology and geographical distribution, allelic differences indicate
that P. ovale curtisi and P. ovale wallikeri are genetically divergent.
Additionally, potential clinical and latency duration differences between P.
ovale curtisi and P. ovale wallikeri demonstrate the need for investigation into
the contribution of this neglected malaria parasite to the global malaria burden.
METHODS: In order to detect all P. ovale subspecies simultaneously, we developed
an inclusive P. ovale-specific real-time PCR assay based on conserved regions
between P. ovale curtisi and P. ovale wallikeri in the reticulocyte binding
protein 2 (rbp2) gene. Additionally, we characterized the P. ovale subspecies
prevalence from 22 asymptomatic malaria infections using multilocus genotyping to
discriminate P. ovale curtisi and P. ovale wallikeri. RESULTS: Our P. ovale rbp2
qPCR assay validation experiments demonstrated a linear dynamic range from 6.25
rbp2 plasmid copies/microliter to 100,000 rbp2 plasmid copies/microliter and a
limit of detection of 1.5 rbp2 plasmid copies/microliter. Specificity experiments
showed the ability of the rbp2 qPCR assay to detect low-levels of P. ovale in the
presence of additional malaria parasite species, including P. falciparum, P.
vivax, and P. malariae. We identified P. ovale curtisi and P. ovale wallikeri in
Western Kenya by DNA sequencing of the tryptophan-rich antigen gene, the small
subunit ribosomal RNA gene, and the rbp2 gene. CONCLUSIONS: Our novel P. ovale
rbp2 qPCR assay detects P. ovale curtisi and P. ovale wallikeri simultaneously
and can be utilized to characterize the prevalence, distribution, and burden of
P. ovale in malaria endemic regions. Using multilocus genotyping, we also
provided the first description of the prevalence of P. ovale curtisi and P. ovale
wallikeri in Western Kenya, a region holoendemic for malaria transmission.
PMID- 25590589
TI - Incubation temperature influences trade-off between structural size and energy
reserves in mallard hatchlings.
AB - The reproductive success of precocial birds depends on investments in clutch
formation and incubation. Egg quality strongly affects the phenotypic traits
correlated with survival of the hatchling, but parental ability to maintain
incubation temperature can also influence hatchling outcomes. The effect of
incubation temperature on hatchling phenotype has been widely studied in reptiles
but not in birds. The aim of this study was to explore the effects of egg mass
and incubation temperature on the incubation period, hatchability, and hatchling
phenotype of the mallard (Anas platyrhynchos). Mallard eggs were incubated under
six constant incubation temperatures (ranging from 35.0 degrees to 39.0 degrees
C). Hatchlings were weighed, and their structural size was measured. Some
hatchlings were used for an examination of residual yolk sac mass and basic
chemical composition of the yolk-free body. All investigated phenotypic traits
except for chemical composition were positively correlated with egg mass.
Incubation temperature did not affect hatchling body mass, but increased
temperatures led to a decreased yolk-free body mass and structural size of
hatchlings and to increased yolk sac mass. Our results suggest that there is a
trade-off between the yolk-free body size and energetic reserves in the form of
the yolk sac and that this trade-off is modulated by incubation temperature.
PMID- 25590590
TI - Epaulet size and current condition in red-winged blackbirds: examining a
semistatic signal, testosterone, immune function, and parasites.
AB - Some sexually selected signals are thought to convey information about the
current condition and genetic/epigenetic quality of the individual signaling,
including the ability to resist parasites. However, it is unclear whether
semistatic sexual signals that develop periodically and remain stable over
protracted periods, such as avian breeding plumage, can relate to measures of
current condition and health. We examined a semistatic signal (wing epaulet size)
in male red-winged blackbirds (Agelaius phoeniceus) during the breeding season
and looked for relationships between this trait and circulating testosterone (T),
hematocrit, bacteria-killing ability (BKA) of the blood, and the infection
status, richness, and abundance of four functional categories of parasite. We
found that epaulet size was positively related to circulating levels of T and
ectoparasite infections. We found no relationships between T and parasite
infections. In adult males there was a negative relationship between T and BKA,
whereas in yearling males there was no relationship. We found no evidence for a
general reduction in immunocompetence in males with larger epaulets but rather an
increase in susceptibility to specific types of parasites. Our results suggest
that semistatic signals can be linked to measures of current condition, and we
postulate that these relationships are modulated via activity levels related to
breeding-season activities.
PMID- 25590591
TI - Effect of nutritional status on the osmoregulation of green sturgeon (Acipenser
medirostris).
AB - Anthropogenic climate change is linked to food web and salinity fluctuations in
estuarine environments. Both decreased nutritional status and environmental
salinity influence the physiological tolerance and health of fish populations;
however, limited information on the interaction of these two factors and their
physiological consequences is available. The green sturgeon (Acipenser
medirostris) is a species of special concern in California, and the southern
distinct population segment is listed as threatened. To test the hypothesis that
poor nutrition negatively affects osmoregulation, juvenile green sturgeon (222 d
posthatch) were randomly assigned to four feed restriction groups (12.5%, 25%,
50%, and 100% of the optimal feeding rate for 4 wk). Fish were then acutely
exposed to 0-, 8-, 16-, or 32-ppt salinities and sampled at three time points
(12, 72, or 120 h). Feed restriction significantly (P < 0.05) decreased specific
growth rate, feed efficiency, condition factor, whole-body lipids, and protein
content as well as plasma glucose, triglycerides, and proteins. Furthermore, feed
restriction, salinity concentration, and salinity exposure time had significant
effects on hematological indexes (hematocrit, hemoglobin), plasma values
(osmolality, Na(+), K(+), Cl(-), glucose, lactate, cortisol), enzymatic activity
(gill and pyloric ceca Na(+)/K(+) ATPase), and morphology of gill mitochondria
rich cells. The largest disturbances were observed at the highest salinity
treatments across all feeding regimes. In addition, the interaction between feed
restriction and acute salinity exposure at the highest salinity treatment
resulted in high mortality rates during the first 72 h of salinity exposure.
Evaluating the interactions of these environmental stressors and their
implications on green sturgeon physiological tolerance will inform restoration
and management efforts in rapidly changing estuarine environments.
PMID- 25590592
TI - Metabolomic differentiation of nutritional stress in an aquatic invertebrate.
AB - Poor diet quality frequently constrains the growth and reproduction of primary
consumers, altering their population dynamics, interactions in food webs, and
contributions to ecosystem services such as nutrient cycling. The identification
and measurement of an animal's nutritional state are thus central to studying the
connections between diet and animal ecology. Here we show how the nutritional
state of a freshwater invertebrate, Daphnia magna, can be determined by analyzing
its endogenous metabolites using hydrogen nuclear magnetic resonance-based
metabolomics. With a multivariate analysis, we observed the differentiation of
the metabolite composition of animals grown under control conditions (good food
and no environmental stress), raised on different diets (low quantity, nitrogen
limited, and phosphorus limited), and exposed to two common environmental
stressors (bacterial infection and salt stress). We identified 18 metabolites
that were significantly different between control animals and at least one
limiting food type or environmental stressor. The unique metabolite responses of
animals caused by inadequate nutrition and environmental stress are reflective of
dramatic and distinctive effects that each stressor has on animal metabolism. Our
results suggest that dietary-specific induced changes in metabolite composition
of animal consumers hold considerable promise as indicators of nutritional stress
and will be invaluable to future studies of animal nutrition.
PMID- 25590593
TI - Effects of starvation and molting on the metabolic rate of the bed bug (Cimex
lectularius L.).
AB - The bed bug (Cimex lectularius L.) is a common hematophagous pest in the urban
environment and is capable of surviving extended periods of starvation. However,
the relationship between starvation and metabolism in bed bugs is not well
understood. To better understand this relationship, we measured the metabolism of
all life stages for >900 h after feeding (starvation) using closed-system
respirometry. Measurements were made around molting for the immature life stages,
which occurs only after a blood meal. In addition, both mated and unmated adults
were measured. Starvation and molting had significant effects on the metabolism
of the bed bug. Mass-specific metabolic rate (V(O2); mL g(-1) h(-1)) declined in
a curvilinear fashion with the period of starvation for adults and with the
postmolting period for immature bed bugs (used to standardize all immature life
stages). A standard curve was developed to depict the generalized pattern of
metabolic decline observed in all life stages that molted. Individual metabolic
comparisons among life stages that molted revealed some differences in metabolic
rate between unmated males and females. In addition, the mass scaling coefficient
was found to decline with starvation time (postmolting time) for all life stages
that molted. In most life stages, the ratio of V(CO2) to V(O2) (respiratory
exchange ratio) declined over time, indicating a change in metabolic substrate
with starvation. Finally, daily percent loss in body mass declined in a pattern
similar to that of V(O2). The observed patterns in metabolic decline are
evaluated in relation to the life history of bed bugs. In addition, the
evolutionary development of these patterns is discussed. The metabolic pattern
after feeding was also found to share several similarities with that of other
ectothermic species.
PMID- 25590594
TI - Natural variation in resistance to desiccation and heat shock protein expression
in the land snail Theba pisana along a climatic gradient.
AB - Land snails frequently encounter desiccating conditions, and their survival
depends on a suite of morphological, physiological, and molecular adaptations to
the specific microhabitat. Strategies of survival can be determined by
integrating information from various levels of biological organization. In this
study, we used a combination of physiological parameters related to water economy
and molecular factors (stress protein expression) to investigate the strategies
of survival adopted by seven populations of the Mediterranean-type land snail
Theba pisana from different habitats. We analyzed water compartmentalization
during aestivation and used experimental desiccation to compare desiccation
resistance. We also measured the endogenous levels of heat shock proteins (HSPs)
Hsp72, Hsp74, and Hsp90 under nonstress conditions and analyzed the HSP response
to desiccation in two populations that differed mostly in their resistance to
desiccation. We revealed significant intraspecific differences in resistance to
desiccation that seem to be determined by the speed of recruitment of the water
preserving mechanisms. The ability to cope with desiccating conditions was
correlated with habitat temperature but not with the rainfall gradient, implying
that in the coastal region, temperature is likely to have a major impact on
desiccation resistance rather than precipitation. Also, higher desiccation
resistance was correlated with higher constitutive levels of Hsp74 in the foot
tissue. HSPs were upregulated during desiccation, but the response was delayed
and was milder in the most resistant population compared to the most susceptible
one. Our study suggests that T. pisana populations from warmer habitats were more
resistant to desiccation and developed distinct strategies of HSP expression for
survival, namely, the maintenance of high constitutive levels of Hsp70 together
with a delayed and limited response to stress.
PMID- 25590595
TI - Thermogenic capacity at subzero temperatures: how low can a hibernator go?
AB - Abstract Hibernation in mammals is a physiological and behavioral adaptation to
survive intervals of low resource availability through profound decreases in
metabolic rate (MR), core body temperature (Tb), and activity. Most small
mammalian hibernators thermoconform, with Tb approximating ambient temperature
(Ta); arctic species are an exception, since they must actively defend what can
be large thermal gradients between Tb and Ta. Here we compare the thermogenic
capacity of the arctic ground squirrel (Urocitellus parryii) to that of the
golden-mantled ground squirrel (Callospermophilus lateralis), a temperate-zone
montane hibernator. We allowed animals to reenter torpor at sequentially lower
Ta's and found that arctic ground squirrels maintained steady state torpor at
Ta's as low as -26 degrees C, through a 36-fold increase in torpid MR (TMR),
compared to their minimum TMR, exhibited at a Ta of 0 degrees C. Golden-mantled
ground squirrels are able to maintain steady state torpor at Ta's at least as low
as -8 degrees C, through a 13.5-fold increase in MR, compared to their minimum
TMR at a Ta of 2 degrees C. In a second experiment, torpid animals were exposed
to continuously decreasing Ta's (0.25 degrees C/30 min); individuals of both
species increased their metabolism while remaining torpid at low Ta's (as low as
30 degrees C for arctic ground squirrels and -10 degrees C for golden-mantled
ground squirrels). Although the capacity to hibernate at subfreezing Ta's is not
unique to arctic ground squirrels, their large body size, greater torpid
metabolic scope, and previously ascribed capacity to supercool allow them to
occupy much colder hibernacula for prolonged seasons of hibernation.
PMID- 25590596
TI - Microsatellite alterations are also present in the less aggressive types of adult
T-cell leukemia-lymphoma.
AB - BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasia
etiologically linked to HTLV-1. Manifestations of ATL are diverse and different
clinical types with different tissue involvement and aggressiveness have been
described. The mechanisms that lead to the development of ATL clinical types have
not yet been clarified. Considering that in ATL patients HTLV-1 infection
generally occurs in childhood, a multistep carcinogenesis model has been
proposed. Microsatellite alterations are important genetic events in cancer
development and these alterations have been reported in the aggressive types of
ATL. Little is known about oncogenesis of the less aggressive types.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the role of the
microsatellite alterations in the pathogenesis mediated by HTLV-1 in the
different types of ATL. We examined the presence of microsatellite instability
(MSI) and loss of heterozigosity (LOH) in matched pair samples (tumoral and
normal) of 24 patients with less aggressive types (smoldering and chronic) and in
aggressive types (acute and lymphoma) of ATL. Four microsatellite markers
D10S190, D10S191, D1391 and DCC were analyzed. MSI was found in four patients,
three smoldering and one chronic, and LOH in four patients, three smoldering and
one acute. None of the smoldering patients with microsatellite alterations
progressed to aggressive ATL. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is
the first report describing the presence of MSI and LOH in the less aggressive
types of ATL. These results indicate that microsatellite alterations may
participate in the development of the less aggressive types of ATL.
PMID- 25590597
TI - Thyroid-stimulating hormone inhibits adipose triglyceride lipase in 3T3-L1
adipocytes through the PKA pathway.
AB - Thyroid-stimulating hormone (TSH) has been shown to play an important role in the
regulation of triglyceride (TG) metabolism in adipose tissue. Adipose
triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis
of TG. Thus far, it is unclear whether TSH has a direct effect on the expression
of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR
knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this
study to determine the effects of TSHR deletion on ATGL expression. These effects
were verified in 3T3-L1 adipocytes and potential underlying mechanisms were
explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was
significantly increased compared with that in Tshr+/+ mice. ATGL expression was
observed to increase with the differentiation process of 3T3-L1 preadipocytes. In
mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both
the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an
activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1
adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by
H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH
has an inhibitory effect on ATGL expression in mature adipocytes. The associated
mechanism is related to PKA activation.
PMID- 25590598
TI - Effect of cause-of-death training on agreement between hospital discharge
diagnoses and cause of death reported, inpatient hospital deaths, New York City,
2008-2010.
AB - INTRODUCTION: Accurate cause-of-death reporting is required for mortality data to
validly inform public health programming and evaluation. Research demonstrates
overreporting of heart disease on New York City death certificates. We describe
changes in reported causes of death following a New York City health department
training conducted in 2009 to improve accuracy of cause-of-death reporting at 8
hospitals. The objective of our study was to assess the degree to which death
certificates citing heart disease as cause of death agreed with hospital
discharge data and the degree to which training improved accuracy of reporting.
METHODS: We analyzed 74,373 death certificates for 2008 through 2010 that were
linked with hospital discharge records for New York City inpatient deaths and
calculated the proportion of discordant deaths, that is, death certificates
reporting an underlying cause of heart disease with no corresponding discharge
record diagnosis. We also summarized top principal diagnoses among discordant
reports and calculated the proportion of inpatient deaths reporting sepsis, a
condition underreported in New York City, to assess whether documentation
practices changed in response to clarifications made during the intervention.
RESULTS: Citywide discordance between death certificates and discharge data
decreased from 14.9% in 2008 to 9.6% in 2010 (P < .001), driven by a decrease in
discordance at intervention hospitals (20.2% in 2008 to 8.9% in 2010; P < .001).
At intervention hospitals, reporting of sepsis increased from 3.7% of inpatient
deaths in 2008 to 20.6% in 2010 (P < .001). CONCLUSION: Overreporting of heart
disease as cause of death declined at intervention hospitals, driving a citywide
decline, and sepsis reporting practices changed in accordance with health
department training. Researchers should consider the effect of overreporting and
data-quality changes when analyzing New York City heart disease mortality trends.
Other vital records jurisdictions should employ similar interventions to improve
cause-of-death reporting and use linked discharge data to monitor data quality.
PMID- 25590599
TI - Administrative data linkage to evaluate a quality improvement program in acute
stroke care, Georgia, 2006-2009.
AB - INTRODUCTION: Tracking the vital status of stroke patients through death data is
one approach to assessing the impact of quality improvement in stroke care. We
assessed the feasibility of linking Georgia hospital discharge data with
mortality data to evaluate the effect of participation in the Georgia Coverdell
Acute Stroke Registry on survival rates among acute ischemic stroke patients.
METHODS: Multistage probabilistic matching, using a fine-grained record
integration and linkage software program and combinations of key variables, was
used to link Georgia hospital discharge data for 2005 through 2009 with mortality
data for 2006 through 2010. Data from patients admitted with principal diagnoses
of acute ischemic stroke were analyzed by using the extended Cox proportional
hazard model. The survival times of patients cared for by hospitals participating
in the stroke registry and of those treated at nonparticipating hospitals were
compared. RESULTS: Average age of the 50,579 patients analyzed was 69 years, and
56% of patients were treated in Georgia Coverdell Acute Stroke Registry
hospitals. Thirty-day and 365-day mortality after first admission for stroke were
8.1% and 18.5%, respectively. Patients treated at nonparticipating facilities had
a hazard ratio for death of 1.14 (95% confidence interval, 1.03-1.26; P = .01)
after the first week of admission compared with patients cared for by hospitals
participating in the registry. CONCLUSION: Hospital discharge data can be linked
with death data to assess the impact of clinical-level or community-level chronic
disease control initiatives. Hospitals need to undertake quality improvement
activities for a better patient outcome.
PMID- 25590600
TI - Behavioral economics: "nudging" underserved populations to be screened for
cancer.
AB - Persistent disparities in cancer screening by race/ethnicity and socioeconomic
status require innovative prevention tools and techniques. Behavioral economics
provides tools to potentially reduce disparities by informing strategies and
systems to increase prevention of breast, cervical, and colorectal cancers. With
an emphasis on the predictable, but sometimes flawed, mental shortcuts
(heuristics) people use to make decisions, behavioral economics offers insights
that practitioners can use to enhance evidence-based cancer screening
interventions that rely on judgments about the probability of developing and
detecting cancer, decisions about competing screening options, and the optimal
presentation of complex choices (choice architecture). In the area of judgment,
we describe ways practitioners can use the availability and representativeness of
heuristics and the tendency toward unrealistic optimism to increase perceptions
of risk and highlight benefits of screening. We describe how several behavioral
economic principles involved in decision-making can influence screening
attitudes, including how framing and context effects can be manipulated to
highlight personally salient features of cancer screening tests. Finally, we
offer suggestions about ways practitioners can apply principles related to choice
architecture to health care systems in which cancer screening takes place. These
recommendations include the use of incentives to increase screening, introduction
of default options, appropriate feedback throughout the decision-making and
behavior completion process, and clear presentation of complex choices,
particularly in the context of colorectal cancer screening. We conclude by noting
gaps in knowledge and propose future research questions to guide this promising
area of research and practice.
PMID- 25590602
TI - Identification and validation of long noncoding RNA biomarkers in human non-small
cell lung carcinomas.
AB - INTRODUCTION: Dysregulation of long noncoding RNAs (lncRNAs) has been regarded as
a primary feature of several human cancers. However, the genome-wide expression
and functional significance of lncRNAs in non-small-cell lung carcinomas (NSCLC)
remains unclear. The aim of this study was to identify novel lncRNAs that may
play an important role in contributing to NSCLC pathogenesis. METHODS: We
performed an integrative analysis of two NSCLC microarray datasets comprising 165
and 90 patients, respectively. The candidate lncRNAs were identified using the
GSE19188 dataset, and then confirmed in the GSE18842 dataset. In addition, an
independent cohort of 73 clinical samples was analyzed to validate the selected
lncRNAs by quantitative real-time polymerase chain reaction analysis. RESULTS:
With microarray gene expression analysis, we identified and validated a list of
64 lncRNAs significantly dysregulated in NSCLC tumors compared with normal lung
tissues; and a panel of 181 lncRNAs that were specific to histological subtypes
of NSCLC (adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma). The
quantitative real-time polymerase chain reaction analysis of six selected lncRNAs
in clinical samples further confirmed the results of microarray analysis.
CONCLUSIONS: We have identified and validated multiple novel lncRNAs associated
with tumorigenesis and histological differentiation in human NSCLC. These lncRNAs
could be further exploited for the development of useful biomarkers in diagnosis,
prognosis, and treatment of NSCLC.
PMID- 25590601
TI - Fission yeast Ryh1 GTPase activates TOR Complex 2 in response to glucose.
AB - The Target Of Rapamycin (TOR) is an evolutionarily conserved protein kinase that
forms 2 distinct protein complexes referred to as TOR complex 1 (TORC1) and 2
(TORC2). Recent extensive studies have demonstrated that TORC1 is under the
control of the small GTPases Rheb and Rag that funnel multiple input signals
including those derived from nutritional sources; however, information is scarce
as to the regulation of TORC2. A previous study using the model system provided
by the fission yeast Schizosaccharomyces pombe identified Ryh1, a Rab-family
GTPase, as an activator of TORC2. Here, we show that the nucleotide-binding state
of Ryh1 is regulated in response to glucose, mediating this major nutrient signal
to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2
dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast.
Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8
pathway. During glucose starvation, however, Gad8 phosphorylation by TORC2
gradually recovers independently of Ryh1, implying an additional TORC2 activator
that is regulated negatively by glucose. The paired positive and negative
regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway, which is
essential for growth under glucose-limited environment.
PMID- 25590603
TI - Conditional survival of malignant thymoma using national population-based
surveillance, epidemiology, and end results (SEER) registry (1973-2011).
AB - INTRODUCTION: Thymoma is a rare and unique tumor with a long natural history that
makes it difficult to study. Consequently, there is a dearth of prospective
diagnostic or therapeutic clinical trials. To our knowledge, there has not been
an analysis of conditional survival of thymoma in the literature. The specific
aim of this study was to study the 5-year conditional survivals of a large
population of thymoma patients. METHODS: Cases of thymoma were extracted from the
Surveillance, Epidemiology, and End Results registry (1973-2011) and categorized
into Masaoka-Koga stage groupings. The primary outcomes compared overall survival
(OS), cause specific survival (CSS), and 5-year conditional OS and CSS, by stage.
OS and CSS were calculated using the Kaplan-Meier method with the log-rank test
for significance using SAS v9.3. Conditional survival was the probability of
surviving an additional 5 years at any point in follow-up, and used analysis of
variance to test significance. RESULTS: A total of 2182 patients met inclusion
criteria and were categorized as Masaoka-Koga stage groupings of I and IIA
("localized," 24%), IIB ("regional," 16%), III and IV ("distant," 50%), and
unknown (10%). Median age was 56 (18-91), and 53% were male. Earlier stages had
better OS (p < 0.0001) and CSS (p < 0.0001). Twenty-year OS for local, regional,
and distant stages were 42%, 30%, and 18%, respectively. Conditional survivals
remained largely unchanged throughout follow-up. CONCLUSIONS: Conditional
survival provides more relevant survival estimates for patients during follow-up.
Further studies should investigate the possibility that thymoma should be
considered a chronic disease.
PMID- 25590605
TI - Relationship between tumor size and survival in non-small-cell lung cancer
(NSCLC): an analysis of the surveillance, epidemiology, and end results (SEER)
registry.
AB - INTRODUCTION: Tumor size is a known prognostic factor for early stage non-small
cell lung cancer (NSCLC), but its significance in node-positive and locally
invasive NSCLC has not been extensively characterized. We queried the
Surveillance, Epidemiology, and End Results database to evaluate the prognostic
value of tumor size for early stage and node-positive and locally invasive NSCLC.
METHODS: Patients in Surveillance, Epidemiology, and End Results registry with
NSCLC diagnosed between 1998 and 2003 were analyzed. Tumor size was analyzed as a
continuous variable. Other demographic variables included age, gender, race,
histology, primary tumor extension, node status, and primary treatment modality
(surgery vs. radiation). The Kaplan-Meier method was used to estimate overall
survival (OS). Cox proportional hazard model was used to evaluate whether tumor
size was an independent prognostic factor. RESULTS: In all, 52,287 eligible
patients were subgrouped based on tumor extension and node status. Tumor size had
a significant effect on OS in all subgroups defined by tumor extension or node
status. In addition, tumor size also had statistically significant effect on OS
in 15 of 16 subgroups defined by tumor extension and nodal status after
adjustment for other clinical variables. Our model incorporating tumor size had
significantly better predictive accuracy than our alternative model without tumor
size. CONCLUSIONS: Tumor size is an independent prognostic factor, for early
stage and node-positive and locally invasive disease. Prediction tools, such as
nomograms, incorporating more detailed information not captured in detail by the
routine tumor, node, metastasis classification, may improve prediction accuracy
of OS in NSCLC.
PMID- 25590606
TI - Cost-effectiveness of multiplexed predictive biomarker screening in non-small
cell lung cancer.
AB - INTRODUCTION: Population-wide screening for epidermal growth factor receptor
(EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements to
inform cancer therapy in non-small-cell lung cancer (NSCLC) is recommended by
guidelines. We estimated cost-effectiveness of multiplexed predictive biomarker
screening in metastatic NSCLC from a societal perspective in the United States.
METHODS: We constructed a microsimulation model to compare the life expectancy
and costs of multiplexed testing and molecularly guided therapy versus treatment
with cisplatin-pemetrexed (CisPem). All testing interventions included a two-step
algorithm of concurrent EGFR mutation and ALK overexpression testing with
immunohistochemistry followed by ALK rearrangement confirmation with a
fluorescence in situ hybridization assay for immunohistochemistry-positive
results. Three strategies were included: "Test-treat" approach, where molecularly
guided therapy was initiated after obtainment of test results; "Empiric switch
therapy," with concurrent initiation of CisPem and testing and immediate switch
to test-result conditional treatment after one cycle of CisPem; and "Empiric
therapy" approach in which CisPem was continued for four cycles before start of a
tyrosine kinase inhibitor. RESULTS: The incremental cost-effectiveness ratio for
"Test-treat" compared with treatment with CisPem was $136,000 per quality
adjusted life year gained. Both empiric treatment approaches had less favorable
incremental cost-effectiveness ratios. "Test-treat" and "Empiric switch therapy"
yielded higher expected outcomes in terms of quality-adjusted life years and life
years than "Empiric therapy." These results were robust across plausible ranges
of model inputs. CONCLUSION: From a societal perspective, our cost-effectiveness
results support the value of multiplexed genetic screening and molecularly guided
therapy in metastatic NSCLC.
PMID- 25590604
TI - Validation of a multiprotein plasma classifier to identify benign lung nodules.
AB - INTRODUCTION: Indeterminate pulmonary nodules (IPNs) lack clinical or
radiographic features of benign etiologies and often undergo invasive procedures
unnecessarily, suggesting potential roles for diagnostic adjuncts using molecular
biomarkers. The primary objective was to validate a multivariate classifier that
identifies likely benign lung nodules by assaying plasma protein expression
levels, yielding a range of probability estimates based on high negative
predictive values (NPVs) for patients with 8 to 30 mm IPNs. METHODS: A
retrospective, multicenter, case-control study was performed using multiple
reaction monitoring mass spectrometry, a classifier comprising five diagnostic
and six normalization proteins, and blinded analysis of an independent validation
set of plasma samples. RESULTS: The classifier achieved validation on 141 lung
nodule-associated plasma samples based on predefined statistical goals to
optimize sensitivity. Using a population based nonsmall-cell lung cancer
prevalence estimate of 23% for 8 to 30 mm IPNs, the classifier identified likely
benign lung nodules with 90% negative predictive value and 26% positive
predictive value, as shown in our prior work, at 92% sensitivity and 20%
specificity, with the lower bound of the classifier's performance at 70%
sensitivity and 48% specificity. Classifier scores for the overall cohort were
statistically independent of patient age, tobacco use, nodule size, and chronic
obstructive pulmonary disease diagnosis. The classifier also demonstrated
incremental diagnostic performance in combination with a four-parameter clinical
model. CONCLUSIONS: This proteomic classifier provides a range of probability
estimates for the likelihood of a benign etiology that may serve as a
noninvasive, diagnostic adjunct for clinical assessments of patients with IPNs.
PMID- 25590608
TI - Enhanced reductive dechlorination of tetrachloroethene by nano-sized mackinawite
with cyanocobalamin in a highly alkaline condition.
AB - In this study, we characterize the reductive dechlorination of tetrachloroethene
(PCE) by nano-sized mackinawite (nFeS) with cobalamin (Cbl(III)) at a high pH and
investigate the effects of environmental factors, including the concentrations of
the target contaminant, reductant, and catalyst and suspension ions on the
dechlorination kinetics of PCE. Ninety five percent of the PCE was degraded by
nFeS with Cbl(III) in 15 h. Cyclic voltammetry conducted with regard to the
reductive dechlorination showed a higher redox potential of mackinawite under a
high-pH condition (-1.01 V), suggesting that the oxidation state of the central
cobalt ion in the cobalamin could be reduced to Cbl(I). The change of cobalamin
species on the nFeS surface was verified under different pH conditions by UV-vis
spectroscopy. The rate constant of PCE dechlorination increased from 0.1582 to
0.4284 h(-1) due to the increase in the nFeS content (2.085-20.85 g/L). As the
concentration of Cbl(III) increased from 0 to 0.5 mM, the dechlorination kinetics
of PCE was accelerated (0-1.4091 h(-1)) but reached a state of equilibrium from
0.5 to 1 mM. The increase in the initial PCE concentration (0.035-1.0 mM) slowed
down the dechlorination kinetics (0.2036-0.0962 h(-1)). The dechlorination
kinetics was enhanced by 1.5-11 times when 10 mM of ions (Na(+), K(+), Mg(2+),
Ca(2+), CO3(2-), SO4(2-), and NO3(-)) were added, while an addition of HCO3
decelerated it by 10 times. This study can provide background knowledge
pertaining to the PCE dechlorination by a natural reductant under a high-pH
condition and the effect of environmental factors on the dechlorination kinetics
for the development of novel remediation technologies.
PMID- 25590609
TI - The complexity of biosorption treatments for oxyanions in a multi-element mine
effluent.
AB - Selenium (Se) is a contaminant in effluents from coal mines and coal-fired power
stations, where it is encountered as the oxyanion selenate (SeO4(2-), hereafter
Se(VI)). Se(VI) can be removed from solution with Fe-treated biosorbents, but the
efficacy of these treatments in effluents with multiple contaminants is unclear.
This study investigates the interactions between Se(VI) and the oxyanions SO4(2-)
and NO3(-). We produce a sustainable biosorbent, Gracilaria Modified Biochar
(GMB), by treating a waste product generated after the commercial extraction of
agar from cultivated seaweeds with ferric chloride (FeCl3) and converting it to
biochar through pyrolysis. We then test interactions between Se(VI) and competing
oxyanions in mock solutions and a real-world mine effluent with high
concentrations of SO4(2-) and NO3(-). GMB immediately removed 98% of the Se(VI)
from the mock solution, but only 3% from the mine effluent with the same initial
Se(VI) concentration. Notably, 83-89% of the Se(VI) was removed by GMB when
concentrations of Se(VI) and SO4(2-) were less than or equimolar in mock
solutions. Higher concentrations of SO4(2-) reduced the uptake of Se(VI). There
was no interference from NO3(-) on the biosorption of Se(VI). GMB is a successful
biosorbent for Se(VI), however, high concentrations of SO4(2-) will compromise
the biosorption of Se(VI).
PMID- 25590611
TI - Modular continuing professional development for emergency physicians - the MNSHA
masterclass programme.
AB - INTRODUCTION: Emergency physician (EP) training in the Netherlands is currently a
3-year competency-based programme. Upon its completion, many Dutch EPs feel that
they lack some of the skills and the knowledge necessary to be fully prepared for
the challenges of emergency medicine. We perceived a need for new methods to
deliver continuing professional development (CPD). METHODS: A needs analysis
survey was conducted to ascertain whether our perceived need for a new CPD
programme was genuine. A new course was developed, incorporating innovative
learning methods. The results of the needs analysis were incorporated into the
programme. Another survey was held among participants of the first two editions
of the programme. RESULTS, DISCUSSION AND CONCLUSION: Modular CPD for Emergency
Physicians (Dutch: MNSHA) is a modular programme that aims to deliver CPD to
Dutch EPs. It combines innovative educational methods, such as asynchronous
learning in a flipped classroom, with web-based mentoring. The aim is for
participants to develop effective, individualized and sustainable methods to gain
and maintain knowledge and skills as a part of their ongoing professional
education. The participant survey showed encouraging results, strongly suggesting
an improvement in confidence. A more robust study would be required to better
assess the outcomes of our programme.
PMID- 25590610
TI - MicroRNA targets: potential candidates for indirect regulation by drugs.
AB - BACKGROUND: Gene expression is regulated by trans-acting transcription factors
and microRNAs (miRNAs) through interactions with their respective cis-regulatory
elements. The effects that drugs induce result from complex interactions in
pathways downstream from their primary targets. These interactions, from gene
regulatory apparatus and from drug-induced pathways, form a complex, multilayered
network. METHODS: Knowing that drugs can perturb miRNA expression profiles, a
genomewide analysis of drug-induced intronic miRNA perturbations has been
presented here. RESULTS: By comparative analysis of control and drugged data sets
from 27 independent gene expression experiments, it was feasible to detect the
effect of drugs on miRNA target genes. Signatures of 21 of 28 miRNAs, predicted
to be influenced by drug action, were detected. CONCLUSION: This study
demonstrates that the action of drugs on mRNA expression can be mediated through
the combinatorial effects of miRNAs. In addition, transcription factors, through
miRNAs within the introns of their target genes, can exert an indirect effect on
the expression of distal mRNAs.
PMID- 25590607
TI - Discovery of CLC transport proteins: cloning, structure, function and
pathophysiology.
AB - After providing a personal description of the convoluted path leading 25 years
ago to the molecular identification of the Torpedo Cl(-) channel ClC-0 and the
discovery of the CLC gene family, I succinctly describe the general structural
and functional features of these ion transporters before giving a short overview
of mammalian CLCs. These can be categorized into plasma membrane Cl(-) channels
and vesicular Cl(-) /H(+) -exchangers. They are involved in the regulation of
membrane excitability, transepithelial transport, extracellular ion homeostasis,
endocytosis and lysosomal function. Diseases caused by CLC dysfunction include
myotonia, neurodegeneration, deafness, blindness, leukodystrophy, male
infertility, renal salt loss, kidney stones and osteopetrosis, revealing a
surprisingly broad spectrum of biological roles for chloride transport that was
unsuspected when I set out to clone the first voltage-gated chloride channel.
PMID- 25590612
TI - The interaction between seasonality and pulsed interventions against malaria in
their effects on the reproduction number.
AB - The basic reproduction number (R0) is an important quantity summarising the
dynamics of an infectious disease, as it quantifies how much effort is needed to
control transmission. The relative change in R0 due to an intervention is
referred to as the effect size. However malaria and other diseases are often
highly seasonal and some interventions have time-varying effects, meaning that
simple reproduction number formulae cannot be used. Methods have recently been
developed for calculating R0 for diseases with seasonally varying transmission. I
extend those methods to calculate the effect size of repeated rounds of mass drug
administration, indoor residual spraying and other interventions against
Plasmodium falciparum malaria in seasonal settings in Africa. I show that if an
intervention reduces transmission from one host to another by a constant factor,
then its effect size is the same in a seasonal as in a non-seasonal setting. The
optimal time of year for drug administration is in the low season, whereas the
best time for indoor residual spraying or a vaccine which reduces infection rates
is just before the high season. In general, the impact of time-varying
interventions increases with increasing seasonality, if carried out at the
optimal time of year. The effect of combinations of interventions that act at
different stages of the transmission cycle is roughly the product of the separate
effects. However for individual time-varying interventions, it is necessary to
use methods such as those developed here rather than inserting the average
efficacy into a simple formula.
PMID- 25590613
TI - Macrophage activation in acute exacerbation of idiopathic pulmonary fibrosis.
AB - BACKGROUND: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a
common cause of disease acceleration in IPF and has a major impact on mortality.
The role of macrophage activation in AE of IPF has never been addressed before.
METHODS: We evaluated BAL cell cytokine profiles and BAL differential cell counts
in 71 IPF patients w/wo AE and in 20 healthy volunteers. Twelve patients suffered
from AE at initial diagnosis while sixteen patients developed AE in the 24 months
of follow-up. The levels of IL-1ra, CCL2, CCL17, CCL18, CCL22, TNF-alpha, IL
1beta, CXCL1 and IL-8 spontaneously produced by BAL-cells were analysed by ELISA.
RESULTS: In patients with AE, the percentage of BAL neutrophils was significantly
increased compared to stable patients. We found an increase in the production
rate of the pro-inflammatory cytokines CXCL1 and IL-8 combined with an increase
in all tested M2 cytokines by BAL-cells. An increase in CCL18 levels and
neutrophil counts during AE was observed in BAL cells from patients from whom
serial lavages were obtained. Furthermore, high baseline levels of CCL18
production by BAL cells were significantly predictive for the development of
future AE. CONCLUSIONS: BAL cell cytokine production levels at acute exacerbation
show up-regulation of pro-inflammatory as well as anti-inflammatory/ M2
cytokines. Our data suggest that AE in IPF is not an incidental event but rather
driven by cellular mechanisms including M2 macrophage activation.
PMID- 25590616
TI - Glutamine and antioxidants: status of their use in critical illness.
AB - PURPOSE OF REVIEW: Many studies in critically ill patients have addressed enteral
or parenteral supplementation of glutamine and antioxidants to counteract assumed
deficiencies and induce immune-modulating effects to reduce infections and
improve outcome. Older studies showed marked reductions in mortality, infectious
morbidity and length of stay. Recent studies no longer show beneficial effects
and in contrast even demonstrated increased mortality. This opiniating review
focuses on the latest information and the consequences for the use of glutamine
and antioxidants in critically ill patients. RECENT FINDINGS: Positive effects in
systematic reviews and meta-analyses are based on results from older, smaller and
mainly single-centre studies. New information has challenged the conditional
deficiency hypothesis concerning glutamine in critically ill patients. The recent
REDOXS and MetaPlus trials studying the effects of glutamine, selenium and other
antioxidants have shown no benefits and increased mortality. SUMMARY: Given that
the first dictum in medicine is to do no harm, we cannot be confident that immune
modulating nutrient supplementation with glutamine and antioxidants is effective
and well tolerated for critically ill patients. Until more data are available, it
is probably better not to routinely administer glutamine and antioxidants in
nonphysiological doses to mechanically ventilated critically ill patients.
PMID- 25590614
TI - The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo.
AB - The human herpes virus Epstein-Barr virus (EBV) latently infects and drives the
proliferation of B lymphocytes in vitro and is associated with several forms of
lymphoma and carcinoma in vivo. The virus encodes ~30 miRNAs in the BART region,
the function of most of which remains elusive. Here we have used a new mouse
xenograft model of EBV driven carcinomagenesis to demonstrate that the BART
miRNAs potentiate tumor growth and development in vivo. No effect was seen on
invasion or metastasis, and the growth promoting activity was not seen in vitro.
In vivo tumor growth was not associated with the expression of specific BART
miRNAs but with up regulation of all the BART miRNAs, consistent with previous
observations that all the BART miRNAs are highly expressed in all of the EBV
associated cancers. Based on these observations, we suggest that deregulated
expression of the BART miRNAs potentiates tumor growth and represents a general
mechanism behind EBV associated oncogenesis.
PMID- 25590615
TI - Small indels induced by CRISPR/Cas9 in the 5' region of microRNA lead to its
depletion and Drosha processing retardance.
AB - MicroRNA knockout by genome editing technologies is promising. In order to extend
the application of the technology and to investigate the function of a specific
miRNA, we used CRISPR/Cas9 to deplete human miR-93 from a cluster by targeting
its 5' region in HeLa cells. Various small indels were induced in the targeted
region containing the Drosha processing site and seed sequences. Interestingly,
we found that even a single nucleotide deletion led to complete knockout of the
target miRNA with high specificity. Functional knockout was confirmed by
phenotype analysis. Furthermore, de novo microRNAs were not found by RNA-seq.
Nevertheless, expression of the pri-microRNAs was increased. When combined with
structural analysis, the data indicated that biogenesis was impaired. Altogether,
we showed that small indels in the 5' region of a microRNA result in sequence
depletion as well as Drosha processing retard.
PMID- 25590617
TI - Hydrolysis of ketene catalyzed by formic acid: modification of reaction
mechanism, energetics, and kinetics with organic acid catalysis.
AB - The hydrolysis of ketene (H2C?C?O) to form acetic acid involving two water
molecules and also separately in the presence of one to two water molecules and
formic acid (FA) was investigated. Our results show that, while the currently
accepted indirect mechanism, involving addition of water across the carbonyl C?O
bond of ketene to form an ene-diol followed by tautomerization of the ene-diol to
form acetic acid, is the preferred pathway when water alone is present, with
formic acid as catalyst, addition of water across the ketene C?C double bond to
directly produce acetic acid becomes the kinetically favored pathway for
temperatures below 400 K. We find not only that the overall barrier for ketene
hydrolysis involving one water molecule and formic acid (H2C2O + H2O + FA) is
significantly lower than that involving two water molecules (H2C2O + 2H2O) but
also that FA is able to reduce the barrier height for the direct path, involving
addition of water across the C?C double bond, so that it is essentially identical
with (6.4 kcal/mol) that for the indirect ene-diol formation path involving
addition of water across the C?O bond. For the case of ketene hydrolysis
involving two water molecules and formic acid (H2C2O + 2H2O + FA), the barrier
for the direct addition of water across the C?C double bond is reduced even
further and is 2.5 kcal/mol lower relative to the ene-diol path involving
addition of water across the C?O bond. In fact, the hydrolysis barrier for the
H2C2O + 2H2O + FA reaction through the direct path is sufficiently low (2.5
kcal/mol) for it to be an energetically accessible pathway for acetic acid
formation under atmospheric conditions. Given the structural similarity between
acetic and formic acid, our results also have potential implications for aqueous
phase chemistry. Thus, in an aqueous environment, even in the absence of formic
acid, though the initial mechanism for ketene hydrolysis is expected to involve
addition of water across the carbonyl bond as is currently accepted, the
production and accumulation of acetic acid will likely alter the preferred
pathway to one involving addition of water across the ketene C?C double bond as
the reaction proceeds.
PMID- 25590619
TI - BMI as a mediator of the relationship between muscular fitness and
cardiometabolic risk in children: a mediation analysis.
AB - OBJECTIVE: Muscular fitness levels have been associated with cardiometabolic risk
in children, although whether body weight acts as a confounder or as an
intermediate variable in this relationship remains controversial. The aim of this
study was to examine whether the association between muscular fitness and
cardiometabolic risk factors is mediated by body mass index (BMI). DESIGN AND
METHODS: Cross-sectional study using a sample of 1158 schoolchildren aged 8-11
years from the province of Cuenca, Spain. We measured anthropometrics and
biochemical variables and we calculated a muscular fitness index as the sum of z
scores of handgrip dynamometry/weight and standing long jump, and we estimated a
previously validated cardiometabolic risk index (CMRI). Linear regression models
were fitted for mediation analysis to assess whether the association between
muscular fitness and cardiometabolic risk was mediated by BMI. RESULTS: Children
with normal weight (NW) had a better cardiometabolic risk profile than their
overweight (OW) or obese (OB) peers after controlling for muscular fitness.
Marginal estimated mean +/- SE values for NW, OW and OB categories of CMRI were
0.75 +/- 0.06 < 0.84 +/- 0.10 < 2.18 +/- 0.16 in boys and -0.73 +/- 0.06 < 0.96
+/- 0.10 < 2.71 +/- 0.17 in girls, both p < 0.001. Children with higher levels of
muscular fitness had a better cardiometabolic risk profile (CMRI marginal
estimated mean +/- SE 1.04 +/- 0.13 > 0.05 +/- 0.09 >-1.16 +/- 0.13 for lower,
middle and upper quartiles of muscular fitness in boys and 1.01 +/- 0.16 > 0.10
+/- 0.09 > -1.02 +/- 0.15 in girls, both p < 0.001), but differences disappeared
when controlling for BMI. BMI acted as a full mediator between muscular fitness
and most cardiometabolic risk factors (Sobel test z = -11.44 for boys; z = -11.83
for girls; p < 0.001 in CMRI mediation model) and as a partial mediator in the
case of waist circumference (Sobel test z=-14.86 for boys; z=-14.51 for girls;
p<0.001). CONCLUSIONS: BMI mediates the association between muscular fitness and
cardiometabolic risk in schoolchildren. Overall, good muscular fitness is
associated with lower cardiometabolic risk, but particularly when accompanied by
normal weight.
PMID- 25590620
TI - Acoustic and temporal partitioning of cicada assemblages in city and mountain
environments.
AB - Comparing adaptations to noisy city environments with those to natural mountain
environments on the community level can provide significant insights that allow
an understanding of the impact of anthropogenic noise on invertebrates that
employ loud calling songs for mate attraction, especially when each species has
its distinct song, as in the case of cicadas. In this study, we investigated the
partitioning strategy of cicada assemblages in city and mountain environments by
comparing the acoustic features and calling activity patterns of each species,
recorded using automated digital recording systems. Our comparison of activity
patterns of seasonal and diel calling revealed that there was no significant
temporal partitioning of cicada assemblages in either environment. In addition,
there was no correlation between the acoustic distance based on spectral features
and temporal segregation. Heterospecific spectral overlap was low in both city
and mountain environments, although city and mountain cicada assemblages were
subject to significantly different levels of anthropogenic or interspecific
noise. Furthermore, for the common species found in both environments, the
calling activity patterns at both seasonal and diel time scales were
significantly consistent across sites and across environments. We suggest that
the temporal calling activity is constrained by endogenous factors for each
species and is less flexible in response to external factors, such as
anthropogenic noise. As a result, cicada assemblages in city environments with
low species diversity do not demonstrate a more significant temporal partitioning
than those in mountain environments with high species diversity.
PMID- 25590621
TI - DNA is an antimicrobial component of neutrophil extracellular traps.
AB - Neutrophil extracellular traps (NETs) comprise an ejected lattice of chromatin
enmeshed with granular and nuclear proteins that are capable of capturing and
killing microbial invaders. Although widely employed to combat infection, the
antimicrobial mechanism of NETs remains enigmatic. Efforts to elucidate the
bactericidal component of NETs have focused on the role of NET-bound proteins
including histones, calprotectin and cathepsin G protease; however, exogenous and
microbial derived deoxyribonuclease (DNase) remains the most potent inhibitor of
NET function. DNA possesses a rapid bactericidal activity due to its ability to
sequester surface bound cations, disrupt membrane integrity and lyse bacterial
cells. Here we demonstrate that direct contact and the phosphodiester backbone
are required for the cation chelating, antimicrobial property of DNA. By treating
NETs with excess cations or phosphatase enzyme, the antimicrobial activity of
NETs is neutralized, but NET structure, including the localization and function
of NET-bound proteins, is maintained. Using intravital microscopy, we visualized
NET-like structures in the skin of a mouse during infection with Pseudomonas
aeruginosa. Relative to other bacteria, P. aeruginosa is a weak inducer of
NETosis and is more resistant to NETs. During NET exposure, we demonstrate that
P. aeruginosa responds by inducing the expression of surface modifications to
defend against DNA-induced membrane destabilization and NET-mediated killing.
Further, we show induction of this bacterial response to NETs is largely due to
the bacterial detection of DNA. Therefore, we conclude that the DNA backbone
contributes both to the antibacterial nature of NETs and as a signal perceived by
microbes to elicit host-resistance strategies.
PMID- 25590618
TI - Deep sequencing of the murine olfactory receptor neuron transcriptome.
AB - The ability of animals to sense and differentiate among thousands of odorants
relies on a large set of olfactory receptors (OR) and a multitude of accessory
proteins within the olfactory epithelium (OE). ORs and related signaling
mechanisms have been the subject of intensive studies over the past years, but
our knowledge regarding olfactory processing remains limited. The recent
development of next generation sequencing (NGS) techniques encouraged us to
assess the transcriptome of the murine OE. We analyzed RNA from OEs of female and
male adult mice and from fluorescence-activated cell sorting (FACS)-sorted
olfactory receptor neurons (ORNs) obtained from transgenic OMP-GFP mice. The
Illumina RNA-Seq protocol was utilized to generate up to 86 million reads per
transcriptome. In OE samples, nearly all OR and trace amine-associated receptor
(TAAR) genes involved in the perception of volatile amines were detectably
expressed. Other genes known to participate in olfactory signaling pathways were
among the 200 genes with the highest expression levels in the OE. To identify OE
specific genes, we compared olfactory neuron expression profiles with RNA-Seq
transcriptome data from different murine tissues. By analyzing different
transcript classes, we detected the expression of non-olfactory GPCRs in ORNs and
established an expression ranking for GPCRs detected in the OE. We also
identified other previously undescribed membrane proteins as potential new
players in olfaction. The quantitative and comprehensive transcriptome data
provide a virtually complete catalogue of genes expressed in the OE and present a
useful tool to uncover candidate genes involved in, for example, olfactory
signaling, OR trafficking and recycling, and proliferation.
PMID- 25590622
TI - Interaction between Helicobacter pylori and latent toxoplasmosis and demographic
variables on cognitive function in young to middle-aged adults.
AB - Helicobacter pylori and latent toxoplasmosis are widespread diseases that have
been associated with cognitive deficits and Alzheimer's disease. We sought to
determine whether interactions between Helicobacter pylori and latent
toxoplasmosis, age, race-ethnicity, educational attainment, economic status, and
general health predict cognitive function in young and middle-aged adults. To do
so, we used multivariable regression and multivariate models to analyze data
obtained from the United States' National Health and Nutrition Examination Survey
from the Centers for Disease Control and Prevention, which can be weighted to
represent the US population. In this sample, we found that 31.6 percent of women
and 36.2 percent of men of the overall sample had IgG Antibodies against
Helicobacter pylori, although the seroprevalence of Helicobacter pylori varied
with sociodemographic variables. There were no main effects for Helicobacter
pylori or latent toxoplasmosis for any of the cognitive measures in models
adjusting for age, sex, race-ethnicity, educational attainment, economic
standing, and self-rated health predicting cognitive function. However,
interactions between Helicobacter pylori and race-ethnicity, educational
attainment, latent toxoplasmosis in the fully adjusted models predicted cognitive
function. People seropositive for both Helicobacter pylori and latent
toxoplasmosis - both of which appear to be common in the general population -
appear to be more susceptible to cognitive deficits than are people seropositive
for either Helicobacter pylori and or latent toxoplasmosis alone, suggesting a
synergistic effect between these two infectious diseases on cognition in young to
middle-aged adults.
PMID- 25590623
TI - Growth differentiation factor 15 (GDF-15) plasma levels increase during bleomycin
and cisplatin-based treatment of testicular cancer patients and relate to
endothelial damage.
AB - INTRODUCTION: Chemotherapy-related endothelial damage contributes to the early
development of cardiovascular morbidity in testicular cancer patients. We aimed
to identify relevant mechanisms of and search for candidate biomarkers for this
endothelial damage. METHODS: Human micro-vascular endothelial cells (HMEC-1) were
exposed to bleomycin or cisplatin with untreated samples as control. 18k cDNA
microarrays were used. Gene expression differences were analysed at single gene
level and in gene sets clustered in biological pathways and validated by qRT-PCR.
Protein levels of a candidate biomarker were measured in testicular cancer
patient plasma before, during and after bleomycin-etoposide-cisplatin
chemotherapy, and related to endothelial damage biomarkers (von Willebrand Factor
(vWF), high-sensitivity C-Reactive Protein (hsCRP)). RESULTS: Microarray data
identified several genes with highly differential expression; e.g. Growth
Differentiation Factor 15 (GDF-15), Activating Transcription Factor 3 (ATF3) and
Amphiregulin (AREG). Pathway analysis revealed strong associations with 'p53' and
'Diabetes Mellitus' gene sets. Based on known function, we measured GDF-15
protein levels in 41 testicular patients during clinical follow-up. Pre
chemotherapy GDF-15 levels equalled controls. Throughout chemotherapy GDF-15, vWF
and hsCRP levels increased, and were correlated at different time-points.
CONCLUSION: An unbiased approach in a preclinical model revealed genes related to
chemotherapy-induced endothelial damage, like GDF-15. The increases in plasma GDF
15 levels in testicular cancer patients during chemotherapy and its association
with vWF and hsCRP suggest that GDF-15 is a potentially useful biomarker related
to endothelial damage.
PMID- 25590624
TI - Metabolism of androstenone, 17beta-estradiol and dihydrotestosterone in primary
cultured pig hepatocytes and the role of 3beta-hydroxysteroid dehydrogenase in
this process.
AB - Steroids metabolism plays an important role in mammals and contributes to quality
of pig meat. The main objective of this study was to identify metabolites of
androstenone, 17beta-estradiol and dihydrotestosterone using primary cultured pig
hepatocytes as a model system. The role of 3beta-hydroxysteroid dehydrogenase
(3betaHSD) in regulation of steroid metabolism was also validated using
trilostane, a specific 3betaHSD inhibitor. Steroid glucuronide conjugated
metabolites were detected by liquid chromatography time of flight mass
spectrometry (LC-TOF-MS). 3betaHSD enzyme was essential for metabolism of
androstenone to 5alpha-androst-16-en-3beta-ol, which then formed androstenone
glucuronide conjugate. Metabolism of 17beta-estradiol was accompanied by
formation of glucuronide-conjugated estrone and glucuronide-conjugated estradiol.
The ratio of the two metabolites was around 5:1. 3betaHSD enzyme was not involved
in 17beta-estradiol metabolism. 5alpha-Dihydrotestosterone-17beta-glucuronide was
identified as a dihydrotestosterone metabolite, and this metabolism was related
to 3betaHSD enzyme activity as demonstrated by inhibition study.
PMID- 25590625
TI - Emission of titanium dioxide nanoparticles from building materials to the
environment by wear and weather.
AB - In the present work, we investigate the effect of weathering duration on a
commercial photocatalytic nanocoating on the basis of its nanoparticle emission
tendency into two media, air and water. It is found that increased weathering
duration results in stepwise structural deterioration of the nanocoating, which
in turn decreases the nanocoating life, changes the nanocoating removal
mechanism, and increases the particle emission concentration. Emission of free
TiO2 nanoparticles is found to be weathering duration dependent. Three quantities
are introduced: emission transition pace (ETP), stable emission level (SEL), and
stable emission duration (SED). By linear extrapolation of these quantities from
short weathering durations, complete failure of the nanocoatings can be predicted
and, moreover, the potential increase of nanoparticles release into the air.
PMID- 25590626
TI - Male mosquitoes as vehicles for insecticide.
AB - BACKGROUND: The auto-dissemination approach has been shown effective at treating
cryptic refugia that remain unaffected by existing mosquito control methods. This
approach relies on adult mosquito behavior to spread larvicide to breeding sites
at levels that are lethal to immature mosquitoes. Prior studies demonstrate that
'dissemination stations,' deployed in mosquito-infested areas, can contaminate
adult mosquitoes, which subsequently deliver the larvicide to breeding sites. In
some situations, however, preventative measures are needed, e.g., to mitigate
seasonal population increases. Here we examine a novel approach that combines
elements of autocidal and auto-dissemination strategies by releasing artificially
reared, male mosquitoes that are contaminated with an insecticide. METHODOLOGY:
Laboratory and field experiments examine for model-predicted impacts of
pyriproxyfen (PPF) directly applied to adult male Aedes albopictus, including (1)
the ability of PPF-treated males to cross-contaminate females and to (2) deliver
PPF to breeding sites. PRINCIPAL FINDINGS: Similar survivorship was observed in
comparisons of PPF-treated and untreated males. Males contaminated both female
adults and oviposition containers in field cage tests, at levels that eliminated
immature survivorship. Field trials demonstrate an ability of PPF-treated males
to transmit lethal doses to introduced oviposition containers, both in the
presence and absence of indigenous females. A decline in the Ae. albopictus
population was observed following the introduction of PPF-treated males, which
was not observed in two untreated field sites. CONCLUSIONS/SIGNIFICANCE: The
results demonstrate that, in cage and open field trials, adult male Ae.
albopictus can tolerate PPF and contaminate, either directly or indirectly, adult
females and immature breeding sites. The results support additional development
of the proposed approach, in which male mosquitoes act as vehicles for
insecticide delivery, including exploration of the approach with additional
medically important mosquito species. The novelty and importance of this approach
is an ability to safely achieve auto-dissemination at levels of intensity that
may not be possible with an auto-dissemination approach that is based on
indigenous females. Specifically, artificially-reared males can be released and
sustained at any density required, so that the potential for impact is limited
only by the practical logistics of mosquito rearing and release, rather than
natural population densities and the self-limiting impact of an intervention upon
them.
PMID- 25590627
TI - Baseline and strategic effects behind mindful emotion regulation: behavioral and
physiological investigation.
AB - One of the consequences of extensive mindfulness practice is a reduction of
anxiety and depression, but also a capacity to regulate negative emotions. In
this study, we explored four key questions concerning mindfulness training: (1)
What are the processes by which mindfulness regulates our emotions? (2) Can
mindfulness be applied to social emotions? (3) Does mindfulness training affect
emotionally driven behavior towards others? (4) Does mindfulness alter
physiological reactivity? To address these questions, we tested, in two
experiments, the ability of mindfulness meditators to regulate interpersonal
emotions (Experiment 1) and interactive behaviors (Experiment 2) as compared to
naive controls. To better understand the mechanisms by which mindfulness
regulates emotions, we asked participants to apply two strategies: a cognitive
strategy (mentalizing, a form of reappraisal focused on the intentions of others)
and an experiential strategy derived from mindfulness principles (mindful
detachment). Both groups were able to regulate interpersonal emotions by means of
cognitive (mentalizing) and experiential (mindful detachment) strategies. In
Experiment 1, a simple effect of meditation, independent from the implementation
of the strategies, resulted in reduced emotional and physiological reactivity, as
well as in increased pleasantness for meditators when compared to controls,
providing evidence of baseline regulation. In Experiment 2, one visible effect of
the strategy was that meditators outperformed controls in the experiential
(mindful detachment) but not in the cognitive (mentalize) strategy, showing
stronger modulation of their interactive behavior (less punishments) and
providing evidence of a strategic behavioral regulation. Based on these results,
we suggest that mindfulness can influence interpersonal emotional reactions
through an experiential mechanism, both at a baseline level and a strategic
level, thereby altering the subjective and physiological perception of emotions,
but also biasing interactive social behavior.
PMID- 25590628
TI - Reprogramming of Yersinia from virulent to persistent mode revealed by complex in
vivo RNA-seq analysis.
AB - We recently found that Yersinia pseudotuberculosis can be used as a model of
persistent bacterial infections. We performed in vivo RNA-seq of bacteria in
small cecal tissue biopsies at early and persistent stages of infection to
determine strategies associated with persistence. Comprehensive analysis of mixed
RNA populations from infected tissues revealed that Y. pseudotuberculosis
undergoes transcriptional reprogramming with drastic down-regulation of T3SS
virulence genes during persistence when the pathogen resides within the cecum. At
the persistent stage, the expression pattern in many respects resembles the
pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes
and invA. These findings are expected to have impact on future rationales to
identify suitable bacterial targets for new antibiotics. Other genes that are up
regulated during persistence are genes involved in anaerobiosis, chemotaxis, and
protection against oxidative and acidic stress, which indicates the influence of
different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades
influence the pattern of bacterial gene expression during persistence.
Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our
findings suggest a model for the life cycle of this enteropathogen with
reprogramming from a virulent to an adapted phenotype capable of persisting and
spreading by fecal shedding.
PMID- 25590629
TI - A hormone-responsive C1-domain-containing protein At5g17960 mediates stress
response in Arabidopsis thaliana.
AB - Phytohormones play a critical role in mediating plant stress response. They
employ a variety of proteins for coordinating such processes. In Arabidopsis
thaliana, some members of a Cys-rich protein family known as C1-clan proteins
were involved in stress response, but the actual function of the protein family
is largely unknown. We studied At5g17960, a C1-clan protein member that possesses
three unique C1 signature domains viz. C1_2, C1_3 and ZZ/PHD type. Additionally,
we identified 72 other proteins in A. thaliana that contain all three unique
signature domains. Subsequently, the 73 proteins were phylogenetically classified
into IX subgroups. Promoter motif analysis of the 73 genes identified the
presence of hormone-responsive and stress-responsive putative cis-regulatory
elements. Furthermore, we observed that transcript levels of At5g17960 were
induced in response to different hormones and stress treatments. At1g35610 and
At3g13760, two other members of subgroup IV, also showed upregulation upon GA3,
biotic and abiotic stress treatments. Moreover, seedlings of independent
transgenic A. thaliana lines ectopically expressing or suppressing At5g17960 also
showed differential regulation of several abiotic stress-responsive marker genes.
Thus, our data suggest that C1-domain-containing proteins have a role to play in
plant hormone-mediated stress responses, thereby assigning a putative function
for the C1-clan protein family.
PMID- 25590630
TI - Positive effect of human milk feeding during NICU hospitalization on 24 month
neurodevelopment of very low birth weight infants: an Italian cohort study.
AB - The aim of this study was to determine the effect of human milk feeding during
NICU hospitalization on neurodevelopment at 24 months of corrected age in very
low birth weight infants. A cohort of 316 very low birth weight newborns (weight
<= 1500 g) was prospectively enrolled in a follow-up program on admission to the
Neonatal Intensive Care Unit of S. Orsola Hospital, Bologna, Italy, from January
2005 to June 2011. Neurodevelopment was evaluated at 24 months corrected age
using the Griffiths Mental Development Scale. The effect of human milk nutrition
on neurodevelopment was first investigated using a multiple linear regression
model, to adjust for the effects of gestational age, small for gestational age,
complications at birth and during hospitalization, growth restriction at
discharge and socio-economic status. Path analysis was then used to refine the
multiple regression model, taking into account the relationships among predictors
and their temporal sequence. Human milk feeding during NICU hospitalization and
higher socio-economic status were associated with better neurodevelopment at 24
months in both models. In the path analysis model intraventricular hemorrhage
periventricular leukomalacia and growth restriction at discharge proved to be
directly and independently associated with poorer neurodevelopment. Gestational
age and growth restriction at birth had indirect significant effects on
neurodevelopment, which were mediated by complications that occurred at birth and
during hospitalization, growth restriction at discharge and type of feeding. In
conclusion, our findings suggest that mother's human milk feeding during
hospitalization can be encouraged because it may improve neurodevelopment at 24
months corrected age.
PMID- 25590631
TI - Long-term exposure to traffic emissions and fine particulate matter and lung
function decline in the Framingham heart study.
AB - RATIONALE: Few studies have examined associations between long-term exposure to
fine particulate matter (PM2.5) and lung function decline in adults. OBJECTIVES:
To determine if exposure to traffic and PM2.5 is associated with longitudinal
changes in lung function in a population-based cohort in the Northeastern United
States, where pollution levels are relatively low. METHODS: FEV1 and FVC were
measured up to two times between 1995 and 2011 among 6,339 participants of the
Framingham Offspring or Third Generation studies. We tested associations between
residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by
a land-use model using satellite measurements of aerosol optical thickness) and
lung function. We examined differences in average lung function using mixed
effects models and differences in lung function decline using linear regression
models. Current smokers were excluded. Models were adjusted for age, sex, height,
weight, pack-years, socioeconomic status indicators, cohort, time, season, and
weather. MEASUREMENTS AND MAIN RESULTS: Living less than 100 m from a major
roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to
1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1
compared with more than 400 m. Each 2 MUg/m(3) increase in average of PM2.5 was
associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95%
CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with
FVC. Associations with FEV1/FVC ratio were weak or absent. CONCLUSIONS: Long-term
exposure to traffic and PM2.5, at relatively low levels, was associated with
lower FEV1 and FVC and an accelerated rate of lung function decline.
PMID- 25590634
TI - Effect of running speed and leg prostheses on mediolateral foot placement and its
variability.
AB - This study examined the effects of speed and leg prostheses on mediolateral (ML)
foot placement and its variability in sprinters with and without transtibial
amputations. We hypothesized that ML foot placement variability would: 1.
increase with running speed up to maximum speed and 2. be symmetrical between the
legs of non-amputee sprinters but asymmetrically greater for the affected leg of
sprinters with a unilateral transtibial amputation. We measured the midline of
the body (kinematic data) and center of pressure (kinetic data) in the ML
direction while 12 non-amputee sprinters and 7 Paralympic sprinters with
transtibial amputations (6 unilateral, 1 bilateral) ran across a range of speeds
up to maximum speed on a high-speed force measuring treadmill. We quantified ML
foot placement relative to the body's midline and its variability. We interpret
our results with respect to a hypothesized relation between ML foot placement
variability and lateral balance. We infer that greater ML foot placement
variability indicates greater challenges with maintaining lateral balance. In non
amputee sprinters, ML foot placement variability for each leg increased
substantially and symmetrically across speed. In sprinters with a unilateral
amputation, ML foot placement variability for the affected and unaffected leg
also increased substantially, but was asymmetric across speeds. In general, ML
foot placement variability for sprinters with a unilateral amputation was within
the range observed in non-amputee sprinters. For the sprinter with bilateral
amputations, both affected legs exhibited the greatest increase in ML foot
placement variability with speed. Overall, we find that maintaining lateral
balance becomes increasingly challenging at faster speeds up to maximum speed but
was equally challenging for sprinters with and without a unilateral transtibial
amputation. Finally, when compared to all other sprinters in our subject pool,
maintaining lateral balance appears to be the most challenging for the Paralympic
sprinter with bilateral transtibial amputations.
PMID- 25590632
TI - Emerging role of RNA*DNA hybrids in C9orf72-linked neurodegeneration.
AB - RNA plays an active role in structural polymorphism of the genome through the
formation of stable RNA*DNA hybrids (R-loops). R-loops can modulate normal
physiological processes and are also associated with pathological conditions,
such as those related to nucleotide repeat expansions. A guanine-rich
hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72)
has been linked to a spectrum of neurological conditions including amyotrophic
lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we discuss the
possible roles, both locally and genome-wide, of R-loops that may arise from the
C9orf72 hexanucleotide repeat. R-loops have the potential to influence the
pathological processes identified in many repeat expansion diseases, such as
repeat instability, transcriptional dysregulation, epigenetic modification, and
antisense-mediated gene regulation. We propose that, given the wide-ranging
consequences of R-loops in the cell, these structures could underlie multiple
pathological processes in C9orf72-linked neurodegeneration.
PMID- 25590633
TI - Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA
damage-response pathway in SCA3.
AB - Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD),
is an untreatable autosomal dominant neurodegenerative disease, and the most
common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of
a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region
of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding
expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo,
and is deposited as aggregates in the SCA3 brain. A large body of literature
suggests that the loss of function of the native ATNX3-interacting proteins that
are deposited in the polyQ aggregates contributes to cellular toxicity, systemic
neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a
significant understanding of the disease etiology of SCA3, the molecular
mechanism by which the polyQ expansions in the mutant ATXN3 induce
neurodegeneration in SCA3 has remained elusive. In the present study, we show
that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'
phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting
in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks,
and subsequent chronic activation of the DNA damage-response ataxia
telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent
accumulation of DNA damage/strand breaks and chronic activation of the
serine/threonine kinase ATM and the downstream p53 and protein kinase C-delta pro
apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in
SCA3. Either PNKP overexpression or pharmacological inhibition of ATM
dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism
by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling
pathways provides a molecular basis for neurodegeneration due to PNKP
inactivation in SCA3, and for the first time offers a possible approach to
treatment.
PMID- 25590635
TI - Sequence analysis of the capsid gene during a genotype II.4 dominated norovirus
season in one university hospital: identification of possible transmission
routes.
AB - Norovirus (NoV) is a leading cause of gastroenteritis and genotype II.4 (GII.4)
is responsible for the majority of nosocomial NoV infections. Our objective was
to examine whether sequencing of the capsid gene might be a useful tool for the
hospital outbreak investigation to define possible transmission routes. All NoV
positive samples submitted from one university hospital during the 2007/8 season
were selected. Genotyping of selected samples by partial polymerase gene
sequencing had shown that the majority belonged to the GII.4 variant Den Haag
2006b and had identical polymerase sequences. Sequences of the capsid gene (1412
nucleotides) were obtained from the first available sample from 55 patients. From
six immunocompromised patients with persistent infections a second sample was
also included. As a control for a point-source outbreak, five samples from a
foodborne outbreak caused by the same GII.4 variant were analyzed. Forty-seven of
the inpatients (85%) were infected with the GII.4 variant Den Haag 2006b.
Phylogenetic analysis of the Den Haag 2006b sequences identified four distinct
outbreaks in different departments and a fifth outbreak with possible inter
department spread. In addition, a more heterogeneous cluster with evidence of
repeated introductions from the community, but also possible inter-department
spread was observed. In all six patients with paired sequences, evidence for in
vivo evolution of the virus was found. Capsid gene sequencing showed substantial
sequence variation among NoV GII.4 variant Den Haag 2006b strains from one single
institution during a nine months' period. This method proved useful to understand
the local epidemiology and, when used promptly, has the potential to make
infection control measures more targeted.
PMID- 25590636
TI - Altered Ca2+ kinetics associated with alpha-actinin-3 deficiency may explain
positive selection for ACTN3 null allele in human evolution.
AB - Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein alpha
actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3
gene. alpha-Actinin-3 deficiency is detrimental to sprint performance in elite
athletes and beneficial to endurance activities. In the human genome, it is very
difficult to find single-gene loss-of-function variants that bear signatures of
positive selection, yet intriguingly, the ACTN3 null variant has undergone strong
positive selection during recent evolution, appearing to provide a survival
advantage where food resources are scarce and climate is cold. We have previously
demonstrated that alpha-actinin-3 deficiency in the Actn3 KO mouse results in a
shift in fast-twitch fibres towards oxidative metabolism, which would be more
"energy efficient" in famine, and beneficial to endurance performance. Prolonged
exposure to cold can also induce changes in skeletal muscle similar to those
observed with endurance training, and changes in Ca2+ handling by the
sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On
this basis, we explored the effects of alpha-actinin-3 deficiency on Ca2+
kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice,
using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO
mice showed: (i) an increased rate of decay of the twitch transient; (ii) a
fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the
rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during
fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin
and sarcalumenin, showed markedly increased expression in muscles of KO mice.
Together, these changes in Ca2+ handling in the absence of alpha-actinin-3 are
consistent with cold acclimatisation and thermogenesis, and offer an additional
explanation for the positive selection of the ACTN3 577X null allele in
populations living in cold environments during recent evolution.
PMID- 25590638
TI - Household costs of leprosy reactions (ENL) in rural India.
AB - BACKGROUND: Erythema nodosum leprosum (ENL) is a common immune-mediated
complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most
patients experience chronic or multiple acute ENL over many years during an
economically active period of their lives. Understanding the economic burden of
ENL is essential to provide effective patient support, yet this area has not been
investigated. METHODS: Ninety-one patients with LL or BL leprosy attending a
leprosy hospital in Purulia district of West Bengal, India, were interviewed
using a structured questionnaire. Cases (n = 53) were identified as those who had
one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or
BL leprosy but no history of ENL. Data were collected on household income, direct
and indirect costs, and coping strategies. FINDINGS: The total household cost was
Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases,
and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for
controls. Indirect costs accounted for 65% of total household costs for cases.
Direct costs accounted for the remaining 35% of household costs, and resulted
almost entirely from treatment-seeking in the private sector. Total household
costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of
controls (n = 1) [1 USD = 59 INR]. INTERPRETATION: Households affected by ENL
face significant economic burden and are at risk of being pushed further into
poverty. Health policy should acknowledge the importance of private sector
provision and the significant contribution to total household costs of lost
productivity (indirect cost). Further work is needed to explore this area and
identify solutions.
PMID- 25590639
TI - Combination therapy in the extended cardiovascular continuum: a focus on
perindopril and amlodipine.
AB - The progression of cardiovascular disease could be regarded as following
atherosclerosis-related and age-related pathways. The starting points for these
pathways are different--risk factors or aortic ageing--but they conclude in the
same way: end-stage heart disease. Together these interlinked pathways form the
extended cardiovascular continuum. Renin-angiotensin-aldosterone system (RAAS)
inhibitors have been shown to interrupt or slow the progression of cardiovascular
disease along one pathway, the cardiovascular atherosclerotic continuum.
Cardiovascular protection with RAAS inhibitors varies; different RAAS inhibitors
offer different levels of protection. Similarly, calcium channel blockers (CCBs)
also have clearly shown protective effect of cardiovascular system, especially as
it regards cerebrovascular disease risk. The AngloScandinavian Cardiac Outcomes
Trial (ASCOT) showed that a combination of the angiotensin-converting enzyme
(ACE) inhibitor perindopril and CCB amlodipine offered better cardiovascular
protection in at-risk hypertensive patients than beta-blocker and thiazide. By
attenuating the deleterious effects of cardiovascular disease at multiple stages
of the extended cardiovascular continuum on top of lowering blood pressure (BP),
perindopril and amlodipine could interrupt and slow the progression of
cardiovascular disease. These antihypertensive agents have complementary vascular
effects that enhance cardiovascular protection and reduce side-effects. Evidence
from ASCOT shows that antihypertensive and vascular effects of amlodipine with
and without perindopril have translated into real-life clinical benefits. A
strategy using ACE inhibitors and CCBs, such as perindopril and amlodipine, to
target multiple stages in both pathways of cardiovascular disease could
effectively reduce cardiovascular risk and lower BP.
PMID- 25590640
TI - Choroidal hyperreflective foci in Stargardt disease shown by spectral-domain
optical coherence tomography imaging: correlation with disease severity.
AB - IMPORTANCE: The presence of choroidal hyperreflective foci in Stargardt disease
is, to our knowledge, a potentially new finding. Evaluation of these foci may aid
in better understanding of the disease process. OBJECTIVES: To report the
presence of choroidal hyperreflective foci in spectral-domain optical coherence
tomography (SD-OCT) images from eyes with Stargardt disease and investigate the
relationship between the number of hyperreflective foci and disease severity.
DESIGN, SETTING, AND PARTICIPANTS: Twenty-six eyes of 13 patients with a clinical
diagnosis of Stargardt disease were evaluated in a retrospective case series.
Patient data were collected between January 1, 2009, and August 31, 2014. MAIN
OUTCOMES AND MEASURES: The number of choroidal hyperreflective foci in Stargardt
disease as well as correlation with visual acuity, central macular thickness
(CMT), and disease duration were the main outcomes. A total of 707 macular SD-OCT
scans of 13 patients with Stargardt disease were reviewed and evaluated for the
presence and number of retinal/choroidal hyperreflective foci, central macular
thickness, visual acuity, and disease duration. Enhanced depth imaging with OCT
(EDI-OCT) scans available for 2 patients were compared with SD-OCT scans. A
PubMed/Google search was performed to identify SD-OCT images in Stargardt
disease; these findings were reviewed for the presence of choroidal
hyperreflective foci. RESULTS: The mean (SD) numbers of hyperreflective foci in
each retinal/choroidal layer in decreasing frequency were as follows: Bruch
membrane/retinal pigment epithelial (RPE) complex, 78.22 (24.39);
choriocapillaris, 25.77 (17.57); Sattler layer, 18.59 (12.89); outer retina,
16.64 (6.96); inner retina, 0.95 (1.58); and Haller layer, 0.73 (0.87). The
number of hyperreflective foci in the Bruch membrane/RPE complex increased
exponentially with decreasing CMT (R2 = 0.99; P = .008). The number of
hyperreflective foci in the Bruch membrane/RPE complex, choriocapillaris, and
Sattler layer increased proportionally with decreasing visual acuity (R2 = 0.97,
R2 = 0.95, and R2 = 0.99, respectively; and P = .007, P = .006, and P = .008,
respectively). Direct correlation existed between the number of hyperreflective
foci in the choriocapillaris and the Sattler layer and disease duration (R2 =
0.98 and R2 = 0.99, respectively; and P = .006 and P =.009, respectively). In the
10 studies on Stargardt disease, choroidal hyperreflective foci were present in
51 of 54 SD-OCT images (94%). CONCLUSIONS AND RELEVANCE: Based on the findings of
the present study, choroidal hyperreflective foci in Stargardt disease, prominent
at the Bruch membrane/RPE complex, choriocapillaris, and Sattler layer, correlate
with disease severity in terms of retinal atrophy, decline in vision, and disease
duration. Further studies are necessary to assess whether these findings are
unique to Stargardt disease.
PMID- 25590641
TI - Antidiabetic and Renal Protective Properties of Berrycactus Fruit (Myrtillocactus
geometrizans).
AB - Native plants are exceedingly valuable because they are sources of natural
products with applications for the treatment of various diseases. Berrycactus
fruit (Myrtillocactus geometrizans) has been consumed in Mexico since ancient
times due to its sweetness. The hypoglycemic and antioxidant effects of this
fruit were evaluated in streptozotocin-induced diabetic rats by replacing the
drinking water with berrycactus juice (2 or 4 g/kg). After 4 weeks of treatment,
the diabetic animals showed an improvement in their conditions, as reflected by
diminished circulating glucose levels (up to 50%), diminished triglycerides (up
to 67%), and diminished total cholesterol (up to 35%) compared with diabetic
nontreated controls, and these effects were dose dependent. The dose of 4 g/kg
produced the best results. The administration of the juice improved renal
function and helped to restore normal levels of glutathione and glutathione S
transferase in the kidney. The expressions of two transcription factors that are
relevant to normal functioning of the kidney changed due to the administration of
the juice; compared to the diabetic nontreated controls, the level of nuclear
factor kappa of B-cells diminished, and the total level of peroxisome
proliferator-activated receptor gamma increased. The results of this study
highlight the importance of the compounds that are present in berrycactus fruit
as adjuvants in the treatment of diabetes and its renal complications.
PMID- 25590643
TI - Fe(II)(pap-5NO2)2 and Fe(II)(qsal-5NO2)2 Schiff-base spin-crossover complexes: a
rare example with photomagnetism and room-temperature bistability.
AB - We focus here on the properties of Fe complexes formed with Schiff bases involved
in the chemistry of Fe(III) spin-transition archetypes. The neutral Fe(pap-5NO2)2
(1) and Fe(qsal-5NO2)2.Solv (2 and 2.Solv) compounds (Solv = 2H2O) derive from
the reaction of Fe(II) salts with the condensation products of pyridine-2
carbaldehyde with 2-hydroxy-5-nitroaniline (Hpap-5NO2) or 5-nitrosalicylaldehyde
with quinolin-8-amine (Hqsal-5NO2), respectively. While the Fe(qsal-5NO2)2.Solv
solid is essentially low spin (S = 0) and requires temperatures above 300 K to
undergo a S = 0 <-> S = 2 spin-state switching, the Fe(pap-5NO2)2 one presents a
strongly cooperative first-order transition (T? = 291 K, T? = 308 K) centered at
room temperature associated with a photomagnetic effect at 10 K (TLIESST = 58 K).
The investigation of these magnetic behaviors was conducted with single-crystal X
ray diffraction (1, 100 and 320 K; 2, 100 K), Mossbauer, IR, UV-vis (1 and
2.Solv), and differential scanning calorimetry (1) measurements. The Mossbauer
analysis supports a description of these compounds as Fe(II) Schiff-base
complexes and the occurrence of a metal-centered spin crossover process. In
comparison with Fe(III) analogues, it appears that an expanded coordination
sphere stabilizes the valence 2+ state of the Fe ion in both complexes. Strong
hydrogen-bonding interactions that implicate the phenolato group bound to Fe(II)
promote the required extra-stabilization of the S = 2 state and thus determines
the spin transition of 1 centered at room temperature. In the lattice, the
hydrogen-bonded sites form infinite chains interconnected via a three-dimensional
network of intermolecular van der Waals contacts and pi-pi interactions.
Therefore, the spin transition of 1 involves the synergetic influence of
electrostatic and elastic interactions, which cause the enhancement of
cooperativity and result in the bistability at room temperature.
PMID- 25590642
TI - Rapid Pore Cranial Drilling With External Ventricular Drainage for Treatment of
Intraventricular Hemorrhage: A 36-Year Case Series.
AB - This study aimed to describe the technique details of rapid pore cranial drilling
with external ventricular drainage and document its clinical outcomes by
highlighting the advantages over the traditional and modified cranial drilling
technique. Intraventricular hemorrhage is one of the most severe subtypes of
hemorrhagic stroke with high mortality. The amount of blood in the ventricles is
associated with severity of outcomes, and fast removal of the blood clot is the
key to a good prognosis. Between 1977 and 2013, 3773 patients admitted for
intraventricular hemorrhage underwent rapid pore cranial drilling drainage. The
therapeutic effects and clinical outcomes were retrospectively analyzed. Of these
patients, 1049 (27.8%) experienced complete remission, 1788 (47.4%) had improved
condition, and 936 (24.8%) died. A total of 3229 (85.6%) patients gained
immediate remission. One typical case was illustrated to demonstrate the efficacy
of the rapid pore drilling technique. Rapid pore cranial drilling drainage in
patients with intraventricular hemorrhage is fast, effective, and provides
immediate relief in patients with severe conditions. It could be a better
alternative to the conventional drilling approach for treatment of
intraventricular hemorrhage. A randomized controlled trial for direct comparison
between the rapid pore cranial drilling drainage and conventional drilling
technique is in urgent need.
PMID- 25590645
TI - Do patients' illness beliefs predict depression measures at six months in primary
care; a longitudinal study.
AB - BACKGROUND: Depressive disorders are prevalent and costly but there is a lack of
evidence on how best to select treatments for mild to moderate depression in
primary care. Illness beliefs have been shown to affect the outcome from physical
illness, but there is limited information on the beliefs of patients who are
depressed. AIMS: To measure patients' beliefs about depression at baseline and
determine whether these relate to depression severity at six months. METHODS:
Primary care patients with a recently diagnosed episode of depression completed
the Beliefs about Depression Questionnaire and depression severity scores at
baseline. The primary outcome was the change in depression severity score on the
Hospital Anxiety and Depression Scale after six months. RESULTS: 227/292 (78%)
participants completed follow-up questionnaires. Initial severity of depression
at baseline, and particular beliefs about the causes, consequences and timeline
of depression predicted poorer outcomes, whereas a belief in using exercise or
keeping busy to treat depression predicted improved outcomes. Prescription of
antidepressants did not appear to mediate these relationships. LIMITATIONS: This
was an initial study using a new validated questionnaire and it cannot be
predicted whether these results are representative or would be reproduced in
other populations. Although participants were primary care patients whose GP
(General Practitioner) had coded as having a new incident episode of depression
in the preceding six months, 43% of participants stated they had been depressed
for more than a year. Sufficient participants were recruited to ensure the study
was adequately powered but participation rate was 30%, raising the possibility of
response bias. CONCLUSIONS AND CLINICAL RELEVANCE: Illness beliefs may help to
predict outcomes in depression and therefore assessing and addressing patients'
beliefs about their depression may enhance treatment.
PMID- 25590644
TI - DExD-box RNA-helicases in Listeria monocytogenes are important for growth,
ribosomal maturation, rRNA processing and virulence factor expression.
AB - RNA-helicases are proteins required for the unwinding of occluding secondary RNA
structures, especially at low temperatures. In this work, we have deleted all 4
DExD-box RNA helicases in various combinations in the Gram-positive pathogen
Listeria monocytogenes. Our results show that 3 out of 4 RNA-helicases were
important for growth at low temperatures, whereas the effect was less prominent
at 37 degrees C. Over-expression of one RNA-helicase, Lmo1450, was able to
overcome the reduced growth of the quadruple mutant strain at temperatures above
26 degrees C, but not at lower temperatures. The maturation of ribosomes was
affected in different degrees in the various strains at 20 degrees C, whereas the
effect was marginal at 37 degrees C. This was accompanied by an increased level
of immature 23S rRNA precursors in some of the RNA-helicase mutants at low
temperatures. Although the expression of the PrfA regulated virulence factors
ActA and LLO decreased in the quadruple mutant strain, this strain showed a
slightly increased infection ability. Interestingly, even though the level of the
virulence factor LLO was decreased in the quadruple mutant strain as compared
with the wild-type strain, the hly-transcript (encoding LLO) was increased.
Hence, our results could suggest a role for the RNA-helicases during translation.
In this work, we show that DExD-box RNA-helicases are involved in bacterial
virulence gene-expression and infection of eukaryotic cells.
PMID- 25590647
TI - Post trauma abdominal cocoon.
AB - Abdominal cocoon or sclerosing peritonitis refers to a rare cause of intestinal
obstruction due to formation of a membrane encasing the bowel. We report a case
of abdominal cocoon post blunt trauma abdomen. The patient presented with a
history of subacute intestinal obstruction and a mobile abdomen lump. Abdominal
cocoon was diagnosed on computed tomography. He underwent adhesiolysis with
excision of membrane.
PMID- 25590646
TI - Th17 down-regulation is involved in reduced progression of schistosomiasis
fibrosis in ICOSL KO mice.
AB - BACKGROUND: Granulomatous and fibrosing inflammation in response to parasite eggs
is the main pathology that occurs during infection with Schistosoma spp. CD4+ T
cells play critical roles in both host immune responses against parasitic
infection and immunopathology in schistosomiasis,and coordinate many types of
immune cells that contribute to fibrosis. ICOSL plays an important role in
controlling specific aspects of T cell activation, differentiation, and function.
Previous work has suggested that ICOS is essential for Th17 cell development.
However, the immunopathogenesis of this pathway in schistosomiasis fibrosisis
still unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using models of schistosomiasis in
ICOSL KO and the C57BL/6 WT mice, we studied the role of the ICOSL/ICOS
interaction in the mediation of the Th17 response in host granulomatous
inflammation, particularly in liver fibrosis during S. japonicum infection, and
investigated the immune responses and pathology of ICOSL KO mice in these models.
The results showed that ICOSL KO mice exhibited improved survival, reduced liver
granulomatous inflammation around parasite eggs, markedly inhibited hepatic
fibrosis development, lower levels of Th17-related cytokines (IL-17/IL-21), Th2
related cytokines (IL-4/IL-6/IL-10), a pro-fibrotic cytokine (IL-13), and TGF
beta1, but higher level of Th1-related cytokine (IFN-gamma) compared to wild-type
(WT) mice. The reduced progression of fibrogenesis was correlated with the down
regulation of Th17 and Th2 and the elimination of ICOSL/ICOS interactions.
CONCLUSIONS/SIGNIFICANCE: Our findings suggest that IL-17-producing cells
contribute to the hepatic granulomatous inflammation and subsequent fibrosis.
Importantly, there was a clearly positive correlation between the presence of IL
17-producing cells and ICOS expression in ICOSL KO mice, and additional results
indicated that Th17 was involved in the pathological tissue remodeling in liver
fibrosis induced by schistosomiasis.
PMID- 25590648
TI - Colovaginal anastomosis: A totally unacceptable surgical error.
AB - INTRODUCTION: The low anterior rectal resection and double stapling technique are
well-established surgical procedures with well-known pitfalls, potential
complications, and preventive measures. Colovaginal anastomosis is a surgical
error which should not occur. PRESENTATION OF CASE: A 39-year old woman underwent
low anterior resection with double stapling technique, for rectal carcinoma in
the City Hospital. On the fifth postoperative day she noticed passage of gas and
two days later passage of feces from vagina. The surgeons who performed the
operation explained to her that it is a normal condition for such modern
procedure that is supervised by international educator engaged by the Government.
The patient lived with this condition, passage of gas and feces from the vagina
and nothing from anus for three months when her oncologist referred her for a
second opinion at the University Clinic for Digestive Surgery. The digital
examinations revealed a blind rectal stump, and feces in vagina; thus having the
patient's history in mind, we assumed that the patient had a colovaginal
anastomosis. Our assumption was confirmed by two succeeding radiological
examinations. Initially, water soluble contrast enema was performed to assess the
colon, when a clear-cut blind rectal stump was detected. Afterwards, the
vaginography revealed a copious flow of contrast material from the vagina toward
the sigmoid colon. After a few days, a restorative surgery was done. DISCUSSION:
Most of the early postoperative complications are a result of surgical errors.
CONCLUSION: We believe that there is no excuse for such a surgical error and
postoperative follow-up.
PMID- 25590649
TI - ZO-oming on growth control by junctional proteins.
PMID- 25590652
TI - Cell proliferation-inducing protein 52/mitofilin is a surface antigen on
undifferentiated human dental pulp stem cells.
AB - Dental pulp is a soft tissue located inside the hard part of a tooth and it
contains a stem cell population that can regenerate damaged dentin and/or pulp
itself. Human dental pulp stem cells (hDPSCs) are multipotent adult stem cells
that have the potential to be differentiated into a variety of cell types.
Although cells cultured primarily from pulp tissue show heterogeneous phenotypes
and variable efficiency in their dentinogenic differentiation, proper selection
markers, which are specific to hDPSCs, are essential for the osteo/dentinogenic
study of human dental pulp cells. We had previously screened a set of
undifferentiation-specific cell surface antibodies of hDPSCs through decoy
immunization. In this study, we show that one of these surface monoclonal
antibodies, 3C4, is bound to intact pulp cells in a highly undifferentiation
specific manner. The surface antigen protein bound specifically to 3C4 antibody
was identified through direct immunoprecipitation and liquid chromatography
tandem mass spectrometry as the cell proliferation-inducing protein 52/Mitofilin,
which is a protein of the inner mitochondrial membrane and is a possible
antagonist to maintaining mitochondrial activation during differentiation. The
expression of mitofilin/3C4 antigen dramatically decreased during
differentiation, and the depletion of mitofilin/3C4 antigen induced the
expression of osteogenic/dentinogenic markers earlier than during normal
differentiation. The 3C4-positive cells isolated by a magnetic-activated cell
sorting system were differentiated with a higher efficiency than 3C4-negative
cells. These results indicate that finding mitochondria-related stem cell markers
is valuable to be able to identify and isolate primitive stem cells.
PMID- 25590650
TI - Reliable cell cycle commitment in budding yeast is ensured by signal integration.
AB - Cell fate decisions are critical for life, yet little is known about how their
reliability is achieved when signals are noisy and fluctuating with time. In this
study, we show that in budding yeast, the decision of cell cycle commitment
(Start) is determined by the time integration of its triggering signal Cln3. We
further identify the Start repressor, Whi5, as the integrator. The instantaneous
kinase activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5,
and the decision is made only when phosphorylated Whi5 reaches a threshold. Cells
adjust the threshold by modulating Whi5 concentration in different nutrient
conditions to coordinate growth and division. Our work shows that the strategy of
signal integration, which was previously found in decision-making behaviors of
animals, is adopted at the cellular level to reduce noise and minimize
uncertainty.
PMID- 25590651
TI - The topography of frequency and time representation in primate auditory cortices.
AB - Natural sounds can be characterised by their spectral content and temporal
modulation, but how the brain is organized to analyse these two critical sound
dimensions remains uncertain. Using functional magnetic resonance imaging, we
demonstrate a topographical representation of amplitude modulation rate in the
auditory cortex of awake macaques. The representation of this temporal dimension
is organized in approximately concentric bands of equal rates across the superior
temporal plane in both hemispheres, progressing from high rates in the posterior
core to low rates in the anterior core and lateral belt cortex. In A1 the
resulting gradient of modulation rate runs approximately perpendicular to the
axis of the tonotopic gradient, suggesting an orthogonal organisation of spectral
and temporal sound dimensions. In auditory belt areas this relationship is more
complex. The data suggest a continuous representation of modulation rate across
several physiological areas, in contradistinction to a separate representation of
frequency within each area.
PMID- 25590653
TI - Investigators of studies of n = 1: pioneers or kamikazes?
PMID- 25590654
TI - Catalytic metal ions and enzymatic processing of DNA and RNA.
AB - CONSPECTUS: Two-metal-ion-dependent nucleases cleave the phosphodiester bonds of
nucleic acids via the two-metal-ion (2M) mechanism. Several high-resolution X-ray
structures portraying the two-metal-aided catalytic site, together with
mutagenesis and kinetics studies, have demonstrated a functional role of the ions
for catalysis in numerous metallonucleases. Overall, the experimental data
confirm the general mechanistic hypothesis for 2M-aided phosphoryl transfer
originally reported by Steitz and Steitz ( Proc. Natl. Acad. Sci. U.S.A. 1993 ,
90 ( 14 ), 6498 - 6502 ). This seminal paper proposed that one metal ion favors
the formation of the nucleophile, while the nearby second metal ion facilitates
leaving group departure during RNA hydrolysis. Both metals were suggested to
stabilize the enzymatic transition state. Nevertheless, static X-ray structures
alone cannot exhaustively unravel how the two ions execute their functional role
along the enzymatic reaction during processing of DNA or RNA strands when moving
from reactants to products, passing through metastable intermediates and high
energy transition states. In this Account, we discuss the role of multiscale
molecular simulations in further disclosing mechanistic insights of 2M-aided
catalysis for two prototypical enzymatic targets for drug discovery, namely,
ribonuclease H (RNase H) and type II topoisomerase (topoII). In both examples,
first-principles molecular simulations, integrated with structural data,
emphasize a cooperative motion of the bimetal motif during catalysis. The
coordinated motion of both ions is crucial for maintaining a flexible metal
centered structural architecture exquisitely tailored to accommodate the DNA or
RNA sugar-phosphate backbone during phosphodiester bond cleavage. Furthermore,
our analysis of RNase H and the N-terminal domain (PAN) of influenza polymerase
shows that classical molecular dynamics simulations coupled with enhanced
sampling techniques have contributed to describe the modulatory effect of metal
ion concentration and metal uptake on the 2M mechanism and efficiency. These
aspects all point to the emerging and intriguing role of additional adjacent ions
potentially involved in the modulation of phosphoryl transfer reactions and
enzymatic turnover in 2M-catalysis, as recently observed experimentally in
polymerase eta and homing endonuclease I-DmoI. These computational results,
integrated with experimental findings, describe and reinforce the nascent concept
of a functional and cooperative dynamics of the catalytic metal ions during the
2M-dependent enzymatic processing of DNA and RNA. Encouraged by the insights
provided by computational approaches, we foresee further experiments that will
feature the functional and joint dynamics of the catalytic metal ions for nucleic
acid processing. This could impact the de novo design of artificial
metallonucleases and the rational design of potent metal-chelating inhibitors of
pharmaceutically relevant enzymes.
PMID- 25590655
TI - Proof of concept study for designed multiple ligands targeting the dopamine D2,
serotonin 5-HT2A, and muscarinic M1 acetylcholine receptors.
AB - Herein we describe the hybridization of a benzoxazinone M1 scaffold with D2
privileged structures derived from putative and clinically relevant
antipsychotics to develop designed multiple ligands. The M1 mAChR is an
attractive target for the cognitive deficits in key CNS disorders. Moreover,
activity at D2 and 5-HT2A receptors has proven useful for antipsychotic efficacy.
We identified 9 which retained functional activity at the target M1 mAChR and D2R
and demonstrated high affinity for the 5-HT2AR.
PMID- 25590656
TI - Application of fluorescent nanoparticles to study remodeling of the endo
lysosomal system by intracellular bacteria.
AB - Fluorescent nanoparticles (NPs) with desirable chemical, optical and mechanical
properties are promising tools to label intracellular organelles. Here, we
introduce a method using gold-BSA-rhodamine NPs to label the endo-lysosomal
system of eukaryotic cells and monitor manipulations of host cellular pathways by
the intracellular pathogen Salmonella enterica. The NPs were readily internalized
by HeLa cells and localized in late endosomes/lysosomes. Salmonella infection
induced rearrangement of the vesicles and accumulation of NPs in Salmonella
induced membrane structures. We deployed the Imaris software package for
quantitative analyses of confocal microscopy images. The number of objects and
their size distribution in non-infected cells were distinct from the ones in
Salmonella-infected cells, indicating extremely remodeling of the endo-lysosomal
system by WT Salmonella.
PMID- 25590658
TI - A scalp lesion with intracranial extension. Atretic cephalocele.
PMID- 25590657
TI - Epigenome-wide analysis of piRNAs in gene-specific DNA methylation.
AB - PIWI-interacting RNAs (piRNAs) have long been associated with the silencing of
transposable elements (TEs). However, over 20,000 unique species of piRNAs mapped
to the human genome are more than the relatively few presumably required to
regulate the known human transposon classes. Here, we present the results of the
first genome-wide effort to study the effects of piRNAs on gene specific DNA
methylation. We found that exon-derived piRNAs consist almost universally of
species with 10 or fewer genomic copies, whereas piRNAs existing in high copies
originate predominately from intronic and intergenic regions. Genome-wide
methylation profiling following transfection of human somatic cells with piRNA
mimics revealed methylation changes at numerous genic loci in single copy piRNA
transfected cells. Moreover, genomic regions directly adjacent to differentially
methylated CpG sites were enriched for sequence matches to the transfected
piRNAs. These findings suggest that a subset of single copy piRNAs may be able to
induce DNA methylation at non-TE genic loci, a process that may be mediated in
part by direct binding to either genomic DNA or nascent mRNA near target CpG
sites.
PMID- 25590659
TI - When is feeding via a percutaneous endoscopic gastrostomy indicated?
AB - PURPOSE OF REVIEW: This review addresses current controversies regarding
appropriate indications for percutaneous endoscopic gastrostomy (PEG) insertion.
We address specific indications, namely, dementia, stroke, aspiration, motor
neurone disease/amyotrophic lateral sclerosis, and head and neck cancer. We
recommend practical strategies for improving patient selection. RECENT FINDINGS:
There is now a general consensus in the United States that PEG feeding does not
benefit patients with advanced dementia. 'Early' PEG insertion following stroke
is similarly of no benefit. It is currently unclear whether patients with
amyotrophic lateral sclerosis and head and neck tumors should have PEG or
radiologically inserted gastrostomy. SUMMARY: Decisions relating to PEG insertion
remain difficult. The gastroenterologist, working as a member of a
multidisciplinary nutrition team, needs to take a lead role in this regard,
rather than functioning as a technician.
PMID- 25590661
TI - TCTEX1D2, a potential link to skeletal ciliopathies.
PMID- 25590660
TI - Empirical caspofungin therapy in clinical practice for suspected invasive fungal
disease in adults with acute lymphoblastic leukaemia.
AB - Patients with acute lymphoblastic leukaemia (ALL) after cytotoxic chemotherapy or
haematopoietic stem cell transplantation (HSCT) are at risk for life-threatening
invasive fungal disease (IFD). The aim was to evaluate the characteristics,
antifungal therapy and outcome of adult patients with ALL after chemotherapy or
HSCT receiving caspofungin empirically in a clinical setting. Retrospective chart
reviews were conducted at nine large tertiary care centres in Germany. Adult
patients with ALL treated empirically with caspofungin according to the product
label between 2006 and 2012 were eligible. Data were extracted as case reports.
In total, 25 patients (12 males, 13 females; median age 37 years; 19 with B-ALL,
6 with T-ALL) with 28 treatment episodes because of suspected IFD (18 episodes
after chemotherapy, 10 episodes after allogeneic HSCT) were included in the
analysis. Empirical caspofungin therapy (median duration: 19 days, range 1-105
days) was given as first-line monotherapy in 20 (71.4%), second-line monotherapy
in five (17.9%) and combination therapy in three (10.7%) episodes respectively.
Therapy rated successful according to the physician's overall assessment
(inflammatory parameters, clinical symptoms): 20 (95%) of 21 evaluable episodes
with therapy duration of at least 8 days. Empirical caspofungin appears to be an
effective therapeutic option in critically ill adult ALL patients with suspected
IFD in clinical practice.
PMID- 25590662
TI - Disease outcomes for skull base and spinal chordomas: a single center experience.
AB - OBJECTIVE: Chordomas carry significant morbidity due to their growth patterns and
surgical constraints in resection. En bloc resection, when feasible, is the ideal
treatment goal, but is associated with significant morbidity. We sought to
elucidate the relationship between extent of surgery, location and radiotherapy
in relation to overall disease and progression free survival (PFS). METHODS: We
reviewed case records for all patients with a primary histopathological diagnosis
of clival and spinal chordomas that was presented to our institution between 1978
and 2010. RESULTS: A total of 49 patients (location: n=30, skull base/clival;
n=12 vertebral column; n=7 sacrum) were identified with mean follow-up period of
6.3 years (range 0.25 months-33 years). Improved 5 year and 10 year survival
rates were noted following gross total resection (n=8, 5 year and 10 year
survival=88%) as compared to patients that underwent subtotal resection (n=41,
55% and 31%, respectively), (p-value>0.05, GTR versus STR). Adjuvant high-dose
stereotactic fractionated radiotherapy (HS-FSRT) significantly improved 5 year
PFS in craniocervical chordoma patients (70%, n=13) as compared to standard dose
radiation therapy (20%, n=16; p-value=0.03). Overall 10 year survival for
craniocervical patients undergoing HD-FSRT (40%) was however not significantly
different in comparison with conventional radiotherapy (45%). Sacral chordomas
had the worst prognosis with 3 year survival of 28.6%. CONCLUSIONS: GTR offers
the best prognosis for improved long-term survival. Adjuvant HD FSRT for cranio
cervical/clival chordomas significantly improves disease free survival though the
long-term benefits on survival have yet to be established. Sacral chordomas are
associated with a worse prognosis and poor long-term survival.
PMID- 25590663
TI - Brain metabolism assessed via proton magnetic resonance spectroscopy in patients
with amnestic or vascular mild cognitive impairment.
AB - BACKGROUND AND OBJECTIVES: To address the possible role of brain regional
metabolic differences between different types of mild cognitive impairment (MCI).
PATIENTS AND METHODS: Brain regional metabolites in patients with amnestic mild
cognitive impairment (A-MCI) and vascular mild cognitive impairment (V-MCI) were
measured via proton magnetic resonance spectroscopy (1H MRS) technique. Twenty
eight patients with A-MCI, 24 patients with V-MCI and 34 normal controls (NC)
were tested by a battery of neuropsychological screens. All the subjects
underwent the single voxel 1H MRS with the regions of interest (ROIs) located in
the left frontal lobe, left basal ganglia and left hippocampus. RESULTS: The A
MCI showed lower NAA/Cr ratio in the left hippocampus. There was a significant
correlation between recent memory score and the NAA/Cr ratio. In V-MCI, NAA/Cr
ratio in the left frontal lobe was positively correlated with the cognitive score
evaluated with Cambridge Cognitive Examination-Chinese version (CAMCOG-C) and its
subscores of orientation, praxi, language and language comprehension.
CONCLUSIONS: This study indicated that there are differences in metabolism
related to brain regions between A-MCI and V-MCI, thus it may be concluded that
1H MRS may be a useful tool to differentiate A-MCI and V-MCI.
PMID- 25590664
TI - Ommaya reservoir with ventricular catheter placement for chemotherapy with
frameless and pinless electromagnetic surgical neuronavigation.
AB - BACKGROUND: Accuracy in Ommaya reservoir catheter placement is critical to
chemotherapy infusion. Most frameless image guidance is light emitting diode
(LED) based, requiring a direct line of communication between instrument and
tracker, limiting freedom of instrument movement within the surgical field.
Electromagnetic neuronavigation may overcome this challenge. OBJECTIVE: To
compare Ommaya reservoir ventricular catheter placement using electromagnetic
neuronavigation to LED-based optical navigation, with emphasis on placement
accuracy, operative time and complication rate. METHODS: Twenty-eight patients
who underwent placement of Ommaya reservoirs at our institution between 2010 and
2014 with either electromagnetic (12 patients) or optical neuronavigation (16
patients) were retrospectively reviewed. RESULTS: Half of the patients were male.
Their mean age was 56 years (range 28-87 years). Accuracy and precision in
catheter tip placement at the target site (foramen of Monro) were both higher
(p=0.038 and p=0.043, respectively) with electromagnetic neuronavigation.
Unintended placement of the distal catheter contralateral to the target site
occurred more frequently with optical navigation, as did superior or inferior
positioning by more than 5 mm. Mean operative times were shorter (p=0.027) with
electromagnetic neuronavigation (43.2 min) than with optical navigation (51.0
min). There were three complications (10.7%)--one case each of cytotoxic edema,
post-operative wound infection, and urinary tract infection. The rate of
complication did not differ between groups. CONCLUSION: In contrast with optical
neuronavigation, frameless and pinless electromagnetic image guidance allows the
ability to track instrument depth in real-time. It may increase ventricular
catheter placement accuracy and precision, and decrease operative times.
PMID- 25590665
TI - Changing the needle for lumbar punctures: results from a prospective study.
AB - OBJECTIVE: Post-dural puncture headache (PDPH) is a common complication of
diagnostic lumbar punctures. Both a non-cutting needle design and the use of
smaller size needles have been shown to greatly reduce the risk of PDPH.
Nevertheless, larger cutting needles are still widely used. This study describes
the process of changing the needle in an outpatient clinic of a Danish neurology
department. METHODS: Prospective interventional trial. Phase 1: 22G cutting
needle. Phase 2: 25G non-cutting needle. Practical usability of each needle was
recorded during the procedure, while the rate of PDPH and the occurrence of
socioeconomic complications were acquired from a standardized questionnaire.
RESULTS: 651 patients scheduled for diagnostic lumbar punctures were screened for
participation and 501 patients were included. The response rate was 80% in both
phases. In phase 2, significant reductions were observed in occurrence of PDPH
(21 vs. 50, p=0.001), number of days spent away from work (55 vs. 175, p<0.001),
hospitalizations (2 vs. 17, p<0.001), and number of bloodpatch treatments (2 vs.
10, p=0.019). Furthermore, during the procedure, both the need for multiple
attempts (30% vs. 44%, p=0.001), and the failure-rate of the first operator (17%
vs. 29%, p=0.005) were reduced. CONCLUSIONS: Our study showed that smaller, non
cutting needles reduce the incidence of PDPH and are easily implemented in an
outpatient clinic. Changing the needle resulted in fewer socioeconomic
complications and fewer overall costs, while also reducing procedural difficulty.
PMID- 25590666
TI - Are we able to predict survival in ER-positive HER2-negative breast cancer? A
comparison of web-based models.
AB - BACKGROUND: Several prognostic models have been proposed and demonstrated to be
predictive of survival outcomes in breast cancer. In the present article, we
assessed whether three of these models are comparable at an individual level.
METHODS: We used a large data set (n=965) of women with hormone receptor-positive
and HER2-negative early breast cancer from the public data set of the METABRIC
(Molecular Taxonomy of Breast Cancer International Consortium) study. We compared
the overall performance of three validated web-based models: Adjuvant!,
CancerMath.net and PREDICT, and we assessed concordance of these models in 10
year survival prediction. RESULTS: Discrimination performances of the three
calculators to predict 10-year survival were similar for the Adjuvant! Model,
0.74 (95% CI 0.71-0.77) for the Cancermath.net model and 0.72 (95% CI 0.69-0.75)
for the PREDICT model). Calibration performances, assessed graphically, were
satisfactory. Predictions were concordant and stable in the subgroup, with a
predicted survival higher than 90% with a median score dispersion at 0.08 (range
0.06-0.10). Dispersion, however, reached 30% for the subgroups with a predicted
survival between 10 and 50%. CONCLUSION: This study revealed that the three web
based predictors equally perform well at the population level, but exhibit a high
degree of discordance in the intermediate and poor prognosis groups.
PMID- 25590669
TI - An investigation into motorcycle crashes in work zones.
AB - OBJECTIVE: There were 454 motorcycle crashes in work zones within the state of
Ohio between January 2006 and July 2012. Pavement degradation derived from work
zones tend to have a hazardous effect on motorcycles and their safe passage. The
objective of this study is to research the work zones where motorcycle crashes
have taken place in order to determine any contributing factors. METHODS: This
study incorporates the collection of motorcycle crash data, including
construction documents associated with the work zones in which the crashes
occurred. Crash documents from the Ohio Department of Public safety and the Ohio
Department of Transportation are used to identify the initial factors to be
studied. RESULTS: Construction documents associated with 183 of the crashes are
able to be retrieved. From these documents, the frequency of associated crashes
and rates of fatalities per work type are able to be determined. CONCLUSIONS: It
is found that work types that take place on lower functional class roadways, such
as sewer repair, are found to have higher fatality rates. In contrast, those work
zones on higher functional class roadways often incorporate speed calming
measures and have a clear division between the traveled way and the actual
construction work.
PMID- 25590667
TI - Television watching and risk of colorectal adenoma.
AB - BACKGROUND: Prolonged TV watching, a major sedentary behaviour, is associated
with increased risk of obesity and diabetes and may involve in colorectal
carcinogenesis. METHODS: We conducted a cross-sectional analysis among 31 065 men
with ?1 endoscopy in the Health Professionals Follow-up Study (1988-2008) to
evaluate sitting while watching TV and its joint influence with leisure-time
physical activity on risk of colorectal adenoma. Logistic regression was used to
calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:
Prolonged sitting while watching TV was significantly associated with increased
risk of colorectal adenoma (n=4280), and adjusting for physical activity or a
potential mediator body mass index did not change the estimates. The ORs (95%
CIs) across categories of TV watching (0-6, 7-13, 14-20, and 21+ h per week) were
1.00 (referent), 1.09 (1.01-1.17), 1.16 (1.06-1.27), and 1.10 (0.97-1.25) (OR per
14-h per week increment=1.11; 95% CI: 1.04-1.18; Ptrend=0.001). Compared with the
least sedentary (0-6 h per week of TV) and most physically active (highest
quintile) men, the most sedentary (14+ h per week) and least active (lowest
quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05
1.49), particularly for high-risk adenoma. CONCLUSIONS: Prolonged TV viewing is
associated with modest increased risk of colorectal adenoma independent of
leisure-time physical activity and minimally mediated by obesity.
PMID- 25590668
TI - Racial/Ethnic variation in all-cause mortality among United States medicaid
recipients with systemic lupus erythematosus: a Hispanic and asian paradox.
AB - OBJECTIVE: The incidence of systemic lupus erythematosus (SLE) is
disproportionately high in nonwhite patients compared with white patients.
However, variation in mortality according to race/ethnicity has not been well
studied. The aim of this study was to examine all-cause mortality according to
race/ethnicity among SLE patients enrolled in Medicaid. METHODS: We used Medicaid
Analytic eXtract data, with billing claims from 47 US states and Washington, DC,
to identify individuals ages 18-65 years who were enrolled in Medicaid for >=3
months in 2000-2006. Individuals were classified as having SLE if they had >=3
visits >=30 days apart with an International Classification of Diseases, Ninth
Revision (ICD-9) code for SLE (710.0). Among the individuals with SLE, those with
lupus nephritis (LN) were identified by the presence of >=2 ICD-9 claims for
glomerulonephritis, proteinuria, or renal failure. We calculated mortality rates
per 1,000 person-years, with 95% confidence intervals (95% CIs), according to
race/ethnicity. Multivariable Cox proportional hazards regression models were
used to estimate mortality risks, adjusting for age, sex, demographics, and
comorbidities. RESULTS: Among 42,221 prevalent cases of SLE, 8,191 prevalent
cases of LN were identified. Blacks represented 40.1%, whites 38.4%, and
Hispanics 15.3%. Overall SLE mortality rates per 1,000 person-years were highest
among Native American (27.52), white (20.17), and black (24.13) patients and were
lower among Hispanic (7.12) or Asian (5.18) patients. After multivariable
adjustment, Hispanic and Asian patients had lower mortality risks (hazard ratio
[HR] 0.48 [95% CI 0.40-0.59] and 0.59 [95% CI 0.40-0.86], respectively) compared
with whites. Conversely, the risk of death was significantly higher among Native
American (HR 1.40 [95% CI 1.04-1.90]) and black (HR 1.21 [95% CI 1.10-1.33])
patients compared with white patients. Among patients with LN, mortality risks
were lower in Hispanic and Asian patients compared with white patients.
CONCLUSION: After accounting for demographic and clinical factors, mortality
among Asian and Hispanic Medicaid patients with SLE was lower than that among
black, white, or Native American patients.
PMID- 25590670
TI - Simultaneous orthogonal dual-click approach to tough, in-situ-forming hydrogels
for cell encapsulation.
AB - The use of tough hydrogels as biomaterials is limited as a consequence of time
consuming fabrication techniques, toxic starting materials, and large strain
hysteresis under deformation. Herein, we report the simultaneous application of
nucleophilic thiol-yne and inverse electron-demand Diels-Alder additions to
independently create two interpenetrating networks in a simple one-step
procedure. The resultant hydrogels display compressive stresses of 14-15 MPa at
98% compression without fracture or hysteresis upon repeated load. The hydrogel
networks can be spatially and temporally postfunctionalized via radical
thiylation and/or inverse electron-demand Diels-Alder addition to residual
functional groups within the network. Furthermore, gelation occurs rapidly under
physiological conditions, enabling encapsulation of human cells.
PMID- 25590671
TI - Role of vibrational dynamics in electronic relaxation of Cr(acac)3.
AB - Ultrafast energy relaxation of Cr(acac)3 dissolved in tetrachloroethylene (TCE)
is studied by time-resolved infrared (TRIR) spectroscopy by using electronic and
vibrational excitation. After electronic excitation at 400 or 345 nm, the ground
state recovers in two time scales: 15 ps (major pathway) and 800 ps (minor
pathway), corresponding to fast electronic transition to the ground state and
intermediate trapping on the long-lived (2)E state followed by intersystem
crossing (ISC) to the ground state. The quantum yield for the fast recovery of
the ground state depends on the excitation wavelength, being higher for 345 nm.
Vibrational cooling (VC) occurs on the electronic excited states with a time
constant of ~7 ps and on the ground electronic state with a time constant of ~12
ps. A kinetic model that explains the observed dynamics is presented. The key
point of the model is that the ground-state recovery occurs via thermally
activated back-intersystem-crossing (b-ISC) to the quartet manifold presumably
via multiple curve crossings that are sampled while the system is vibrationally
hot. This underlines the importance of vibrational cooling as a determining
factor for the electronic relaxation chain. Vibrational excitation of the nuC?C
and nuCO vibrations also revealed a subpicosecond (300-700 fs) intramolecular
vibrational redistribution (IVR) process from the localized vibrational states to
the bath of vibrational excitations.
PMID- 25590672
TI - Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation
inhibitor.
AB - The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the
ADP-induced aggregation of human platelets, is described. The monomer and
dipeptide fragments were prepared using conventional chemistry and subsequently
assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel
bis-alkylation-elimination of cysteine on-resin was employed to introduce the
unnatural N-methyldehydroalanine moiety. The final step involved execution of a
key macrolactamization reaction between the hindered unnatural N,O
dimethylthreonine and beta-hydroxyleucine residues.
PMID- 25590673
TI - Detoxification of chlorella supplement on heterocyclic amines in Korean young
adults.
AB - Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) have been
established as carcinogenic chemicals in Western diet. This study was performed
to estimate HCA exposure levels in Korean daily life and to assess the ability of
Chlorella vulgaris to detoxify carcinogenic HCAs in a randomized, double blind,
placebo-controlled crossover study with chlorella supplement (N=6, all females,
age: 27.17+/-7.73yr) for 2 weeks. We analyzed HCAs in hydrolyzed urine specimens
using LC/TOF-MS. As results, urinary levels of MeIQx, PhIP, and IQx-8-COOH were
323.36+/-220.11ng/L, 351.59+/-254.93ng/L, and 130.85+/-83.22ng/L, respectively.
Effects of chlorella to reduce urinary MeIQx were marginally significant (before,
430+/-226.86pg/mL vs. after, 174.45+/-101.65pg/mL: 0.05=4 weeks
before conception and continuing through the first 12 weeks of pregnancy. To
learn whether folic acid supplementation (from multivitamins or single-
ingredient supplements) was commonly used during pregnancy by women with a
previous NTD-affected pregnancy, supplement use was assessed among a convenience
sample of women with a previous NTD-affected pregnancy who participated in the
National Birth Defects Prevention Study (NBDPS), a case-control study of major
birth defects in the United States. Characteristics of women who previously had
an NTD-affected pregnancy and whose index pregnancy (pregnancy included in NBDPS)
was either affected by an NTD (N = 17) (i.e., recurrence-cases) or resulted in a
live-born infant without a major birth defect (N = 10) (i.e., recurrence
controls) were assessed. Taking a supplement that included folic acid was more
common among recurrence-control mothers (80%) than recurrence-case mothers (35%).
The recommendation that women should take folic acid supplements just before and
during early pregnancy is not being followed by many women and offers an
opportunity for NTD prevention, especially among women who are at a higher risk
because they have had a previous pregnancy affected by an NTD.
PMID- 25590680
TI - Early estimates of seasonal influenza vaccine effectiveness - United States,
January 2015.
AB - In the United States, annual vaccination against seasonal influenza is
recommended for all persons aged >=6 months. Each season since 2004-05, CDC has
estimated the effectiveness of seasonal influenza vaccine in preventing medically
attended acute respiratory illness (ARI) associated with laboratory-confirmed
influenza. This season, early estimates of influenza vaccine effectiveness are
possible because of widespread, early circulation of influenza viruses. By
January 3, 2015, 46 states were experiencing widespread flu activity, with
predominance of influenza A (H3N2) viruses. This report presents an initial
estimate of seasonal influenza vaccine effectiveness at preventing laboratory
confirmed influenza virus infection associated with medically attended ARI based
on data from 2,321 children and adults enrolled in the U.S. Influenza Vaccine
Effectiveness Network (Flu VE) during November 10, 2014-January 2, 2015. During
this period, overall vaccine effectiveness (VE) (adjusted for study site, age,
sex, race/ethnicity, self-rated health, and days from illness onset to
enrollment) against laboratory-confirmed influenza associated with medically
attended ARI was 23% (95% confidence interval [CI] = 8%-36%). Most influenza
infections were due to A (H3N2) viruses. This interim VE estimate is relatively
low compared with previous seasons when circulating viruses and vaccine viruses
were well-matched and likely reflects the fact that more than two-thirds of
circulating A (H3N2) viruses are antigenically and genetically different
(drifted) from the A (H3N2) vaccine component of 2014-15 Northern Hemisphere
seasonal influenza vaccines. These early, low VE estimates underscore the need
for ongoing influenza prevention and treatment measures. CDC continues to
recommend influenza vaccination because the vaccine can still prevent some
infections with the currently circulating A (H3N2) viruses as well as other
viruses that might circulate later in the season, including influenza B viruses.
Even when VE is reduced, vaccination still prevents some illness and serious
influenza-related complications, including thousands of hospitalizations and
deaths. Persons aged >=6 months who have not yet been vaccinated this season
should be vaccinated, including persons who might already have been ill with
influenza this season.
PMID- 25590681
TI - Incidence of notifiable diseases among American Indians/Alaska Natives - United
States, 2007-2011.
AB - American Indian/Alaska Native (AI/AN) populations experience substantial
disparities in the incidence of multiple diseases compared with other
racial/ethnic groups in the United States. A major goal of Healthy People 2020 is
to eliminate health disparities, monitor disease trends, and identify population
groups and diseases for targeted interventions. High rates of certain infectious
diseases continue to be a major problem facing AI/AN populations. During 1990
2011, incidence rates for some infectious diseases declined among AI/AN
populations, but disparities remain and AI/AN populations are still
disproportionately affected. To describe disparities in selected notifiable
diseases among AI/ANs, CDC analyzed data from the National Notifiable Diseases
Surveillance System (NNDSS) for 2007-2011, the most recent 5 years for which data
are available. The results of this analysis of 26 infectious diseases indicate
that incidence rates of 14 diseases were higher for AI/ANs than for whites.
Interventions are needed to address and reduce disparities in chlamydia,
gonorrhea, West Nile virus, spotted fever rickettsiosis, and other infections
among AI/ANs.
PMID- 25590682
TI - Improving burial practices and cemetery management during an Ebola virus disease
epidemic - Sierra Leone, 2014.
AB - As of January 3, 2015, Ebola virus disease (Ebola) has killed more than 2,500
persons in Sierra Leone since the epidemic began there in May 2014. Ebola virus
is transmitted principally by direct physical contact with an infected person or
their body fluids during the later stages of illness or after death. Contact with
the bodies and fluids of persons who have died of Ebola is especially common in
West Africa, where family and community members often touch and wash the body of
the deceased in preparation for funerals. These cultural practices have been a
route of Ebola transmission. In September 2014, CDC, in collaboration with the
Sierra Leone Ministry of Health and Sanitation (MOH), assessed burial practices,
cemetery management, and adherence to practices recommended to reduce the risk
for Ebola virus transmission. The assessment was conducted by directly observing
burials and cemetery operations in three high-incidence districts. In addition, a
community assessment was conducted to assess the acceptability to the population
of safe, nontraditional burial practices and cemetery management intended to
reduce the risk for Ebola virus transmission. This report summarizes the results
of these assessments, which found that 1) there were not enough burial teams to
manage the number of reported deaths, 2) Ebola surveillance, swab collection, and
burial team responses to a dead body alert were not coordinated, 3) systematic
procedures for testing and reporting of Ebola laboratory results for dead bodies
were lacking, 4) cemetery space and management were inadequate, and 5) safe
burial practices, as initially implemented, were not well accepted by
communities. These findings were used to inform the development of a national
standard operating procedure (SOP) for safe, dignified medical burials, released
on October 1. A second, national-level, assessment was conducted during October
10-15 to assess burial team practices and training and resource needs for SOP
implementation across all 14 districts in Sierra Leone. The national-level
assessment confirmed that burial practices, challenges, and needs at the national
level were similar to those found during the assessment conducted in the three
districts. Recommendations based on the assessments included 1) district-level
trainings on the components of the SOP and 2) rapid deployment across the 14
districts of additional trained burial teams supplied with adequate personal
protective equipment (PPE), other equipment (e.g., chlorine, chlorine sprayers,
body bags, and shovels), and vehicles. Although these assessments were conducted
very early on in the response, during October-December national implementation of
the SOP and recommendations might have made dignified burial safer and increased
community support for these practices; an evaluation of this observation is
planned.
PMID- 25590683
TI - Use of a nationwide call center for Ebola response and monitoring during a 3-day
house-to-house campaign - Sierra Leone, September 2014.
AB - During May 23, 2014-January 10, 2015, Sierra Leone reported 7,777 confirmed cases
of Ebola virus disease (Ebola). In response to the epidemic, on August 5, Sierra
Leone's Emergency Operations Center established a toll-free, nationwide Ebola
call center. The purpose of the call center is to encourage public reporting of
possible Ebola cases and deaths to public health officials and to provide health
education about Ebola to callers. This information also functions as an "alert"
system for public health officials and supports surveillance efforts for the
response. National call center dispatchers call district-level response teams
composed of surveillance officers and burial teams to inform them of reported
deaths and possible Ebola cases. Members of these response teams investigate
cases and conduct follow-up actions such as transporting ill persons to Ebola
treatment units or providing safe, dignified medical burials as resources permit.
The call center continues to operate. This report describes calls received during
a 3-day national campaign and reports the results of an assessment of the call
center operation during the campaign.
PMID- 25590684
TI - Notes from the field: outbreak of diarrheal illness caused by Shigella flexneri -
American Samoa, May-June 2014.
AB - On May 9, 2014, a physician at hospital A in American Samoa noticed an abnormally
high number of children presenting to the emergency department with bloody
diarrhea. Based on preliminary testing of stool specimens, Entamoeba histolytica
infection was suspected as a possible cause. Shigella was also suspected in a
subset of samples. On May 22, the American Samoa Department of Health requested
assistance from CDC with the outbreak investigation. The goals of the
investigation were to establish the presence of an outbreak, characterize its
epidemiology and etiology, and recommend control measures. The CDC field team
reviewed the emergency department log book for cases of diarrheal illness during
April 15-June 13, 2014. During this period, 280 cases of diarrheal illness were
recorded, with a peak occurring on May 10. Twice as many cases occurred during
this period in 2014 compared with the same period in 2011, the most recent year
for which comparable surveillance data were available. Cases were widely
distributed across the island. The highest number of cases occurred in children
aged 0-9 years. Across age groups, cases were similarly distributed among males
and females. These patterns are not consistent with the epidemiology of disease
caused by E. histolytica, which tends to cause more cases in males of all ages.
PMID- 25590685
TI - Ethylene and pollination decrease transcript abundance of an ethylene receptor
gene in Dendrobium petals.
AB - We studied the expression of a gene encoding an ethylene receptor, called
Ethylene Response Sensor 1 (Den-ERS1), in the petals of Dendrobium orchid
flowers. Transcripts accumulated during the young floral bud stage and declined
by the time the flowers had been open for several days. Pollination or exposure
to exogenous ethylene resulted in earlier flower senescence, an increase in
ethylene production and a lower Den-ERS1 transcript abundance. Treatment with 1
methylcyclopropene (1-MCP), an inhibitor of the ethylene receptor, decreased
ethylene production and resulted in high transcript abundance. The literature
indicates two kinds of ethylene receptor genes with regard to the effects of
ethylene. One group shows ethylene-induced down-regulated transcription, while
the other has ethylene-induced up-regulation. The present gene is an example of
the first group. The 5' flanking region showed binding sites for Myb and myb
like, homeodomain, MADS domain, NAC, TCP, bHLH and EIN3-like transcription
factors. The binding site for the EIN3-like factor might explain the ethylene
effect on transcription. A few other transcription factors (RAV1 and NAC) seem
also related to ethylene effects.
PMID- 25590686
TI - Tubulin marker line of grapevine suspension cells as a tool to follow early
stress responses.
AB - Plant microtubules (MTs), in addition to their role in cell division and cell
expansion, respond to various stress signals. To understand the biological
function of this early response requires non-destructive strategies for
visualization in cellular models that are highly responsive to stress signals. We
have therefore generated a transgenic tubulin marker line for a cell line from
the grapevine Vitis rupestris that readily responds to stress factors of defense
related and abiotic stresses based on a fusion of the green fluorescent protein
with Arabidopsis beta-tubulin 6. By a combination of spinning-disk confocal
microscopy with quantitative image analysis, we could detect early and specific
responses of MTs to defense-related and abiotic stress factors in vivo. We
observed that Harpin Z (HrpZ), a bacterial elicitor that can trigger programmed
cell death, rapidly eliminated radial MTs, followed by a slower depletion of the
cortical array. Jasmonic acid (JA), in contrast, induced bundling of cortical
MTs. Auxin reduced the thickness of cortical MTs. This effect followed a
characteristic bell-shaped dose-dependency and could revert JA-induced bundling.
Impeded cell expansion as a consequence of stress treatment or superoptimal auxin
was linked with the appearance of intranuclear tubulin speckles. The early and
stimulus-specific responses of MTs are discussed with respect to a function in
processing or decoding of stress signals.
PMID- 25590688
TI - Assessing leukocyte-endothelial interactions under flow conditions in an ex vivo
autoperfused microflow chamber assay.
AB - Leukocyte-endothelial interactions are early and critical events in acute and
chronic inflammation and can, when dysregulated, mediate tissue injury leading to
permanent pathological damage. Existing conventional assays allow the analysis of
leukocyte adhesion molecules only after the extraction of leukocytes from the
blood. This requires the blood to undergo several steps before peripheral blood
leukocytes (PBLs) can be ready for analysis, which in turn can stimulate PBLs
influencing the research findings. The autoperfused micro flow chamber assay,
however, allows scientists to study early leukocytes functional dysregulation
using the systemic flow of a live mouse while having the freedom of manipulating
a coated chamber. Through a disease model, the functional expression of leukocyte
adhesion molecules can be assessed and quantified in a micro-glass chamber coated
with immobilized endothelial adhesion molecules ex vivo. In this model, the blood
flows between the right common carotid artery and left external jugular vein of a
live mouse under anesthesia, allowing the interaction of native PBLs in the
chamber. Real-time experimental analysis is achieved with the assistance of an
intravital microscope as well as a Harvard Apparatus pressure device. The
application of a flow regulator at the input point of the glass chamber allows
comparable physiological flow conditions amongst the experiments. Leukocyte
rolling velocity is the main outcome and is measured using the National
Institutes of Health open-access software ImageJ. In summary, the autoperfused
micro flow chamber assay provides an optimal physiological environment to study
leukocytes endothelial interaction and allows researchers to draw accurate
conclusions when studying inflammation.
PMID- 25590689
TI - Polyelectrolyte complexes of a cationic all conjugated fluorene-thiophene diblock
copolymer with aqueous DNA.
AB - We report on the structural and colorimetric effects of interaction of aqueous
~0.06-1% poly[9,9-bis(2-ethylhexyl)fluorene]-b-poly[3-(6
trimethylammoniumhexyl)thiophene] bromide (PF2/6-P3TMAHT) with double-stranded
DNA to form PF2/6-P3TMAHT(DNA)x where x is the molar ratio of DNA base pairs to
P3TMAHT repeat units; x = 0.5 equals the nominal charge neutralization. PF2/6
P3TMAHT forms 20-40 nm sized particles with PF2/6 core and hydrated P3TMAHT
exterior. The polymer particles form loose one-dimensional chains giving
micrometer long branched chains (0.19 <= x <= 0.76) and subsequently randomly
shaped aggregates (x = 1.89) upon DNA addition. Compaction of the P3TMAHT block
and the 20-30 nm sized core is observed for x = 0.38-0.76 and attributed to the
DNA merged within P3TMAHT domain with this structure disassembling with DNA
excess. Structural transformations are followed by chromic changes seen as color
changes from deep red (x < 0.076) to yellow (x = 0.19), nearly colorless (x =
0.38-0.76), and back to orange (x = 1.89). Both absorption and photoluminescence
spectra display the distinct fluorene and thiophene bands and subsequent blue and
red shifts when passing x = 0.5. Thiophene photoluminescence (PL) is
significantly quenched by DNA with increasing x, and the changing P3TMAHT/PF2/6
band ratio allows quantitative DNA detection. Sixteen-fold dilution does not
change aggregate structure, but PL is blue-shifted, indicating weakened
intermolecular interactions.
PMID- 25590687
TI - Neuronal cell cycle: the neuron itself and its circumstances.
AB - Neurons are usually regarded as postmitotic cells that undergo apoptosis in
response to cell cycle reactivation. Nevertheless, recent evidence indicates the
existence of a defined developmental program that induces DNA replication in
specific populations of neurons, which remain in a tetraploid state for the rest
of their adult life. Similarly, de novo neuronal tetraploidization has also been
described in the adult brain as an early hallmark of neurodegeneration. The aim
of this review is to integrate these recent developments in the context of cell
cycle regulation and apoptotic cell death in neurons. We conclude that a variety
of mechanisms exists in neuronal cells for G1/S and G2/M checkpoint regulation.
These mechanisms, which are connected with the apoptotic machinery, can be
modulated by environmental signals and the neuronal phenotype itself, thus
resulting in a variety of outcomes ranging from cell death at the G1/S checkpoint
to full proliferation of differentiated neurons.
PMID- 25590690
TI - PPM1D regulates p21 expression via dephoshporylation at serine 123.
AB - The cyclin-dependent kinase inhibitor p21 plays a critical role in regulating
cell cycle and cell proliferation. We previously cloned the dog p21 gene and
found that unlike human p21, dog p21 is expressed as 2 isoforms due to the
proline-directed phosphorylation at serine 123 (S123). Here, we identified that
PPM1D, also called Wip1 and a Mg(2+)-dependent phosphatase, dephosphorylates dog
p21 protein at serine 123. Specifically, we showed that the level of S123
phosphorylated dog p21 is increased by a PPM1D inhibitor in a dose-dependent
manner. We also showed that over-expression of PPM1D decreases, whereas knockdown
of PPM1D increases, the level of S123-phosphorylated dog p21 regardless of p53.
Additionally, in vitro phosphatase assay was performed and showed that
phosphorylated S123 in dog p21 is dephosphorylated by recombinant rPPM1D, which
contains the catalytic domain of human PPM1D (residue 1-420), but not by the
phosphatase dead rPPM1D (D314A). Furthermore, dephosphorylation of S123 by rPPM1D
can be abrogated by PPM1D inhibitor or by withdrawal of Mg(2+). Finally, we
showed that upon PPM1D inhibition, the level of S123-phosphorylated dog p21 was
increased, concomitantly with decreased expression of cyclin A, cyclin B, Rb, and
PCNA. Together, our results indicate that PPM1D functions as a phosphatase of dog
p21 at serine 123 and plays a role in cell cycle control via p21.
PMID- 25590692
TI - Laser direct synthesis of silicon nanowire field effect transistors.
AB - We demonstrate a single-step, laser-based technique to fabricate silicon nanowire
field effect transistors. Boron-doped silicon nanowires are synthesized using a
laser-direct-write chemical vapor deposition process, which can produce nanowires
as small as 60 nm, far below the diffraction limit of the laser wavelength of 395
nm. In addition, the method has the advantages of in situ doping, catalyst-free
growth, and precise control of nanowire position, orientation, and length.
Silicon nanowires are directly fabricated on an insulating surface and ready for
subsequent device fabrication without the need for transfer and alignment, thus
greatly simplifying device fabrication processes. Schottky barrier nanowire field
effect transistors with a back-gate configuration are fabricated from the laser
direct-written Si nanowires and electrically characterized.
PMID- 25590691
TI - Saponins, especially platyconic acid A, from Platycodon grandiflorum reduce
airway inflammation in ovalbumin-induced mice and PMA-exposed A549 cells.
AB - We investigated the inhibitory effects of Platycodon grandiflorum root-derived
saponins (Changkil saponins: CKS) on ovalbumin-induced airway inflammation in
mice. CKS suppressed leukocytes number, IgE, Th1/Th2 cytokines, and MCP-1
chemokine secretion in bronchoalveolar lavage fluid. Also, ovalbumin-increased
MUC5AC, MMP-2/9, and TIMP-1/-2 mRNA expression, NF-kappaB activation, leukocytes
recruitment, and mucus secretion were inhibited by CKS treatment. Moreover, the
active component of CKS, platyconic acid A (PA), suppressed PMA-induced MUC5AC
mRNA expression (from 2.1 +/- 0.2 to 1.1 +/- 0.1) by inhibiting NF-kappaB
activation (from 2.3 +/- 0.2 to 1.2 +/- 0.1) via Akt (from 3.7 +/- 0.3 to 2.1 +/-
0.2) (p < 0.01) in A549 cells. Therefore, we demonstrate that CKS or PA
suppressed the development of respiratory inflammation, hyperresponsiveness, and
remodeling by reducing allergic responses, and they may be potential herbal drugs
for allergen-induced respiratory disease prevention.
PMID- 25590693
TI - Transformation of the excited state and photovoltaic efficiency of CH3NH3PbI3
perovskite upon controlled exposure to humidified air.
AB - Humidity has been an important factor, in both negative and positive ways, in the
development of perovskite solar cells and will prove critical in the push to
commercialize this exciting new photovoltaic technology. The interaction between
CH(3)NH(3)PbI(3) and H(2)O vapor is investigated by characterizing the ground
state and excited-state optical absorption properties and probing morphology and
crystal structure. These undertakings reveal that H(2)O exposure does not simply
cause CH(3)NH(3)PbI(3) to revert to PbI(2). It is shown that, in the dark, H(2)O
is able to complex with the perovskite, forming a hydrate product similar to
(CH(3)NH(3))(4)PbI(6).2H(2)O. This causes a decrease in absorption across the
visible region of the spectrum and a distinct change in the crystal structure of
the material. Femtosecond transient absorption spectroscopic measurements show
the effect that humidity has on the ultrafast excited state dynamics of
CH(3)NH(3)PbI(3). More importantly, the deleterious effects of humidity on
complete solar cells, specifically on photovoltaic efficiency and stability, are
explored in the light of these spectroscopic understandings.
PMID- 25590695
TI - PTSD-related paradoxical insomnia: an actigraphic study among veterans with
chronic PTSD.
AB - BACKGROUND: Sleep disturbance is a common self-reported complaint by PTSD
patients. However, there are controversies in documenting objective indices of
disrupted sleep in these patients. The aim of the present study was to assess
sleep disturbances in veterans with chronic PTSD, using both subjective and
objective assessments. METHODS: Thirty two PTSD patients with complaints of
insomnia were evaluated using the Clinician Administrated PTSD Scale version 1
(CAPS) and completed the Pittsburg Sleep Quality Index (PSQI) for subjective
evaluation of their sleep. For objective evaluation, participants underwent two
consecutive overnight actigraphic assessments. Total Sleep Time (TST), Sleep
Latency (SL), Sleep Efficiency (SE) and Number of Awakening (NWAK) were measured
in all participants. RESULTS: Participants underestimated TST (p less than
0.0001), SE (p less than 0.0001) as well as NASO (0.03) in the questionnaire
compared to the actigraphic assessment and overestimated SL (p less than 0.0001).
CONCLUSIONS: Objective sleep parameters do not adversely affect veterans with
chronic PTSD. Self-reported sleep disturbance in these patients is not reliable
and objective sleep assessments are necessary.
PMID- 25590696
TI - Bio-inspired multiproperty materials: strong, self-healing, and transparent
artificial wood nanostructures.
AB - Nanocomposite films possessing multiple interesting properties (mechanical
strength, optical transparency, self-healing, and partial biodegradability) are
discussed. We used Layer-by-Layer assembly to prepare micron thick wood-inspired
films from anionic nanofibrillated cellulose and cationic poly(vinyl amine). The
film growth was carried out at different pH values to obtain films of different
chemical composition, whereby, and as expected, higher pH values led to a higher
polycation content and also to 6 times higher film growth increments (from 9 to
55 nm per layer pair). In the pH range from 8 to 11, micron thick and optically
transparent LbL films are obtained by automated dipping when dried regularly in a
stream of air. Films with a size of 10 cm(2) or more can be peeled from flat
surfaces; they show tensile strengths up to about 250 MPa and Young's moduli up
to about 18 GPa as controlled by the polycation/polyanion ratio of the film.
Experiments at different humidities revealed the plasticizing effect of water in
the films and allowed reversible switching of their mechanical properties.
Whereas dry films are strong and brittle (Young's modulus: 16 GPa, strain at
break: 1.7%), wet films are soft and ductile (Young's modulus: 0.1 GPa, strain at
break: 49%). Wet film surfaces even amalgamate upon contact to yield mechanically
stable junctions. We attribute the switchability of the mechanical properties and
the propensity for self-repair to changes in the polycation mobility that are
brought about by the plastifying effect of water.
PMID- 25590698
TI - New information on molecular features of the dengue virus type 3, panorama of the
amphibian research in Brazil, and a new extinct Cretaceous angiosperm.
PMID- 25590697
TI - Graphene oxide as efficient high-concentration formaldehyde scavenger and
reutilization in supercapacitor.
AB - Graphene oxide (GO) was investigated as a low-cost and high-efficient scavenger
for high-concentration formaldehyde in alkali media. It showed very high removal
capacity, 411 mg of formaldehyde per milligram of GO, and strong resistant to
temperature changes. Additionally, the used GO can be easily renewed by a simple
electrochemical method. By analyzing the componential and electrochemical
characterizations of GO before and after use, the results showed that the
degradation mechanism of formaldehyde is a collaborative process of chemical
oxidation and physical adsorption, and the former dominates the degradation
process. With the aid of oxygen-containing groups in GO, most formaldehyde can be
easily oxidized by GO in alkaline media (this is equivalent to GO was reduced by
formaldehyde). On the other hand, the used GO (reduced GO, noted as rGO) exhibits
more ideal electronic double-layer capacitor (EDLC) feature than GO, along with
higher rate capacitance (up to 136 F g(-1) at 50 A g(-1)). In short, GO is not
only an efficient formaldehyde scavenger, but the used GO (rGO) can serve as
promising electrical energy storage material. This study provides new insights
for us to reutilize the discarded adsorbents generated from the environmental
protection.
PMID- 25590699
TI - Evaluation of the use of Leptodactylus ocellatus (Anura: Leptodactylidae) frog
tissues as bioindicator of metal contamination in Contas River, Northeastern
Brazil.
AB - This paper presents a study on the viability of the use of tissues of the
Leptodactylus ocellatus species (Anura Leptodactylidae) as a bioindicator of
metal pollution. The study is based on the determination and correlation of the
concentrations of manganese, chromium, zinc, nickel, copper and iron in sediments
and tissues (skin, muscles and viscera) of the frog Leptodactylus ocellatus
collected in the middle region of the Contas River in Bahia, Brazil. The highest
levels of the metals studied were found in the viscera of this animal. In this
tissue, a higher correlation of the concentration of these metals with those
found in sediments was also observed. The concentrations of elements found in the
skin and muscles of these amphibians have revealed no correlation with the
sediment where they were collected. According to the results obtained, the
viscera of the L. ocellatus species presents itself as a good bioindicator of
contamination by the metals studied.
PMID- 25590700
TI - Complete assignments of NMR data and assessment of trypanocidal activity of new
eremantholide C derivatives.
AB - Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was
isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1',2'
epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1',2'-epoxyeremantholide C
(3), 5-n-propylammonium-4,5-dihydro-1',2'-epoxyeremantholide C chloride (4), 5-n
propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide
C (6). The structures of all these derivatives were assigned on the basis of IR,
MS, 1H and 13C NMR data by 1D and 2D techniques. Eremantholide C and the
derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of
Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the
parasites strains while all derivatives were partially active against the CL
strain and inactive against the Y strain.
PMID- 25590702
TI - Coastline changes and sedimentation related with the opening of an artificial
channel: the Valo Grande Delta, SE Brazil.
AB - The role played by human activity in coastline changes indicates a general
tendency of retreating coasts, especially deltaic environments, as a result of
the recent trend of sea level rise as well as the blockage of the transfer of
sediments towards the coast, especially due to the construction of dams. This is
particularly important in deltaic environments which have been suffering a
dramatic loss of area in the last decades. In contrast, in this paper, we report
the origin and evolution of an anthropogenic delta, the Valo Grande delta, on the
south-eastern Brazilian coast, whose origin is related to the opening of an
artificial channel and the diversion of the main flow of the Ribeira de Iguape
River. The methodology included the analysis of coastline changes, bathymetry and
coring, which were used to determine the sedimentation rates and grain-size
changes over time. The results allowed us to recognize the different facies of
the anthropogenic delta and establish its lateral and vertical depositional
trends. Despite not being very frequent, anthropogenic deltas represent a
favorable environment for the record of natural and anthropogenic changes in
historical times and, thus, deserve more attention from researchers of different
subjects.
PMID- 25590701
TI - The sea-level highstand correlated to marine isotope stage (MIS) 7 in the coastal
plain of the state of Rio Grande do Sul, Brazil.
AB - The coastal plain of the state of Rio Grande do Sul, in southern Brazil, includes
four barrier-lagoon depositional systems formed by successive Quaternary sea
level highstands that were correlated to marine isotope stages (MIS) 11, 9, 5 and
1, despite the scarcity of absolute ages. This study describes a sea-level
highstand older than MIS 5, based on the stratigraphy, ages and fossils of the
shallow marine facies found in coastal barrier (Barrier II). This facies outcrops
along the banks of Chui Creek, it is composed of fine, well-sorted quartz sand
and contains ichnofossils Ophiomorpha nodosa and Rosselia sp., and molluscan
shells. The sedimentary record indicates coastal aggradation followed by sea
level fall and progradation of the coastline. Thermoluminescence (TL) and
electron spin resonance (ESR) ages from sediments and fossil shells point to an
age of ~220 ka for the end of this marine transgression, thus correlating it to
MIS 7 (substage 7e). Altimetric data point to a maximum amplitude of about 10
meters above present-day mean sea-level, but tectonic processes may be involved.
Paleoceanographic conditions at the time of the highstand and correlations with
other deposits in the Brazilian coasts are also discussed.
PMID- 25590703
TI - An experimental study of the partitioning of trace elements between rutile and
silicate melt as a function of oxygen fugacity.
AB - Subduction zone or arc magmas are known to display a characteristic depletion of
High Field Strength Elements (HFSE) relative to other similarly incompatible
elements, which can be attributed to the presence of the accessory mineral rutile
(TiO2) in the residual slab. Here we show that the partitioning behavior of
vanadium between rutile and silicate melt varies from incompatible (~0.1) to
compatible (~18) as a function of oxygen fugacity. We also confirm that the HFSE
are compatible in rutile, with D(Ta)> D(Nb)>> (D(Hf)>/~ D(Zr), but that the level
of compatibility is strongly dependent on melt composition, with partition
coefficients increasing about one order of magnitude with increasing melt
polymerization (or decreasing basicity). Our partitioning results also indicate
that residual rutile may fractionate U from Th due to the contrasting (over 2
orders of magnitude) partitioning between these two elements. We confirm that, in
addition to the HFSE, Cr, Cu, Zn and W are compatible in rutile at all oxygen
fugacity conditions.
PMID- 25590704
TI - Seismogenic faulting in the Meruoca granite, NE Brazil, consistent with a local
weak fracture zone.
AB - A sequence of earthquakes occurred in 2008 in the Meruoca granitic pluton,
located in the northwestern part of the Borborema Province, NE Brazil. A
seismological study defined the seismic activity occurring along the seismically
defined Riacho Fundo fault, a 081 degrees striking, 8 km deep structure. The
objective of this study was to analyze the correlation between this seismic
activity and geological structures in the Meruoca granite. We carried out
geological mapping in the epicentral area, analyzed the mineralogy of fault
rocks, and compared the seismically-defined Riacho Fundo fault with geological
data. We concluded that the seismically-defined fault coincides with ~E-W
striking faults observed at outcrop scale and a swarm of Mesozoic basalt dikes.
We propose that seismicity reactivated brittle structures in the Meruoca granite.
Our study highlights the importance of geological mapping and mineralogical
analysis in order to establish the relationships between geological structures
and seismicity at a given area.
PMID- 25590705
TI - Late Pleistocene carnivores (Carnivora: Mammalia) from a cave sedimentary deposit
in northern Brazil.
AB - The Brazilian Quaternary terrestrial Carnivora are represented by the following
families: Canidae, Felidae, Ursidae, Procyonidae Mephitidae and Mustelidae. Their
recent evolutionary history in South America is associated with the uplift of the
Panamanian Isthmus, and which enabled the Great American Biotic Interchange
(GABI). Here we present new fossil records of Carnivora found in a cave in Aurora
do Tocantins, Tocantins, northern Brazil. A stratigraphical controlled collection
in the sedimentary deposit of the studied cave revealed a fossiliferous level
where the following Carnivora taxa were present: Panthera onca, Leopardus sp.,
Galictis cuja, Procyon cancrivorus, Nasua nasua and Arctotherium wingei. Dating
by Electron Spinning Resonance indicates that this assemblage was deposited
during the Last Glacial Maximum (LGM), at least, 22.000 YBP. The weasel, G. cuja,
is currently reported much further south than the record presented here. This may
suggest that the environment around the cave was relatively drier during the LGM,
with more open vegetation, and more moderate temperatures than the current
Brazilian Cerrado.
PMID- 25590706
TI - A new angiosperm from the Crato Formation (Araripe Basin, Brazil) and comments on
the Early Cretaceous monocotyledons.
AB - The Crato Formation paleoflora is one of the few equatorial floras of the Early
Cretaceous. It is diverse, with many angiosperms, especially representatives of
the clades magnoliids, monocotyledons and eudicots, which confirms the assumption
that angiosperm diversity during the last part of the Early Cretaceous was
reasonably high. The morphology of a new fossil monocot is studied and compared
to all other Smilacaceae genus, especially in the venation. Cratosmilax jacksoni
gen. et sp. nov. can be related to the Smilacaceae family, becoming the oldest
record of the family so far. Cratosmilax jacksoni is a single mesophilic leaf
with entire margins, ovate shape, with acute apex and base, four venation orders
and main acrodromous veins. It is the first terrestrial monocot described for the
Crato Formation, monocots were previously described for the same formation, and
are considered aquatics. Cratosmilax jacksoni is the first fossil record of
Smilacaceae in Brazil, and the oldest record of this family.
PMID- 25590707
TI - A new prozostrodontian cynodont (Therapsida) from the Late Triassic Riograndia
Assemblage Zone (Santa Maria Supersequence) of Southern Brazil.
AB - We report here on a new prozostrodontian cynodont, Botucaraitherium belarminoi
gen. et sp. nov., from the Late Triassic Riograndia Assemblage Zone (AZ) of the
Candelaria Sequence (Santa Maria Supersequence), collected in the Botucarai Hill
Site, Candelaria Municipality, state of Rio Grande do Sul, Brazil. The new taxon
is based on a single specimen (holotype MMACR-PV-003-T) which includes the left
lower jaw, without postdentary bones, bearing the root of the last incisor,
canine and four postcanines plus one partial crown inside the dentary, not
erupted, and two maxillary fragments, one with a broken canine and another with
one postcanine. The features of the lower jaw and lower/upper postcanines
resemble those of the prozostrodontians Prozostrodon brasiliensis from the older
Hyperodapedon AZ and Brasilodon quadrangularis and Brasilitherium riograndensis
from the same Riograndia AZ. The inclusion of Botucaraitherium within a broad
phylogenetic analysis, positioned it as a more derived taxon than tritylodontids,
being the sister-taxon of Brasilodon, Brasilitherium plus Mammaliaformes.
Although the new taxon is based on few cranial elements, it represents a
additional faunal component of the Triassic Riograndia AZ of southern Brazil, in
which small-sized derived non-mammaliaform cynodonts, closely related to the
origin of mammaliaforms, were ecologically well succeed and taxonomically
diverse.
PMID- 25590708
TI - Reproductive phenology and sharing of floral resource among hummingbirds
(Trochilidae) in inflorescences of Dahlstedtia pinnata (Benth.) Malme. (Fabaceae)
in the Atlantic forest.
AB - The purpose of this study was to investigate the reproductive phenology and
sharing of floral resource (nectar) of Dahlstedtia pinnata (Benth.) Malme.
(Fabaceae), endemic of Atlantic forest, among hummingbirds. For the phenology, we
looked at the presence of reproductive structures in the plants, and for floral
resource sharing, the frequency of potential pollinators and foraging behaviors
were examined. This study was conducted in Pedra Branca State Park, in state of
Rio de Janeiro, in a dense ombrophilous forest, between August 2010 and August
2011. Flowering occurred between December 2010 and March 2011, and fruiting
between April and June 2011. Hummingbirds' foraging schedules differed
significantly, with legitimate visits to the flowers occurring in the morning and
illegitimate visits occurring during late morning and the afternoon. Five species
visited flowers, three of which were legitimate visitors: Phaethornis ruber, P.
pretrei, and Ramphodon naevius. Amazilia fimbriata and Thalurania glaucopis
females only visited illegitimately. Phaethornis ruber robbed nectar (78% of
illegitimate visits, n=337). Ramphodon naevius, with a territorial foraging
behavior and a body size bigger than that of other observed hummingbird species,
dominated the floral visits, which suggests that D. pinnata is an important
nourishing resource for this endemic bird of the Atlantic forest, currently
globally categorized as Near Threatened.
PMID- 25590709
TI - Gene homozygosis and mitotic recombination induced by camptothecin and irinotecan
in Aspergillus nidulans diploid cells.
AB - Mitotic recombination is a process involved in carcinogenesis which can lead to
genetic loss through the loss of heterozygosity. The recombinogenic potentials of
two anticancer drugs topoisomerase I inhibitors, camptothecin (CPT) and
irinotecan (CPT-11), were evaluated in the present study. The homozygotization
assay, which assess the induction of mitotic recombination and gene homozygosis,
as well as the heterozygous A757//UT448 diploid strain of Aspergillus nidulans
were employed. The three non-cytotoxic concentrations of CPT (3.5 ng mL-1, 10.5
ng mL-1 and 17.4 ng mL-1) were found to induce both mitotic recombination and
gene homozygosis. CPT treatment produced three diploids homozygous, for
nutritional and conidia color genes, and Homozygotization Indices (HI)
significantly different from negative control. On the other hand, only the
highest CPT-11 concentration tested (18 ug mL-1), corresponding to the maximal
single chemotherapeutic dose, produced HI values higher than 2.0 and
significantly different from negative control HI values. The recombinogenic
effects of both topoisomerase I blockers were associated with the recombinational
repair of DNA strand breaks induced by CPT and CPT-11. The anticancer drugs CPT
and CPT-11 may be characterized as secondary malignancies promoters in cancer
patients after chemotherapy treatment.
PMID- 25590710
TI - Richness and abundance of the cardini group of Drosophila (Diptera,
Drosophilidae) in the Caatinga and Atlantic Forest biomes in northeastern Brazil.
AB - Brazil has a high diversity of flies of the genus Drosophila, and part of this
richness is represented by the cardini group. We analyzed the fluctuations in the
richness and abundance of this group, in environments that had never previously
been studied in the northeastern region of Brazil. Among the 28,204 drosophilids
sampled, 1,294 belonged to the cardini group and were represented by D.
polymorpha, D. cardini, D. neocardini and D. cardinoides. Occurrences of D.
neocardini and D. cardinoides were registered for the first time in the Caatinga.
In this biome, D. cardini stood out as having the highest abundance, and D.
polymorpha was not observed. In the coastal Atlantic Forest, D. cardini was not
registered, but D. polymorpha was found in all the localities investigated.
Mangrove swamps were the environment with the lowest abundance and richness of
the cardini group. The High-altitude Forest presented the highest richness of
this group. We suggest that the high abundance of D. polymorpha in the High
altitude Forest and in the coastal Atlantic Forest may be a reflection of the
historical relationship between these two environments.
PMID- 25590711
TI - Copepod distribution and production in a Mid-Atlantic Ridge archipelago.
AB - The Saint Peter and Saint Paul Archipelago (SPSPA) are located close to the
Equator in the Atlantic Ocean. The aim of this study was to assess the spatial
variations in the copepod community abundance, and the biomass and production
patterns of the three most abundant calanoid species in the SPSPA. Plankton
samples were collected with a 300 um mesh size net along four transects (north,
east, south and west of the SPSPA), with four stations plotted in each transect.
All transects exhibited a tendency toward a decrease in copepod density with
increasing distance from the SPSPA, statistically proved in the North. Density
varied from 3.33 to 182.18 ind.m-3, and differences were also found between the
first perimeter (first circular distance band) and the others. The total biomass
varied from 15.25 to 524.50 10-3 mg C m-3 and production from 1.19 to 22.04 10-3
mg C m-3d-1. The biomass and production of Undinula vulgaris (Dana, 1849),
Acrocalanus longicornis Giesbrecht, 1888 and Calocalanus pavo (Dana, 1849) showed
differences between some transects. A trend of declining biodiversity and
production with increasing distance from archipelago was observed, suggesting
that even small features like the SPSPA can affect the copepod community in
tropical oligotrophic oceanic areas.
PMID- 25590712
TI - Effect of land use on mayfly assemblages structure in Neotropical headwater
streams.
AB - The aim of this study was to test the effect of agricultural and forestry land
use on the structure of mayfly assemblages in low-order streams. Twenty-nine
headwater streams were investigated in the state of Sao Paulo. We analyzed 15
streams in pristine areas (mixed tropical rainforest, semideciduous forest and
dense tropical rainforest), and 14 streams covered with sugarcane, eucalyptus and
pasture. Mayfly richness obtained by rarefaction curves was higher in pristine
areas (21 genera), especially in mixed and semideciduous forest when compared to
land use (9 genera), where values were particularly low in sugarcane plantation
(3 genera). The non-metric multidimensional scaling (NMDS) ordination showed
clear difference in mayfly assemblages between land uses and pristine areas,
supported by analysis of similarity (R=0.67, p=0.001). In partial redundancy
analysis (pRDA), the environmental descriptors that best explained differences in
assemblage structure were Riparian, Channel and Environmental Inventory (RCE)
index score, percentage of fine sediment stream substrate, water pH and land
elevation. Our results show that agricultural and forestry land use has a strong
negative effect on the structure of mayfly assemblages. These results also
support the use of mayflies as environmental indicators, as some genera were
sensitive to changes in land use, while others responded to naturally occurring
changes in the study area.
PMID- 25590713
TI - A two-plasmid strategy for engineering a dengue virus type 3 infectious clone
from primary Brazilian isolate.
AB - Dengue infections represent one of the most prevalent arthropod-borne diseases
worldwide, causing a wide spectrum of clinical outcomes. Engineered infectious
clone is an important tool to study Dengue virus (DENV) biology. Functional full
length cDNA clones have been constructed for many positive-strand RNA viruses and
have provided valuable tools for studying the molecular mechanisms involved in
viral genome replication, virion assembly, virus pathogenesis and vaccine
development. We report herein the successful development of an infectious clone
from a primary Brazilian isolate of dengue virus 3 (DENV3) of the genotype III.
Using a two-plasmid strategy, DENV3 genome was divided in two parts and cloned
separately into a yeast-bacteria shuttle vector. All plasmids were assembled in
yeast by homologous recombination technique and a full-length template for
transcription was obtained by in vitro ligation of the two parts of the genome.
Transcript-derived DENV3 is infectious upon transfection into BHK-21 cells and in
vitro characterization confirmed its identity. Growth kinetics of transcript
derived DENV3 was indistinguishable from wild type DENV3. This system is a
powerful tool that will help shed light on molecular features of DENV biology, as
the relationship of specific mutations and DENV pathogenesis.
PMID- 25590714
TI - Pequi leaves incorporated into the soil reduce the initial growth of cultivated,
invasive and native species.
AB - Studies have identified the phytotoxicity of many native species of the Cerrado;
however, most of them were conducted either in inert substrates, or using
exaggerate proportions of plant material. We investigated the phytotoxicity of
pequi leaves added to substrate soil in quantities compatible with the litter
produced by this species. Pequi leaves were triturated and added to red latosol
in concentrations of 0.75%, 1.5% and 3%; the control was constituted of leafless
soil. These mixtures were added to pots and irrigated daily to keep them moist.
Germinated seeds of the cultivated sorghum and sesame, of the invasive brachiaria
and of the native purple ipe, were disposed in the pots to grow for five to seven
days at 30 degrees C within a photoperiod of 12 h. Seedlings of all the species
presented a reduction in their initial growth in a dose-dependent way. In
general, the root growth was more affected by the treatments than the shoot
growth; moreover, signs of necrosis were observed in the roots of the sorghum,
sesame and brachiaria. The phytotoxic effects generated by relatively small
quantities of leaves, in a reasonable range of species within a soil substrate,
suggest potential allelopathy of pequi leaves under natural conditions.
PMID- 25590715
TI - The population structure of two sympatric hermit-crab species on a subtidal rocky
shore of an island in southeastern Brazil.
AB - The main goal of this investigation was to characterize the population structure
and shell occupancy of two sympatric hermit-crab species, Pagurus brevidactylus
and Paguristes tortugae. The study was undertaken at Couves Island on the
southeastern coast of Brazil, from March 2010 through February 2011, on subtidal
rocky bottoms. Specimens were collected by SCUBA diving sessions. A total of 195
individuals of P. brevidactylus and 132 of P. tortugae were examined. Both
populations showed unimodal size-frequency distributions, which were non-normal
for P. brevidactylus and normal for P. tortugae. The median size of P.
brevidactylus was significantly smaller than P. tortugae; in both species, males
were significantly larger than females. For both, juveniles and ovigerous females
were recorded in all size classes and in almost the entire sampling period. No
significant departures from the 1:1 sex ratio were detected, although some size
classes were skewed. Overlaps in shell occupation were recorded. Pagurus
brevidactylus and P. tortugae showed similar population features; they reached
sexual maturity at small sizes, and the nearly year-round presence of young and
ovigerous females suggests continuous reproduction. These inter-specific
interactions involving resource partitioning suggest a regulatory process that is
probably part of the equilibrium strategy of these populations.
PMID- 25590716
TI - Composition of functional ecological guilds of the fish fauna of the internal
sector of the Amazon Estuary, Para, Brazil.
AB - The present study describes the spatial and temporal structure of the estuarine
fish community in the internal sector of the Amazon Estuary. Samples were
obtained in the main channels and tidal creeks of Guajara and Marajo Bays and
Guama River. A total of 41,516 fish specimens were collected, representing 136
taxa, 38 families and 12 orders. In the dry season, the mean salinity of the main
channel increased along a limnic-marine gradient, between the Guama River and the
Marajo Bay. Species richness was lowest in the mouth of the Guama River and in
the right margin of the Guajara Bay. Fish species composition and environmental
guilds differed markedly among areas: Migrants and Freshwater Stragglers were
dominant in the Guama River and the Guajara Bay, while Estuarine, Marine
Stragglers and Migrants predominated in the Marajo Bay. However, the trophic
guilds were still relatively well balanced, in functional terms. Piscivores and
Zoobenthivores were the dominant feeding functional groups in all the studied
areas. In this study, the assessment of the community and the use of the guild
approach were efficient to describe the structure and functioning of the
assemblages of estuarine fish also helping to assess the anthropogenic pressures
in the area.
PMID- 25590717
TI - Preferential accumulation of sex and Bs chromosomes in biarmed karyotypes by
meiotic drive and rates of chromosomal changes in fishes.
AB - Mechanisms of accumulation based on typical centromeric drive or of chromosomes
carrying pericentric inversions are adjusted to the general karyotype
differentiation in the principal Actinopterygii orders. Here, we show that
meiotic drive in fish is also supported by preferential establishment of sex
chromosome systems and B chromosomes in orders with predominantly bi-brachial
chromosomes. The mosaic of trends acting at an infra-familiar level in fish could
be explained as the interaction of the directional process of meiotic drive as
background, modulated on a smaller scale by adaptive factors or specific
karyotypic properties of each group, as proposed for the orthoselection model.
PMID- 25590718
TI - Antibiotic resistance and enterotoxin genes in Staphylococcus sp. isolates from
polluted water in Southern Brazil.
AB - The aim of this study was to evaluate the species distribution, antibiotic
resistance profile and presence of enterotoxin (SE) genes in staphylococci
isolated from the Diluvio stream in South Brazil. Eighty-eight staphylococci were
identified, 93.18% were identified as coagulase-negative (CNS) and 6.82%
coagulase-positive (CPS). Fourteen Staphylococcus species were detected and the
most frequently were Staphylococcus cohnii (30.48%) and S. haemolyticus (21.95%).
Resistance to erythromycin was verified in 37.50% of the strains, followed by
27.27% to penicillin, 12.50% to clindamycin, 6.81% to trimethoprim
sulfamethoxazole, 5.68% to chloramphenicol and 2.27% to norfloxacin. None of the
investigated strains showed gentamicin and ciprofloxacin resistance. The strains
were tested for the presence of sea, seb, sec, sed and see genes by PCR and only
CNS strains (43.18%) showed positive results to one or more SE genes. The
scientific importance of our results is due to the lack of data about these
topics in polluted waters in Brazil. In conclusion, polluted waters from the
Diluvio stream may constitute a reservoir for disseminating antibiotic-resistance
and enterotoxin into the community. In addition, the detection of staphylococci
in the polluted waters of the Diluvio stream indicated a situation of
environmental contamination and poor sanitation conditions.
PMID- 25590719
TI - Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and
aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of
rats.
AB - In our previous study, the ethanolic and aqueous extracts of Crocus sativus
elicited antinociceptive effects in the chronic constriction injury (CCI) model
of neuropathic pain. In this study, we explored anti-inflammatory, anti-oxidant
and anti-apoptotic effects of such extracts in CCI animals. A total of 72 animals
were divided as vehicle-treated CCI rats, sham group, CCI animals treated with
the effective dose of aqueous and ethanolic extracts (200 mg/kg, i.p.). The
lumbar spinal cord levels of proinflammatory cytokines including tumor necrosis
factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin 6 (IL-6),
were evaluated at days 3 and 7 after CCI (n=3, for each group). The apoptotic
protein changes were evaluated at days 3 and 7 by western blotting. Oxidative
stress markers including malondialdehyde (MDA) and glutathione reduced (GSH),
were measured on day 7 after CCI. Inflammatory cytokines levels increased in CCI
animals on days 3 and 7, which were suppressed by both extracts. The ratio of
Bax/ Bcl2 was elevated on day 3 but not on day 7, in CCI animals as compared to
sham operated animals and decreased following treatment with both extracts at
this time. Both extracts attenuated MDA and increased GSH levels in CCI animals.
It may be concluded that saffron alleviates neuropathic pain, at least in part,
through attenuation of proinflammatory cytokines, antioxidant activity and
apoptotic pathways.
PMID- 25590720
TI - Food restriction beginning at lactation interferes with the cellular dynamics of
the mucosa and colonic myenteric innervation in adult rats.
AB - The effects of food restriction (FR) on the morphoquantitative aspects of the
wall and myenteric neurons of the proximal colon in adult rats were analysed. FR
was imposed by duplication of the experimental brood size in relation to the
control brood during lactation. The FR group received a 50% reduction of food
from weaning until 90 days of age. Samples of the colon underwent histological
processing to morphometrically analyze the crypts, muscularis mucosae, tunica
mucosa, and muscularis externa. We determined the number of goblet cells and
serotoninergic enteroendocrine cells, and morphoquantitatively studied the
myenteric neuronal population. FR caused hypertrophy in the tunica mucosa,
increase in crypt depth and in the muscular layer of the mucosa, a decrease in
the thickness of the tunica muscularis and in the number of goblet cells and an
increase in serotoninergic cells. A higher neuronal density in the ganglia and a
reduction of the cell profile area were observed in the FR group. FR imposed
since lactation led to hypertrophy of the tunica mucosa, a reduction of neutral
mucin production, atrophy of the tunica muscularis, and an increase in the
survival neuronal in adult rats, attributable to an increase in the number of
serotoninergic enteroendocrine cells in mucosa.
PMID- 25590721
TI - Karyotype characterization and nuclear DNA content measurement in Bromeliaceae:
state of the art and future perspectives.
AB - In Bromeliaceae, cytogenetic and flow cytometry analyses have been performed to
clarify systematic and evolutionary aspects. Karyotyping approaches have shown
the relatively high chromosome number, similar morphology and small size of the
chromosomes. These facts have prevented a correct chromosome counting and
characterization. Authors have established a basic chromosome number of x = 25
for Bromeliaceae. Recently, one karyomorphological analysis revealed that x = 25
is no longer the basic chromosome number, whose genome may have a polyploid
origin. Besides cytogenetic characterization, the 2C DNA content of bromeliads
has been measured. Nuclear DNA content has varied from 2C = 0.60 to 2C = 3.34
picograms. Thus, in relation to most angiosperms, the 2C DNA content of
Bromeliaceae species as well as their chromosome size can be considered
relatively small. In spite of some advances, cytogenetic and flow cytometry data
are extremely scarce in this group. In this context, this review reports the
state of the art in karyotype characterization and nuclear DNA content
measurement in Bromeliaceae, emphasizing the main problems and suggesting
prospective solutions and ideas for future research.
PMID- 25590722
TI - Seasonal changes of water quality in a tropical shallow and eutrophic reservoir
in the metropolitan region of Recife (Pernambuco-Brazil).
AB - This study investigated the water quality in an urban eutrophic reservoir in
Northeastern Brazil, considering the influence of seasonality. Monthly, samples
were collected in the sub-surface reservoir. The following abiotic variables were
analyzed: temperature, pH, dissolved oxygen, apparent color, turbidity,
conductivity, fluoride, total nitrogen, chlorides, total dissolved solids, total
hardness, iron, copper, manganese, aluminum, chlorophyll-a and phaeophytin. Total
and thermotolerant coliforms were analyzed according to APHA (2012).
Cyanobacteria density was quantified through its biomass. The data were analyzed
using one- way ANOVA and Pearson correlation test. Higher values mean
phytoplankton biomass (26.3mm3.L-1) occurred in the dry season, especially
Planktothrix agardhii and Geiterinema amphibium, which occurred in 100% of
samples. High trophic state index was detected throughout the year. Seasonality
exerted some influence on both biotic and abiotc variables, leading to changes in
water quality of the reservoir.
PMID- 25590723
TI - Diversity patterns, research trends and mismatches of the investigative efforts
to amphibian conservation in Brazil.
AB - The number of papers on biology of amphibians has increased in the recent years.
A detailed overview of the publications on amphibians can be very useful in
assessing the status of our knowledge about this taxonomic group. Due to the
large number of articles published, we aimed to assess the scientific
contribution of herpetological researches carried out between the years 2001 and
2010 on Brazilian amphibians, considering the diversity patterns, the threats and
the research topics that have been published most often. We applied scientometric
attention indexes in the reviewed studies from seven scientific databases. To
examine the relationship between the numbers of species recorded locally and
regionally at different spatial scales, we used an additive partitioning of
diversity in three hierarchical levels (i.e., states, geographic regions and
biomes). We evaluated 892 articles and 914 species, which showed that 65 % of the
total diversity of Brazilian amphibian species was represented by the beta
diversity among the biomes. We identified many differences in the allocation of
research efforts for taxonomic groups, threats categories, geographic regions,
and research topics, highlighting the main research trends conducted and the
priority themes for investigation of further papers on Brazilian amphibians.
PMID- 25590724
TI - Chaco ansilta new species from Mendoza province, Western Argentina (Araneae:
Nemesiidae).
AB - A new species of Chaco Tullgren, 1905 is described and illustrated from the
Andean foothills of Mendoza province, western Argentina. This is the tenth
species of the genus and the first record of Chaco in Mendoza. An updated key is
presented for all Chaco species. The cladistic analysis based on a previously
published morphological character matrix resulted in the consensus tree: (C.
obscura, C. tucumana, C. castanea, (C. socos + C. tigre) (C. tecka (C. sanjuanina
(C. Patagonia + C. ansilta sp. nov.)))).
PMID- 25590725
TI - Effects of atmospheric pollutants on somatic and germ cells of Tradescantia
pallida (Rose) D.R. Hunt cv. purpurea.
AB - Anatomical alterations in leaves and DNA damage in cells caused by the
accumulation of atmospheric pollutants can be measured by epidermal leaf analyses
and Tradescantia micronuclei assay with early pollen tetrad cells. The present
study examined the feasibility of using somatic and germ cells of Tradescantia
pallida for biomonitoring purposes in the city of Dourados, state of Mato Grosso
do Sul (MS), Brazil. Stomatal, micronucleus and epidermal leaf analyses were
performed, using standard methodologies, on plants growing at three locations
during six different time periods. Tradescantia micronuclei data were analyzed
using SAS 9.2 software package and stomatal data were analyzed using SANEST
software. Analyses of stomatal characteristics and micronuclei examination in T.
pallida were found to be an efficient tool for monitoring atmospheric pollution.
The micronucleus assay suggested that the number of micronuclei in early pollen
tetrad cells was related to the intensity of vehicular traffic. Increased number
of epidermal cells and stomata and increased stomatal density observed at
locations with greater vehicular traffic are likely physiological responses of
those plants to the increased gas exchange in highly polluted environments.
PMID- 25590726
TI - Biflorin: an o-naphthoquinone of clinical significance.
AB - Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells
showing antimicrobial, antitumor and antimutagenic activities. Biflorin is an
isolated compound taken from the roots of the plant Capraria biflora L.
(Schrophulariaceae), indigenous of the West Indies and South America, which is
located in temperate or tropical areas. This compound has shown to be strongly
active against grampositive and alcohol-acid-resistant bacteria. It has been
efficient in inhibiting the proliferation tumor cell lines CEM, HL-60, B16, HCT-8
and MCF-7. Recently, SK-Br3 cell line was treated with biflorin showing important
cytotoxic effects. In this article, information related to the first structural
characterization studies are presented, as well as the latest reports concerning
the biological activity of this molecule.
PMID- 25590727
TI - Soluble fractalkine in the plasma of fibromyalgia patients.
AB - Fibromyalgia is a form of non-articular rheumatism in which inflammatory
cytokines seem to be involved. However, there is still no analytical specific
diagnostic criterion for this disease. The aim was to examine a possible role of
fractalkine as a biomarker in fibromyalgia. Plasma levels of soluble fractalkine
were compared between women diagnosed with fibromyalgia (n=17) and healthy women
(n=10) as controls. Fractalkine released by monocytes was also evaluated.
Fibromyalgia patients showed lower plasma fractalkine than healthy women. Since
most inflammatory pathologies show elevated plasma levels of soluble fractalkine,
the results may contribute towards a differential diagnosis for fibromyalgia.
PMID- 25590728
TI - In vivo and in vitro effects of fructose on rat brain acetylcholinesterase
activity: an ontogenetic study.
AB - Increased fructose concentrations are the biochemical hallmark of fructosemia, a
group of inherited disorders on the metabolic pathway of this sugar. The main
clinical findings observed in patients affected by fructosemia include
neurological abnormalities with developmental delay, whose pathophysiology is
still undefined. In the present work we investigated the in vitro and in vivo
effects of fructose on acetylcholinesterase (AchE) activity in brain structures
of developing rats. For the in vitro experiments, fructose was added at
increasing concentrations to the incubation medium. It was observed that fructose
provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30
day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments,
rats were killed 1 h after a single fructose administration (5 umol/g). Control
group received the same volume of saline solution. We found that AchE activity
was increased in cerebral cortex of 30- and 60-day-old rats receiving fructose
administration. Finally, we observed that AchE activity was unaffected by acute
fructose administration in cerebral cortex, striatum or hippocampus of 15- and 90
day-old rats. The present data suggest that a disruption in cholinergic
homeostasis may be involved in the pathophysiology of brain damage observed in
young patients affected by fructosemia.
PMID- 25590729
TI - Abeta(1-42) induces abnormal alternative splicing of tau exons 2/3 in NGF-induced
PC12 cells.
AB - Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease,
where its hyperphos-phorylation promotes aggregation and microtubule
destabilization. Tau undergoes alternative splicing which generates six isoforms
in the human brain, due to inclusion/exclusion of exons 2, 3 and 10.
Dysregulation of the splicing process of tau exon 10 is sufficient to cause
tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing
of other exons is less studied. We studied the effects of beta-amyloid(42) in the
alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth
Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to
retract in differentiated cells and altered the expression of exons 2/3 in both
undifferentiated and differentiated cells. Expression of exon 6 was repressed in
undifferentiated cells only. Our results suggest that beta-amyloid interferes
with the splicing process of exons 2/3, favoring their exclusion and thus the
expression of immature tau isoforms that are less efficient in stabilizing
microtubules and may also be more prone to hyperphosphorylation. The molecular
mechanism for this amyloid-tau interaction remains to be determined, but may have
potential implications for the understanding of the underlying neuropathological
processes in Alzheimer's disease.
PMID- 25590730
TI - Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by
mangiferin: role of adiponectin and TNF-alpha.
AB - Mangiferin, present in Mangifera indica bark, was reported to produce
hypoglycemic and antidiabetic activity in an animal model of genetic type 2
diabetes and in streptozotocin diabetic rats. Its effect on diabetic insulin
resistant animals has not been investigated. The current work aimed to explore
the effect of mangiferin on diabetic insulin-resistant rat model. Diabetes was
induced by high-fat/high fructose diet for eight weeks followed by a
subdiabetogenic dose of streptozotocin (HFD-Fr-STZ). Rats were treated with
mangiferin (20 mg/kg i.p.) for 28 days starting one week after STZ and its
effects were compared to the standard insulin sensitizer, rosiglitazone. HFD-Fr
STZ, induced obesity, hyperglycemia and insulin resistance accompanied by
depletion in liver glycogen and dyslipidemia. Moreover, there was an elevation in
serum TNF-alpha and a reduction in adiponectin. Mangiferin ameliorated the
consequences of HFD-Fr-STZ and its actions were comparable to the effects of the
standard insulin sensitizer, rosiglitazone. The results obtained in this study
provide evidence that mangiferin is a possible beneficial natural compound for
type 2 diabetes and metabolic disorders associated with the metabolic syndrome.
This effect is mediated through improving insulin sensitivity, modulating lipid
profile and reverting adipokine levels to normal.
PMID- 25590731
TI - Differential effect of solution conditions on the conformation of the
actinoporins Sticholysin II and Equinatoxin II.
AB - Actinoporins are a family of pore-forming proteins with hemolytic activity. The
structural basis for such activity appears to depend on their correct folding.
Such folding encompasses a phosphocholine binding site, a tryptophan-rich region
and the activity-related N-terminus segment. Additionally, different solution
conditions are known to be able to influence the pore formation by actinoporins,
as for Sticholysin II (StnII) and Equinatoxin II (EqtxII). In this context, the
current work intends to characterize the influence of distinct solution
conditions in the conformational behavior of these proteins through molecular
dynamics (MD) simulations. The obtained data offer structural insights into
actinoporins dynamics in solution, characterizing its conformational behavior at
the atomic level, in accordance with previous experimental data on StnII and
EqtxII hemolytic activities.
PMID- 25590732
TI - Endothelial, renal and hepatic variables in Wistar rats treated with Vancomycin.
AB - Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it
is not considered a first-choice drug because of its adverse effects. It is
believed that oxidative stress is the primary mechanism of endothelial injury and
the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity.
Moreover, dose recommendations, dilution, rates and types of infusion are still
controversial. The aim of this study was to determine the effect of different VCM
dilutions in endothelial, liver and kidney injuries by biochemical parameters and
histopathological analysis. Wistar rats were randomly divided into six groups and
subjected to femoral vein cannulation for drug administration. Control groups
received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions
of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT,
urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were
analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This
study showed alterations in ALT which featured hepatotoxicity. However, drug
dilutions were not able to show changes in other biochemical parameters. In
contrast, kidney and endothelium pathological changes were observed. More studies
are needed to characterize VCM induced kidney and endothelium toxicity and
biochemical markers able to show such morphological modifications.
PMID- 25590733
TI - Sublethal effect of concentrations of Metarhizium anisopliae (Metsch.) Sorok on
the larval stage and immunologic characteristics of Diatraea flavipennella (BOX)
(Lepidoptera: Crambidae).
AB - This work aimed to evaluate the effects of Metarhizium anisopliae on Diatraea
flavipennella and investigate their immune response. Was observed the effect of
M. anisopliae against larvae of D. flavipennella sprayed at concentrations of
103, 104, 105 conidia / mL, in which showed differences relative the larval
period, extending up to 72.0 days in treatment and 25.0 days in the control. The
results for hemocytes revealed that the most frequent cells when sprayed at the
concentrations of 103, 105, 107 conidia / mL were the prohemocytes,
spherulocytes, plasmatocytes and granulocytes in relation to adipohemocytes and
oenocytoids. The level of nitric oxide was different between the control and the
concentration 107 spores / mL (24), while the activity of phenoloxidase was
similar among treatments in 24 and higher concentration 107 spores / mL (60h). In
biochemical profile of hemocytes was a change in carbohydrates, lipids and
proteins in response to the fungus. The results indicate that the fungus M.
anisopliae can be used in the Integrated Management of D. flavipennella by
presenting pathogenicity and interfere with their development even when exposed
to small concentrations.
PMID- 25590734
TI - Analysis of morpho-agronomic and climatic variables in successive agricultural
years provides novel information regarding the phenological cycle of Jatropha in
conditions of the Brazilian cerrado.
AB - Phenological studies can provide information that enables the understanding of
the dynamics of plants and how these dynamics are related to the biotic and
abiotic environment. In order to study the phenological phases of Jatropha during
two agricultural years, agronomic and climatic variables, such as temperature and
rainfall, were evaluated. Data for each variable in each year and each genotype
were subjected to analysis of variance (ANOVA) and the differences were tested at
5% probability by F test. In addition, the correlation of growth behavior and
reproductive development of two Jatropha accessions (CNPAE-102 and CNPAE-169) as
a function of time elapsed after the start of the phenological cycle with
climatic variables were analyzed through Pearson's correlation. It was found
that: (i) the resuming of plant growth by producing new branches and flowers of
both genotypes coincides with the start of the rainy season, (ii) the flowering
may be related to the increase in temperature and rainfall; (iii) the number of
inflorescences per plant and number of female flowers determine the number of
green fruits, (iv) the environmental changes are responsible for the delimitation
of phenophases; and finally that (v) the responses to phenological changes are
genotype-dependent.
PMID- 25590735
TI - Spatial variability of soil potassium in sugarcane areas subjected to the
application of vinasse.
AB - When deposited on land the vinasse can promote improvement in fertility, however,
often fertilizer application occurs in areas considered homogeneous, without
taking into account the variability of the soil. The objective of this study was
to evaluate the effect of vinasse application on potassium content in two classes
of soils cultivated with sugarcane, and characterize the spatial variability of
soil using geostatistical techniques. In the 2010 and 2011 crop year, soil
samples were collected from an experimental grid at 0-0.2 and 0.2-0.4 m depth in
three soils cultivated with sugarcane, totaling 90 samplings in each grid, for
the determination of pH, calcium (Ca), magnesium (Mg), potassium (K), phosphorus
(P), aluminum (Al) and potential acidity (H + Al). The data have been submitted
to analysis of descriptive statistics and the K attribute was subjected to
geostatistical analysis. The coefficient of variation indicated medium and high
variability of K for the three soils. The results showed that the spatial
dependence of K increased in depth to FRce and decreased to PHlv, indicating that
the attribute could have followed the pattern of distribution of clay in depth.
The investigation of the spatial variability of K on the surface and subsurface
soils provided the definition of management zones with different levels of
fertility, which can be organized into sub-areas for a more efficient management
of the resources and the environment.
PMID- 25590736
TI - Cotesia flavipes (CAM) (Hymenoptera: Braconidae) supresses immune responses in
Diatraea flavipennella (BOX) (Lepidoptera: Crambidae).
AB - The present research aimed to elucidate which aspects of immune responses in
Diatraea flavipennella are suppressed by the parasitoid Cotesia flavipes, thus,
ensuring parasitism success. We investigated the presence of apoptosis in fat
body cells through the TUNEL technique. According to the results, reduced levels
of nitric oxide and phenoloxidase activity were observed in larvae parasitized
for three days, and reduced total number of hemocytes, after three and seven
days. An increase in plasmatocytes and decrease in spherulocytes numbers were
observed in the differential count on the third day of parasitism. The number of
melanized microspheres in parasitized larvae was low and indicated less intense
melanization. The ultrastructural analysis confirmed the immunosuppressive effect
of C. flavipes on the encapsulation response of D. flavipennella because only the
formation of hemocytes capsules, adhered to the microspheres' surface, was
evidenced in non-parasitized caterpillars. The effect of parasitism was also
recorded on the third day with the presence of hemocytes and apoptosis in fat
body cells, including aspects of degeneration in the latter. We concluded that C.
flavipes suppresses cellular and humoral immunological responses in D.
flavipennella and drastically affects the host's fat tissue.
PMID- 25590737
TI - Mapping of sites in forest stands.
AB - Generally, the forest companies use the total one year planting area as a minimum
stratum of the total population and, consequently, the forest inventory
processing has been conducted by applying the stratified random sampling to it.
This study was carried out in the National Forest of Tres Barras, Brazil, and it
aimed to classify and map the sites of Pinus elliottii stands. A systematic
sampling was structured into clusters and applied independently by compartments.
The clusters, in maltese cross, were composed of four sampling subunits, using
Prodan sampling method with a fixed number of six trees. By analysis of the
methodology it was possible to confirm the hypothesis: a) the selective thinning
cause expressive increase of volumetric variability within compartments; b) the
variation of sites within the compartments causes volumetric expansion of
variance and this grows proportionally to the quality of the sites; c) the
stratification in sites results in minimum variance within them; d) the
stratification in sites resulted in until to 91% reduction of variances within
them.
PMID- 25590738
TI - Photosynthetic metabolism and quality of Eugenia pyriformis Cambess. seedlings on
substrate function and water levels.
AB - The aim of this research was to evaluate the quality and photosynthetic
metabolism of "uvaia" seedlings (Eugenia pyriformis Cambess.) on different
substrates and water regimes. The seeds were sown in tubes of 50 x 190 mm in the
following substrates: Sand (S), Latosol + Sand (L + S) (1:1), Latosol + Sand +
Semi Decomposed Poultry Litter (L + S1 + PL) ( 1:1:0.5), Latosol + Sand + Semi
Decomposed Poultry Litter (L + S2 + PL) (1:2:0.5), Latosol + Bioplant(r) (L + B)
(1:1), and the water levels assessed were 50, 75 and 100% of water retention
capacity. At 60, 90, 120 and 150 days the seedlings were evaluated according to
their chlorophyll index, leaf area (cm2) and Dickson Quality Index (DQI) and at
150 days their internal concentration of carbon (mol m-2 s-1), stomatal
conductance (mol m-2 s-1), transpiration rate (mmol m-2 s-1), photosynthesis
(umol m-2 s-1) and efficiency of water use (umol de CO2 / mmol de H2O). Until
their 150th days, the seedlings had higher quality and photosynthetic metabolism
when cultured with substrates containing latosol + sand + poultry litter on the
two variations assessed and water retention capacity of 50%.
PMID- 25590740
TI - Ultra-low temperature conservation of Brazilian pine embryogenic cultures.
AB - This study aimed to establish a cryopreservation protocol for embryogenic
cultures of A. angustifolia, enabling the ex situ conservation of the species.
Embryogenic cultures were established from immature seeds and treated with
variations of the cryoprotectant solutions SuDG, SoD and PVS2 prior to immersion
in liquid nitrogen. Cell viability was evaluated after 30, 60 and 90 days of re
growth. The highest re-growth without morphological alterations and with normal
biochemical composition was obtained with the PVS2 solution with 40 min immersion
in ethanol (-20 degrees C). This procedure opens new horizons for the ex situ
conservation of the species genetic.
PMID- 25590739
TI - Frequency and foraging behavior of Apis mellifera in two melon hybrids in
Juazeiro, state of Bahia, Brazil.
AB - The study was carried out to verify if there are differences in foraging
frequency and behavior of Apis mellifera in two melon hybrids (10:00 - 'Yellow
melon' and Sancho -'Piel de Sapo') in the municipality of Juazeiro, state of
Bahia, Brazil. The frequency, behavior of visitors and the floral resource
foraged were registered from 5:00 am to 6:00 pm. There was a significant
difference in the frequency of visits when comparing hydrids (F = 103.74, p
<0.0001), floral type (F = 47.25, p <0.0001) and resource foraged (F = 239.14, p
<0.0001). The flowers of Sancho were more attractive to A. mellifera when
compared with hybrid 10:00, which may be correlated to the morphology and floral
resources available. This could be solved with scaled planting, avoiding the
overlapping of flowering of both types.
PMID- 25590741
TI - Elaboration of garlic and salt spice with reduced sodium intake.
AB - Garlic and salt spice is widely used in Brazilian cookery, but it has a high
sodium content; as high sodium intake has been strongly correlated to the
incidence of chronic diseases. This study aimed to develop a garlic and salt
spice with reduced sodium intake. Sensory evaluation was conducted by applying
the spices to cooked rice. First, the optimal concentration of spice added during
rice preparation was determined. Subsequently, seasonings (3:1) were prepared
containing 0%, 50% and 25% less NaCl using a mixture of salts consisting of KCl
and monosodium glutamate; a seasoning with a 0% NaCl reduction was established as
a control. Three formulations of rice with different spices were assessed
according to sensory testing acceptance, time-intensity and temporal domain of
sensations. The proportions of salts used in the garlic and salt spice did not
generate a strange or bad taste in the products; instead, the mixtures were less
salty. However, the seasonings with lower sodium levels (F2 and F3) were better
accepted in comparison to the traditional seasoning (F1). Therefore, a mixture of
NaCl, KCl and monosodium glutamate is a viable alternative to develop a garlic
and salt spice with reduced sodium intake.
PMID- 25590742
TI - Effect of storage in overcoming seed dormancy of Annona coriacea Mart. seeds.
AB - The aim of this study was to evaluate the effect of pre-treatments on overcoming
dormancy of A. coriacea seeds. Seeds were processed and stored in polyethylene
bags at temperatures of at -18 degrees C (42% RH), 5 degrees C (34% RH), 15
degrees C (60% RH) and 25 degrees C (34% RH), during 0, 30, 60, 90, 120 and 150
days. After storage, seeds were immersed in 350 mg.L-1 gibberellic acid for 144
hours. Sowing was carried out in plastic bags containing Red Latosol +
Bioplant(r). Moisture content, emergence percentage, emergence speed index,
length and dry mass of seedlings, were evaluated. The experimental design was
completely randomized in a factorial with four replications of 50 seeds each. The
seed storage at 5 degrees C and subsequent immersion in gibberellic acid was
efficient to reach high percentage, emergence speed and plant growth. A. coriacea
seeds showed non-deep simple morphophysiological dormancy wherein the
physiological component can be overcome after the seeds are storage at 5 degrees
C for a maximum period of 53 days and subsequent immersed in exogenous GA (350
mg.L-1 for 144 hours).
PMID- 25590743
TI - Pollination of rapeseed (Brassica napus) by Africanized honeybees (Hymenoptera:
Apidae) on two sowing dates.
AB - In this study, performed in the western part of the state of Parana, Brazil, two
self-fertile hybrid commercial rapeseed genotypes were evaluated for yield
components and physiological quality using three pollination tests and spanning
two sowing dates. The treatments consisted of combinations of two rapeseed
genotypes (Hyola 61 and Hyola 433), three pollination tests (uncovered area,
covered area without insects and covered area containing a single colony of
Africanized Apis mellifera honeybees) and two sowing dates (May 25th, 2011 and
June 25th, 2011). The presence of Africanized honeybees during flowering time
increased the productivity of the rapeseed. Losses in the productivity of the
hybrids caused by weather conditions unfavorable for rapeseed development were
mitigated through cross-pollination performed by the Africanized honeybees.
Weather conditions may limit the foraging activity of Africanized honeybees,
causing decreased cross-pollination by potential pollinators, especially the
Africanized A. mellifera honeybee. The rapeseed hybrids respond differently
depending on the sowing date, and the short-cycle Hyola 433 hybrid is the most
suitable hybrid for sowing under less favorable weather conditions.
PMID- 25590745
TI - Behavior and performance of sows fed different levels of fiber and reared in
individual cages or collective pens.
AB - Sixteen pregnant sows were used. The experimental design was completely
randomized with a 2x2 factorial scheme consisting of two housing systems
(individual cages and collective pens) and two diets (low [2.67%] and high
[13.14%] level of crude fiber). Physiological, behavioral, environmental, and
hormonal parameters were studied. In addition, the following productive and
reproductive parameters were evaluated: weight gain, feed intake, feed conversion
of the sow and piglets, number of piglets born dead and alive, number and weight
at weaning, and backfat thickness of sows. Pregnant sows reared in collective
pens and fed a high-fiber diet exhibited better physiological responses,
indicating greater comfort and better animal welfare. The environmental variables
were close to the comfort zone of the animals. In addition to providing a more
comfortable environment, housing pigs in collective pens reduced stereotypy,
permitting the sows to express a more natural behavior. The high-fiber diet did
not interfere with female productive performance. Tifton hay can therefore be
indicated as an alternative for the formulation of sow diets to improve animal
welfare.
PMID- 25590746
TI - Feasible domain of Walker's unsteady wall-layer model for the velocity profile in
turbulent flows.
AB - The present work studies, in detail, the unsteady wall-layer model of Walker et
al. (1989, AIAA J., 27, 140 - 149) for the velocity profile in turbulent flows.
Two new terms are included in the transcendental nonlinear system of equations
that is used to determine the three main model parameters. The mathematical and
physical feasible domains of the model are determined as a function of the non
dimensional pressure gradient parameter (p+). An explicit parameterization is
presented for the average period between bursts (T+B), the origin of time (t+0 )
and the integration constant of the time dependent equation (A0) in terms of p+.
In the present procedure, all working systems of differential equations are
transformed, resulting in a very fast computational procedure that can be used to
develop real-time flow simulators.
PMID- 25590744
TI - Stenospermy and seed development in the "Brazilian seedless" variety of sugar
apple (Annona squamosa).
AB - Stenospermy was identified in naturally occurring sugar-apple (Annona squamosa)
mutants with great potential for use in genetic improvement programs. However, to
date, there have been no detailed studies of the development of aspermic fruit in
this species. The aim of the present study was to characterize the anatomy of
developing fruit in the 'Brazilian Seedless' mutant. Flower buds in pre-anthesis
and developing fruits were subjected to common plant anatomy techniques. The
abnormal ovules are unitegmic and orthotropic and have a long funiculus. There is
evidence of fertilization, including the presence of embryos in early development
and the proliferation of starch grains in the embryo sac. However, the embryos
and embryo sac degenerate, although this does not affect pericarp development.
Ovule abortion does not occur. The perisperm, which is formed from the peripheral
layers of the nucellus, fills the cavity left by the embryo sac. The mature fruit
contains numerous small sterile seeds with abundant perisperm and unlignified
integument that is restricted to the micropylar region. The majority of perisperm
cells are living and appear to be metabolically active in the periphery.
Therefore, stenospermy leads to the formation of sterile seeds in A. squamosa,
and the perisperm possibly play an important role in fruit development.
PMID- 25590748
TI - The environmental risk as a culture in the Sinos Valley, Brazil.
AB - The proposal of analysis of the social-environmental perception will be developed
from the discourse as a constitutive element of reality. The discourse practices
and their concretion will be the source of meaning and social-cultural value.
Thus, the chosen research method was the qualitative and quantitative case study.
In the first part of the text we will recapture a theoretical input by Mary
Douglas on risk and culture, as well as on the acceptance of the risks in
society. In the second part, we cover a few data of the case of the risks
resulting from the tanning industry and on how the society of the "Vale do Rio
dos Sinos" relates to these risks. In this article we conclude that risk
perception of the population is directly related with past experiences, thus,
assigning a meaning to all new events. This meaning is the result of a
sociocultural construction. It is worth noting that behind this history, there
are basic issues related to population survival, i.e., both the industrialists
and workers establish partnerships when the society creates a movement against
the leather industry.
PMID- 25590750
TI - Nuclear G protein signaling: new tricks for old dogs.
AB - According to the standard model of G protein-coupled receptor (GPCR) signaling,
GPCRs are localized to the cell membrane where they respond to extracellular
signals. Stimulation of GPCRs leads to the activation of heterotrimeric G
proteins and their intracellular signaling pathways. However, this model fails to
accommodate GPCRs, G proteins, and their downstream effectors that are found on
the nuclear membrane or in the nucleus. Evidence from isolated nuclei indicates
the presence of GPCRs on the nuclear membrane that can activate similar G protein
dependent signaling pathways in the nucleus as at the cell surface. These
pathways also include activation of cyclic adenosine monophosphate, calcium and
nitric oxide synthase signaling in cardiomyocytes. In addition, a number of
distinct heterotrimeric and monomeric G proteins have been found in the nucleus
of various cell types. This review will focus on understanding the function of
nuclear G proteins with a focus on cardiac signaling where applicable.
PMID- 25590749
TI - A nonpeptide angiotensin II type 2 receptor agonist prevents renal inflammation
in early diabetes.
AB - We hypothesized that direct AT2R stimulation improves albuminuria in diabetes by
preventing renal inflammation and improving oxidative stress. Normoglycemic
controls (NCs) and streptozotocin-induced diabetes Sprague-Dawley rats (DM) were
treated for 4 weeks with vehicle (V) or the AT2R agonist Compound 21 (C21). At
the end of study, we evaluated blood pressure, urinary albumin to creatinine
ratio (UACR), renal interstitial fluid (RIF) levels of tumor necrosis factor
alpha (TNF-alpha), interleukin 6 (IL-6), nitric oxide (NO), cGMP, and 8
isoprostane, and renal expression of TNF-alpha, IL-6, and AT2R. There were no
significant differences in blood pressure between different treatments. DM rats
demonstrated increased UACR, RIF TNF-alpha, IL-6 and 8-isoprostane, and messenger
RNA (mRNA) for TNF-alpha and IL-6. DM rats also had reduced RIF NO and cGMP. C21
treatment of DM rats limited the increase in UACR, normalized RIF TNF-alpha, IL-6
and 8-isoprostane, and in mRNA for TNF-alpha and IL-6, and increased RIF NO and
cGMP. In NC rats, C21 treatment did not change these parameters. AT2R mRNA and
protein expressions increased in DM rats compared with NC but were not influenced
by C21 treatment. We conclude that direct AT2R stimulation in diabetic rats
improves diabetic albuminuria through the prevention of renal inflammation and
improved production of NO and cGMP.
PMID- 25590751
TI - Influence of silicon dioxide capping layers on pore characteristics in
nanocrystalline silicon membranes.
AB - Porous nanocrystalline silicon (pnc-Si) membranes are a new class of membrane
material with promising applications in biological separations. Pores are formed
in a silicon film sandwiched between nm thick silicon dioxide layers during rapid
thermal annealing. Controlling pore size is critical in the size-dependent
separation applications. In this work, we systematically studied the influence of
the silicon dioxide capping layers on pnc-Si membranes. Even a single nm thick
top oxide layer is enough to switch from agglomeration to pore formation after
annealing. Both the pore size and porosity increase with the thickness of the top
oxide, but quickly reach a plateau after 10 nm of oxide. The bottom oxide layer
acts as a barrier layer to prevent the a-Si film from undergoing homo-epitaxial
growth during annealing. Both the pore size and porosity decrease as the
thickness of the bottom oxide layer increases to 100 nm. The decrease of the pore
size and porosity is correlated with the increased roughness of the bottom oxide
layer, which hinders nanocrystal nucleation and nanopore formation.
PMID- 25590752
TI - What's one phosphate between friends (and foe)?
AB - Body surfaces are colonized by resident microbes that are remarkably resilient to
recurrent immune responses. In the latest issue of Science, Cullen et al. (2015)
report that, contrary to prevailing assumptions, bacteria of the colonizing
microbiota are resistant to antimicrobial peptides, and identify a common
mechanism of resistance.
PMID- 25590753
TI - Murine gut microbiota-diet trumps genes.
AB - Both environmental factors and host genetics shape the composition of gut
microbiota in mammals, but what matters more is insufficiently understood. In
this issue of Cell Host & Microbe, Carmody et al. (2015) show that diet can
overrule genotype-related differences in gut microbiota composition in different
mouse populations.
PMID- 25590754
TI - Interferons coordinate a multifaceted defense.
AB - While interferons help kill virally infected cells, they can also promote
systemic immune responses in distant tissues. In this issue of Cell Host &
Microbe, Sun et al. (2015) demonstrate that type I interferon induces intestinal
epithelial proliferation. This may help maintain a healthy gut and promote
recovery from viral gastroenteritis.
PMID- 25590755
TI - HIV-1/HIV-2 versus SAMHD1 restriction: a tale of two viruses.
AB - The deoxynucleoside triphosphate triphosphohydrolase SAMHD1 is a myeloid cell
specific retroviral restriction factor that can be inactivated by viral protein
Vpx from HIV-2 and certain SIV. In this issue of Cell Host & Microbe, Kyei et al.
(2015) report that cyclin L2 enhances HIV-1 infection in macrophages by
regulating SAMHD1.
PMID- 25590756
TI - PfEMP1's magical embrace of EPCR.
AB - Since discovering PfEMP1 virulence proteins in Plasmodium falciparum,
malariologists have struggled to reconcile their limitless sequence diversity
with their binding to relatively few host receptors. In this issue of Cell Host &
Microbe, Lau et al. (2015) explore how diverse PfEMP1s embrace EPCR, promoting
parasite survival and killing African children.
PMID- 25590757
TI - Heterogeneous host-pathogen encounters: act locally, think globally.
AB - Recent studies are revealing astonishing heterogeneity in host-pathogen
interactions occurring simultaneously within the same host tissue. As highlighted
in this review, growing knowledge of the in vivo complexity is altering our
understanding of infection biology. In particular, pathogen subsets reside in
diverse tissue microenvironments and detect and respond to local conditions. The
individual pathogen-host encounters have disparate outcomes, depending on
differential molecular interactions. As a result, disease progression can result
from failure to control individual infection foci, despite successful eradication
of others, and antibiotic therapy can be delayed by distinct pre-existing
pathogen subsets. Together, these data are unraveling rich biology with
implications for infectious disease progression and control.
PMID- 25590759
TI - The integrase cofactor LEDGF/p75 associates with Iws1 and Spt6 for
postintegration silencing of HIV-1 gene expression in latently infected cells.
AB - The persistence of a latent reservoir containing transcriptionally silent, but
replication-competent, integrated provirus is a serious challenge to HIV
eradication. HIV integration is under the control of LEDGF/p75, the cellular
cofactor of viral integrase. Investigating possible postintegration roles for
LEDGF/p75, we find that LEDGF/p75 represses HIV expression in latently infected
cells. LEDGF/p75 associated with two proteins involved in the control of gene
expression and chromatin structure, Spt6 and Iws1, to form a stable complex. Iws1
plays a role in the establishment of latent infection, whereas Spt6 functions to
recruit Iws1 and LEDGF/p75 to the silenced provirus and maintains histone
occupancy at the HIV promoter. In latently infected cells, depletion of the
complex results in reactivation of HIV expression Altogether, our results
indicate that a complex containing LEDGF/p75, Iws1, and Spt6 participates in
regulating postintegration steps of HIV latency.
PMID- 25590758
TI - Hepcidin-induced hypoferremia is a critical host defense mechanism against the
siderophilic bacterium Vibrio vulnificus.
AB - Hereditary hemochromatosis, an iron overload disease caused by a deficiency in
the iron-regulatory hormone hepcidin, is associated with lethal infections by
siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we
infected wild-type and hepcidin-deficient mice with the siderophilic bacterium
Vibrio vulnificus and found that hepcidin deficiency results in increased
bacteremia and decreased survival of infected mice, which can be partially
ameliorated by dietary iron depletion. Additionally, timely administration of
hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases
bacterial loads and rescues these mice from death, regardless of initial iron
levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from
hepcidin-deficient mice support extraordinarily rapid bacterial growth and that
this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin
mediated hypoferremia is a host defense mechanism against siderophilic pathogens
and suggest that hepcidin agonists may improve infection outcomes in patients
with hereditary hemochromatosis or thalassemia.
PMID- 25590761
TI - Clinical efficacy of formula-based bifrontal versus right unilateral
electroconvulsive therapy (ECT) in the treatment of major depression among
elderly patients: a pragmatic, randomized, assessor-blinded, controlled trial.
AB - BACKGROUND: No prior study has compared the efficacy of bifrontal (BF) vs right
unilateral (RUL) electroconvulsive therapy (ECT) by including the subgroup that
is most likely to receive it: only elderly patients with major depression (MD).
METHODS: This single-site, randomized, assessor-blinded, controlled trial was
conducted from 2009 to 2013. Seventy-three elderly patients with MD, unipolar and
bipolar, were treated with a course of formula-based BF ECT or RUL ECT. The 17
item Hamilton Rating Scale for Depression (HRSD17) was used to measure efficacy.
Safety was assessed with the Mini Mental State Examination (MMSE). RESULTS: Both
electrode placements resulted in highly significant downward trends in symptom
severity (all p<0.001), with a non-significant difference between methods
(p=0.703). At the end of the ECT course, response rates for the BF and RUL group
were 63.9% and 67.6%, respectively. Short-term remission, defined as an HRSD17
score<=7, was achieved in 14 (38.9%) patients in the BF group and 19 (51.4%)
patients in the RUL group. Global cognitive function, as measured by the MMSE,
did not deteriorate in the two treatment groups. LIMITATIONS: The small number of
subjects may have led to reduced power to detect real differences. The MMSE is
not sufficient to ascertain the negative effect of ECT on cognition. CONCLUSIONS:
This study indicates that formula-based BF and RUL ECT are equally efficacious,
and that remission rates of formula-based dosing are lower than those previously
reported for titrated dosing, in a clinical sample of elderly patients with MD.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01559324.
PMID- 25590762
TI - Prevalence and incidence of perinatal depression and depressive symptoms among
Mexican women.
AB - BACKGROUND: The aim of this study was to assess point and period prevalence and
incidence of perinatal depression in Mexican women. METHODS: The Structured
Clinical Interview for DSM-IV and the Patient Health Questionnaire (PHQ-9) were
administered at three points in time to 210 women: during the third trimester of
pregnancy, at six weeks and at six months after delivery. RESULTS: Prevalence of
prenatal depression was 9.0%, and 13.8% at six weeks and 13.3% at six months
postpartum. Incidence of postpartum depression (PPD) was 10.0% at six weeks and
8.2% at six months. Prevalence of prenatal depressive symptoms was 16.6%; and
17.1% at six weeks and 20.0% at six months postpartum. Incidence of postpartum
depressive symptoms (PPDS) was 11.4% at six weeks and 9.0% at six months. At six
months postpartum, women with depression were younger (OR=2.45, p=0.02), had
fewer years' schooling (OR=5.61, p=0.00), were unpartnered (OR=3.03, p=0.01),
unemployed (OR=3.48, p=0.00) and poorer (OR=4.00, p=0.00) than women without
depression. LIMITATIONS: 25% of the initial sample was not retained to complete
the three assessments. Non completers were younger, less educated and reported
more depressive symptoms. This may have resulted in an underestimation of
prevalence. CONCLUSIONS: This is the first longitudinal study in Latin America to
assess perinatal depression at three different points in times, reporting point
and period prevalence and incidence of clinical depression and depressive
symptoms. Most LA countries have yet to recognize the importance of providing
mental health care for expectant and postpartum mothers to reduce disability in
mothers and infants.
PMID- 25590760
TI - A PfRH5-based vaccine is efficacious against heterologous strain blood-stage
Plasmodium falciparum infection in aotus monkeys.
AB - Antigenic diversity has posed a critical barrier to vaccine development against
the pathogenic blood-stage infection of the human malaria parasite Plasmodium
falciparum. To date, only strain-specific protection has been reported by trials
of such vaccines in nonhuman primates. We recently showed that P. falciparum
reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for
erythrocyte invasion, is highly susceptible to vaccine-inducible strain
transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based
vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based
vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P.
falciparum challenge and show that such protection can be achieved by a human
compatible vaccine formulation. Protection was associated with anti-PfRH5
antibody concentration and in vitro parasite-neutralizing activity, supporting
the use of this in vitro assay to predict the in vivo efficacy of future vaccine
candidates. These data suggest that PfRH5-based vaccines have potential to
achieve strain-transcending efficacy in humans.
PMID- 25590763
TI - Autonomic arousal in childhood anxiety disorders: associations with state anxiety
and social anxiety disorder.
AB - BACKGROUND: Psychophysiological theories suggest that individuals with anxiety
disorders may evidence inflexibility in their autonomic activity at rest and when
responding to stressors. In addition, theories of social anxiety disorder, in
particular, highlight the importance of physical symptoms. Research on autonomic
activity in childhood (social) anxiety disorders, however, is scarce and has
produced inconsistent findings, possibly because of methodological limitations.
METHOD: The present study aimed to account for limitations of previous studies
and measured respiratory sinus arrhythmia (RSA) and heart rate (HR) using
Actiheart heart rate monitors and software (Version 4) during rest and in
response to a social and a non-social stressor in 60 anxious (30 socially anxious
and 30 'other' anxious), and 30 nonanxious sex-and age-matched 7-12 year olds. In
addition, the effect of state anxiety during the tasks was explored. RESULTS: No
group differences at rest or in response to stress were found. Importantly,
however, with increases in state anxiety, all children, regardless of their
anxiety diagnoses showed less autonomic responding (i.e., less change in HR and
RSA from baseline in response to task) and took longer to recover once the
stressor had passed. LIMITATIONS: This study focused primarily on parasympathetic
arousal and lacked measures of sympathetic arousal. CONCLUSION: The findings
suggest that childhood anxiety disorders may not be characterized by inflexible
autonomic responding, and that previous findings to the contrary may have been
the result of differences in subjective anxiety between anxious and nonanxious
groups during the tasks, rather than a function of chronic autonomic
dysregulation.
PMID- 25590764
TI - Magnitude and risk factors for postpartum symptoms: a literature review.
AB - BACKGROUND: The prevalence of postpartum depression worldwide varies from 0.5% to
60.8% in the first 12 months postpartum using self-reported questionnaire. This
review aims to update the current magnitude of postpartum depression based on
self-reported questionnaire and clinical interview and explore its associated
factors in developed and developing countries. METHODS: A literature search
conducted between 2005 and 2014 identified 203 studies, of which 191 used self
reported questionnaire in 42 countries and 21 used structured clinical interview
in 15 countries. Nine studies used a combination of self-reported questionnaire
and clinical interview. RESULT: The prevalence of postpartum depression varies
from 1.9% to 82.1% in developing countries and from 5.2% to 74.0% in developed
countries using self-reported questionnaire. Structured clinical interview shows
a much lower prevalence range from 0.1% in Finland to 26.3% in India. Antenatal
depression and anxiety, previous psychiatric illness, poor marital relationship,
stressful life events, negative attitude towards pregnancy, and lack of social
support are significant contributors to postpartum depression. LIMITATION: All
studies are included irrespective of the methodological quality, such as small
sample size and their inclusion could affect the generalizability of the results.
CONCLUSION: The current prevalence of postpartum depression is much higher than
that previously reported, and similar risk factors are documented. A culturally
sensitive cut-off score with adequate psychometric properties of the screening
instruments should be available. In future studies, examining the physical,
biological, and cultural factors in qualitative studies and in those with
adequate methodological qualities is recommended.
PMID- 25590765
TI - Newer Therapies for Management of Stable Ischemic Heart Disease With Focus on
Refractory Angina.
AB - Ischemic heart disease remains a major public health problem nationally and
internationally. Stable ischemic heart disease (SIHD) is one of the clinical
manifestations of ischemic heart disease and is generally characterized by
episodes of reversible myocardial demand/supply mismatch, related to ischemia or
hypoxia, which are usually inducible by exercise, emotion, or other stress and
reproducible-but which may also be occurring spontaneously. Improvements in the
treatment of acute coronary syndromes along with increasing prevalence of
cardiovascular risk factors, including diabetes and obesity, have led to
increasing population of patients with SIHD. A significant number of these
continue to have severe angina despite medical management and revascularization
procedures performed and may progress to refractory angina. This article reviews
the newer therapies in the treatment of SIHD with special focus in treating
patients with refractory angina.
PMID- 25590767
TI - Isolation of carboxylic acid-protected Au25 clusters using a borohydride
purification strategy.
AB - We report the synthesis of 11-mercaptoundecanoic acid (11-MUA) and 16
mercaptohexadecanoic acid (16-MHA) protected Au25 clusters with moderate yields
(~15%) using a NaBH4 purification strategy. UV-vis spectroscopy, transmission
electron microscopy (TEM), and matrix-assisted laser desorption/ionization
(MALDI) mass spectrometry were employed to study the entire process of the
isolation of 11-MUA-protected Au25 clusters from a polydisperse Au cluster
solution. UV-vis and TEM data clearly show the formation of a polydisperse
mixture, which upon the addition of NaBH4 leads to the growth and precipitation
of non-Au25 clusters, leaving the Au25 clusters behind. MALDI MS shows the
molecular ion peak for the 11-MUA-protected Au25 cluster. 11-MUA-protected Au25
clusters in THF were purified by slowly increasing the pH of the solution, which
leads to the complete deprotonation of carboxyl groups on the surface and
eventually precipitation of Au25 clusters. Further protonation of these clusters
by acetic acid leads to their solubilization in THF. These results show that,
owing to the inherent stability of Au25 clusters, a NaBH4 purification strategy
can be used to isolate Au25 clusters with surface carboxylic acid functionalities
from a polydisperse Au cluster solution.
PMID- 25590766
TI - Establishment of developmental charts for the larvae of the blow fly Calliphora
vicina using quantile regression.
AB - Developmental data of necrophagous blow fly species can be used to estimate a
minimum postmortem interval (PMImin) in death investigations by estimating the
age of larvae sampled from the cadaver. The most important parameter used in this
age estimation is the increase in larval length during growth. Larval length can
be compared to species-specific reference data to get an age estimate for the
larval specimen. The exploration of this type of data and the use of an
appropriate statistical method are the major challenges in evaluating forensic
entomological data sets. In Europe, Calliphora vicina is one of the most dominant
species with forensic entomological relevance. Despite its frequency and
importance, there are currently no published developmental studies for German
populations of this blow fly that can be referenced for larval age estimations.
This is regrettable because the geographical origin of different populations may
lead to phenotypic plasticity in the same species and population-specific growth
patterns that differ from published data sets. To address this shortcoming, the
objective of the present research was to generate growth data for C. vicina which
can be used for age estimation in German casework. We present, for the first
time, local developmental data for the larval stages of German C. vicina, reared
at three constant temperatures (15, 20 and 25 degrees C) and compare the results
with published studies on C. vicina development from elsewhere. To analyse the
development we chose a quantile mixed effects model because of its robustness and
insensitivity towards outliers. Quantile regression was developed as an extension
of the linear model to estimate rates of change in all parts of the distribution
of a response variable and to discover more useful predictive relationships
between variables. By applying a linear quantile mixed effect model, we estimated
the 0.1 and 0.9 quantile functions of the larval age for each temperature.
Graphically, these quantile functions act like reference bands and therefore,
plots for larval stages 1-3 can be used to estimate the age of a larva.
Nevertheless, the post-feeding stage still remains difficult to describe with
linear models and need to be further investigated. A comparison of the results
from this present study with the currently applied methods for age estimation of
C. vicina still demonstrates the importance of collecting growth rates for local
blow fly populations and of standardising experimental designs and statistical
analyses.
PMID- 25590768
TI - Marteilia sp. and other parasites and pathological conditions in Solen marginatus
populations along the Galician coast (NW Spain).
AB - This paper reports the results of the survey developed after the first detection
of protozoan Marteilia sp. infection of the grooved razor shell Solen marginatus
(Pulteney, 1799) from Galicia (NW Spain) in 2006. Furthermore, we analysed other
parasites and pathological conditions found in grooved razor shell populations
throughout this survey, such as metacercariae of trematodes, prokaryotic
infections and disseminated neoplasms, some of which could cause moderate or
severe damage to the host depending on the intensity of infection. A total of 17
natural beds distributed along the Galician coast were analysed, and Marteilia
sp. was detected in 6 of them with low prevalence, moderate intensity and no
negative effects over the populations.
PMID- 25590769
TI - Differential expression of serine protease inhibitors 1 and 2 in Crassostrea
corteziensis and C. virginica infected with Perkinsus marinus.
AB - Proliferation of Perkinsus marinus (Dermo) in vitro is inhibited by the action of
2 serine protease inhibitors belonging to the I-84 family. We compared the levels
of expression of serine protease inhibitors 1 and 2 (SPI-1 and SPI-2) in 2 oyster
species (Crassostrea virginica and C. corteziensis) inoculated with the parasite
P. marinus. C. virginica is well known to be susceptible to this parasite,
whereas C. corteziensis is apparently more tolerant. Oysters were inoculated with
trophozoites (1 * 106 trophozoites oyster-1) of P. marinus while control oysters
were injected with saline solution. Oysters were maintained in a closed water
system for 2 wk. The oysters were then sacrificed and parasite burden,
histological damage, and gene expression were evaluated. The results showed that
the challenged oysters presented a significant increase in parasite burden, which
generated histological damage in digestive gland and gills. Quantitative PCR
detected significant differences in SPI-1 and SPI-2 expression levels in the 2
oyster species, with C. corteziensis showing higher expression levels than C.
virginica as a response to P. marinus inoculation. Our results provide valuable
information for the understanding of the defense response in C. corteziensis and
a possible explanation for its tolerance to the parasite.
PMID- 25590770
TI - Recruitment of the parasitic pea crab Nepinnotheres novaezelandiae into green
lipped mussels Perna canaliculus.
AB - Pea crab species are globally ubiquitous parasites of marine bivalves including
several major aquaculture species. However, little is known about the
environmental factors that affect their recruitment into aquacultured mussels.
The effect of depth and distance from shore on the recruitment of the parasitic
pea crab Nepinnotheres novaezelandiae into New Zealand green-lipped mussels Perna
canaliculus was examined with a field experiment. The incidence of pea crab
infection of mussels over 295 d was nearly double when deployed at 5-10 m depth
(1.97%) compared to 20-30 m depth (0.96%), although it was not significantly
different due to the overall low period prevalence in the experimental
population. The sex ratio of crabs recovered was significantly skewed towards
females with a ratio of 1:14 (chi = 11.3, p < 0.001). Infection with pea crabs
was found to significantly reduce final mussel shell height on average by 28%
(21.0 mm) over 295 d (Mann-Whitney U = 6.0, p < 0.0001). This study confirms that
parasitism of green-lipped mussels by pea crabs has a significant impact on the
growth of the mussels and suggests that the incidence of pea crabs will be higher
in shallower water and when mussels are in closer proximity to the shore. With no
control methods available for preventing pea crab infection, these results
suggest that moving mussel farms offshore has the potential to reduce the
incidence of pea crabs in mussels and warrants larger-scale assessment.
PMID- 25590771
TI - Disease, parasite, and commensal prevalences for blue crab Callinectes sapidus at
shedding facilities in Louisiana, USA.
AB - Blue crab diseases, parasites, and commensals are not well studied in the Gulf of
Mexico, and their prevalence rates have only been sporadically determined.
Commercial soft shell shedding facilities in Louisiana experience high mortality
rates of pre-molt crabs, and some of these deaths may be attributable to diseases
or parasites. During the active shedding season in 2013, we determined the
prevalence of shell disease, Vibrio spp., Lagenophrys callinectes, and
Hematodinium perezi at 4 commercial shedding facilities along the Louisiana
coast. We also detected Ameson michaelis and reo-like virus infections. Shell
disease was moderately prevalent at rates above 50% and varied by shedding
facility, collection month, and crab size. Vibrio spp. bacteria were prevalent in
the hemolymph of 37% of the pre-molt crabs. Lagenophrys callinectes was highly
prevalent in the pre-molt crabs, but because it is a commensal species, it may
not cause high mortality rates. Hematodinium perezi was absent in all pre-molt
crabs.
PMID- 25590772
TI - Eroded swimmeret syndrome in female crayfish Pacifastacus leniusculus associated
with Aphanomyces astaci and Fusarium spp. infections.
AB - We describe a novel syndrome in crayfish, eroded swimmeret syndrome (ESS),
affecting wild female signal crayfish Pacifastacus leniusculus. ESS causes
partial or total swimmeret erosion. We observed ESS only in female signal
crayfish larger than 40 mm carapace length, i.e. sexually mature and probably
having carried eggs at least once. The eroded swimmerets were melanised,
indicating a crayfish immune system response. We isolated Fusarium tricinctum
species complex (SC), F. sambucinum SC, Saprolegnia parasitica and S. australis
from the melanised tissue of the eroded swimmerets. ESS includes chronic
Aphanomyces astaci infection and a secondary infection by Fusarium sp. In Sweden,
we found female signal crayfish with ESS in 6 out of 11 populations with a
prevalence below 1% in lakes with commercially productive signal crayfish
populations and higher than 29% in lakes with documented signal crayfish
population crashes. In Finland, the ESS prevalence was from 3.4 to 6.2% in a
commercially productive population. None of the sampled male signal crayfish
showed signs of ESS. A caging experiment indicated that females with at least 1
lost swimmeret carried on average 25% fewer fertilized eggs compared to females
with intact swimmerets. ESS could significantly reduce individual female
fecundity and thus could also affect fecundity at the population level. The
decline in reproductive success due to ESS could be among the factors
contributing to fluctuations in wild signal crayfish populations.
PMID- 25590773
TI - Batrachochytrium dendrobatidis in natural and farmed Louisiana crayfish
populations: prevalence and implications.
AB - The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) has been linked
to global declines and extinctions of amphibians, making it one of the most
devastating wildlife pathogens known. Understanding the factors that affect
disease dynamics in this system is critical for mitigating infection and
protecting threatened species. Crayfish are hosts of this pathogen and can
transmit Bd to amphibians. Because they co-occur with susceptible amphibian
communities, crayfish may be important alternative hosts for Bd. Understanding
the prevalence and seasonal dynamics of crayfish infections is of agricultural
and ecological interest in areas where crayfish are farmed and traded for human
consumption. We conducted a survey of Bd in farmed and natural crayfish
(Procambarus spp.) populations in Louisiana, USA. We found that Bd prevalence and
infection intensity was low in both farmed and native populations and that
prevalence varied seasonally in wild Louisiana crayfish. This seasonal pattern
mirrors that seen in local amphibians. As crayfish are an important globally
traded freshwater taxon, even with low prevalence, they could be an important
vector in the spread of Bd.
PMID- 25590774
TI - Batrachochytrium dendrobatidis exposure effects on foraging efficiencies and body
size in anuran tadpoles.
AB - Chytridiomycosis, the amphibian disease caused by the pathogenic fungus
Batrachochytrium dendrobatidis (Bd), is fatal to adults of many species. Bd is
largely sublethal to amphibian larvae; however, it is known to reduce larval
(i.e. tadpole) growth rates, with possible long-term effects on population
dynamics and fitness. We conducted an experiment to test how Bd altered southern
leopard frog Lithobates sphenocephalus tadpole mouthpart damage, percentage of
food ingested, and subsequent body size. We examined our results using path
analyses. We hypothesized that Bd would increase mouthpart damage, causing less
food to be ingested, and ultimately reduce body size. In our model, both Bd
exposure and increased mouthpart damage significantly reduced food ingested and
subsequent body size. However, our study provides evidence against the long
standing hypothesis of mouthpart damage as a pathway for Bd-induced reductions in
larval group. Here we provide evidence for reduced foraging efficiency
(percentage of food ingested) as a mechanism for Bd-induced reductions in body
size. This work highlights the importance of studying the sublethal effects of Bd
on larval amphibians.
PMID- 25590775
TI - Itraconazole treatment reduces Batrachochytrium dendrobatidis prevalence and
increases overwinter field survival in juvenile Cascades frogs.
AB - The global spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd) has
led to widespread extirpation of amphibian populations. During an intervention
aimed at stabilizing at-risk populations, we treated wild-caught Cascades frogs
Rana cascadae with the antifungal drug itraconazole. In fall 2012, we collected
60 recently metamorphosed R. cascadae from 1 of the 11 remnant populations in the
Cascades Mountains (CA, USA). Of these, 30 randomly selected frogs were treated
with itraconazole and the other 30 frogs served as experimental controls; all
were released at the capture site. Bd prevalence was low at the time of treatment
and did not differ between treated frogs and controls immediately following
treatment. Following release, Bd prevalence gradually increased in controls but
not in treated frogs, with noticeable (but still non-significant) differences 3
wk after treatment (27% [4/15] vs. 0% [0/13]) and strong differences 5 wk after
treatment (67% [8/12] vs. 13% [1/8]). We did not detect any differences in Bd
prevalence and load between experimental controls and untreated wild frogs during
this time period. In spring 2013, we recaptured 7 treated frogs but none of the
experimental control frogs, suggesting that over-winter survival was higher for
treated frogs. The itraconazole treatment did appear to reduce growth rates:
treated frogs weighed 22% less than control frogs 3 wk after treatment (0.7 vs.
0.9 g) and were 9% shorter than control frogs 5 wk after treatment (18.4 vs. 20.2
mm). However, for critically small populations, increased survival of the most at
risk life stage could prevent or delay extinction. Our results show that
itraconazole treatment can be effective against Bd infection in wild amphibians,
and therefore the beneficial effects on survivorship may outweigh the detrimental
effects on growth.
PMID- 25590776
TI - Asian strain of Batrachochytrium dendrobatidis is widespread in the Western
Ghats, India.
AB - We investigated the distribution of Batrachochytrium dendrobatidis (Bd) fungal
infections in amphibians of the Western Ghats mountain range in India, based on
data from 497 samples. Eight individuals were positive, with genomic equivalents
ranging from 2 to 785 zoospores. A single widespread Bd strain identical to the
haplotype endemic to Asia was isolated. Our findings suggest that
chytridiomycosis is widespread among the endemic and threatened amphibians of the
entire stretch of the Western Ghats. An ecological niche-based prediction model
based on all Bd-positive reports from the Western Ghats to date suggested a
higher probability of infection in the central Western Ghats of Karnataka and
northern Kerala states, which host a rich diversity of endemic and threatened
amphibians.
PMID- 25590777
TI - Anisakis spp. induced granulomatous dermatitis in a harbour porpoise Phocoena
phocoena and a bottlenose dolphin Tursiops truncatus.
AB - Cetaceans are well known definitive hosts of parasitic nematodes of the genus
Anisakis (Nematoda: Anisakidae). Anisakid nematodes are also a health hazard for
humans, potentially causing gastrointestinal infections or allergic reactions
following the consumption of infected fish. In marine mammals, the nematodes
develop from third-stage larvae to adults in the stomachs. In the first (or fore
) stomach, these parasites are typically associated with mucosal ulceration;
parasites have not been identified in other organs. Two small cetaceans, a
bottlenose dolphin Tursiops truncatus and a harbour porpoise Phocoena phocoena,
presented marked gastric A. simplex infection, as well as chronic granulomatous
and ulcerative dermatitis with intralesional nematodes, bordered by epithelial
hyperplasia. Nematodes in the skin of the bottlenose dolphin were morphologically
similar to Anisakis spp. Morphology of the parasitic remnants in the skin lesion
of the harbour porpoise was indistinct, but molecular identification confirmed
the presence of A. simplex. This is the first report of Anisakis spp. infection
in the skin of marine mammals.
PMID- 25590782
TI - Properties of bacterial laccases and their application in bioremediation of
industrial wastes.
AB - The bioremediation process of industrial waste can be made more efficient using
ligninolytic laccase enzymes, which are obtained from fungi, bacteria, higher
plants, insects, and also in lichen. Laccase are catalyzed in the mono-electronic
oxidation of a substrate from the expenditure of molecular oxygen. This enzyme
belongs to the multicopper oxidases and participates in the cross linking of
monomers, involved in the degradation of wide range industrial pollutants. In
recent years, these enzymes have gained application in pulp and paper, textile
and food industries. There are numerous reviews on laccases; however, a lot of
information is still unknown due to their broad range of functions and
applications. In this review, the bacterial laccases are focused for the
bioremediation of various industrial pollutants. A brief description on
structural molecular and physicochemical properties has been made. Moreover, the
mechanism by which the reaction is catalyzed, the physical basis of
thermostability and enantioselectivity, which requires more attention from
researchers, and applications of laccase in various fields of biotechnology are
pointed out.
PMID- 25590783
TI - An update on the management of Budd-Chiari syndrome: the issues of timing and
choice of treatment.
AB - Because of the rarity of Budd-Chiari syndrome (BCS), the flow chart of management
comes from expert opinion and is not evidence based. To report an update on the
management of BCS. I performed a review on published papers on BCS in an attempt
to speculate in particular on the timing and the choice of treatment. Some
authors suggest that the management of BCS should follow a step-wise strategy.
Anticoagulation and medical therapy should be the first-line treatment.
Revascularization or transjugular intrahepatic portosystemic shunt should be
performed in case of no response to medical therapy. Orthotopic liver transplant
should be used as a rescue therapy. The biggest criticism of this flow chart is
that it is based on the assumption that patients with BCS should receive further
treatment only when hemodynamic effects on portal hypertension become clinically
evident, thus paying little attention to the chronic ischemic liver damage
effects on hepatic function and to the possibility of preventing liver failure by
relieving impaired hepatic veins outflow. Recently, I presented a proposal of a
new algorithm for the management of BCS, in which medical therapy alone is
suggested only for patients without any sign of portal hypertension, irrespective
of whether early interventional treatment is suggested when either any symptoms
or signs of portal hypertension appear, with the aim of preventing hepatic
fibrosis development, disease progression, and finally improving outcome. Given
that the benefit of treatments for BCS is not under debate, guidelines for the
management of BCS should be re-evaluated and updated, with particular attention
to both the timing and the choice of treatment.
PMID- 25590779
TI - Active contractility at E-cadherin junctions and its implications for cell
extrusion in cancer.
AB - Cellular contractility regulates tissue cohesion and morphogenesis. In epithelia,
E-cadherin adhesion couples the contractile cortices of neighboring cells
together to produce tension at junctions that can be transmitted across the
epithelium in a planar fashion. We have recently demonstrated that contractility
is also patterned in the apical-lateral axis within epithelial junctions. Our
findings highlight the role that cytoskeletal regulation plays in controlling the
levels of intra-junctional tension. Of note, dysregulation of this apicolateral
pattern of tension can drive oncogenic cell extrusion. In this article, we
provide a detailed description of the actomyosin cytoskeleton organization during
oncogenic extrusion and discuss the implications of cell extrusion in cancer.
PMID- 25590784
TI - Prasugrel and ticagrelor compared to clopidogrel in non-ST-segment elevation
acute coronary syndromes undergoing percutaneous coronary interventions:
Certainties and uncertainties.
PMID- 25590785
TI - Plasmapheresis in cast nephropathy: yes or no?
AB - PURPOSE OF REVIEW: Renal failure is a frequent complication of multiple myeloma
and portends a poor prognosis. Plasmapheresis has been suggested as an adjunct to
chemotherapy to halt or reverse renal injury associated with multiple myeloma.
The purpose of this article is to review the rationale for using plasmapheresis
for this indication and then provide a discussion of the evidence regarding its
use. RECENT FINDINGS: The outcome of patients with multiple myeloma has improved
considerably in recent years, mostly owing to the introduction of new highly
effective chemotherapeutic agents. However, patients with renal failure who do
not recover independent renal function continue to have very poor prognosis.
Recent evidence now indicates that an early and sustained reduction in
circulating free light chains (FLCs) is associated with improved renal recovery
in patients with myeloma kidney. Extracorporeal removal of FLCs with
plasmapheresis, or other techniques, can achieve rapid and sustained reduction in
serum FLC concentration in patients with acute myeloma kidney. Unfortunately,
there is currently no convincing evidence in the literature that the addition of
mechanical removal of FLC to standard chemotherapy translates into clinical
benefits for patients. SUMMARY: Plasmapheresis is theoretically attractive as a
means of rapidly lowering serum FLC burden in the hope of reducing nephrotoxicity
in patients with multiple myeloma. However, the role of plasmapheresis in
improving renal prognosis and patient survival remains to be demonstrated.
PMID- 25590786
TI - Regulating Greatwall for mitosis.
PMID- 25590787
TI - Tuning Salmonella for cancer therapy.
PMID- 25590788
TI - Mitochondrial and metabolic remodeling during reprogramming and differentiation
of the reprogrammed cells.
AB - Reprogramming is one of the most essential areas of research in stem cell
biology. Despite this importance, the mechanism and correlates of reprogramming
remain largely unknown. In this study, we investigated the cytoplasmic remodeling
and changes in metabolism that occur during reprogramming and differentiation of
pluripotent stem cells. Specifically, we examined the cellular organelles of
three pluripotent stem cells, embryonic stem cells (ESCs), induced pluripotent
stem cells (iPSCs), and epiblast stem cells (EpiSCs), by electron microscopy. We
found that the cellular organelles of primed pluripotent EpiSCs were more similar
to those of naive pluripotent ESCs and iPSCs than somatic cells. EpiSCs, as well
as ESCs and iPSCs, contain large nuclei, poorly developed endoplasmic reticula,
and underdeveloped cristae; however, their mitochondria were still mature
relative to the mitochondria of ESCs and iPSCs. Next, we differentiated these
pluripotent stem cells into neural stem cells (NSCs) in vitro and compared the
morphology of organelles. We found that the morphology of organelles of NSCs
differentiated from ESCs, iPSCs, and EpiSCs was indistinguishable from brain
derived NSCs. Finally, we examined the changes in energy metabolism that
accompanied mitochondrial remodeling during reprogramming and differentiation. We
found that the glycolytic activity of ESCs and iPSCs was greater compared with
EpiSCs, and that the glycolytic activity of EpiSCs was greater compared with NSCs
differentiated from ESCs, iPSCs, and EpiSCs. These results suggest that a change
in the cellular state is accompanied by dynamic changes in the morphology of
cytoplasmic organelles and corresponding changes in energy metabolism.
PMID- 25590789
TI - 5-HT6 Receptor: A New Player Controlling the Development of Neural Circuits.
AB - 5-HT6 receptor (5-HT6R) is a G protein-coupled receptor that has recently emerged
as a new regulator of neural development. In addition to the canonical Gs
adenylyl cyclase pathway, recent proteomics approaches reveal that 5-HT6R is able
to engage key developmental signaling pathways controlling neuronal circuit
formation, neuronal connectivity, and psychiatric-relevant behaviors. For
example, at early stages of neuronal development, expression of 5-HT6R
constitutively regulates the activity of the cyclin-dependent kinase (Cdk)5 and,
through this mechanism, controls cellular processes involved in circuit
formation, including neuronal migration and neurite outgrowth. In addition to the
Cdk5 pathway, 5-HT6R modulates a variety of key developmental targets such as
Fyn, Jab1, and mammalian target of rapamycin (mTOR). Engagement of developmental
pathways through 5-HT6R pharmacological manipulation has led to interesting new
therapeutic perspectives in the field of psychiatric-related disorders. Indeed, 5
HT6R blockade can rescue a pathological overactivation of the mTOR pathway
induced by early life insults in rodents and normalizes the associated social and
episodic memory deficits. Here, we review recent evidence supporting the notion
that 5-HT6R is at the interface of key developmental signaling pathways and a
novel actor in the orchestration of neural circuit formation.
PMID- 25590790
TI - The reliability of the current perception threshold in volunteers and its
applicability in a clinical setting.
AB - BACKGROUND: Even though current perception threshold (CPT) has been used for
evaluating the effectiveness of sensory block in patients before surgery, its
reliability under controlled conditions has not been investigated. Two
independent investigations were performed. The primary objective of the first
study was to determine the test-retest reliability of CPT measures after repeated
stimulations in a group of healthy volunteers. The primary objective of the
second study was to evaluate the clinical applicability of this technique to
assess the sensory onset of a femoral nerve block in patients undergoing knee
surgery. METHODS: Thirty healthy subjects participated in 2 identical sessions,
separated by at least 24 hours, in which CPTs were measured after 5 consecutive
stimulations over the anteromedial aspect of the thigh. Similar measures were
obtained in 15 orthopedic patients receiving a femoral nerve block with 20 mL of
ropivacaine 0.5%. Test-retest reliability was assessed using intraclass
correlation (ICC) and standard error of measurement (expressed as coefficient of
variation [CV(SEM)]), whereas Student t test (P < 0.05) compared the increase in
CPTs over baseline. RESULTS: Within-day ICC values ranged (% confidence interval
[CI]) from 0.66 to 0.95 with a CV(SEM) of approximately 39% (% CI: 17%-58%).
Between-day ICC values, ranging from 0.57 to 0.94 (CV(SEM): approximately 45%, %
CI: 13%-71%), indicated that day-to-day CPT measurements are also variable. The
current intensity needed for sensory perception in orthopedic patients
significantly increased, varying from a mean CPT value of 82.5 +/- 66.5 MUA (SD)
at time zero to an average of 481 +/- 338 MUA, 22 +/- 8 minutes after the
administration of the local anesthetic. CONCLUSIONS: CPT proved to be a reliable
assessment tool for within-day sensory perception in healthy volunteers. Our
study also suggests that CPT can be applied to characterize, in a quantitative
manner, the sensory onset of a peripheral nerve block in a clinical setting,
thereby supporting its use in future studies comparing different regional
anesthetic modalities or approaches.
PMID- 25590791
TI - The Impact of Incident Postoperative Delirium on Survival of Elderly Patients
After Surgery for Hip Fracture Repair.
AB - BACKGROUND: The impact of delirium on survival of elderly patients remains
undetermined with conflicting results from clinical studies and meta-analysis. In
this study, we assessed the relationship between long-term mortality and incident
postoperative delirium in elderly patients undergoing hip fracture repair.
METHODS: Patients >=65 years old who were not delirious before undergoing hip
fracture repair were included in a database maintained prospectively from March
1999 to July 2009. All participating patients underwent delirium assessment on
the second postoperative day by using the confusion assessment method. Survival
of the participants was determined as of October 2012. RESULTS: In 459 patients,
the mean (SD) period of evaluation from surgery until death or study closure was
4.1 (3.5) years with patients followed for as long as 13.6 years. Preoperative
cognitive impairment was present in 120 patients (26.1%), and delirium on the
second postoperative day was observed in 151 (32.9%) of these patients. Although
univariate analysis demonstrated a strong association between incident
postoperative delirium and survival, this relationship did not persist in a
multivariate model. Survival was a function of age at the time of surgery (P <
0.001), illness severity as determined by the ASA physical status score (P <
0.001), and duration of admission to the intensive care unit after surgery (P <
0.001). Incorporation of incident postoperative delirium did not meaningfully (P
= 0.22) enhance the final survival model. In such a model, the hazard ratio (95%
confidence interval) for incident postoperative delirium was 1.25 (0.92-1.48).
CONCLUSIONS: Incident postoperative delirium was not significantly associated
with decreased survival in elderly patients undergoing hip fracture repair.
PMID- 25590792
TI - Yogurt Containing the Probacteria Lactobacillus acidophilus Combined with Natural
Antioxidants Mitigates Doxorubicin-Induced Cardiomyopathy in Rats.
AB - Probiotics and antioxidants have a definite improving effect in cardiovascular
diseases. This study aims at mitigating doxorubicin toxicity on cardiac function
through consuming a functional food. Five groups of adult male Sprague-Dawley
rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with
yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet,
respectively) from the first week, group II received carvedilol 30 mg/kg/day
orally from week 17, group III received both carvedilol and tested food, and
groups IV and V were +ve and -ve control groups, respectively. In week 17,
cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h
for 2 weeks. Histopathological and electrophysiological examinations and
biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart
failure compensatory mediators, and proinflammatory cytokines were assessed.
Tested food normalized time between the start of Q wave and the end of T wave on
electrocardiogram (QT interval) and heart rate compared to the doxorubicin group
(P<.05). It also improved hypertrophy indicated by a significant (P<.05) decrease
in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic
peptide (ANP) serum levels. Histopathological examination of cardiac sections
from the tested food group revealed less marked vacuolization and low
perivascular fibrosis percentage (0.7803 +/- 0.04). A significant (P<.001)
decrease in serum creatine kinase-membrane bound, lactate dehydrogenase,
triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue
malondialdehyde (MDA) levels was observed in addition to an increase in serum
Na(+)/K(+) ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also
lowered the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and
interleukin-6 (IL-6) serum levels significantly (P<.01). Probiotic food
containing Lactobacillus acidophilus, green tea, and carrots can improve membrane
integrity and cardiac contractility in doxorubicin-induced cardiomyopathy by
decreasing TNF-alpha, IL-6, MDA, increasing GSH, and modulating compensatory
mediators such as Ang-II and ANP.
PMID- 25590793
TI - Looking into Candida albicans infection, host response, and antifungal
strategies.
AB - Candida albicans, a commonly encountered fungal pathogen, causes diseases varying
from superficial mucosal complaints to life-threatening systemic disorders. Among
the virulence traits of C. albicans, yeast-to-hypha transition is most widely
acknowledged. Host innate immunity to C. albicans critically requires pattern
recognition receptors (PRRs), and defence against C. albicans infection is
provided by an exquisite interplay between the innate and adaptive arms of the
host immune system.
PMID- 25590794
TI - Antimicrobial and bacteria-releasing multifunctional surfaces: oligo (p-phenylene
ethynylene)/poly (N-isopropylacrylamide) films deposited by RIR-MAPLE.
AB - Antimicrobial oligo (p-phenylene-ethynylene) (OPE) films have previously been
demonstrated to show effective ultraviolet A (UVA) light-induced biocidal
activity; however, a serious problem arises from the accumulation of dead
bacteria and debris on the films that limits their effectiveness and application.
In this work, we address this challenge by incorporating thermally-responsive
poly (N-isopropylacrylamide) (PNIPAAm), which provides on-demand bacteria
releasing functionality. Multifunctional surfaces comprising blended films of OPE
and PNIPAAm were deposited on substrates by resonant infrared, matrix-assisted
pulsed laser evaporation (RIR-MAPLE) using a sequential co-deposition mode. In
this way, RIR-MAPLE enabled the deposition of multifunctional films with surface
properties and film functionality that can be tailored, precisely and
systematically, by controlling the chemical composition of the deposited film.
The surface properties of these films were characterized by UV-visible (UV-vis)
absorbance spectroscopy, X-ray photoelectron spectroscopy (XPS), atomic force
microscopy (AFM), and water contact angle measurements. The interactions between
bacteria and the deposited films were tested using two model bacteria:
Escherichia coli K12 (Gram-negative) and Staphylococcus epidermidis (Gram
positive). The antimicrobial and bacteria-release properties of the blended films
were controlled by varying the OPE/PNIPAAm ratio in the RIR-MAPLE emulsion
target, providing an easy way to optimize the multifunctional surface. The
OPE/PNIPAAm blended films with optimized composition killed a majority of
attached E. coli bacteria at 37 degrees C and under UVA exposure, and the dead
bacteria were then removed from the films simply by rinsing with water at 25
degrees C.
PMID- 25590796
TI - Structures of [CoO(CO2)n]- and [NiO(CO2)n]- clusters studied by infrared
spectroscopy.
AB - We present infrared spectra of [CoO(CO2)n](-) and [NiO(CO2)n](-) clusters and
interpret them in the framework of computational results employing density
functional theory. We find that both [CoO(CO2)n](-) and [NiO(CO2)n](-) clusters
are generally composed of the same core isomers. The dominant isomers consist of
an eta(2) CO2 ligand and a CO3 moiety that can be bound to the metal atom with
monodentate (eta(1)) or bidentate (eta(2)) connectivity. Minor structural isomers
observed are composed of a C2O4 moiety with a lone oxygen atom or a CO3 unit.
PMID- 25590795
TI - Genetic and environmental factors in conjunctival UV autofluorescence.
AB - IMPORTANCE: Conjunctival UV autofluorescence (CUVAF) photography was developed to
detect and characterize preclinical sunlight-induced ocular damage. Ocular sun
exposure has been related to cases of pterygia and was recently negatively
correlated with myopia. Hence, CUVAF has excellent potential as an objective
biomarker of sun exposure. However, much variation in CUVAF has been observed,
and the relative contributions of genes and environment to this variation have
not yet been identified. OBJECTIVE: To investigate sources of variation in CUVAF
in relation to its potential clinical relevance. DESIGN, SETTING, AND
PARTICIPANTS: We performed a cross-sectional analysis of 3 population-based
cohort studies in the general community, including the Twins Eye Study in
Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian
Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and
2009, and the 20-year follow-up of the Raine Study was completed between March
2010 and February 2012. We included genotypic and phenotypic data from 295
Australian families in the Tasmanian and Brisbane twin studies and from 661
participants in the 20-year follow-up of the Raine Study. We compared CUVAF
levels in the 3 cohorts and performed a classic twin study to partition variation
in CUVAF. We also conducted a genome-wide association analysis to identify
specific genetic variants associated with CUVAF. MAIN OUTCOMES AND MEASURES: The
total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms
(SNPs) associated with CUVAF from the genome-wide association study. RESULTS:
Within twin cohorts, individuals living closer to the equator (latitude, 27.47
degrees S) had higher levels of CUVAF compared with individuals from southern
regions (latitude, 42.88 degrees S) (median [interquartile range], 45.4 [26.8
68.5] vs 28.7 [15.0-42.3] mm2; P < .001). The variation in CUVAF explained by the
additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation
due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043,
located approximately 800 base pairs away from the SLC1A5 gene, a member of the
solute carrier family 1, had a genome-wide significant association with a P value
of 3.2 * 10-8. Gene-based analysis did not improve our power to detect
association with other genes. CONCLUSIONS AND RELEVANCE: Our findings confirm
that, although a large environmental component to CUVAF (equivalent of sun
exposure) exists, genes also play a significant role. We identified a SNP
(rs1060043) as being significantly associated with CUVAF; replication of this
finding in future studies is warranted.
PMID- 25590797
TI - A rapidly enlarging maxillary lesion. Left maxillary giant cell reparative
granuloma (GCRG).
PMID- 25590799
TI - Germ cell-specific Atg7 knockout results in primary ovarian insufficiency in
female mice.
AB - Primary ovarian insufficiency (POI) is a common cause of infertility in around 1
2% of women aged <40 years. However, the mechanisms that cause POI are still
poorly understood. Here we showed that germ cell-specific knockout of an
essential autophagy induction gene Atg7 led to subfertility in female mice. The
subfertility of Atg7 deletion females was caused by severe ovarian follicle loss,
which is very similar to human POI patients. Further investigation revealed that
germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal
transition period. In addition, our in vitro studies also demonstrated that
autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries
under the starvation condition. Taken together, our results uncover a new role
for autophagy in the regulation of ovarian primordial follicle reservation and
hint that autophagy-related genes might be potential pathogenic genes to POI of
women.
PMID- 25590798
TI - Interplay between ROS and autophagy in cancer cells, from tumor initiation to
cancer therapy.
AB - Cancer formation is a complex and highly regulated multi-step process which is
highly dependent of its environment, from the tissue to the patient. This
complexity implies the development of specific treatments adapted to each type of
tumor. The initial step of cancer formation requires the transformation of a
healthy cell to a cancer cell, a process regulated by multiple intracellular and
extracellular stimuli. The further steps, from the anarchic proliferation of
cancer cells to form a primary tumor to the migration of cancer cells to distant
organs to form metastasis, are also highly dependent of the tumor environment but
of intracellular molecules and pathways as well. In this review, we will focus on
the regulatory role of reactive oxygen species (ROS) and autophagy levels during
the course of cancer development, from cellular transformation to the formation
of metastasis. These data will allow us to discuss the potential of this molecule
or pathway as putative future therapeutic targets.
PMID- 25590800
TI - Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer
cell killing activity as single agents and in combination with ABT-263
(navitoclax).
AB - The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a
known resistance factor for small-molecule BCL-2 family inhibitors such as ABT
263 (navitoclax), making it an attractive therapeutic target. However, directly
inhibiting this target requires the disruption of high-affinity protein-protein
interactions, and therefore designing small molecules potent enough to inhibit
MCL-1 in cells has proven extremely challenging. Here, we describe a series of
indole-2-carboxylic acids, exemplified by the compound A-1210477, that bind to
MCL-1 selectively and with sufficient affinity to disrupt MCL-1-BIM complexes in
living cells. A-1210477 induces the hallmarks of intrinsic apoptosis and
demonstrates single agent killing of multiple myeloma and non-small cell lung
cancer cell lines demonstrated to be MCL-1 dependent by BH3 profiling or siRNA
rescue experiments. As predicted, A-1210477 synergizes with the BCL-2/BCL-XL
inhibitor navitoclax to kill a variety of cancer cell lines. This work represents
the first description of small-molecule MCL-1 inhibitors with sufficient potency
to induce clear on-target cellular activity. It also demonstrates the utility of
these molecules as chemical tools for dissecting the basic biology of MCL-1 and
the promise of small-molecule MCL-1 inhibitors as potential therapeutics for the
treatment of cancer.
PMID- 25590801
TI - Phosphorylation of the translation initiation factor eIF2alpha at serine 51
determines the cell fate decisions of Akt in response to oxidative stress.
AB - Phosphorylation of the alpha subunit of the translation initiation factor eIF2 at
serine 51 (eIF2alphaP) is a master regulator of cell adaptation to various forms
of stress with implications in antitumor treatments with chemotherapeutic drugs.
Herein, we demonstrate that genetic loss of the eIF2alpha kinases PERK and GCN2
or impaired eIF2alphaP by genetic means renders immortalized mouse fibroblasts as
well as human tumor cells increasingly susceptible to death by oxidative stress.
We also show that eIF2alphaP facilitates Akt activation in cells subjected to
oxidative insults. However, whereas Akt activation has a pro-survival role in
eIF2alphaP-proficient cells, the lesser amount of activated Akt in eIF2alphaP
deficient cells promotes death. At the molecular level, we demonstrate that
eIF2alphaP acts through an ATF4-independent mechanism to control Akt activity via
the regulation of mTORC1. Specifically, eIF2alphaP downregulates mTORC1 activity,
which in turn relieves the feedback inhibition of PI3K resulting in the
upregulation of the mTORC2-Akt arm. Inhibition of mTORC1 by rapamycin restores
Akt activity in eIF2alphaP-deficient cells but renders them highly susceptible to
Akt-mediated death by oxidative stress. Our data demonstrate that eIF2alphaP acts
as a molecular switch that dictates either cell survival or death by activated
Akt in response to oxidative stress. Hence, we propose that inactivation of
eIF2alphaP may be a suitable approach to unleash the killing power of Akt in
tumor cells treated with pro-oxidant drugs.
PMID- 25590802
TI - Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.
AB - Pancreatic ductal adenocarcinoma (PDA) is a critical health issue in the field of
cancer, with few therapeutic options. Evidence supports an implication of the
intratumoral microenvironment (stroma) on PDA progression. However, its
contribution to the role of neuroplastic changes within the pathophysiology and
clinical course of PDA, through tumor recurrence and neuropathic pain, remains
unknown, neglecting a putative, therapeutic window. Here, we report that the
intratumoral microenvironment is a mediator of PDA-associated neural remodeling
(PANR), and we highlight factors such as 'SLIT2' (an axon guidance molecule),
which is expressed by cancer-associated fibroblasts (CAFs), that impact on
neuroplastic changes in human PDA. We showed that 'CAF-secreted SLIT2' increases
neurite outgrowth from dorsal root ganglia neurons as well as from Schwann cell
migration/proliferation by modulating N-cadherin/beta-catenin signaling.
Importantly, SLIT2/ROBO signaling inhibition disrupts this stromal/neural
connection. Finally, we revealed that SLIT2 expression and CAFs are correlated
with neural remodeling within human and mouse PDA. All together, our data
demonstrate the implication of CAFs, through the secretion of axon guidance
molecule, in PANR. Furthermore, it provides rationale to investigate the
disruption of the stromal/neural compartment connection with SLIT2/ROBO
inhibitors for the treatment of pancreatic cancer recurrence and pain.
PMID- 25590803
TI - MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be
overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies.
AB - Overexpression of anti-apoptotic BCL-2 family members is a hallmark of many
lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and non
Hodgkin lymphoma (NHL) that can be targeted with small molecule inhibitors. ABT
199 is a rationally designed BCL-2 homology (BH)-3 mimetic that specifically
binds to BCL-2, but not to MCL-1 and BCL-xL. Although the thrombocytopenia that
occurs with navitoclax treatment has not been a problem with ABT-199, clinical
trials in CLL could benefit by lowering the ABT-199 concentration through
targeting other survival pathways. In this study, we investigated the mechanisms
of resistance that develops to ABT-199 therapy by generating ABT-199-resistant
(ABT199-R) cell lines via chronic exposure of NHL cell lines to ABT-199. Acquired
resistance resulted in substantial AKT activation and upregulation of MCL-1 and
BCL-xL levels that sequestered BIM. ABT199-R cells exhibited increased MCL-1
stability and failed to activate BAX in response to ABT-199. The ABT-199 acquired
and inherent resistant cells were sensitized to treatment with ABT-199 by
inhibitors of the PI3K, AKT, and mTOR pathways, NVP-BEZ235 and GS-1101. NVP
BEZ235, a dual inhibitor of p-AKT and mTOR, reduced MCL-1 levels causing BIM
release from MCL-1 and BCL-xL, thus leading to cell death by BAX activation. The
PI3Kdelta inhibitor GS-1101 (idelalisib) downregulated MCL-1 and sensitized
ABT199-R cells through AKT-mediated BAX activation. A genetic approach, through
siRNA-mediated down-regulation of AKT, MCL-1, and BCL-xL, significantly decreased
cell survival, demonstrating the importance of these cell survival factors for
ABT-199 resistance. Our findings suggest a novel mechanism that modulates the
expression and activity of pro-survival proteins to confer treatment resistance
that could be exploited by a rational combination therapeutic regimen that could
be effective for treating lymphoid malignancies.
PMID- 25590804
TI - PKR downregulation prevents neurodegeneration and beta-amyloid production in a
thiamine-deficient model.
AB - Brain thiamine homeostasis has an important role in energy metabolism and
displays reduced activity in Alzheimer's disease (AD). Thiamine deficiency (TD)
induces regionally specific neuronal death in the animal and human brains
associated with a mild chronic impairment of oxidative metabolism. These features
make the TD model amenable to investigate the cellular mechanisms of
neurodegeneration. Once activated by various cellular stresses, including
oxidative stress, PKR acts as a pro-apoptotic kinase and negatively controls the
protein translation leading to an increase of BACE1 translation. In this study,
we used a mouse TD model to assess the involvement of PKR in neuronal death and
the molecular mechanisms of AD. Our results showed that the TD model activates
the PKR-eIF2alpha pathway, increases the BACE1 expression levels of Abeta in
specific thalamus nuclei and induces motor deficits and neurodegeneration. These
effects are reversed by PKR downregulation (using a specific inhibitor or in PKR
knockout mice).
PMID- 25590805
TI - Targeting heat-shock protein 90 with ganetespib for molecularly targeted therapy
of gastric cancer.
AB - Gastric cancer (GC) remains the fifth most common cancer worldwide. Heat-shock
protein 90 (HSP90) has become an attractive therapeutic target in treating
cancers, because of its abnormally high expression in cancers. Several successful
cases of HSP90 inhibitors capable of inhibiting GC inspired us to try ganetespib,
a clinically promising and actively investigated second-generation HSP90
inhibitor in GC treatment. In our study, we show that ganetespib markedly reduced
the growth of MGC-803 and also significantly inhibited the growth of SGC-7901 and
MKN-28 in a dose-dependent manner. It induced G2/M cell-cycle arrest and
apoptosis in all three cell lines, together with the related markers affected
significantly. Mechanistically, ganetespib caused pronounced decrease of
expression of classic HSP90 client proteins. Specifically, it greatly affected
epidermal growth factor receptor (EGFR) signaling cascades by markedly decreasing
the levels of total EGFR and EGFR on cell membranes. EGFR knockdown also induced
cell-cycle arrest and apoptosis accompanied with a decrease of several EGFR
downstream proteins. These results strongly support that EGFR signaling greatly
contributes to the ganetespib inhibitory effects. Besides, we found that the
responses of GC cell lines to ganetespib correlated well with their EGFR
expression levels: MGC-803, as well as AGS and BGC-803, with higher EGFR
expression responded to ganetespib better, whereas SGC-7901 and MKN-28 with lower
EGFR levels were much less sensitive to ganetespib. Although SGC-7901 and MKN-28
were not very sensitive to ganetespib, ganetespib worked synergistically with
radiation and cisplatin in killing them. Importantly, ganetespib significantly
inhibited the growth of xenograft tumors in vivo as a single agent or in
combination with cisplatin. Results of hematoxylin/eosin staining, TUNEL
(terminal deoxynucleotidyl transferase dUTP nick-end labeling) assays, and
immunohistochemistry staining of phosphorylated cyclin-dependent kinase 1
(pCDK1), EGFR and Ki-67 revealed significant differences in ganetespib-treated
tumors. Collectively, our data suggest that ganetespib, as a new potent treatment
option, can be used for the molecularly targeted therapy of GC patients according
to their expression profiles of EGFR.
PMID- 25590806
TI - Dose-dependent effects of selenite (Se(4+)) on arsenite (As(3+))-induced
apoptosis and differentiation in acute promyelocytic leukemia cells.
AB - To enhance the therapeutic effects and decrease the adverse effects of arsenic on
the treatment of acute promyelocytic leukemia, we investigated the co-effects of
selenite (Se(4+)) and arsenite (As(3+)) on the apoptosis and differentiation of
NB4 cells and primary APL cells. A 1.0-MUM concentration of Se(4+) prevented the
cells from undergoing As(3+)-induced apoptosis by inhibiting As(3+) uptake,
eliminating As(3+)-generated reactive oxygen species, and repressing the
mitochondria-mediated intrinsic apoptosis pathway. However, 4.0 MUM Se(4+)
exerted synergistic effects with As(3+) on cell apoptosis by promoting As(3+)
uptake, downregulating nuclear factor-kB, and activating caspase-3. In addition
to apoptosis, 1.0 and 3.2 MUM Se(4+) showed contrasting effects on As(3+)-induced
differentiation in NB4 cells and primary APL cells. The 3.2 MUM Se(4+) enhanced
As(3+)-induced differentiation by promoting the degradation of promyelocytic
leukemia protein-retinoic acid receptor-alpha (PML-RARalpha) oncoprotein, but 1.0
MUM Se(4+) did not have this effect. Based on mechanistic studies, Se(4+), which
is similar to As(3+), might bind directly to Zn(2+)-binding sites of the PML RING
domain, thus controlling the fate of PML-RARalpha oncoprotein.
PMID- 25590807
TI - Macrophage peroxisome proliferator-activated receptor gamma deficiency delays
skin wound healing through impairing apoptotic cell clearance in mice.
AB - Skin wound macrophages are key regulators of skin repair and their dysfunction
causes chronic, non-healing skin wounds. Peroxisome proliferator-activated
receptor gamma (PPARgamma) regulates pleiotropic functions of macrophages, but
its contribution in skin wound healing is poorly defined. We observed that
macrophage PPARgamma expression was upregulated during skin wound healing.
Furthermore, macrophage PPARgamma deficiency (PPARgamma-knock out (KO)) mice
exhibited impaired skin wound healing with reduced collagen deposition,
angiogenesis and granulation formation. The tumor necrosis factor alpha (TNF
alpha) expression in wounds of PPARgamma-KO mice was significantly increased and
local restoration of TNF-alpha reversed the healing deficit in PPARgamma-KO mice.
Wound macrophages produced higher levels of TNF-alpha in PPARgamma-KO mice
compared with control. In vitro, the higher production of TNF-alpha by PPARgamma
KO macrophages was associated with impaired apoptotic cell clearance.
Correspondingly, increased apoptotic cell accumulation was found in skin wound of
PPARgamma-KO mice. Mechanically, peritoneal and skin wound macrophages expressed
lower levels of various phagocytosis-related molecules. In addition, PPARgamma
agonist accelerated wound healing and reduced local TNF-alpha expression and
wound apoptotic cells accumulation in wild type but not PPARgamma-KO mice.
Therefore, PPARgamma has a pivotal role in controlling wound macrophage clearance
of apoptotic cells to ensure efficient skin wound healing, suggesting a potential
new therapeutic target for skin wound healing.
PMID- 25590808
TI - Glutathione transferases P1/P2 regulate the timing of signaling pathway
activations and cell cycle progression during mouse liver regeneration.
AB - Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification
of endogenous noxious compounds and xenobiotics. They also regulate
phosphorylation activities of MAPKinases in a catalytic-independent manner.
Previous studies have demonstrated the regulation of JNK-dependent pathway by
GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte
cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte
proliferation following partial hepatectomy (PH). Using a conventional double
knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of
GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first
wave of hepatocyte proliferation. The lowered proliferation was associated with
the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF
expression and delayed and/or altered activation of STAT3, JNK and ERK1/2
signaling pathways. In addition, the expression and/or activation of cell cycle
regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating
that the absence of GSTP1/2 delayed the entry into and progression through the G1
phase of the cell cycle and impaired the synchrony of proliferation in
hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun
and ATF2 were activated during the early steps of the liver regeneration in wild
type animals, the constitutively active JNK found in the quiescent liver of
Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient
induction of antioxidant enzymes and nitric oxide synthase were also delayed or
repressed during the regenerative response. Altogether our results demonstrate
that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial
phases of liver regeneration.
PMID- 25590809
TI - NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective,
PAR-independent metabolic catastrophe and cell death induced by beta-lapachone.
AB - Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors (e.g., FK866) target
the most active pathway of NAD(+) synthesis in tumor cells, but lack tumor
selectivity for use as a single agent. Reducing NAD(+) pools by inhibiting NAMPT
primed pancreatic ductal adenocarcinoma (PDA) cells for poly(ADP ribose)
polymerase (PARP1)-dependent cell death induced by the targeted cancer
therapeutic, beta-lapachone (beta-lap, ARQ761), independent of poly(ADP ribose)
(PAR) accumulation. beta-Lap is bioactivated by NADPH:quinone oxidoreductase 1
(NQO1) in a futile redox cycle that consumes oxygen and generates high levels of
reactive oxygen species (ROS) that cause extensive DNA damage and rapid PARP1
mediated NAD(+) consumption. Synergy with FK866+beta-lap was tumor-selective,
only occurring in NQO1-overexpressing cancer cells, which is noted in a majority
(~85%) of PDA cases. This treatment strategy simultaneously decreases NAD(+)
synthesis while increasing NAD(+) consumption, reducing required doses and
treatment times for both drugs and increasing potency. These complementary
mechanisms caused profound NAD(P)(+) depletion and inhibited glycolysis, driving
down adenosine triphosphate levels and preventing recovery normally observed with
either agent alone. Cancer cells died through an ROS-induced, MU-calpain-mediated
programmed cell death process that kills independent of caspase activation and is
not driven by PAR accumulation, which we call NAD(+)-Keresis. Non-overlapping
specificities of FK866 for PDA tumors that rely heavily on NAMPT-catalyzed NAD(+)
synthesis and beta-lap for cancer cells with elevated NQO1 levels affords high
tumor-selectivity. The concept of reducing NAD(+) pools in cancer cells to
sensitize them to ROS-mediated cell death by beta-lap is a novel strategy with
potential application for pancreatic and other types of NQO1+ solid tumors.
PMID- 25590810
TI - The role of hypoxia-inducible factor-2 in digestive system cancers.
AB - Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia
inducible factors (HIFs), HIF-1alpha and HIF-2alpha, primarily mediate the
transcriptional response to hypoxia. Despite the high homology between HIF-1alpha
and HIF-2alpha, emerging evidence suggests differences between both molecules in
terms of transcriptional targets as well as impact on multiple physiological
pathways and tumorigenesis. To date, much progress has been made toward
understanding the roles of HIF-2alpha in digestive system cancers. Indeed, HIF
2alpha has been shown to regulate multiple aspects of digestive system cancers,
including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis
and resistance to chemotherapy. These findings make HIF-2alpha a critical
regulator of this malignant phenotype. Here we summarize the function of HIF-2
during cancer development as well as its contribution to tumorigenesis in
digestive system malignancies.
PMID- 25590811
TI - Reactive oxygen species-mediated therapeutic response and resistance in
glioblastoma.
AB - Glioblastoma (GBM) resistance to therapy is the most common cause of tumor
recurrence, which is ultimately fatal in 90% of the patients 5 years after
initial diagnosis. A sub-population of tumor cells with stem-like properties,
glioma stem cells (GSCs), is specifically endowed to resist or adapt to the
standard therapies, leading to therapeutic resistance. Several anticancer agents,
collectively termed redox therapeutics, act by increasing intracellular levels of
reactive oxygen species (ROS). In this study, we investigated mechanisms
underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non
psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that
CBD induced a robust increase in ROS, which led to the inhibition of cell
survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the
survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the
activation of the p-p38 pathway and downregulation of key stem cell regulators
Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully
adapted, leading to tumor regrowth. Microarray, Taqman and functional assays
revealed that therapeutic resistance was mediated by enhanced expression of the
antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier
family 7 (anionic amino-acid transporter light chain), member 11)) and ROS
dependent upregulation of mesenchymal (MES) markers with concomitant
downregulation of proneural (PN) markers, also known as PN-MES transition. This
'reprogramming' of GSCs occurred in culture and in vivo and was partially due to
activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like))
transcriptional network. Using genetic knockdown and pharmacological inhibitors
of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of
system Xc resulted in synergistic ROS increase leading to robust antitumor
effects, that is, decreased GSC survival, self-renewal, and invasion. Our
investigation provides novel mechanistic insights into the antitumor activity of
redox therapeutics and suggests that combinatorial approaches using small
molecule modulators of ROS offer therapeutic benefits in GBM.
PMID- 25590815
TI - Two high-pressure phases of SiS2 as missing links between the extremes of only
edge-sharing and only corner-sharing tetrahedra.
AB - The ambient pressure phase of silicon disulfide (NP-SiS2), published in 1935, is
orthorhombic and contains chains of distorted, edge-sharing SiS4 tetrahedra. The
first high pressure phase, HP3-SiS2, published in 1965 and quenchable to ambient
conditions, is tetragonal and contains distorted corner-sharing SiS4 tetrahedra.
Here, we report on the crystal structures of two monoclinic phases, HP1-SiS2 and
HP2-SiS2, which can be considered as missing links between the orthorhombic and
the tetragonal phase. Both monoclinic phases contain edge- as well as corner
sharing SiS4 tetrahedra. With increasing pressure, the volume contraction (
DeltaV/V) and the density, compared to the orthorhombic NP-phase, increase from
only edge-sharing tetrahedra to only corner-sharing tetrahedra. The lattice and
the positional parameters of NP-SiS2, HP1-SiS2, HP2-SiS2, and HP3-SiS2 were
derived in good agreement with the experimental data from group-subgroup
relationships with the CaF2 structure as aristotype. In addition, the Raman
spectra of SiS2 show that the most intense bands of the new phases HP1-SiS2 and
HP2-SiS2 (408 and 404 cm(-1), respectively) lie between those of NP-SiS2 (434 cm(
1)) and HP3-SiS2 (324 cm(-1)). Density functional theory (DFT) calculations
confirm these observations.
PMID- 25590813
TI - Structure-activity relationship for the oxadiazole class of antibiotics.
AB - The structure-activity relationship (SAR) for the newly discovered oxadiazole
class of antibiotics is described with evaluation of 120 derivatives of the lead
structure. This class of antibiotics was discovered by in silico docking and
scoring against the crystal structure of a penicillin-binding protein. They
impair cell-wall biosynthesis and exhibit activities against the Gram-positive
bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA)
and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3
(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was
efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a
high volume of distribution, and low clearance. This antibiotic is bactericidal
and is orally bioavailable in mice. This class of antibiotics holds great promise
in recourse against infections by MRSA.
PMID- 25590814
TI - CaMKKbeta-AMPKalpha2 signaling contributes to mitotic Golgi fragmentation and the
G2/M transition in mammalian cells.
AB - Before a cell enters mitosis, the Golgi apparatus undergoes extensive
fragmentation. This is required for the correct partitioning of the Golgi
apparatus into daughter cells, and inhibition of this process leads to cell cycle
arrest in G2 phase. AMP-activated protein kinase (AMPK) plays critical roles in
regulating growth and reprogramming metabolism. Recent studies have suggested
that AMPK promotes mitotic progression and Golgi disassembly, and that this seems
independent of the cellular energy status. However, the molecular mechanism
underlying these events is not well understood. Here, we show that both treatment
with compound C and depletion of AMPKalpha2 (but not AMPKalpha1) delays the G2/M
transition in synchronized HeLa cells, as evidenced by flow cytometry and mitotic
index analysis. Furthermore, knockdown of AMPKalpha2 specifically delays further
fragmentation of isolated Golgi stacks. Interestingly, pAMPKalpha(Thr172) signals
transiently appear in the perinuclear region of late G2/early prophase cells,
partially co-localizing with the Golgi matrix protein, GM-130. These Golgi
pAMPKalpha(Thr172) signals were also specifically abolished by AMPKalpha2
knockdown, indicating specific spatio-temporal activation of AMPKalpha2 at Golgi
complex during late G2/early prophases. We also found that the specific CaMKKbeta
inhibitor, STO-609, reduces the pAMPKalpha (Thr172) signals in the perinuclear
region of G2 phase cells and delays mitotic Golgi fragmentation. Taken together,
these data suggest that AMPKalpha2 is the major catalytic subunit of AMPKalpha
which regulates Golgi fragmentation and G2/M transition, and that the CaMKKbeta
activates AMPKalpha2 during late G2 phase.
PMID- 25590812
TI - Blue journal conference. Aging and susceptibility to lung disease.
AB - The aging of the population in the United States and throughout the developed
world has increased morbidity and mortality attributable to lung disease, while
the morbidity and mortality from other prevalent diseases has declined or
remained stable. Recognizing the importance of aging in the development of lung
disease, the American Thoracic Society (ATS) highlighted this topic as a core
theme for the 2014 annual meeting. The relationship between aging and lung
disease was discussed in several oral symposiums and poster sessions at the
annual ATS meeting. In this article, we used the input gathered at the conference
to develop a broad framework and perspective to stimulate basic, clinical, and
translational research to understand how the aging process contributes to the
onset and/or progression of lung diseases. A consistent theme that emerged from
the conference was the need to apply novel, systems-based approaches to integrate
a growing body of genomic, epigenomic, transcriptomic, and proteomic data and
elucidate the relationship between biologic hallmarks of aging, altered lung
function, and increased susceptibility to lung diseases in the older population.
The challenge remains to causally link the molecular and cellular changes of
aging with age-related changes in lung physiology and disease susceptibility. The
purpose of this review is to stimulate further research to identify new
strategies to prevent or treat age-related lung disease.
PMID- 25590816
TI - Highly sensitive and selective H2 sensing by ZnO nanofibers and the underlying
sensing mechanism.
AB - We report, and propose a mechanism for, the exceptional hydrogen gas (H2) sensing
ability of ZnO nanofibers. In comparison to SnO2 nanofibers, ZnO nanofibers show
outstanding H2 gas response and unmistakable H2 selectivity. Different from the
reducing gas effect observed in SnO2 nanofibers, a semiconductor-to-metal
transition that occurs in the presence of H2 gas molecules is responsible for the
exceptional response and selectivity of ZnO nanofibers to H2. Notably, the
presence of nanograins within nanofibers further intensifies the resistance
modulation observed due to this transition.
PMID- 25590817
TI - Effect of dissolved humic acid on the Pb bioavailability in soil solution and its
consequence on ecological risk.
AB - Current risk characterization in ecological risk assessment does not consider
bioavailability of heavy metals, which highly depends on physicochemical
properties of environmental media. This study was set to investigate the effect
of humic acid (HA), used as a surrogate of organic matter, on Pb toxicity and the
subsequent effect on risk characterization in ecological risk assessment. Pb
toxicity was assessed using Microtox((r)) in the presence and absence of two
different forms of HA, particulate HA (pHA) and dissolved HA (dHA). With
increasing contact time, the EC10 values increased (i.e., the toxic effects
decreased) and the dissolved Pb concentrations of the filtrates decreased. The
high correlation (R = 0.88, p < 0.001) between toxic effects determined using
both the mixture and its filtrate as exposure media leads us to conclude that the
Pb toxicity highly depends on the soluble fraction. Also, reduced Pb toxicity
with increasing dHA concentrations, probably due to formation of Pb-dHA
complexes, indicated that Pb toxicity largely comes from free Pb ions. Overall,
this study shows the effect of HA on metal toxicity alleviation, and emphasizes
the need for incorporating the bioavailable heavy metal concentrations in
environmental media as a point of exposure in ecological risk assessment.
PMID- 25590818
TI - Preparation of clinker from paper pulp industry wastes.
AB - The production of paper pulp by the Kraft method generates considerable amounts
of wastes. Namely, lime mud generated in the recovery circuit of chemical
reagents, biological sludge from the wastewater treatment of wood digestion
process and fly ash collected in the fluidized bed combustor used to generate
electricity from biomass burning. The final destination of such wastes is an
important concern, since environmental regulations are becoming stricter
regarding their landfill. Driven by this fact, industries are looking for more
sustainable solutions, such as the recycling in distinct products. This work
tested these wastes as secondary raw materials to produce clinker/cement that was
then experienced in mortar formulations. The first step involved the residues
detailed characterization and a generated amounts survey. Then, specific but
simple steps were suggested, aiming to facilitate transport and manipulation.
Distinct blends were prepared and fired in order to get belitic and Portland
clinkers. The Portland clinkers were processed at lower temperatures than the
normally used in the industry due to the presence of mineralizing impurities in
some wastes. Belite-based cements were used to produce mortars that developed
satisfactory mechanical strength and did not reveal signs of deterioration or
durability weaknesses.
PMID- 25590819
TI - Mature landfill leachate treatment by coagulation/flocculation combined with
Fenton and solar photo-Fenton processes.
AB - This work reports the treatment of a mature landfill leachate through the
application of chemical-based treatment processes in order to achieve the
discharge legal limits into natural water courses. Firstly, the effect of
coagulation/flocculation with different chemicals was studied, evaluating the
role of different initial pH and chemicals concentration. Afterwards, the
efficiency of two different advanced oxidation processes for leachate remediation
was assessed. Fenton and solar photo-Fenton processes were applied alone and in
combination with a coagulation/flocculation pre-treatment. This physicochemical
conditioning step, with 2 g L(-1) of FeCl3 . 6H2O at pH 5, allowed removing 63%
of COD, 80% of turbidity and 74% of total polyphenols. Combining the
coagulation/flocculation pre-treatment with Fenton reagent, it was possible to
reach 89% of COD removal in 96 h. Moreover, coagulation/flocculation combined
with solar photo-Fenton revealed higher DOC (75%) reductions than single solar
photo-Fenton (54%). In the combined treatment (coagulation/flocculation and solar
photo-Fenton), it was reached a DOC reduction of 50% after the chemical
oxidation, with 110 kJ L(-1) of accumulated UV energy and a H2O2 consumption of
116 mM. Toxicity and biodegradability assays were performed to evaluate possible
variations along the oxidation processes. After the combined treatment, the
leachate under study presented non-toxicity but biodegradability increased.
PMID- 25590820
TI - Enhanced tolerance and remediation to mixed contaminates of PCBs and 2,4-DCP by
transgenic alfalfa plants expressing the 2,3-dihydroxybiphenyl-1,2-dioxygenase.
AB - Polychlorinated biphenyls (PCBs) and 2,4-dichlorophenol (2,4-DCP) generally led
to mixed contamination of soils as a result of commercial and agricultural
activities. Their accumulation in the environment poses great risks to human and
animal health. Therefore, the effective strategies for disposal of these
pollutants are urgently needed. In this study, genetic engineering to enhance
PCBs/2,4-DCP phytoremediation is a focus. We cloned the 2,3-dihydroxybiphenyl-1,2
dioxygenase (BphC.B) from a soil metagenomic library, which is the key enzyme of
aerobic catabolism of a variety of aromatic compounds, and then it was expressed
in alfalfa driven by CaMV 35S promoter using Agrobacterium-mediated
transformation. Transgenic line BB11 was selected out through PCR, Western blot
analysis and enzyme activity assays. Its disposal and tolerance to both PCBs and
2,4-DCP were examined. The tolerance capability of transgenic line BB11 towards
complex contaminants of PCBs/2,4-DCP significantly increased compared with non
transgenic plants. Strong dissipation of PCBs and high removal efficiency of 2,4
DCP were exhibited in a short time. It was confirmed expressing BphC.B would be a
feasible strategy to help achieving phytoremediation in mixed contaminated soils
with PCBs and 2,4-DCP.
PMID- 25590821
TI - Mechanism for enhanced degradation of clofibric acid in aqueous by catalytic
ozonation over MnOx/SBA-15.
AB - Comparative experiments were conducted to investigate the catalytic ability of
MnO(x)/SBA-15 for the ozonation of clofibric acid (CA) and its reaction
mechanism. Compared with ozonation alone, the degradation of CA was barely
enhanced, while the removal of TOC was significantly improved by catalytic
ozonation (O3/MnO(x)/SBA-15). Adsorption of CA and its intermediates by
MnO(x)/SBA-15 was proved unimportant in O3/MnO(x)/SBA-15 due to the insignificant
adsorption of CA and little TOC variation after ceasing ozone in stopped-flow
experiment. The more remarkably inhibition effect of sodium bisulfite (NaHSO3) on
the removal of TOC in catalytic ozonation than in ozonation alone elucidated that
MnO(x)/SBA-15 facilitated the generation of hydroxyl radicals (OH), which was
further verified by electron spin-resonance spectroscopy (ESR). Highly dispersed
MnO(x) on SBA-15 were believed to be the main active component in MnO(x)/SBA-15.
Some intermediates were indentified and different degradation routes of CA were
proposed in both ozonation alone and catalytic ozonation. The amounts of small
molecular carboxylic acids (i.e., formic acid (FA), acetic acid (AA) and oxalic
acid (OA)) generated in catalytic ozonation were lower than in ozonation alone,
resulting from the generation of more OH.
PMID- 25590822
TI - Biodegradation of bisphenol A with diverse microorganisms from river sediment.
AB - The wide distribution of bisphenol A (BPA) in the environment is problematic
because of its endocrine-disrupting characteristics and toxicity. Developing cost
effective remediation methods for wide implementation is crucial. Therefore, this
study investigated the BPA biodegradation ability of various microorganisms from
river sediment. An acclimated microcosm completely degraded 10 mg L(-1) BPA
within 28 h and transformed the contaminant into several metabolic intermediates.
During the degradation process, the microbial compositions fluctuated and the
final, predominant microorganisms were Pseudomonas knackmussii and Methylomonas
clara. From the original river sediment, we isolated four distinct strains, which
deplete the BPA over 7-9 days. They were all genetically similar to P.
knackmussii. The degradation ability of mixed strains was higher than that of
single strain but was far less than that of the microbial consortium. The novel
BPA degradation ability of P. knackmussii and its role in the decomposing
microcosm were first demonstrated. Our results revealed that microbial diversity
plays a crucial role in pollutant decomposition.
PMID- 25590823
TI - Reductive dissolution of ferrihydrite with the release of As(V) in the presence
of dissolved S(-II).
AB - In this study, reductive dissolution of As(V)-ferrihydrite and the mobilization
of As(V) in the presence of S(-II) were investigated under anoxic conditions.
Mobilization of As(V) strongly depended on the S(-II):Fe ratio and the amount of
As(V) loading on ferrihydrite. High S(-II):Fe ratio caused a more complete
dissolution of ferrihydrite and a large fraction of As(V) could be released into
solution. The percentages of the released As(V) were 2.5% and 7.5% at S(-II):Fe
ratios of 0.240 and 24.0, respectively, at pH 6.1, while the released As(V) were
5.5%, 16.3% at pH 8.0 under similar conditions. As(V) loading showed a negative
effect on the release of arsenate, with smaller fraction of arsenate released
into solution when more As (V) adsorbed on ferrihydrite. After 43 h, 14.1%, 5.5%,
1.6% and 0.7% of As(V) were released as for 10, 20, 50 and 100 mg L(-1) of As(V)
loading, respectively, at pH 8.0. During the dissolution, secondary minerals such
as goethite, magnetite and FeS were detected and played different roles in the
mobilization of As(V). The released As(V) was mainly repartitioned on the
residual ferrihydrite, the newly-formed goethite and magnetite but not FeS.
PMID- 25590824
TI - Interactions between nano-TiO2 and the oral cavity: impact of nanomaterial
surface hydrophilicity/hydrophobicity.
AB - Titanium dioxide (TiO2) nanoparticles are available in a variety of oral
applications, such as food additives and cosmetic products. Thus, questions about
their potential impact on the oro-gastrointestinal route rise. The oral cavity
represents the first portal of entry and is known to rapidly interact with
nanoparticles. Surface charge and size contribute actively to the particle-cell
interactions, but the influence of surface hydrophilicity/hydrophobicity has
never been shown before. This study addresses the biological impact of
hydrophilic (NM 103, rutile, 20 nm) and hydrophobic (NM 104, rutile, 20 nm) TiO2
particles within the buccal mucosa. Particle characterization was addressed with
dynamic light scattering and laser diffraction. Despite a high agglomeration
tendency, 10% of the particles/agglomerates were present in the nanosized range
and penetrated into the mucosa, independent of the surface properties. However,
significant differences were observed in intracellular particle localization. NM
104 particles were found freely distributed in the cytoplasm, whereas their
hydrophobic counterparts were engulfed in vesicular structures. Although cell
viability/membrane integrity was not affected negatively, screening assays
demonstrated that NM 104 particles showed a higher potential to decrease the
physiological mitochondrial membrane potential than NM 103, resulting in a
pronounced generation of reactive oxygen species.
PMID- 25590825
TI - Anaerobic biodegradation of nonylphenol in river sediment under nitrate- or
sulfate-reducing conditions and associated bacterial community.
AB - Nonylphenol (NP) is a commonly detected pollutant in aquatic ecosystem and can be
harmful to aquatic organisms. Anaerobic degradation is of great importance for
the clean-up of NP in sediment. However, information on anaerobic NP
biodegradation in the environment is still very limited. The present study
investigated the shift in bacterial community structure associated with NP
degradation in river sediment microcosms under nitrate- or sulfate-reducing
conditions. Nearly 80% of NP (100 mg kg(-1)) could be removed under these two
anaerobic conditions after 90 or 110 days' incubation. Illumina MiSeq sequencing
analysis indicated that Proteobacteria, Firmicutes, Bacteroidetes and Chloroflexi
became the dominant phylum groups with NP biodegradation. The proportion of
Gammaproteobacteria, Deltaproteobacteria and Choloroflexi showed a marked
increase in nitrate-reducing microcosm, while Gammaproteobacteria and Firmicutes
in sulfate-reducing microcosm. Moreover, sediment bacterial diversity changed
with NP biodegradation, which was dependent on type of electron acceptor.
PMID- 25590826
TI - Facile functionalized of SBA-15 via a biomimetic coating and its application in
efficient removal of uranium ions from aqueous solution.
AB - A novel dopamine-functionalized mesoporous silica (DMS), synthesized by grafting
dopamine onto a mesoporous molecular sieve (SBA-15), was developed as a sorbent
to extract U(VI) from aqueous solution. The method used to modify SBA-15 was
simple, facile and cost-effective. The DMS was characterized by SEM, TEM, XRD and
BET, showing that the material had an ordered mesoporous structure and a large
surface area. The effect of contact time, pH, ionic strength, temperature, and
solid-liquid ratio on the sorption process was investigated. It was demonstrated
that the adsorption of U(VI) by DMS was fast and that it can be described by the
pseudo-second order-equation where the equilibrium time was 20 min. Additionally,
the adsorption isotherm data were fitted well by the Langmuir model with the
maximum adsorption capacity of DMS of 196 mg/g at pH 6.0. Furthermore, the
influence of the K(+) and Na(+) concentrations and solid-to-liquid ratio on the
sorption was very weak, and the values of the thermodynamic parameters revealed
that the sorption process was exothermic and spontaneous. All the results
suggested that the DMS could be used as an excellent adsorbent to remove U(VI)
from aqueous solution.
PMID- 25590827
TI - Dispersive liquid-liquid microextraction based on the solidification of floating
organic drop followed by ICP-MS for the simultaneous determination of heavy
metals in wastewaters.
AB - In the present work, a dispersive liquid-liquid microextraction based on the
solidification of floating organic drop (DLLME-SFO) combined with inductively
coupled plasma mass spectrometry (ICP-MS) was developed for the determination of
Pb, Co, Cu, Ni, Zn. The influences of analytical parameters, including pH,
extraction solvent volume, disperser solvent volume, concentration of chelating
agent on the quantitative recoveries of Pb, Co, Cu, Ni, Zn were investigated. The
effect of the interfering ions on the analytes recovery was also investigated.
Under the optimized conditions, the limits of detection were 0.97-2.18 ng L(-1).
The relative standard deviations (RSDs) were 2.62-4.51% (n=7, C=20 ng L(-1)). The
proposed method was successfully applied for the analysis of ultra trace metals
in wastewater samples.
PMID- 25590828
TI - 3-Phenylpyridinium hydrogen squarate: experimental and computational study of a
nonlinear optical material.
AB - The detailed investigation of an organic nonlinear optical (NLO) squarate salt of
3-phenylpyridinium hydrogen squarate (1), C11H10N+.C4HO4(-), was reported in this
study. The XRD data indicates that the crystal structure of the title compound is
in the triclinic P-1 space group. In the asymmetric unit, the 3-phenylpyridine
molecule is protonated by one hydrogen atom donation of squaric acid molecule,
forming the salt (1). The X-ray analysis shows that the crystal packing has
hydrogen bonding ring pattern of D2(2)(10) (alpha-dimer) through NH...O
interactions. The structural and vibrational properties of the compound were also
studied by computational methods of ab initio at DFT/B3LYP/6-31++G(d,p) (2) and
HF/6-31++G(d,p) (3) levels of theory. The calculation results on the basis of two
models for both the optimized molecular structure and vibrational properties for
the 1 are presented and compared with the experimental results. Non-linear
optical properties (NLO) of the title compound together with the molecular
electrostatic potential (MEP), electronic absorption spectrum, frontier molecular
orbitals (FMOs) and conformational flexibility were also studied at the 2 level
and the results were reported. In order to evaluate the suitability for NLO
applications thermal analysis (TG, DTA and DTG) data of 1 were also obtained.
PMID- 25590829
TI - A highly sensitive and selective fluorescent chemosensor for detection of Zn2+
based on a Schiff base.
AB - A Schiff-base fluorescent probe - 2-((E)-(quinolin-8-ylimino)methyl)quinolin-8-ol
(H7L) was synthesized and evaluated as a chemoselective Zn2+ sensor. Upon
treatment with Zn2+, the complexation of H7L with Zn2+ resulted in a red shift
with a pronounced enhancement in the fluorescence emission intensity in ethanol
solution. Moreover, other common alkali, alkaline earth and transition metal ions
failed to induce response or minimal spectral changes. Notably, this chemosensor
could distinguish clearly Zn2+ from Cd2+. Fluorescence studies on H7L and H7L
Zn2+ complex reveal that the quantum yield strongly increases upon coordination.
The stoichiometric ratio and association constant were evaluated using Benesi
Hildebrand relation giving 1:1 stoichiometry. This further corroborated 1:1
complex formation based on Job's plot analyses. This chemosensor exhibits a very
good fluorescence sensing ability to Zn2+ over a wide range of pH.
PMID- 25590830
TI - Cytotoxic activity of rearranged drimane meroterpenoids against colon cancer
cells via down-regulation of beta-catenin expression.
AB - Colorectal cancer has emerged as a major cause of death in Western countries.
Down-regulation of beta-catenin expression has been considered a promising
approach for cytotoxic drug formulation. Eight 4,9-friedodrimane-type
sesquiterpenoids (1-8) were acquired using the oxidative potential of Verongula
rigida on bioactive metabolites from two Smenospongia sponges. Compounds 3 and 4
contain a 2,2-dimethylbenzo[d]oxazol-6(2H)-one moiety as their substituted
heterocyclic residues, which is unprecedented in such types of meroterpenoids.
Gauge-invariant atomic orbital NMR chemical shift calculations were employed to
investigate stereochemical details with support of the application of advanced
statistics such as CP3 and DP4. Compounds 2 and 8 and the mixture of 3 and 4
suppressed beta-catenin response transcription (CRT) via degrading beta-catenin
and exhibited cytotoxic activity on colon cancer cells, implying that their anti
CRT potential is, at least in part, one of their underlying antineoplastic
mechanisms.
PMID- 25590831
TI - The Effect of the Use of Synthetic Mesh Soaked in Antibiotic Solution on the Rate
of Graft Infection in Ventral Hernias: A Prospective Randomized Study.
AB - Wound infections and seroma formations are important problems in ventral hernia
repair operations using synthetic mesh grafts. The aim of this study was to
investigate the effect of the use of synthetic mesh soaked in vancomycin solution
on the rate of graft infection. The total number of subjects was 52. The subjects
were randomized into 2 groups using a software program. Group 1 (n = 26) was the
control group. In group 2 (n = 26), synthetic mesh was soaked in a Vancomycin
solution before it was implanted. The patients were compared with respect to
demographic characteristics and preoperative, intraoperative, and postoperative
variables. There were no significant differences between the groups with respect
to the available variables. Seroma development was significantly more common in
group 2 (P < 0.041). Three patients (5.7%) developed superficial wound infection,
and 9 (17%) developed surgical site infection 2-type wound-site infection. No
significant difference was found between the groups in terms of infection. The
use of synthetic mesh soaked in vancomycin solution had no beneficial effects on
the rate of wound-site infection. Future randomized, controlled, large-scale
studies using the same mesh and suture types, and meshes soaked in larger
spectrum antibiotics are needed.
PMID- 25590832
TI - Onychomycosis in Israel: epidemiological aspects.
AB - Onychomycosis is a fungal infection treated orally for prolonged periods of
treatment, caused primarily by Dermatophytes, Candida species and non
dermatophyte moulds (NDMs). The prevalence of specific aetiology may differ in
dependence of environmental, geographic and demographic factors, and may affect
management of the infection. The objective of this survey was to analyse
epidemiologic parameters of onychomycosis in Israel. Data of a cohort of 27,093
patients were collected from six centres during a 2- and 10-year period. The
diagnosis was based on microscopy of KOH/calcofluor mounts of nail scrapings and
culture isolation. A positive result indicates isolation of a fungus in culture.
Data were analysed for each centre and expressed as range for the whole cohort,
using the spss v18 software. Analysis included three epidemiologic parameters:
fungal aetiology in toe- and fingernails; association with gender; association
with age group. Dermatophytes were the major causative agents and Trichophyton
rubrum the most frequent isolate. Candida species were more frequent in women
fingernails; frequency increased with age and C. parapsilosis the most frequent
species. NDMs were isolated at low rate and Aspergillus terreus was the most
frequent isolate. This is a first large cohort of onychomycosis patients from
Israel analysed by defined epidemiological parameters.
PMID- 25590833
TI - Associations of blood pressure with common factors among left-behind farmers in
rural China: a cross-sectional study using quantile regression analysis.
AB - The whole range of blood pressure (BP) has important implications. Yet, published
studies focus primarily on hypertension and hypotension, the two extremes of BP
continuum. This study aims at exploring quantile-specific associations of BP with
common factors. The study used cross-sectional survey, collected information
about gender, age, education, body mass index (BMI), alcohol intake, diet risk
behavior, life event index, physical activity, fasting capillary glucose (FCG),
and systolic/diastolic blood pressure (SBP/DBP) and pulse pressure (PP) from
farmers living in 18 villages from rural Anhui, China, and performed descriptive
and multivariate and quantile regression (QR) analysis of associations of SBP,
DBP, or PP with the 9 factors surveyed. A total of 4040 (86.3%) eligible farmers
completed the survey. Average hypertension prevalence rate and SBP, DBP, and PP
values estimated 43.20 +/- 0.50% and 141.37 +/- 21.98, 87.76 +/- 12.23, and 53.63
+/- 15.72 mm Hg, respectively. Multivariate regression analysis revealed that all
the 9 factors were significantly (P < 0.05) associated with one or more of SBP,
DBP, and PP. QR coefficients of SBP, DBP, or PP with different factors
demonstrated divergent patterns and age, BMI, FCG, and life event index showed
substantial trends along the quantile axis. Hypertension prevalence rate was high
among the farmers. QR modeling provided more detailed view on associations of
SBP, DBP, or PP with different factors and uncovered apparent quantile-related
patterns for part of the factors. Both the population group studied and the
trends in QR coefficients identified merit specific attention.
PMID- 25590834
TI - Low systolic blood pressure and mortality from all-cause and vascular diseases
among the rural elderly in Korea; Kangwha cohort study.
AB - The association between low systolic blood pressure (SBP) and vascular diseases
is unclear. The aim of this study was to prospectively examine the association
between SBP, especially low SBP, and mortality from all causes and vascular
diseases among the elderly in Korea. Six thousand two hundred ninety four
residents in a rural community were followed-up for deaths from 1985 to 2008. The
adjusted hazard ratios (aHR) and 95% confidence intervals were calculated by Cox
proportional hazard model. A stratified analysis was conducted by age at
enrollment. Among the elderly aged 65 and above, the lowest SBP (<100 mm Hg)
group had an elevated aHR for mortality from vascular diseases (aHR = 2.1, 95% CI
= 1.2-3.9) including stroke (aHR = 2.4, 95% CI = 0.9-6.3) and ischemic heart
diseases (aHR = 5.1, 95% CI = 1.0-26.0) compared to those with SBP of 100-119 mm
Hg, while higher SBP was associated with higher mortality. This J-curve
association was generally maintained when analysis was restricted to those with
fair or good self-rated health, or those with no known vascular diseases. In
people below 65, increasing SBP nearly monotonically increased the mortality from
all-cause and vascular diseases. Our results suggest that elderly persons with
low SBP should be treated with caution, since low SBP may increase vascular
mortality.
PMID- 25590835
TI - Erlotinib plus capecitabine as first-line treatment for older Chinese patients
with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm,
multicenter phase II study.
AB - Preclinical studies have shown synergism between epidermal growth factor receptor
(EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is
to investigate the efficacy and tolerability of erlotinib plus capecitabine as
first-line treatment in older Chinese patients (>= 65 years) with lung
adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical
trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma
and age 65 years or above were enrolled at four tertiary teaching hospitals and 2
provincial hospitals in China; 58 patients fulfilled the study requirements.
Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14)
were administered during every 21-day cycle. The primary endpoint was the non
progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using
PCR. Tumor expression of different biomarkers was assessed using
immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease
progression at 12 weeks following treatment. The objective response rate was
29.3%, and the disease control rate was 75.9%. The objective response rate was
significantly higher in patients with EGFR mutations than in those with wild-type
EGFR. Patients with thymidine phosphorylase-negative tumors had significantly
longer overall survival after one year than patients with thymidine phosphorylase
positive tumors. Forty-four patients had at least one primary adverse events
(AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n =
7). This is the first phase II clinical trial to assess erlotinib plus
capecitabine combination therapy as first-line treatment in older patients with
lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better
in patients with EGFR mutations and in those with thymidine phosphorylase
negative tumors. The use of fluorouracil derivatives for the treatment of lung
adenocarcinoma warrants further study.
PMID- 25590836
TI - Potentially modifiable risk factors for acute kidney injury after surgery on the
thoracic aorta: a propensity score matched case-control study.
AB - Perioperative risk factors were identified for acute kidney injury (AKI) defined
by the RIFLE criteria (RIFLE = risk, injury, failure, loss, end stage) after
surgery on the thoracic aorta with cardiopulmonary bypass (CPB) in this case
control study. A retrospective review was completed for 702 patients who
underwent surgery on the thoracic aorta with CPB. A total of 183 patients with
AKI were matched 1:1 with patients without AKI by a propensity score. Matched
variables included age, gender, body-mass index, preoperative creatinine levels,
estimated glomerular filtration rate, a history of hypertension, diabetes
mellitus, cerebrovascular accident, smoking history, or chronic obstructive
pulmonary disease to exclude the influence of patient demographics, preoperative
medical status, and baseline renal function. Multivariate logistic regression
analysis was used to evaluate for independent risk factors in the matched sample
of 366 patients. The incidence of AKI was 28.6% and 5.9% of patients from the
entire sample required renal replacement therapy. AKI was associated with a
prolonged postoperative hospital stay and a higher one-month and one-year
mortality both in the entire and matched sample set. Independent risk factors for
AKI were a left ventricular ejection fraction <55%, preoperative hemoglobin level
<10 g/dL, albumin <4.0 g/dL, diagnosis of dissection, operation time >7 hours,
deep hypothermic circulatory arrest (DHCA) time >30 min, pRBC transfusion >1000
mL, and FFP transfusion >500 mL. Although the incidence of poor glucose control
(blood glucose >180 mg/dL) was higher in patients with AKI in matched sample, it
was not an independent risk factor.AKI was still associated with a poor clinical
outcome in the matched sample. Potentially modifiable risk factors included
preoperative anemia and hypoalbuminemia. Efforts to minimize operation time and
DHCA time along with transfusion amount may protect patients undergoing aortic
surgery against AKI.
PMID- 25590838
TI - A metabolic phenotype based on mitochondrial ribosomal protein expression as a
predictor of lymph node metastasis in papillary thyroid carcinoma.
AB - Metabolic reprogramming has been regarded as an essential component of malignant
transformation. However, the clinical significance of metabolic heterogeneity
remains poorly characterized. The aim of this study was to characterize metabolic
heterogeneity in thyroid cancers via the analysis of the expression of
mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative
phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene
set enrichment analysis (GSEA) verified by reverse transcription polymerase chain
reaction and gene network analysis was performed using public repository data.
Cross-sectional observational study was conducted to classify papillary thyroid
cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to
investigate the clinicopathological features. GSEA clearly showed that the
expression of OxPhos and MRP gene sets was significantly lower in primary thyroid
cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid
tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA
expression. Remarkably, strong positive correlations between MRPL44 expression
and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide
dehydrogenase (ubiquinone) 1 alpha subcomplex, 5; succinate dehydrogenase
complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+
transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5
(MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a
representative marker of OxPhos and MRP expressions. In laboratory experiments,
metabolic heterogeneity in oxygen consumption, extracellular acidification rates
(ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP,
TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to
OxPhos amount defined by expression of MRPL44 mRNA was significantly related to
lymph node metastasis (LNM) (P < 0.001). Furthermore, multivariate analysis
clearly indicated that expression of MRPL44 is associated with an increased risk
of lateral neck LNM (odds ratio 9.267, 95% confidence interval 1.852-46.371, P =
0.007). MRPL44 expression may be a representative marker of metabolic phenotype
according to OxPhos amount and a useful predictor of LNM.
PMID- 25590837
TI - Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa
Rican children with otitis media before and after the introduction of the 7
valent pneumococcal conjugate vaccine in the National Immunization Program: acute
otitis media microbiology in Costa Rican children.
AB - Acute otitis media (AOM) microbiology was evaluated in children after 7-valent
pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector,
2004; National Immunization Program, 2009). This was a combined prospective and
retrospective study conducted in a routine clinical setting in San Jose, Costa
Rica. In the prospective part of the study, which was conducted post-PCV7
introduction (2010-2012), standard bacteriological procedures were used to
evaluate the etiology and serotype distribution of middle ear fluid samples
collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed
with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture
positive samples. Retrospective data recorded between 1999 and 2004 were used for
comparison of bacterial etiology and serotype distribution before and after PCV7
introduction. Statistical significance was evaluated in bivariate analyses at the
P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction,
Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in
87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H.
influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%)
frequently observed in vaccinated (>= 2 PCV7 doses or >= 1 PCV7 dose at >1 year
of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were
1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and
trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non
susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7
introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S.
pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype
proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value =
0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%),
6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and
35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the
distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes
included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines
impact should be further evaluated following broader vaccination coverage.
PMID- 25590839
TI - TLR4 rs1927911, but not TLR2 rs5743708, is associated with atherosclerotic
cerebral infarction in the Southern Han population: a case-control study.
AB - The objective of this study was to explore the association of toll-like receptor
(TLR) 4 rs1927911 and TLR2 rs5743708 with atherosclerotic cerebral infarction
(ACI) and their effects on blood pressure, fasting blood glucose, and blood
lipids in the Han population of Hunan Province. TLR4 rs1927911 and TLR2 rs5743708
were detected by polymerase chain reaction and restriction fragment length
polymorphism in 170 patients with ACI and 149 healthy controls. Our results
indicated that the genotype and allele frequencies of TLR4 rs1927911 were
significantly different between ACI patients and controls, whereas those of TLR2
rs5743708 were not significantly different between the 2 groups. For TLR4
rs1927911, blood pressure, fasting blood sugar, and serum lipid levels were not
significantly different among different genotypes in the ACI and control groups.
The rs1927911 polymorphism of the TLR4 gene may be a risk factor for ACI in the
Southern Han population of Hunan Province; however, it may not be associated with
blood pressure, fasting blood sugar, or blood lipids.
PMID- 25590840
TI - Training in early gastric cancer diagnosis improves the detection rate of early
gastric cancer: an observational study in China.
AB - Few studies have analyzed the training of endoscopists in the diagnosis of early
gastric cancer (EGC). This study assessed whether specific training of
endoscopists improves the detection rate of EGC. The rates of detection of EGC by
endoscopists at the Digestive Endoscopy Center of the Affiliated Nanfang Hospital
of China Southern Medical University between January 2013 and May 2014 were
retrospectively analyzed. Because some endoscopists received training in the
diagnosis of EGC, beginning in September 2013, the study was divided into 3 time
periods: January to September 2013 (period 1), September 2013 to January 2014
(period 2), and January to May 2014 (period 3). The rates of EGC detection during
these 3 periods were analyzed. From January 2013 to May 2014, a total of 25,314
gastroscopy examinations were performed at our center, with 48 of these
examinations (0.2%) detecting EGCs, accounting for 12.1% (48/396) of the total
number of gastric cancers detected. The EGC detection rates by trained
endoscopists during periods 1, 2, and 3 were 0.3%, 0.6%, and 1.5%, respectively,
accounting for 22.0%, 39.0%, and 60.0%, respectively, of the gastric cancers
detected during these time periods. In comparison, the EGC detection rates by
untrained endoscopists during periods 1, 2, and 3 were 0.05%, 0.08%, and 0.10%,
respectively, accounting for 3.1%, 6.0%, and 5.7%, respectively, of the gastric
cancers detected during these times. After training, the detection rate by some
trained endoscopists markedly increased from 0.2% during period 1 to 2.3% during
period 3. Further, the use of magnifying endoscopy with narrow-band imaging (M
NBI) (odds ratio = 3.1, 95% confidence interval 2.4-4.1, P < 0.001) contributed
to the diagnosis of EGC. In conclusion, specific training could improve the
endoscopic detection rate of EGC. M-NBI contributed to the diagnosis of EGC.
PMID- 25590841
TI - Serum IgG subclasses in autoimmune diseases.
AB - To characterize serum IgG subclass levels in several autoimmune diseases,
including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic
lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to
analyze serum IgG subclass distribution and to test whether serum IgG4 levels are
elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100
SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured
using the immunonephelometric assay. The distribution of IgG subclasses among
these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1
(IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with
those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There
were no significant differences in the frequency of elevated serum IgG4 levels
between patients and HC. In pSS, serum IgG1 levels were much higher than those in
other disease groups, whereas serum IgG2 and IgG3 levels were most prominently
increased in PBC. A strikingly different serum IgG subclass distribution was
detected in patients with autoimmune diseases compared with HCs. Serum IgG
subclass levels also showed distinct characteristics among different autoimmune
diseases. Serum IgG4 levels in these patients were lower or not much higher than
those in HCs, which differed from IgG4-related diseases.
PMID- 25590842
TI - Surgical resection improves the outcome of the patients with neuroendocrine tumor
liver metastases: large data from Asia.
AB - How to properly manage neuroendocrine liver metastasis (NELM) remains debatable,
and only limited clinical data have been published from Asian population. The
objective of this study is to identify possible prognostic factors affecting
overall survival time and to provide a guideline for future clinical practice. A
retrospective study was performed on 1286 patients who had neuroendocrine tumors
in our specialized center, and data from 130 patients who had NELM were
summarized. Demographic and clinicopathologic data, tumor grade, treatment
method, and prognosis were statistically analyzed. Most of the NELMs originated
from pancreas (65.4%). Important prognostic factors that included tumor location
and size were identified with multivariate analysis. Patients with either primary
tumor resection or liver metastasis resection showed a 5-year survival of 35.7%
or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year
survival. More importantly, resection was performed on 7 patients with grade 3
(G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%,
and 28.6%, respectively, whereas the other 9 G3 patients without resection died
within 3 years. P = 0.49 comparing the resected group with nonresected group in
G3 patients. Besides, the overall 5-year survival rates for resected and
nonresected patients were 40.5% and 5.4%, respectively. Multiple prognostic
factors influenced the overall outcome of NELM including patient age, tumor
location, and size, etc. Aggressive surgical approaches could be considered for
maximum survival time disregarding the pathological grade of the tumor. Study
with larger sample size should be considered to reevaluate the recommendation of
the WHO guidelines for G3 neuroendocrine tumors.
PMID- 25590843
TI - The role of the harm avoidance personality in depression and anxiety during the
medical internship.
AB - To determine whether physicians with harm avoidance (HA) personality traits were
more prone to developing increased anxiety and depression during the medical
internship. A prospective longitudinal study of 74 medical interns was carried
out using repeated measures of symptoms of anxiety and depression with the Beck
Anxiety and Depression Inventories (BAI and BDI) before, at the 3rd, 6th, and
12th months during the internship, and 2 weeks after the internship was
completed. Baseline personality was assessed by the Tridimensional Personality
Questionnaire with 3 dimensions: novelty-seeking, HA, and reward dependence (RD).
Levels of both depression and anxiety increased (6.4 and 3.4 on scores for BDI
and BAI, respectively) during the internship and returned to baseline 2 weeks
after it ended. HA scores were significantly correlated with depression and
anxiety (0.3 scores on both the BDI and the BAI) and the scores for RD were
significantly correlated with anxiety but not with depression. The interaction of
HA and point in internship showed no significant differences. Internship plays a
major role in the increase in depression and anxiety. A HA personality was also
associated with the development of both depression and anxiety.
PMID- 25590844
TI - Cross-sectional study of the retinal nerve fiber layer thickness at 7 years after
an acute episode of unilateral primary acute angle closure.
AB - The purpose of this article is to investigate the long-term retinal nerve fiber
layer (RNFL) status and determinants of RNFL thinning after an episode of
unilateral primary acute angle closure (AAC). This cross-sectional study analyzed
the medical records of consecutive patients with a single episode of unilateral
AAC from 1999 to 2009 in Hong Kong. The peripapillary RNFL thickness was
correlated with age, gender, presenting intraocular pressure (IOP), time to laser
iridotomy, time to cataract extraction, follow-up duration, as well as the last
IOP, vertical cup-to-disc ratio (CDR), and vision. The fellow uninvolved eye was
used as a proxy comparison of RNFL loss in the attack eye. In 40 eligible
patients, the mean age was 68.3 +/- 8.7 years with a male-to-female ratio of 1:7.
The mean presenting IOP was 49.2 +/- 14.0 mm Hg and the time from presentation to
laser iridotomy was 6.7 +/- 6.9 days. Forty percent of subjects received a
cataract extraction at 3.2 +/- 2.9 years after the attack. The last IOP, CDR, and
LogMAR vision were 16.0 +/- 3.8 mm Hg, 0.6 +/- 0.2, and 0.6 +/- 0.6 LogMAR units,
respectively, at 7.9 +/- 2.4 years. The RNFL thickness in the attack eye (69.2 +/
19.1 MUm) was 25.2 +/- 17.9% thinner than the fellow eye (93.0 +/- 17.8 MUm) at
7.5 +/- 2.9 years post-AAC. Using univariate analysis, the last vertical CDR
(odds ratio [OR] = 17.2, P = 0.049) and LogMAR visual acuity (VA) (OR = 6.6, P =
0.03) were the only significant predictors for RNFL thinning whereas none of the
other covariates showed significant associations (P > 0.1). At 7.5 years
following unilateral AAC, the RNFL thickness was 25% thinner than the fellow eye.
CDR enlargement and poor VA were the only significant predictors for RNFL loss.
PMID- 25590845
TI - Cinacalcet in pediatric and adolescent chronic kidney disease: a single-center
experience.
AB - Cinacalcet, a calcimimetic drug, has been shown to be efficacious in adult
chronic kidney disease (CKD) patients; however, it was not fully studied in
pediatric CKD patients. We aimed at assessing the effect of cinacalcet on intact
parathyroid hormone (iPTH) secretion in children with CKD-4/5 with iPTH
consistently >= 300 pg/mL refractory to conventional treatment. This is a
prospective cohort analysis of 28 children with uncontrolled hyper-parathyroidism
secondary to stage 4 and 5 CKD admitted to a tertiary center during the period
from April 2012 to April 2014. Twenty-eight patients with CKD-4/5 were assessed
prospectively regarding bone biochemistry, renal ultrasonography, serum iPTH
level, and medications. Patients were classified into 3 groups: group 1, 6
patients with CKD-4 on supplemental and supportive therapy; group 2, 6 patients
with CKD-5 on hemodialysis and; group 3, 16 patients with CKD-5 on automated
peritoneal dialysis. Patients were between the ages of 9 months and 18 years on
commencing cinacalcet at doses of 0.5 to 1.5 mg/kg. All patients showed at least
a 60% reduction in iPTH (60%-97%). Highly significant reduction in iPTH and serum
alkaline phosphatase levels was detected post-cinacalcet. The serum calcium (Ca),
phosphate (P), and Ca * P product were unaffected. Treatment was well tolerated
with no hypophosphatemia, hypocalcemia, or other adverse effects almost in all
patients. Cinacalcet use was proven safe for all pediatric and adolescent
patients with CKD-4/5 during the study period, and at the same time most of the
patients reached the suggested iPTH target values.
PMID- 25590846
TI - Establishment and validation of ALPH-Q score to predict mortality risk in
patients with acute-on-chronic hepatitis B liver failure: a prospective cohort
study.
AB - Currently, there are no robust models for predicting the outcome of acute-on
chronic hepatitis B liver failure (ACHBLF). We aimed to establish and validate a
new prognostic scoring system, named ALPH-Q, that integrates electrocardiography
parameters that may be used to predict short-term mortality of patients with
ACHBLF. Two hundred fourteen patients were included in this study. The APLH-Q
score was constructed by Cox proportional hazard regression analysis and was
validated in an independent patient cohort. The area under the receiver-operating
characteristic curve was used to compare the performance of different models,
including APLH-Q, Child-Pugh score (CPS), model of end-stage liver disease
(MELD), and a previously reported logistic regression model (LRM). The APLH-Q
score was constructed with 5 independent risk factors, including age (HR = 1.034,
95% CI: 1.007-1.061), liver cirrhosis (HR = 2.753, 95% CI: 1.366-5.548),
prothrombin time (HR = 1.031, 95% CI: 1.002-1.062), hepatic encephalopathy (HR =
2.703, 95% CI: 1.630-4.480), and QTc (HR = 1.008, 95% CI: 1.001-1.016). The
performance of the ALPH-Q score was significantly better than that of MELD and
CPS in both the training (0.896 vs 0.712, 0.896 vs 0.738, respectively, both P <
0.05) and validation cohorts (0.837 vs 0.689, 0.837 vs 0.585, respectively, both
P < 0.05). Compared with LRM, APLH-Q also showed a better performance (0.896 vs
0.825, 0.837 vs 0.818, respectively).We have developed a novel APLH-Q score with
greater performance than CPS, MELD, and LRM for predicting short-term mortality
of patients with ACHBLF.
PMID- 25590847
TI - Ectopic variceal bleeding from colonic stoma: two case reports.
AB - Parastomal variceal bleeding is a rare complication of portal hypertension, which
often occurs in a recurrent manner and might be life-threatening in extreme
situations. Treatment options vary, and no standard therapy has been established.
Herein, we report 2 such cases. The first patient suffered from parastomal
variceal bleeding after Hartmann procedure for rectal cancer. Stomal revision was
performed, but bleeding recurred 1 month later. The second patient developed the
disease after Miles procedure for rectal cancer. Embolization via the
percutaneous transhepatic approach was performed using the Onyx liquid embolic
system (LES) (Micro Therapeutics Inc, dba ev3 Neurovascular) in combination with
coils, and satisfactory results were obtained after a 4-month follow-up. Our
cases illustrate that surgical revision should be used with caution as a
temporary solution due to the high risk of rebleeding, whereas transhepatic
embolization via the Onyx LES and coils could be considered a safe and effective
choice for skillful managers.
PMID- 25590848
TI - Pediatric fractures through the eyes of parents: an observational study.
AB - The present study is an observational cross-sectional study. The main purpose of
this research was to analyze the perception and behaviors of parents in a series
of pediatric upper extremity fracture cases. Hundred and seventeen patients
younger than 12 years who were conservatively treated for the upper extremity
fracture were included in our study. Parents of the patients were requested to
answer a family-centered questionnaire related to their child's fracture and its
treatment. When the parents were asked whether they believe casting would be
sufficient or not as the treatment of their child's fracture, 84.6% answered
'yes', 13.7% answered 'I am not sure,' and 1.7% answered 'no.' Sixty-four of the
parents were not worried about any residual defect in joint or extremity
functions related to fracture, whereas 21 were worried and 32 were not sure on
this. The rate of searching further information about the child's fracture was
34.2% and the mostly used source was the Internet. Twenty-eight of the 117
respondents (23.9%) emphasized that they would reduce the time their child spend
outside the home at least for a while after the removal of cast. When
conservatively treating a child's fracture, physicians dealing with traumatology
should always consider the parents' perception and behaviors as critically
important.
PMID- 25590849
TI - Dissociative symptoms and mother's marital status in young adult population.
AB - Current findings suggest that mother's marital status indicating father's absence
or conflicting relationship to father may be specifically related to dissociation
and other stress-related symptoms. We have assessed relationships of mother's
marital status, dissociative symptoms, and other psychopathological
manifestations in a sample of 19 years' old young adults (N = 364) participating
in European longitudinal study (European Longitudinal Study of Parenthood and
Childhood). The results show clinically significant manifestations of
dissociative symptoms in young adult men whose mothers were fatherless and in
women whose mothers were re-married. Other psychopathological symptoms did not
reach clinically significant manifestations. The results suggest that significant
factor related to high level of dissociative symptoms in men growing in
fatherless families might be linked with disturbed and conflicting attachment to
a father's figure and pathological dependent attachment to mother. In women
dissociative symptoms likely are linked to conflicting relationship between
mother and daughter associated with stepfather' presence in the family.
PMID- 25590850
TI - Vascular dysregulation in normal-tension glaucoma is not affected by structure
and function of the microcirculation or macrocirculation at rest: a case-control
study.
AB - In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal
intraocular pressure. Studies implicating systemic blood pressure or, more
recently, arterial stiffness in the pathophysiology of NTG have produced
conflicting results. Our aim was to investigate whether NTG is associated with
alterations in the macrocirculation or microcirculation, cardiac function, and
peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years,
range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for
age and sex were included in the study. Exclusion criteria (for both cases and
controls) were history of cardiovascular disease, diabetes mellitus, severe
hypertension, and hypercholesterolemia. Aortic stiffness was measured using
carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid
artery applanation tonometry, and diameter, stiffness, and intima-media thickness
(IMT) of the carotid and femoral artery using echo-tracking. Total peripheral
resistance index (TPRI) was derived from mean arterial pressure and cardiac
index, measured using ultrasound. There were no statistically significant
differences in arterial structure nor function between NTG patients and age and
sex-matched controls. NTG versus controls, respectively: brachial blood pressure
126 +/- 15/77 +/- 8 versus 127 +/- 16/76 +/- 7 mm Hg, P = 0.81; carotid-femoral
PWV 9.8 +/- 2.1 versus 10.1 +/- 1.9 m/s, P = 0.60; TPRI 1833 +/- 609 versus 1779
+/- 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 +/- 0.14 versus 0.68 +/-
0.13 mm, P = 0.39. This study could not show an association of NTG with altered
IMT, arterial stiffness, total peripheral resistance, cardiac output, and
peripheral or central hemodynamics at rest. Although the majority of these NTG
patients do exhibit symptoms of vascular dysregulation, in the present study this
was not translated into alterations in the microcirculation or macrocirculation
at rest.
PMID- 25590851
TI - Impaired systolic blood pressure recovery and heart rate recovery after graded
exercise in patients with metabolic syndrome.
AB - The aim of this study was to evaluate and compare systolic blood pressure
recovery and heart rate recovery (HRR) values obtained at various time intervals
after maximal graded exercise treadmill testing between patients with metabolic
syndrome (MS) and the controls without MS. To our knowledge, this is the first
study indicating systolic blood pressure recovery (SBPR) impairment and its
relations to HRR and other variables in this group of patients. The study
population included 110 patients with MS (67 men, 43 women; mean age: 46 +/- 9
years) and 110 control subjects who did not meet the criteria for MS (58 men, 52
women; mean age: 44 +/- 10 years). All patients were selected from nonobese,
apparently healthy sedentary individuals who had the ability to perform maximum
exercise testing. SBPR was assessed by calculating the ratio of systolic blood
pressure (SBP) obtained in the third minute of the recovery period to either the
peak-exercise SBP or the SBP in the first minute of the recovery period after
graded exercise testing. HRR values were calculated by subtracting the HR at the
first, second, third, fourth, and fifth minutes of the recovery period from the
HR reached at peak exercise. There was no significant difference found between
the 2 groups with respect to age and sex distribution. As expected, patients with
MS had higher waist circumference, fasting plasma glucose and serum triglyceride,
and lower high-density lipoprotein cholesterol compared with control subjects.
All HRR values calculated in the first, second, third, fourth, and fifth minutes
were significantly detected lower in the MS group compared with the control group
(HRR 1st: 32 +/- 10 vs 36 +/- 11; P = 0.009; HRR 2nd: 47 +/- 10 vs 51 +/- 11; P =
0.02; HRR 3rd: 53 +/- 11 vs 58 +/- 12; P = 0.001; HRR 4th: 57 +/- 11 vs 64 +/-
12; P < 0.001; HRR 5th: 60 +/- 16 vs 69 +/- 15; P < 0.001). In addition,
calculated mean values for SBPR1 and SBPR2 were >1 in patients with MS (1.01 +/-
0.2 vs 0.91 +/- 0.1 and 1.01 +/- 0.1 vs 0.94 +/- 0.1) and these were
statistically significant compared with the control group (P < 0.001 and P =
0.002, respectively). The existence of MS was found to be the only parameter that
was independently and positively related to SBPR values in the study population.
Our findings suggest that only the existence of MS itself, not the presence of
any MS components, is independently associated with SBPRs. We are of the opinion
that significantly impaired SBPR values, in addition to the decreased HRR values
observed in this group of patients, such as those with MS, may especially help
identify patients with potentially increased cardiovascular risk despite normal
exercise stress testing findings.
PMID- 25590852
TI - Age-adjusted Charlson comorbidity index scores as predictor of survival in
colorectal cancer patients who underwent surgical resection and chemoradiation.
AB - We studied the effect of Age-Adjusted Comorbidity Index Score in colorectal
cancer patients who underwent similarly aggressive treatment. Using the National
Health Insurance Research Database of Taiwan, we identified 5643 patients with
colorectal cancer who underwent surgical resection and chemoradiation from 2007
through 2011. We estimated survival according to Age-Adjusted Comorbidity Index
Scores and 5-year survival using Cox proportional hazard regression analysis,
adjusting for sex, oxaliplatin-based chemotherapy, socioeconomic status,
geographic region, and hospital characteristics. In the cohort were 3230 patients
with colonic cancer and 2413 patients with rectal cancer, who had undergone
combined surgical resection and either neoadjuvant or adjuvant chemoradiation.
After adjusting for patient characteristics (sex, oxaliplatin-based chemotherapy,
socioeconomic status, geographic region, and hospital-characteristics), colonic
cancer patients with age-adjusted Charlson (AAC) >= 6 had a 106% greater risk of
death within 5 years (adjusted HR = 2.06; 95% CI, 1.66-2.56). In rectal cancer
patients, patients with an AAC score of 4-5 had a 28% greater risk of death
within 5 years (adjusted HR = 1.28; 95% CI, 1.02-1.61), and those with AAC >= 6
had a 47% greater risk (adjusted HR = 1.47; 95% CI, 1.15-1.90). Age and burden of
comorbidities influence survival of patients with colonic or rectal cancer. Age
Adjusted Comorbidity Score remains an independent prognostic factor even after
adjusting for the aggressiveness of treatment.
PMID- 25590854
TI - Use of MALDI-TOF mass spectrometry and a custom database to characterize bacteria
indigenous to a unique cave environment (Kartchner Caverns, AZ, USA).
AB - MALDI-TOF mass spectrometry has been shown to be a rapid and reliable tool for
identification of bacteria at the genus and species, and in some cases, strain
levels. Commercially available and open source software tools have been developed
to facilitate identification; however, no universal/standardized data analysis
pipeline has been described in the literature. Here, we provide a comprehensive
and detailed demonstration of bacterial identification procedures using a MALDI
TOF mass spectrometer. Mass spectra were collected from 15 diverse bacteria
isolated from Kartchner Caverns, AZ, USA, and identified by 16S rDNA sequencing.
Databases were constructed in BioNumerics 7.1. Follow-up analyses of mass spectra
were performed, including cluster analyses, peak matching, and statistical
analyses. Identification was performed using blind-coded samples randomly
selected from these 15 bacteria. Two identification methods are presented:
similarity coefficient-based and biomarker-based methods. Results show that both
identification methods can identify the bacteria to the species level.
PMID- 25590855
TI - Evaluation of 28 cases of mucormycosis.
AB - Mucormycosis is a rare but invasive fungal disease with high mortality. The
present study aimed to retrospectively investigate the demographic
characteristics, as well as the clinical, radiological and laboratory features
and the results of treatment, in the patients followed in our hospital because of
mucormycosis. The present study retrospectively evaluated 28 cases, which were
followed in our hospital because of mucormycosis between January 2002 and July
2013. The clinical form was rhinocerebral in 27 cases (rhinoorbital in 12, nasal
in 8 and rhinoorbitocerebral in 7) and disseminated in one case. With regard to
predisposing factors, diabetes mellitus (n = 20), haematological malignancy (n =
6) and chronic renal insufficiency (n = 5) were the leading concomitant diseases.
Seventeen (61%) of 28 cases showed atypical clinical picture. With regard to the
therapeutic outcomes; it was found that 14 (50%) cases died and six cases
recovered with sequel. Today, when particularly the prevalence of
immunosuppressive diseases and conditions are gradually increasing, the incidence
of mucormycosis is also increased. Considering that the majority of our cases had
atypical clinical involvement and complications, being familiar with the
characteristics of this disease could be life-saving together with early
diagnosis and treatment.
PMID- 25590856
TI - EVOLUTION OF CONTROLLING DIABETIC RETINOPATHY: Changing Trends in the Management
of Diabetic Macular Edema at a Single Institution Over the Past Decade.
AB - PURPOSE: To report the evolution of treatment in managing diabetic macular edema
(DME) in a "real world" clinical setting. METHODS: Retrospective observational
case series of 1,862 patients treated for DME over the last decade. Change in
selection of treatment modalities used for controlling DME, visual acuity, and
degree of DME on optical coherence tomography were recorded. RESULTS: Over the
past decade, there was a linear decrease in laser use, with exponential growth in
the utilization of intravitreal injections. An increase in the frequency of
clinic visits from 3 +/- 2 visits per year to 9 +/- 2 visits per year with
significant visual and anatomical improvements was noted: mean improvement in
visual acuity increased from 0.01 +/- 0.1 logMAR units (which is equivalent to
less than 1 Snellen line) to 0.3 +/- 0.2 logMAR units (which is equivalent to 2
Snellen lines) (P < 0.05), mean decrease in retinal thickness changed from 58 +/-
59 MUm to 162 +/- 91 MUm (P < 0.05). CONCLUSION: An evolution in treatment
strategy for controlling DME over the last decade was reflected by the
replacement of focal laser therapy with intravitreal injections. This has
produced significant improvements in visual and anatomical outcomes but has
increased the frequency of office visits.
PMID- 25590857
TI - Changes of choroidal neovascularization in indocyanine green angiography after
intravitreal ranibizumab injection.
AB - PURPOSE: To investigate vascular structural changes of choroidal
neovascularization (CNV) followed by intravitreal ranibizumab injections using
indocyanine green angiography. METHODS: A total of 31 patients with exudative age
related macular degeneration and CNV whose structures were identifiable in
indocyanine green angiography were included. Ranibizumab was injected into the
vitreous cavity once a month for 3 months and then as needed for the next 3
months prospectively. Indocyanine green angiography was performed at baseline, 3,
and 6 months. Early to midphase images of the indocyanine green angiography in
the details of vascular structure of the CNV were discerned the best were used in
the image analysis. Vascular structures of CNV were described as arteriovenular
and capillary components, and structural changes were assessed. RESULTS:
Arteriovenular components were observed in 29 eyes (94%). Regression of the
capillary components was observed in most cases. Although regression of
arteriovenular component was noted in 14 eyes (48%), complete resolution was not
observed. The eyes were categorized into 3 groups according to CNV structural
changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes,
23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth
of CNV found at 6 months. In Group M, distinct vascular structures were observed
at 3 months and persisted without apparent changes at 6 months. In Group G,
growth or reperfusion of capillary components from the persisting arteriovenular
components was noted at 6 months. CONCLUSION: Both capillary and arteriovenular
components were regressed during monthly ranibizumab injections. However, CNV
regrowth was observed in a group of patients during the as-needed treatment
phase.
PMID- 25590858
TI - Asymmetric alpha-benzoyloxylation of beta-ketocarbonyls by a chiral primary amine
catalyst.
AB - The direct asymmetric alpha-benzoyloxylation of beta-ketocarbonyls catalyzed by a
chiral primary amine is described herein. This protocol demonstrates excellent
enantioselectivity for a broad range of substrates, which allows convenient
access to highly enantioenriched alpha-hydroxy-beta-ketocarbonyls.
PMID- 25590859
TI - High throughput characterization of adult stem cells engineered for delivery of
therapeutic factors for neuroprotective strategies.
AB - Mesenchymal stem cells (MSCs) derived from bone marrow are a powerful cellular
resource and have been used in numerous studies as potential candidates to
develop strategies for treating a variety of diseases. The purpose of this study
was to develop and characterize MSCs as cellular vehicles engineered for delivery
of therapeutic factors as part of a neuroprotective strategy for rescuing the
damaged or diseased nervous system. In this study we used mouse MSCs that were
genetically modified using lentiviral vectors, which encoded brain-derived
neurotrophic factor (BDNF) or glial cell-derived neurotrophic factor (GDNF),
together with green fluorescent protein (GFP). Before proceeding with in vivo
transplant studies it was important to characterize the engineered cells to
determine whether or not the genetic modification altered aspects of normal cell
behavior. Different culture substrates were examined for their ability to support
cell adhesion, proliferation, survival, and cell migration of the four
subpopulations of engineered MSCs. High content screening (HCS) was conducted and
image analysis performed. Substrates examined included: poly-L-lysine,
fibronectin, collagen type I, laminin, entactin-collagen IV-laminin (ECL). Ki67
immunolabeling was used to investigate cell proliferation and Propidium Iodide
staining was used to investigate cell viability. Time-lapse imaging was conducted
using a transmitted light/environmental chamber system on the high content
screening system. Our results demonstrated that the different subpopulations of
the genetically modified MSCs displayed similar behaviors that were in general
comparable to that of the original, non-modified MSCs. The influence of different
culture substrates on cell growth and cell migration was not dramatically
different between groups comparing the different MSC subtypes, as well as culture
substrates. This study provides an experimental strategy to rapidly characterize
engineered stem cells and their behaviors before their application in long-term
in vivo transplant studies for nervous system rescue and repair.
PMID- 25590860
TI - Molecular details of INH-C10 binding to wt KatG and Its S315T mutant.
AB - Isoniazid (INH) is still one of the two most effective antitubercular drugs and
is included in all recommended multitherapeutic regimens. Because of the
increasing resistance of Mycobacterium tuberculosis to INH, mainly associated
with mutations in the katG gene, new INH-based compounds have been proposed to
circumvent this problem. In this work, we present a detailed comparative study of
the molecular determinants of the interactions between wt KatG or its S315T
mutant form and either INH or INH-C10, a new acylated INH derivative. MD
simulations were used to explore the conformational space of both proteins, and
results indicate that the S315T mutation did not have a significant impact on the
average size of the access tunnel in the vicinity of these residues. Our
simulations also indicate that the steric hindrance role assigned to Asp137 is
transient and that electrostatic changes can be important in understanding the
enzyme activity data of mutations in KatG. Additionally, molecular docking
studies were used to determine the preferred modes of binding of the two
substrates. Upon mutation, the apparently less favored docking solution for
reaction became the most abundant, suggesting that S315T mutation favors less
optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the
hydrazine group closer to the heme, thus favoring the apparent most reactive
binding mode, regardless of the enzyme form. The ITC data is in agreement with
our interpretation of the C10 alkyl chain role and helped to rationalize the
significantly lower experimental MIC value observed for INH-C10. This compound
seems to be able to counterbalance most of the conformational restrictions
introduced by the mutation, which are thought to be responsible for the decrease
in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very
promising lead compound for drug development.
PMID- 25590861
TI - Admixed origin of the Kayah (Red Karen) in Northern Thailand revealed by
biparental and paternal markers.
AB - This study analyzes the autosomal short tandem repeats (STRs) variation and the
presence of Y chromosomal haplogroups from 44 individuals of the Kayah or Red
Karen (KA) in Northern Thailand. The results based on autosomal STRs indicated
that the KA exhibited closer genetic relatedness to populations from adjacent
regions in Southeast Asia (SEA) than populations from Northeast Asia (NEA) and
Tibet. Moreover, an admixed origin of the KA forming three population groups was
observed: NEA, Southern China, and Northern Thailand. The NEA populations made a
minor genetic contribution to the KA, while the rest came from populations
speaking Sino-Tibetan (ST) languages from Southern China and Tai-Kadai (TK)
speaking groups from Northern Thailand. The presence of six paternal haplogroups,
composed of dual haplogroups prevalent in NEA (NO, N, and D1) and SEA (O2 and O3)
as well as the intermediate genetic position of the KA between the SEA and NEA
also indicated an admixed origin of male KA lineages. Our genetic results thus
agree with findings in linguistics that Karenic languages are ST languages that
became heavily influenced by TK during their southward spread. A result of the
Mongol invasions during the 13th century A.D. is one possible explanation for
genetic contribution of NEA to the KA.
PMID- 25590862
TI - Novel amide and sulphonamide derivatives of 6-(piperazin-1-yl)phenanthridine as
potent Mycobacterium tuberculosis H37Rv inhibitors.
AB - A series of thirty three novel 6-(piperazin-1-yl)phenanthridine amide and
sulphonamide analogues were synthesized, characterized and screened for their in
vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv
strain. These compounds exhibited minimum inhibitory concentration (MIC) between
1.56 and >=50 MUg/mL. Out of these derivatives, few compounds 6l, 6r, 7b, 7f, 7g
and 7k exhibited moderate activity (MIC = 6.25 MUg/mL) and compounds 6b, 6e, 6k,
6n, 7h, 7i and 7n displayed good activity (MIC = 3.13 MUg/mL), whereas compounds
6m, 6s and 7d exhibited excellent anti-tubercular activity (MIC = 1.56 MUg/mL).
In addition, MTT assay was accomplished on the active analogues of the series
against mouse macrophage (RAW 264.7) cells to evaluate the toxicity profile of
the newly synthesized compounds and selectivity index of the compounds was
determined. Additionally, compounds 6b and 7d were docked to the ATPase domain of
M. tuberculosis GyrB protein to know the interaction profile and structures of
compounds 6b and 7d were further substantiated through single crystal XRD.
PMID- 25590863
TI - Synthesis and bioevaluation of pyrazole-benzimidazolone hybrids as novel human 4
Hydroxyphenylpyruvate dioxygenase inhibitors.
AB - 4-Hydroxyphenylpyruvate dioxygenase (HPPD), an essential enzyme in tyrosine
catabolism, is an important target for treating type I tyrosinemia. Inhibition of
HPPD can effectively alleviate the symptoms of type I tyrosinemia. However, only
one commercial HPPD inhibitor, 2-(2-nitro-4-trifluoromethylbenzoyl) cyclohexane
1,3-dione (NTBC), has been available for clinical use so far. In the present
study, a series of novel pyrazole-benzimidazolone hybrids were designed,
synthesized and evaluated as potent human HPPD inhibitors. Most of the new
compounds displayed significant inhibitory activity against the recombinant human
HPPD. Moreover, compound 9l was identified as the most potent candidate with IC50
value of 0.021 MUM against recombinant human HPPD, about 3-fold more potent than
NTBC. Thus the pyrazole-benzimidazolone hybrid has great potential to be further
developed for the treatment of type I tyrosinemia.
PMID- 25590864
TI - Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated
chalcone natural products and their analogs.
AB - Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a),
xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were
synthesized by using a regio-selective iodination and the Suzuki coupling
reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was
achieved in 36% overall yield. A series of diprenylated and digeranylated
chalcone analogs were also synthesized by alkylation, regio-selective iodination,
aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The
structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and
HRMS. The anticancer activity of these new chalcone derivatives against human
tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested
that the 5'-prenylation/geranylation of the chalcones significantly enhance their
cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent
cytotoxic activity against K562 with IC50 value of 2.7 MUM. The morphology
changes and annexin-V/PI staining studies suggested that those chalcone
derivatives inhibited the proliferation of K562 cells by inducing apoptosis.
PMID- 25590865
TI - Trichinellosis surveillance--United States, 2008-2012.
AB - PROBLEM/CONDITION: Trichinellosis is a parasitic disease caused by nematodes in
the genus Trichinella, which are among the most widespread zoonotic pathogens
globally. Infection occurs following consumption of raw or undercooked meat
infected with Trichinella larvae. Clinical manifestations of the disease range
from asymptomatic infection to fatal disease; the common signs and symptoms
include eosinophilia, fever, periorbital edema, and myalgia. Trichinellosis
surveillance has documented a steady decline in the reported incidence of the
disease in the United States. In recent years, proportionally fewer cases have
been associated with consumption of commercial pork products, and more are
associated with meat from wild game such as bear. PERIOD COVERED: 2008-2012.
DESCRIPTION OF SYSTEM: Trichinellosis has been a nationally notifiable disease in
the United States since 1966 and is reportable in 48 states, New York City, and
the District of Columbia. The purpose of national surveillance is to estimate
incidence of infection, detect outbreaks, and guide prevention efforts. Cases are
defined by clinical characteristics and the results of laboratory testing for
evidence of Trichinella infection. Food exposure histories are obtained at the
local level either at the point of care or through health department interview.
States notify CDC of cases electronically through the National Notifiable Disease
Surveillance System (available at http://wwwn.cdc.gov/nndss). In addition, states
are asked to submit a standardized supplementary case report form that captures
the clinical and epidemiologic information needed to meet the surveillance case
definition. Reported cases are summarized weekly and annually in MMWR. RESULTS:
During 2008-2012, a total of 90 cases of trichinellosis were reported to CDC from
24 states and the District of Columbia. Six (7%) cases were excluded from
analysis because a supplementary case report form was not submitted or the case
did not meet the case definition. A total of 84 confirmed trichinellosis cases,
including five outbreaks that comprised 40 cases, were analyzed and included in
this report. During 2008-2012, the mean annual incidence of trichinellosis in the
United States was 0.1 cases per 1 million population, with a median of 15 cases
per year. Pork products were associated with 22 (26%) cases, including 10 (45%)
that were linked with commercial pork products, six (27%) that were linked with
wild boar, and one (5%) that was linked with home-raised swine; five (23%) were
unspecified. Meats other than pork were associated with 45 (54%) cases, including
41 (91%) that were linked with bear meat, two (4%) that were linked with deer
meat, and two (4%) that were linked with ground beef. The source for 17 (20%)
cases was unknown. Of the 51 patients for whom information was reported on the
manner in which the meat product was cooked, 24 (47%) reported eating raw or
undercooked meat. INTERPRETATION: The risk for Trichinella infection associated
with commercial pork has decreased substantially in the United States since the
1940s, when data collection on trichinellosis cases first began. However, the
continued identification of cases related to both pork and nonpork sources
indicates that public education about trichinellosis and the dangers of consuming
raw or undercooked meat still is needed. PUBLIC HEALTH ACTIONS: Changes in
domestic pork production and public health education regarding the safe
preparation of pork have contributed to the reduction in the incidence of
trichinellosis in the United States; however, consumption of wild game meat such
as bear continues to be an important source of infection. Hunters and consumers
of wild game meat should be educated about the risk associated with consumption
of raw or undercooked meat.
PMID- 25590866
TI - Cordycepin induces cell cycle arrest and apoptosis by inducing DNA damage and up
regulation of p53 in Leukemia cells.
AB - Cordycepin, an adenosine analog derived from Cordyceps militaris has been shown
to exert anti-tumor activity in many ways. However, the mechanisms by which
cordycepin contributes to the anti-tumor still obscure. Here our present work
showed that cordycepin inhibits cell growth in NB-4 and U937 cells by inducing
apoptosis. Further study showed that cordycepin increases the expression of p53
which promotes the release of cytochrome c from mitochondria to the cytosol. The
released cytochrome c can then activate caspase-9 and trigger intrinsic
apoptosis. Cordycepin also blocks MAPK pathway by inhibiting the phosphorylation
of ERK1/2, and thus sensitizes the apoptosis. In addition, our results showed
that cordycepin inhibits the expression of cyclin A2, cyclin E, and CDK2, which
leads to the accumulation of cells in S-phase. Moreover, our study showed that
cordycepin induces DNA damage and causes degradation of Cdc25A, suggesting that
cordycepin-induced S-phase arrest involves activation of Chk2-Cdc25A pathway. In
conclusion, cordycepin-induced DNA damage initiates cell cycle arrest and
apoptosis which leads to the growth inhibition of NB-4 and U937 cells.
PMID- 25590867
TI - A whole cell bioreporter approach to assess transport and bioavailability of
organic contaminants in water unsaturated systems.
AB - Bioavailability of contaminants is a prerequisite for their effective
biodegradation in soil. The average bulk concentration of a contaminant, however,
is not an appropriate measure for its availability; bioavailability rather
depends on the dynamic interplay of potential mass transfer (flux) of a compound
to a microbial cell and the capacity of the latter to degrade the compound. In
water-unsaturated parts of the soil, mycelia have been shown to overcome
bioavailability limitations by actively transporting and mobilizing organic
compounds over the range of centimeters. Whereas the extent of mycelia-based
transport can be quantified easily by chemical means, verification of the
contaminant-bioavailability to bacterial cells requires a biological method.
Addressing this constraint, we chose the PAH fluorene (FLU) as a model compound
and developed a water unsaturated model microcosm linking a spatially separated
FLU point source and the FLU degrading bioreporter bacterium Burkholderia
sartisoli RP037-mChe by a mycelial network of Pythium ultimum. Since the
bioreporter expresses eGFP in response of the PAH flux to the cell, bacterial FLU
exposure and degradation could be monitored directly in the microcosms via
confocal laser scanning microscopy (CLSM). CLSM and image analyses revealed a
significant increase of the eGFP expression in the presence of P. ultimum
compared to controls without mycelia or FLU thus indicating FLU bioavailability
to bacteria after mycelia-mediated transport. CLSM results were supported by
chemical analyses in identical microcosms. The developed microcosm proved
suitable to investigate contaminant bioavailability and to concomitantly
visualize the involved bacteria-mycelial interactions.
PMID- 25590868
TI - Complete thymectomy in adult rats with non-invasive endotracheal intubation.
AB - Thymectomy in neonatal rodents is an established and reliable procedure for
immunological studies. However, in adult rats, complications of hemorrhage and
pneumothorax from pleural disruption can result in a significant mortality rate.
This protocol is a simple method of rat thymectomy that utilizes a mini
sternotomy and endotracheal intubation. Intubation is accomplished with a non
invasive and easily reproducible method and allows for positive pressure
ventilation to prevent pneumothorax and a controlled airway that allows
sufficient time for careful thymus dissection to minimize pleural disruption. A
1.5 cm sternal incision decreases contact with mediastinal vessels and pleura,
while still providing full visualization of the thymus. Following exposure of the
mediastinum, the thymus is removed by blunt dissection under magnification. The
pleural space is then sealed by suture closure of the pre-tracheal muscles
followed by the application of surgical glue. The thorax is then closed by suture
closure of the sternum, followed by suture closure of the skin. All thymectomies
were complete as evidenced by immunohistochemical (IHC) staining of mediastinal
tissue, and absence of naive T-cells by flow cytometry, and the procedure had a
96% survival rate. This method is suitable when complete thymectomy with minimal
complications is desired for further immunological studies in athymic adult rats.
PMID- 25590869
TI - Disentangling volumetric and hydrational properties of proteins.
AB - We used molecular dynamics simulations of a typical monomeric protein, SNase, in
combination with Voronoi-Delaunay tessellation to study and analyze the
temperature dependence of the apparent volume, Vapp, of the solute. We show that
the void volume, VB, created in the boundary region between solute and solvent,
determines the temperature dependence of Vapp to a major extent. The less
pronounced but still significant temperature dependence of the molecular volume
of the solute, VM, is essentially the result of the expansivity of its internal
voids, as the van der Waals contribution to VM is practically independent of
temperature. Results for polypeptides of different chemical nature feature a
similar temperature behavior, suggesting that the boundary/hydration contribution
seems to be a universal part of the temperature dependence of Vapp. The results
presented here shine new light on the discussion surrounding the physical basis
for understanding and decomposing the volumetric properties of proteins and
biomolecules in general.
PMID- 25590870
TI - Exosomal lipids impact on tumoral cell behavior.
PMID- 25590871
TI - Isolation, characterization, and evaluation of bacterial root and nodule
endophytes from chickpea cultivated in Northern India.
AB - Endophytic bacteria from roots (12 isolates) and nodules (76 isolates) of
chickpea legume grown under CCS Haryana Agricultural University farm were
isolated. Among the endophytic bacteria, 50% from roots and 93.4% from nodules
were Gram positive spore formers. Large number of endophytes from roots and
nodules solubilized phosphate and produced ammonia. Isolate CRE3, and CNE215,
were most efficient P solubilizers and. CRE12 and CNE76 being most efficient
ammonia producer. Interestingly, few endophytic bacteria produced organic acid.
Further selected 62 isolates were used to determine molecular diversity by RFLP
of PCR amplified 16S rDNA. Endophytes from roots formed five separate clusters
and nodule endophytes formed 13 clusters. Isolate CNE215 from nodules and CRE1
from roots possessed multiple beneficial traits and belonged two different
clusters. These two isolates were identified after amplification and sequencing
of 16S rRNA gene. Isolate CNE215 showed more than 98% similarity with partial
sequence of 16S rRNA gene of Bacillus subtilis, whereas CRE1 showed more than 98%
similarity with Bacillus licheniformis. Efficacy of these two strains was
evaluated under field conditions and an increase up to 22.5% in grain yield over
uninoculated control was observed with B. subtilis strain CNE215, whereas all the
recommended biofertilizers were able to record an increase upto 14.4%.
PMID- 25590872
TI - Calcium carbonate precipitation by strain Bacillus licheniformis AK01, newly
isolated from loamy soil: a promising alternative for sealing cement-based
materials.
AB - The relevant experiments were designed to determine the ability of indigenous
bacterial strains isolated from limestone caves, mineral springs, and loamy soils
to induce calcium carbonate precipitation. Among all isolates examined in this
study, an efficient carbonate-precipitating soil bacterium was selected from
among the isolates and identified by 16S rRNA gene sequences as Bacillus
licheniformis AK01. The ureolytic isolate was able to grow well on alkaline
carbonate-precipitation medium and precipitate calcium carbonate more than 1 g L(
1). Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD)
analyses, and scanning electron microscopy (SEM)/energy-dispersive X-ray
spectroscopy (EDX) examinations were performed in order to confirm the presence
of calcium carbonate in the precipitate and to determine which polymorphs were
present. The selected isolate was determined to be an appropriate candidate for
application in a surface treatment of cement-based material to improve the
properties of the mortar. Biodeposition of a layer of calcite on the surface of
cement specimens resulted in filling in pore spaces. This could be an alternative
method to improve the durability of the mortar. The kind of bacterial culture and
medium composition had a profound impact on the resultant CaCO(3) crystal
morphology.
PMID- 25590874
TI - The role of nursing in health care.
PMID- 25590873
TI - Diversity of ionizing radiation-resistant bacteria obtained from the Taklimakan
Desert.
AB - So far, little is known about the diversity of the radiation-resistant microbes
of the hyperarid Taklimakan Desert. In this study, ionizing radiation (IR)
resistant bacteria from two sites in Xinjiang were investigated. After exposing
the arid (water content of 0.8 +/- 0.3%) and non-arid (water content of 21.3 +/-
0.9%) sediment samples to IR of 3000 Gy using a (60)Co source, a total of 52
gamma-radiation-resistant bacteria were isolated from the desert sample. The 16S
rRNA genes of all isolates were sequenced. The phylogenetic tree places these
isolates into five groups: Cytophaga-Flavobacterium-Bacteroides, Proteobacteria,
Deinococcus-Thermus, Firmicutes, and Actinobacteria. Interestingly, this is the
first report of radiation-resistant bacteria belonging to the genera Knoellia,
Lysobacter, Nocardioides, Paracoccus, Pontibacter, Rufibacter and Microvirga. The
16s rRNA genes of four isolates showed low sequence similarities to those of the
published species. Phenotypic analysis showed that all bacteria in this study are
able to produce catalase, suggesting that these bacteria possess reactive oxygen
species (ROS)-scavenging enzymes. These radiation-resistant bacteria also
displayed diverse metabolic properties. Moreover, their radiation resistances
were found to differ. The diversity of the radiation-resistant bacteria in the
desert provides further ecological support for the hypothesis that the ionizing
radiation resistance phenotype is a consequence of the evolution of ROS
scavenging systems that protect cells against oxidative damage caused by
desiccation.
PMID- 25590875
TI - [Nursing care as an ethical problem: concepts and principles applied to the act
of caring].
AB - In this paper the authors study the nature of the act of care, emphasize the
importance of ethics in the professions related to the health of people and
develop, in the light of the central tradition of Western moral philosophy, a set
of principles that should guide nursing activity.
PMID- 25590876
TI - Interdisciplinarity and nursing research: opportunities and challenges.
AB - Interdisciplinary collaboration is widely recognized and considered essential for
optimizing the development of knowledge and practice. However,
interdisciplinarity is commonly accepted as an unquestioned good; rarely examined
as both a source of benefit as well as difficulty for nursing and other
disciplines. The aim of this article is to critically examine the opportunities
and challenges that interdisciplinarity can provide for research in nursing and
other disciplines. Based on a North American perspective, I describe the
emergence of uni-disciplinary nursing research and the knowledge exchanges that
occurred between nursing and other disciplines. I discuss the rise of
interdisciplinary research, outline several examples of nursing participation in
interdisciplinarity, and highlight the prominent benefits and difficulties
associated with interdisciplinary research. I argue that authentic collaboration
is required to conduct meaningful interdisciplinary research and describe how
this can be promoted.
PMID- 25590877
TI - [Sexual behaviors and practices of men who have sex with men].
AB - The objective was to identify behaviors and sexual practices of men who have
sexual relations with other men in the context of vulnerability to HIV/AIDS. This
was a cross-sectional, exploratory and descriptive study. It was carried out in a
gay sociability place in Fortaleza, Ceara, Brazil, between November 2010 and
March 2011, through interviews with 189 men who have sex with men. The ethical
aspects were respected. We found a sample consisting mostly by young, single, and
highly educated men. The sexual history demonstrated the early onset of sexual
activity, with a high prevalence of sexual intercourse with a partner of the
opposite sex. There was also a high prevalence of HIV testing. Sexual practices
revealed high prevalence of performing oral and anal sex, as well as high levels
of protection in anal sex, despite the low protection in oral sex. A greater
incorporation of prevention practices was found compared to the national scene in
the beginning of the disease outbreak.
PMID- 25590878
TI - [Decision making satisfaction in health scale: instrument adapted and validated
to Portuguese].
AB - Decision making is an area of health research that has gained importance both for
the partnership models of care that give prominence to the patient and family,
either by growing concern about quality and customer satisfaction with the care
provided. So we decided to make the cultural adaptation and to evaluate the
psychometric properties of the Portuguese version "The Satisfaction with Decision
Scale" de Holmes-Rovner (1996), which aims to assess satisfaction with the
decisions taken in health. The sample consisted of 521 nursing students the
School of Nursing of Porto. The results of reliability tests show good internal
consistency for the total items (Alpha Cronbach = 0.88). The psychometric study
allows us to state that the Portuguese version of "The Satisfaction with Decision
Scale", we call "Escala da Satisfacao com a Decisao em Saude", is an instrument
comparable with the original in terms of validity and reliability.
PMID- 25590879
TI - [Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a hospital in
Distrito Federal].
AB - This study aimed to analyze demographic and clinical aspects of patients
diagnosed with Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis
(TEN), as well as identifying the actions of health professionals for the
management of Adverse Drug Reactions (ADR) in a public hospital in Distrito
Federal, Brazil. A descriptive and retrospective research was held, with
quantitative approach. Data collected from all the records of 22 patients
admitted with diagnosed with SJS and TEN, from January 2005 to September 2012.
Data were analyzed using descriptive statistics. Of these cases, 9 were diagnosed
with NET and 7, with SJS; there were more females (14); aged from 21 to 40 years
(10); 21 were cured; the drugs more used were the antiepileptic ones (10).
Fragility in clinical registers and in the actions to monitor the cases of ADR in
this health service was observed.
PMID- 25590880
TI - [Elderly residents in homes for the aged: adjustment in the light of Callista
Roy].
AB - This study aimed to evaluate the adaptation of elderly individuals voluntarily
reside in Institution for the Aged (LTCF) in the city of Fortaleza-CE, based on
the theoretical model of Roy. Descriptive study, in a IPLI involving thirteen
elderly residents. Data collect was through interviews in the months of October
and December 2011 and organized by thematic content analysis. The following
themes has emerged: I Physical subdivided into body sensation and body image;
Staff and I, subdivided into self-consistency and auto ideal be moral-ethical
spiritual. Thus, the option to live in ILPI not effectively changed the lives of
elderly people. They managed to adapt to the local and coexist well with internal
and external stimuli.
PMID- 25590881
TI - [Level of dependency and quality of life of elderly].
AB - The quality of life (QoL) in older adults is largely determined by their
functional status and health conditions. With the purpose of investigate the QoL
and the factors affecting it, and identify the degree of dependency of the
elderly was carried out an observational cross-sectional exploratory and
descriptive, involving 93 elderly. In collecting data we used the Barthel Index
and MOS SF-36. In the identification of levels of dependency results indicate us
that 40.0% are independent and 18.0% are dependents, minimum being 12.0% total
dependent. The results show us that, 88.0% of the subjects reported a score below
50.0% on average reported a QoL of 39 +/- 10.0%. Checking that are a positive
correlation between the degree of dependence and the index of QoL, especially in
the physical component. It is therefore important to promote healthy aging in an
attempt to favor the preservation of autonomy and functional capacity of the
elderly.
PMID- 25590882
TI - [The elderly care practices of indigenous-performance of health].
AB - This research aims to understand the care practices of health professionals who
assist the elderly Kaingang. It is a qualitative study, supported in ethnography,
conducted by ten professionals working in primary health care in the indigenous
land of Faxinal, Parana, Brazil. The data was collected from November 2010 to
February 2012 by participant observation and interviews, and analyzed based on
the Transcultural Care Theory. Was identified the preoccupation of the carers
practices with the medication and immunization, as well as traditional medical
care. To achieve these, care professionals had strategies that implemented
maintenance of older people in care. We conclude that cultural values and
integrate scientific need assistance to improve the health of elderly indigenous.
PMID- 25590883
TI - [Nonverbal communication between nurses and the elderly based on the proxemics].
AB - The aim is to analyze the nonverbal communication between nurses and the elderly
in the nursing consultation based on the theory by Hall. The research concerns a
descriptive exploratory study and it has a quantitative approach. It took place
through filmings of the nursing consultations which happened in Health Basic
Units in Joao Pessoa, Paraiba, Brazil, observed every minute, a total of 1.575
nonverbal interactions. The analysis has showed the predominance of the female
nurses (90.63%) and the elderly (65.63) and a regular classification for most of
the factors as a prevalence of a sitting set (80.09), opposite chairs (64.46%),
personal distance (91.40%), calm facial expression (59.78%), touch was used for a
technical procedure (53.33%), visual interaction for the manipulation of the
objects (57.69) and no alteration in the voice volume (48.79%). These results
reflect the necessity of the nurses to domain consciously their corporal and
facial manifestations in order to improve the interaction with the elderly.
PMID- 25590884
TI - [Blood transfusion receivers' perception of the transfusion process].
AB - Qualitative research, descriptive exploratory, aimed to know the perception of
blood transfusion recipients as to the process. The research was carried out at a
blood bank in a city in southern Brazil, and the data were analyzed using the
Collective Subject Discourse. Were interviewed using a semistructured instrument,
eleven patients, men and women between 30 and 95 years, post-surgical recovery of
cardiac surgery, underwent blood transfusion. Four central ideas emerged: loss
and blood replacement; Preservation of life; Recognition of the transfusion
process; and transfusion safety. The perception about the change that post
transfusion begin to live from the transfusion process raises a reframing of life
itself. This study showed that transfused patients perceive the transfusion
process as a means of survival, and even having knowledge about the process and
their meanings, there is the permanence of fears and anxieties that can be
minimized by the multidisciplinary team.
PMID- 25590885
TI - [Identity of the resilient man in the context of ill with prostate cancer: a
cultural perspective].
AB - The study aimed to understand the context of resilient man when ill with prostate
cancer. This is an ethnographic case study conducted with two prostate cancer
survival men with a high degree of resilience. The data was collected on their
places, in 2012 April and May, using semi-structured in-depth interviews,
participant observation and ecomap. For the data analysis, it was built two units
of meaning: "Identity of the resilient man: contextualizing the informants" and
"The resilient man finding himself ill". It was noticed that the identity of
being a resilient man, to these informants, was marked by historical and cultural
difference which permeated their actions in the process of being ill with
prostate cancer. It is important that nurses pay attention to the cultural
aspects of human health, so that they can feel part of the healing process,
becoming an active subject facing their own health.
PMID- 25590886
TI - [Perception of nurses on the use of computer at the work].
AB - The objective of this study was to apprehend the perception nurses have on the
use of computer in the hospital environment. Took part in the study 14 nurses of
a public hospital. Collection of data took place through recorded interview and
Field Diary. Data was analyzed according to Content Analysis technique. Six
thematic categories emerged from the interviews such as the one that approached
the positive aspects: speed, legibility and accuracy of the information;
patients' safety and; improvements in the quality of care. Among the negative
aspects copy and paste the Medical Prescriptions and Nursing; lack of computers
and the nurse distancing to the patient were highlighted. In spite of the
fragilities, they were all in favor of the use of computer technology at the work
and they pointed it as indispensable resource to the quality of care.
PMID- 25590887
TI - [Parents' needs and concerns at different stages of the life cycle].
AB - OBJECTIVE: this study aimed to identify priority needs and concerns expressed by
fathers in the performance of their role in three stages of the life cycle:
adolescence, productive age, and mature age. METHODOLOGY: this is an exploratory
study with a qualitative approach, conducted with fourteen fathers residing in a
municipality in the extreme south of Brazil. The data were collected between May
and August 2011 by means of the in-depth interview. Through the technique of
written discourse analysis and the array built upon Bronfenbrenner's
bioecological theory, we obtained three categories: fathers' needs/concerns,
generated in their relationship with the world of work; needs/concerns that
emerged from the relationship of care with the children; and fathers' concerns
about the future of the children. CONCLUSIONS: we identified that the concern
with the future of the children was pointed out by fathers of all age groups
investigated.
PMID- 25590888
TI - [Eating habits in the first year of life: social representations of young
mothers].
AB - This is qualitative research that investigates the social representations of
adolescent mothers on child eating habits in the first year of life. Its subjects
were 10 adolescent mothers, whose children were aged seven to twelve months. Data
were collected through semi-structured interview, besides the use of visual
material. The analysis followed the technique of content analysis, relying on the
framework of Social Representations Theory. That analysis revealed four themes:
the conflict of breastfeeding versus consecration of porridge; establishing
complementary feeding of the child; crystallized speech: "yogurt is better than a
little steak"; the (un)definition of maternal eating habits: implications for
infant feeding. The representations that drive maternal practices in selecting,
preparing and offering food follow a particular logic, where adolescents
reinterpret technical speeches in terms of their culture.
PMID- 25590889
TI - [Cross-Mapping: diagnostic labels formulated according to the ICNP(r) versus
diagnosis of NANDA International].
AB - This descriptive study aimed at elaborating nursing diagnostic labels according
to ICNP(r); conducting a cross-mapping between the diagnostic formulations and
the diagnostic labels of NANDA-I; identifying the diagnostic labels thus obtained
that were also listed in the NANDA-I; and mapping them according to Basic Human
Needs. The workshop technique was applied to 32 intensive care nurses, the cross
mapping and validation based on agreement with experts. The workshop produced
1665 diagnostic labels which were further refined into 120 labels. They were then
submitted to a cross-mapping process with both NANDA-I diagnostic labels and the
Basic Human Needs. The mapping results underwent content validation by two expert
nurses leading to concordance rates of 92% and 100%. It was found that 63 labels
were listed in NANDA-I and 47 were not.
PMID- 25590890
TI - [Self-care in family caregiver of dependent adults or elderly persons after
hospital discharge].
AB - This article presents an understanding concerning self-care in family caregivers
according to Dorothea Orem's theory. Resulting from a qualitative research based
on Grounded Theory, this work uses the techniques of home visiting, field notes
and semistructured interviews with 11 caregivers after the hospitalization of a
family member in a teaching Hospital located in Minas Gerais. Four categories
were found and among them a central category is highlighted from which some
facilities, difficulties and strategies for selfcare in caregiver were analyzed.
Considering the difficulties, insufficient time for healthcare was noticed
whereas the support from other family members appeared as a facility. The main
strategies were: faith as a support; shift work in healthcare and community
resources. This study demonstrated that hospital discharge guidelines and nursing
follow-up after discharge were responsible for positive contributions to self
care in caregivers helping them to overcome their difficulties and enhancing
their potentialities.
PMID- 25590891
TI - [Adenosine triphosphate bioluminescence to evaluate the effectiveness of surface
cleaning: an integrative review].
AB - OBJECTIVE: To identify indications and controversies in the literature of the use
of ATP bioluminescence to evaluate the effectiveness of surface cleaning in
healthcare facilities. METHOD: Integrative literature review between 2000 and
2012 in the following databases: MEDLINE, LILACS, Science Direct, SCOPUS and Isi
Web of Knowledge. RESULTS: were selected for this review 15 articles. The ATP
bioluminescence was considered an important educational resource and
complementary method to visual inspection and microbiological evaluation of the
effectiveness of cleaning. The impossibility to indicate surface contamination by
microorganisms, interference by chemicals and the difficulty of interpreting the
results constitute the main controversies in the use of ATP in health services.
CONCLUSION: Although this is an important resource in the evaluation of surface
cleaning, more studies are necessary for effective incorporation of the method in
health services.
PMID- 25590892
TI - [A creative and sensitive way to research].
AB - This experience report describes the application of Creative Sensitive Method in
a qualitative exploratory-descriptive research. Its theoretical foundation and
the way this method was applied objectively presented through the following
stages: introduction, production, presentation, discussion and evaluation.
Finally, one can argue that the method, among others pathways, is a good
alternative methodology for generating data in collective spaces for application
in qualitative research related to nursing or others health contexts.
PMID- 25590893
TI - [History of the child's health: conquers, policies and perspectives].
AB - The aim of this study was describing and reflecting about the aspects related to
the social history and public policies for the children's health assistance in
Brazil. A brief historical contextualization was realized concerning changes on
the way the society views the child in Brazil and around the world, also
perspectives considering public policies for the children's health in the
national context were presented. It was possible to identify that the historical
evolution of the child participation in the society is linked to the changes in
the assistance public policies, which were demonstrated in the child death
decrease and associated to challenges, like the morbimortality reduction caused
by perinatal injuries and avoidable causes. The advances and conquers in the
child's health are evolved in a paradigmatic change movement into a model of a
net formation and a comprehensiveness care. This context requires the human
resources preparation for such area, based on the health promotion and
prevention, as well as a better quality of life of the population.
PMID- 25590894
TI - [The prenatal care program in Primary Care in Portugal - a reflection].
AB - The quality improvement of care provided to the pregnant women and newborn is one
of the priority areas for intervention of the National Health Plan. While
acknowledging that the measures introduced in recent years have contributed to
lower the values of maternal and perinatal mortality, it should also be mentioned
that unplanned pregnancies continue to occur, and that they often result in a
delayed or absent prenatal surveillance. In this paper, we seek to reflect on the
prenatal surveillance program under Primary Health Care relating to quality of
health care provided in the context of reproductive health. We concluded that
prenatal surveillance includes a set of specific care services targeted at a
vulnerable group, constituting an important and susceptible area of evaluation in
primary care.
PMID- 25590896
TI - One-step electroplating porous graphene oxide electrodes of supercapacitors for
ultrahigh capacitance and energy density.
AB - An electroplating method was used for the first time to synthesize 3D porous
graphene oxide (PGO) architectures, exhibiting ultrahigh capacitance and energy
density as electrodes of supercapacitors. Scanning electron microscopy
illustrated the porous structures which promoted the stability and alleviated the
stacking of the graphene oxide layers. As investigated in a three-electrode
supercapacitor cell, PGO electrodes exhibited the maximum capacitance and energy
of 973 F . g(-1) and 98.4 Wh . Kg(-1), which are better than current reports and
comparable to batteries. At 4 A . g(-1) for high-power applications, PGO
electrodes reached a capacitance, energy, and power density of 493 F . g(-1),
49.9 Wh . Kg(-1), and 1700 W . Kg(-1), and they retained ~97.83% of capacitance
after 10 000 charge/discharge processes. Furthermore, when the PGO was bent
exaggeratedly, it still displayed identical properties, which is of important
significance for supporting wearable devices.
PMID- 25590895
TI - Effects of Aspergillus species inoculation and their enzymatic activities on the
formation of volatile components in fermented soybean paste (doenjang).
AB - The volatile components of rice-koji doenjang produced in association with
various Aspergillus species (A. oryzae, A. sojae, and A. kawachii) during 8 weeks
of fermentation were compared using gas chromatography-mass spectrometry analysis
and multivariate statistical analysis. In addition, the activities of diverse
enzymes (alpha-amylase, protease, lipase, and esterase) were determined to
investigate their effects on the formation of volatile compounds. Regardless of
the fungi types, carbonyls including 4-methylheptan-2-one, heptan-2-one, (E)-hept
2-enal, and hexanal were found to contribute mainly to early phase fermentation,
whereas the contents of ethyl esters of long-chained fatty acids were
considerably enhanced in the latter stage of fermentation. With the exception of
alpha-amylase, the activities of the studied enzymes generally increased as
fermentation proceeded, and there were significant differences in enzymes
activities between the species of fungi. The lipase activity was strongly
correlated with the formation of long-chain fatty acid esters, which could be
related to the distinctive organoleptic properties of rice-koji doenjang.
PMID- 25590897
TI - Disorder-to-order transition of MAGI-1 PDZ1 C-terminal extension upon peptide
binding: thermodynamic and dynamic insights.
AB - PDZ domains are highly abundant protein-protein interaction modules commonly
found in multidomain scaffold proteins. The PDZ1 domain of MAGI-1, a protein
present at cellular tight junctions that contains six PDZ domains, is targeted by
the E6 oncoprotein of the high-risk human papilloma virus. Thermodynamic and
dynamic studies using complementary isothermal titration calorimetry and nuclear
magnetic resonance (NMR) (15)N heteronuclear relaxation measurements were
conducted at different temperatures to decipher the molecular mechanism of this
interaction. Binding of E6 peptides to the MAGI-1 PDZ1 domain is accompanied by
an unusually large and negative change in heat capacity (DeltaC(p)) that is
attributed to a disorder-to-order transition of the C-terminal extension of the
PDZ1 domain upon E6 binding. Analysis of temperature-dependent thermodynamic
parameters and (15)N NMR relaxation data of a PDZ1 mutant in which this disorder
to-order transition was abolished allows the unusual thermodynamic signature of
E6 binding to be correlated to local folding of the PDZ1 C-terminal extension.
Comparison of the exchange contributions observed for wild-type and mutant
proteins explains how variation in the solvent-exposed area may compensate for
the loss of conformational entropy and further designates a distinct set of a few
residues that mediate this local folding phenomena.
PMID- 25590898
TI - Healable luminescent self-assembly supramolecular metallogels possessing
lanthanide (Eu/Tb) dependent rheological and morphological properties.
AB - Herein we present the use of lanthanide directed self-assembly formation (Ln(III)
= Eu(III), Tb(III)) in the generation of luminescent supramolecular polymers,
that when swelled with methanol give rise to self-healing supramolecular gels.
These were analyzed by using luminescent and (1)H NMR titrations studies,
allowing for the identification of the various species involved in the subsequent
Ln(III)-gel formation. These highly luminescent gels could be mixed to give a
variety of luminescent colors depending on their Eu(III):Tb(III) stoichiometric
ratios. Imaging and rheological studies showed that these gels prepared using
only Eu(III) or only Tb(III) have different morphological and rheological
properties, that are also different from those determined upon forming gels by
mixing of Eu(III) and Tb(III) gels. Hence, our results demonstrate for the first
time the crucial role the lanthanide ions play in the supramolecular
polymerization process, which is in principle a host-guest interaction, and
consequently in the self-healing properties of the corresponding gels, which are
dictated by the same host-guest interactions.
PMID- 25590899
TI - Embedding cognizance in intellectual development.
AB - This study examined whether cognizance of cognitive processes (i.e., awareness of
the perceptual and inferential origins of knowledge) mediates between basic
processing efficiency functions (i.e., processing speed, attention control, and
working memory) and fluid cognition (e.g., performance on Raven-like matrices)
during development. For this aim, children from 4 to 8 years of age were examined
by various measures addressed to each of these processes. All processes developed
systematically throughout this age period. Structural equation modeling showed
that awareness does have this mediating role, that this mediation is phase
specific based on perceptual awareness and theory of mind during the 5- and 6
year phase and on inferential awareness during the 7- and 8-year phase, and that
it builds up within each developmental cycle. Attention control emerges from,
rather than directs, working memory and largely remains beyond awareness through
the age span studied. Implications for theory of intellectual development are
discussed.
PMID- 25590901
TI - Editorial.
PMID- 25590900
TI - Infant auditory short-term memory for non-linguistic sounds.
AB - This research explores auditory short-term memory (STM) capacity for non
linguistic sounds in 10-month-old infants. Infants were presented with auditory
streams composed of repeating sequences of either 2 or 4 unique instruments
(e.g., flute, piano, cello; 350 or 700 ms in duration) followed by a 500-ms
retention interval. These instrument sequences either stayed the same for every
repetition (Constant) or changed by 1 instrument per sequence (Varying). Using
the head-turn preference procedure, infant listening durations were recorded for
each stream type (2- or 4-instrument sequences composed of 350- or 700-ms notes).
Preference for the Varying stream was taken as evidence of auditory STM because
detection of the novel instrument required memory for all of the instruments in a
given sequence. Results demonstrate that infants listened longer to Varying
streams for 2-instrument sequences, but not 4-instrument sequences, composed of
350-ms notes (Experiment 1), although this effect did not hold when note
durations were increased to 700 ms (Experiment 2). Experiment 3 replicates and
extends results from Experiments 1 and 2 and provides support for a duration
account of capacity limits in infant auditory STM.
PMID- 25590902
TI - Cross-cultural adaptation of Preschool Language Assessment Instrument: Second
Edition.
AB - PURPOSE: In Brazil, formal tools for the evaluation of spoken language are
scarce. Therefore, this study aimed to translate and adapt to Brazilian
Portuguese the Preschool Language Assessment Instrument: Second Edition (PLAI-2).
METHODS: The process of translation and adaptation of this instrument was
conducted in two stages - Stage 1: (1a) translation of the original version to
Brazilian Portuguese, (1b) comparison of the translated versions and synthesis
into a single Portuguese version, (1c) back-translation, (1d) revision of the
translated version; and Step 2: (2a) application of the Portuguese version in a
pilot project with 30 subjects, and (2b) statistical comparison of three age
groups. RESULTS: In the Brazilian version, all items of the original version were
kept. However, it was necessary to modify the application order of one item, and
the change of one picture was suggested in another. The results obtained after
application indicated that the Brazilian version of the PLAI-2 allows us to
distinguish the performance of participants belonging to different age groups,
and that the raw score tends to increase with age. CONCLUSION: Semantic and
syntactic adjustments were required and made to ensure that PLAI-2 would be used
with the same methodological rigor of the original instrument. The adaptation
process observed the theoretical, semantic, and cultural equivalences.
PMID- 25590903
TI - Phonological and semantic verbal fluency: a comparative study in hearing-impaired
and normal-hearing people.
AB - PURPOSE: To compare the performance of hearing-impaired and normal-hearing people
on phonologic and semantic verbal fluency tests. METHODS: A cross-sectional study
was conducted with 48 hearing-impaired adults and 42 individuals (control group)
with no hearing or language complaints. Sociodemographic data were collected, as
well as the characteristics of hearing loss and of the electronic auditory device
(hearing aids or cochlear implant), when relevant. Verbal fluency was tested in
two different tasks: by semantic category (animals) and by phonology (letter F).
RESULTS: Educational level has influenced the results of fluency tests in both
groups, with more evidence in the hearing-impaired subjects (p<0.001). Hearing
impaired subjects showed worse performance in verbal fluency tests when compared
to normal-hearing people in groups with up to 10 years of schooling. In the
comparison of performance in the two tests, both groups showed better results in
the semantic fluency task. CONCLUSION: The hearing-impaired subjects with low
educational level evoked fewer words in semantic and phonologic verbal fluency
tests in comparison to normal-hearing subjects. Educational level is a relevant
issue to the study of verbal fluency in deaf and hearing-impaired people.
PMID- 25590904
TI - School-age children with specific language impairment produce more speech
disfluencies than their peers.
AB - PURPOSE: To compare the occurrence of speech disfluencies during narrative
production in children with specific language impairment (SLI) and their age
matched peers. METHODS: The study included 60 children aged between 7 and 10
years, 40 with typical language development and 20 with SLI. For data collection,
a series of 15 stories was used, each one represented by pictures composed of
four scenes. Narratives were transcripted and the speech disfluencies presented
on them were classified as stuttering-like disfluencies (part-word repetition,
single-syllable word repetition, and dysrhythmic phonation - prolongations,
blocks and broken words) or other disfluencies (interjection, revision/abandoned
utterances, and multisyllable/phrase repetition). The disfluency categories were
compared in each group and its occurrence was also compared between groups.
RESULTS: The occurrence of stuttering-like and other disfluencies did not differ
among children with typical language development, whereas children with SLI
produced other disfluencies. Between-group comparison showed that children with
SLI produced more disfluencies of both types than their age-matched peers.
CONCLUSION: Children with SLI showed more speech disfluencies during narrative
production than their age-matched peers, and the most common disfluencies used by
them were not typical of people who stutter (interjection, revision/abandoned
utterances, and multisyllable/phrase repetition).
PMID- 25590905
TI - Fluency profile: comparison between Brazilian and European Portuguese speakers.
AB - The purpose of the study was to compare the speech fluency of Brazilian
Portuguese speakers with that of European Portuguese speakers. The study
participants were 76 individuals of any ethnicity or skin color aged 18-29 years.
Of the participants, 38 lived in Brazil and 38 in Portugal. Speech samples from
all participants were obtained and analyzed according to the variables of
typology and frequency of speech disruptions and speech rate. Descriptive and
inferential statistical analyses were performed to assess the association between
the fluency profile and linguistic variant variables. We found that the speech
rate of European Portuguese speakers was higher than the speech rate of Brazilian
Portuguese speakers in words per minute (p=0.004). The qualitative distribution
of the typology of common dysfluencies (p<0.001) also discriminated between the
linguistic variants. While a speech fluency profile of European Portuguese
speakers is not available, speech therapists in Portugal can use the same speech
fluency assessment as has been used in Brazil to establish a diagnosis of
stuttering, especially in regard to typical and stuttering dysfluencies, with
care taken when evaluating the speech rate.
PMID- 25590906
TI - Correlation between sleep and quality of life in cerebral palsy.
AB - PURPOSE: To investigate and correlate the sleep pattern and quality of life in
individuals with cerebral palsy (CP) compared to healthy controls. METHODS:
Seventy-eight subjects (aged 4-18 years, both genders) comprised two groups: CP,
composed of 43 individuals with CP, and control, composed of 35 individuals
without neurodevelopmental disorders. General Sleep Habits Questionnaire, Sleep
Disturbance Scale for Children, sleep diary, Child Health Questionnaire, and
Children's Quality of Life Scale were used. RESULTS: This study identified that
60.5% individuals with CP had sleep disorders. The respiratory disorders (25.6%)
and the sleep hyperhidrosis (34.9%) were the most common disturbances in the
group with CP. Moreover, 23.2% individuals of the group with CP reported awaking
in the middle of the night and 37.2% of them snore, both percentages were higher
than those in the control group. The sleep diary showed that individuals in the
group with CP spend more time to initiate sleep (around 21 minutes). The group
with CP also showed deficits in all parameters analyzed by the Child Health
Questionnaire, except in family activity and the sleep-wake pattern, and quality
of life showed negative correlation in several respects. CONCLUSION: The altered
pattern of sleep in individuals with CP directly affects their physical and
emotional well-being.
PMID- 25590907
TI - Verification of the therapeutic process in cleft patients.
AB - PURPOSE: This study was conducted to verify the origin of a longer or even failed
therapeutic process in patients with cleft lip and palate as to its difficulty.
METHODS: Eighteen children undergoing therapeutic process were observed for at
least 6 months and divided into two groups: presenting isolated cleft lip and
palate (group I) and having been diagnosed by a Speech-Language Pathologist with
reading and writing disorders, with manifestation of phonological awareness
deficit (group II). Two tests were applied for the evaluation of speech and
language: ABFW Language Test for Young Children (phonology) and Phonological
Awareness: Instrument of Sequential Assessment (CONFIAS). RESULTS: Group I
presented higher percentages in ABFW test than group II, except in the
"simplification of consonant cluster" and "plosive devoicing" variables. It was
also observed that, in the process of omission, group I hardly omits the vibrant
consonant, as observed in group II. At the syllable level of CONFIAS, the
percentages observed in group I tended to be higher than in group II, with the
exception of the following tasks: "medial syllable," "production of rhyme," and
"exclusion." At the phoneme level, the percentages observed in group II tended to
be higher than in group I, with the exception of the following tasks: "starts
with given sound," "exclusion," "synthesis," and "segmentation." No significant
difference was observed between percentage distributions in groups I and II
(p>0.118). CONCLUSIONS: The differences found between groups I and II, although
not statistically significant, may suggest that the presence of malformation
hinders speech and language acquisition and development and prolongs the
therapeutic process if directive interventions are not carried out, including
phonological awareness therapy.
PMID- 25590908
TI - Myofunctional orofacial examination: comparative analysis in young adults with
and without complaints.
AB - PURPOSE: To verify myofunctional orofacial characteristics in young adults and to
compare data on individuals with and without myofunctional complaints, aiming to
identify the main myofunctional problems and differentiating them from
characteristics that are common for this population, as well as to list items for
myofunctional evaluation in this population. METHODS: Cross-sectional study with
85 adult participants, aged between 19 and 39 years, selected through consecutive
sampling at the Department of Speech, Language and Hearing Sciences of
Universidade Veiga de Almeida. The participants were divided into two groups: G1
(comprising 50 individuals referred for orofacial myofunctional disorders) and G2
(comprising 35 volunteers without complaints). Descriptive evaluation of
craniofacial structures of hard and soft tissues, kinesiology and mandible range
of motion and functional patterns of breathing, chewing, and swallowing was
applied. Three expert Speech-Language pathologists assessed all participants.
Statistical analysis was done using chi2-test, Student's t-test, or Mann-Whitney
test. The reliability level was 99%. RESULTS: A predominance of Angle Class I
pattern of occlusions for G2 (p<0.0001) was found. G1 showed (p<0.0001) mandible
movements with deviations and joint noises, amplitude reduction in lateral and
protrusive movements, unilateral chewing, nonexpected muscle contraction,
temporomandibular joint noises, swallowing with excessive contraction of the
orbicularis oris muscle, loud noise, and residues (p=0.006). CONCLUSION: The main
myofunctional orofacial alterations in young adults with complaints refer to
changes of the mandibular movements and patterns of chewing or of swallowing,
reflecting the main items of the clinical evaluation. Many items of assessment
and characterization do not differ between the groups, and these should be
analyzed regarding their relevance.
PMID- 25590909
TI - Correlation between the reason for referral, clinical, and objective assessment
of the risk for dysphagia.
AB - PURPOSE: To correlate the reason for referral to speech therapy service at a
university hospital with the results of clinical and objective assessment of risk
for dysphagia. METHODS: This is a cross-sectional, observational, retrospective
analytical and quantitative study. The data were gathered from the database, and
the information used was the reason for referral to speech therapy service,
results of clinical assessment of the risk for dysphagia, and also from
swallowing videofluoroscopy. RESULTS: There was a mean difference between the
variables of the reason for the referral, results of the clinical and objective
swallowing assessments, and scale of penetration/aspiration, although the values
were not statistically significant. Statistically significant correlation was
observed between clinical and objective assessments and the penetration scale,
with the largest occurring between the results of objective assessment and
penetration scale. CONCLUSION: There was a correlation between clinical and
objective assessments of swallowing and mean difference between the variables of
the reason for the referral with their respective assessment. This shows the
importance of the association between the data of patient's history and results
of clinical evaluation and complementary tests, such as videofluoroscopy, for
correct identification of the swallowing disorders, being important to combine
the use of severity scales of penetration/aspiration for diagnosis.
PMID- 25590910
TI - Evaluation of the location of capsules swallowed with food during the pharyngeal
phase triggering in asymptomatic adults.
AB - OBJECTIVE: To assess the location of hard gelatin capsules in the pharyngeal
phase triggering among asymptomatic adults. INTRODUCTION: The location of the
bolus during the pharyngeal phase triggering provides information about the
sensorimotor model of the beginning of deglutition onset. PURPOSE: To evaluate
the location of hard gelatin capsules in the pharyngeal phase triggering among
asymptomatic adults. METHODS: A videofluoroscopy swallowing study was carried out
in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years,
who were evaluated with hard gelatin capsules #00 and #3 containing barium
sulfate, swallowed with liquid food and pudding, in free volume. The first
laryngeal elevation movement was the criterion to locate the pharyngeal phase
triggering. Statistical analysis was based on the McNemar test. RESULTS: Capsule
#3 presented higher percentage of location in the tongue dorsum compared to
capsule #00, and capsule #00 presented higher percentage of location in the
tongue base and vallecula compared to capsule #3. There was a difference between
different capsules swallowed with liquid (p=0.016) and pudding (p=0.037).
CONCLUSION: The capsule size influenced the location of the pharyngeal phase
triggering. Smaller capsules started pharyngeal phase in the most anterior region
(tongue dorsum) compared to larger capsules.
PMID- 25590911
TI - Remote programming of cochlear implants.
AB - PURPOSE: To verify the effectiveness of remote programming of cochlear implants
by stimulation levels and results in the perception of speech and free-field
audiometry tests. METHODS: Twelve patients from both genders, aged between 18 and
59 years, users of internal cochlear implant and speech processor of the same
model for at least 12 months, were selected. Both the remote programming (RP) and
the live programming (LP) were performed on the same day, measuring the minimum
(T) and maximum (C) stimulation levels of five electrodes with the interpolation
of the remaining ones. Speech perception tests were applied using 65 dBSPL
(recorded open context sentences and monosyllables). The patients were submitted
to free-field audiometry at 250-8,000 Hz frequencies. The results for the RP and
LP were compared. RESULTS: Differences in mean of the T levels for three
electrodes and the C levels for one electrode were found. No difference between
the results was obtained in the speech perception tests and audiometric
thresholds in the RP and LP. CONCLUSION: The RP is a simple and effective
procedure for programming cochlear implant devices and, although there were
differences in the stimulation levels of some electrodes, it did not interfere in
the speech perception outcomes.
PMID- 25590912
TI - Parental perspectives of children using cochlear implant.
AB - PURPOSE: To evaluate the parents' perspective with regard to evolution of their
child with cochlear implant (CI). METHODS: This was a cross-sectional prospective
study conducted at the Centro de Pesquisas Audiologicas of Hospital de
Reabilitacao de Anomalias Craniofaciais of Universidade de Sao Paulo. The
selection of the sample was performed from the spontaneous demand, among the
months from July to December 2011. The final sample comprised 50 parents or
guardians of children using CI, with minimum 1 year and maximum of 3 years of
device use. The translated and adapted to Brazilian Portuguese version of the
questionnaire "Perspectives of parents of children with cochlear implants" was
applied. This instrument consists of 74 questions and allows quantification of
the parents' perspective on subscales that illustrate the situation of the child
and family. Each question has five options scored from one to five responses. The
Spearman test for comparison of results between the subscales was applied.
RESULTS: The social relationships, self-sufficiency, and communication subscales
showed the highest mean score, whereas the worst score was for child support
subscale, reflecting the independence and autonomy of the patients. The
correlation between the child subscales was realized, and the results showed
themselves significant and positive for communication subscale of communication
with all others subscales. The family subscales also had a positive correlation
with the communication, education, and self-sufficiency. CONCLUSION: These
results demonstrate that parents have good expectations regarding communication,
independence, and social participation of children after CI surgery, and this
questionnaire is a useful tool for use in clinical practice.
PMID- 25590913
TI - Auditory temporal abilities in children with history of recurrent otitis media in
the first years of life and persistent in preschool and school ages.
AB - PURPOSE: To study the temporal auditory ordering and resolution abilities in
children with and without a history of early OME and ROME, as well as to study
the responses according to age. METHODS: A total of 59 children were evaluated,
and all of them presented pure tone thresholds within the normal range at the
time of the conduction of the hearing tests. The children were divided into two
groups according to the occurrence of episodes of recurrent otitis media. Then,
each group was divided into two subgroups according to age: 7- and 8-year olds,
and 9- and 10-year olds. All children were assessed with standard tests of
temporal frequency (ordination) and gaps-in-noise (resolution). RESULTS: For the
temporal abilities studied, children with a history of otitis media presented
significantly lower results compared to the control group. In the frequency
pattern test, the correct answers increased with age in both groups. In the
identification of silence intervals, the control group showed no change in
threshold regarding to age, but this change was present in the group with a
history of otitis media. CONCLUSION: Episodes of otitis media with effusion in
the first year of life, recurrent and persistent in preschool and school ages,
negatively influence the temporal ordering and resolution abilities.
PMID- 25590914
TI - Cognitive Vocal Program applied to individuals with signals presbylarynx:
preliminary results.
AB - PURPOSE: To propose and verify the feasibility of a vocal program intervention in
patients with presbylarynx signs with or without vocal complaints. METHOD: Among
20 elder participants of the current research, 3 female patients with median age
of 67 years were chosen for the pilot study. Laryngological examination, vocal
recording with CAPE-V (Consensus Auditory-Perceptual Evaluation of Voice)
protocol, and Screening Protocol of Risk of Dysphonia (SPRD) were conducted
before and after the program intervention. They joined the Cognitive Vocal
Program for presbyphonia based on the genetic epistemology by Jean Piaget
associated with vocal techniques based on scientific literature. This program is
structured with six sessions and each one of them is focused in different aspects
of vocal production. RESULTS: After the program intervention, some aspects such
as loudness, coordination between breathing and speaking, accuracy in
articulatory movements, jitter, and harmonics-to-noise ratio improved with
parameters within the expected range for the age group. Three female participants
were observed for better vocal quality, higher fundamental frequency, and better
maximum phonation time. In two cases, tension related to loudness elevation and
better scores on SPRD was observed. Using by high-speed laryngeal image, we also
observed reduction of presbylarynx signs, and remarkable improvement in glottis
closure competence and mucosal wave movement of the patients with and without
vocal complaints. CONCLUSION: The preliminary results suggest encouraging
prospects for the proposal with improvement in the aspects analyzed. This program
was well designed and did not require any further adjustments.
PMID- 25590915
TI - Phonological processing deficits as a universal model for dyslexia: evidence from
different orthographies.
AB - PURPOSE: To verify the universal nature of the phonological processing deficit
hypothesis for dyslexia, since the most influential studies on the topic were
conducted in children or adults speakers of English. RESEARCH STRATEGY: A
systematic review was designed, conducted and analyzed using PubMed, Science
Direct, and SciELO databases. SELECTION CRITERIA: The literature search was
conducted using the terms "phonological processing" AND "dyslexia" in
publications of the last ten years (2004-2014). DATA ANALYSIS: Following
screening of (a) titles and abstracts and (b) full papers, 187 articles were
identified as meeting the pre-established inclusion criteria. RESULTS: The
phonological processing deficit hypothesis was explored in studies involving
several languages. More importantly, we identify studies in all types of writing
systems such as ideographic, syllabic and logographic, as well as alphabetic
orthography, with different levels of orthography-phonology consistency.
CONCLUSION: The phonological processing hypothesis was considered as a valid
explanation to dyslexia, in a wide variety of spoken languages and writing
systems.
PMID- 25590916
TI - Ultrasound applicability in Speech Language Pathology and Audiology.
AB - PURPOSE: To present recent studies that used the ultrasound in the fields of
Speech Language Pathology and Audiology, which evidence possibilities of the
applicability of this technique in different subareas. RESEARCH STRATEGY: A
bibliographic research was carried out in the PubMed database, using the keywords
"ultrasonic," "speech," "phonetics," "Speech, Language and Hearing Sciences,"
"voice," "deglutition," and "myofunctional therapy," comprising some areas of
Speech Language Pathology and Audiology Sciences. The keywords "ultrasound,"
"ultrasonography," "swallow," "orofacial myofunctional therapy," and "orofacial
myology" were also used in the search. SELECTION CRITERIA: Studies in humans from
the past 5 years were selected. In the preselection, duplicated studies, articles
not fully available, and those that did not present direct relation between
ultrasound and Speech Language Pathology and Audiology Sciences were discarded.
DATA ANALYSIS: The data were analyzed descriptively and classified subareas of
Speech Language Pathology and Audiology Sciences. The following items were
considered: purposes, participants, procedures, and results. RESULTS: We selected
12 articles for ultrasound versus speech/phonetics subarea, 5 for ultrasound
versus voice, 1 for ultrasound versus muscles of mastication, and 10 for
ultrasound versus swallow. Studies relating "ultrasound" and "Speech Language
Pathology and Audiology Sciences" in the past 5 years were not found. CONCLUSION:
Different studies on the use of ultrasound in Speech Language Pathology and
Audiology Sciences were found. Each of them, according to its purpose, confirms
new possibilities of the use of this instrument in the several subareas, aiming
at a more accurate diagnosis and new evaluative and therapeutic possibilities.
PMID- 25590917
TI - Vocal self-assessment: relation with the type of instrument, gender, age, and
profession in individuals without vocal complaints.
AB - OBJECTIVE: To obtain the vocal self-assessment rates of individuals without vocal
complaints and relate them to gender, occupation, and age range. METHODS: This is
an observational, analytical, and cross-sectional study. In this study, 601
individuals without vocal complaints, 241 men and 360 women, aged between 18 and
59 years (mean of 30.1 years) were included. The individuals were divided into
following age groups: 18-29 years (n=353; 58.7%), 30-44 years (n=159; 26.5%), and
45-59 years (n=89; 14.8%); 136 individuals (22.6%) were voice professionals and
465 (77.4%) were nonprofessionals. The individuals answered a questionnaire with
identification data and the protocols Voice-Related Quality of Life (V-RQOL),
Voice Handicap Index (VHI), and Voice Activity and Participation Profile (VAPP).
The data were statistically analyzed. RESULTS: Mean scores obtained in the V
RQOL, VHI, and VAPP were 95.5, 5.37, and 3.06, respectively. If we transfer these
values to the base 100, differences were found in the scores of the VHI and VAPP.
Women presented significantly lower scores in the V-RQOL and VHI. Moreover, there
were no differences in the mean scores obtained by the different age groups.
Regarding professional vocal use, there were differences in the VHI and VAPP, and
the "nonprofessionals" presented lower VHI than professionals. CONCLUSION: The
type of the instrument, gender, and profession variables can influence the vocal
self-assessment results.
PMID- 25590918
TI - Cross-cultural adaptation of the Brazilian version of the protocol Evaluation of
the Ability to Sing Easily.
AB - PURPOSE: To present the cross-cultural equivalence of the Brazilian version of
the Evaluation of the Ability to Sing Easily (EASE) protocol, through its
cultural and linguistic adaptation. METHODS: After the EASE was translated to
Brazilian Portuguese, the back-translation into English was done. The items of
the translated version were compared with the original instrument and the
discrepancies were modified by consensus of a committee composed of five speech
language pathologists. The Evaluation of the Ability to Sing Easily for Brazil
(EASE-BR) has 22 questions with four alternatives: "no," "mildly," "moderately,"
and "extremely." The score is obtained by the simple sum of all answers. The
three positive items (6, 12, and 21) require reverse score. For cultural
equivalence, the EASE-BR was applied with 41 Brazilian singers, with an extra
item in the answer key - "not applicable." The aim of this extra key was to
identify issues that might not have been understood or were not appropriate for
the target population and the Brazilian culture. RESULTS: Of the 32 singers, 5
who were initially evaluated had difficulties to answer 3 of the 22 questions.
Therefore, the adaptation of those sentences was necessary. Afterward, the
modified EASE-BR was applied to nine singers, and no more cultural and/or
conceptual barriers were found. CONCLUSION: Cultural equivalence was observed
between EASE and its translated version to the Brazilian Portuguese, the EASE-BR.
Validation of the EASE for Brazilian Portuguese is in progress.
PMID- 25590919
TI - Surface layering properties of Intralipid phantoms.
AB - Intralipid has become an extensively studied and widely used reference and
calibration phantom for diffuse optical imaging technologies. In this study we
call attention to the layering properties of Intralipid emulsions, which are
commonly assumed to have homogeneous optical properties. By measurement of
spatial frequency domain reflectance in combination with an analytical solution
of the radiative transfer equation for two-layered media, we make quantitative
investigations on the formation of a surface layer on different dilutions of
Intralipid. Our findings are verified by an independent spatially resolved
reflectance setup giving evidence of a time dependent, thin and highly scattering
surface layer on top of Intralipid-water emulsions. This layer should be
considered when using Intralipid as an optical calibration or reference phantom.
PMID- 25590920
TI - More screen operation than calling: the results of observing cyclists' behaviour
while using mobile phones.
AB - Operating a mobile telephone while riding a bicycle is fairly common practice in
the Netherlands, yet it is unknown if this use is stable or increasing. As such,
whether the prevalence of mobile phone use while cycling has changed over the
past five years was studied via on-road observation. In addition the impact of
mobile phone use on lateral position, i.e. distance from the front wheel to the
curb, was also examined to see if it compared to the results seen in previous
experimental studies. Bicyclists were observed at six different locations and
their behaviour was scored. It was found that compared to five years ago the use
of mobile phones while cycling has changed, not in frequency, but in how cyclists
were operating their phones. As found in 2008, three percent of the bicyclists
were observed to be operating a phone, but a shift from calling (0.7% of cyclists
observed) to operating (typing, texting, 2.3% of cyclists) was found. In 2008
nearly the complete opposite usage was observed: 2.2% of the cyclists were
calling and 0.6% was texting. Another finding was that effects on lateral
position were similar to those seen in experimental studies in that cyclists
using a phone maintained a cycling position which was further away from the curb.
It was also found that when at an intersection, cyclist's operating their phone
made less head movements to the right than cyclists who were just cycling. This
shift from calling to screen operation, when combined with the finding related to
reduced head movements at intersections, is worrying and potentially dangerous.
PMID- 25590921
TI - Young driver licensing: examination of population-level rates using New Jersey's
state licensing database.
AB - Recent surveys have provided insight on the primary reasons why US teens delay
licensure but are limited in their ability to estimate licensing rates and
trends. State administrative licensing data are the ideal source to provide this
information but have not yet been analyzed for this purpose. Our objective was to
analyze New Jersey's (NJ) licensing database to: (1) describe population-based
rates of licensure among 17- to 20-year-olds, overall and by gender and zip code
level indicators of household income, population density, and race/ethnicity; and
(2) examine recent trends in licensure. We obtained records on all licensed NJ
drivers through June 2012 from the NJ Motor Vehicle Commission's licensing
database and determined each young driver's age at the time of intermediate and
full licensure. Data from the US Census and American Community Survey were used
to estimate a fixed cohort of NJ residents who turned 17 years old in 2006-2007
(n=255,833). Licensing data were used to estimate the number of these drivers who
obtained an intermediate license by each month of age (numerators) and, among
those who obtained an intermediate license, time to graduation to full licensure.
Overall, 40% of NJ residents-and half of those who ultimately obtained a license
by age 21-were licensed within a month of NJ's minimum licensing age of 17, 64%
by their 18th birthday, and 81% by their 21st birthday. Starkly different
patterns of licensure were observed by socioeconomic indicators; for example, 65%
of 17-year-olds residing in the highest-income zip codes were licensed in the
first month of eligibility compared with 13% of residents living in the lowest
income zip codes. The younger an individual obtained their intermediate license,
the earlier they graduated to a full license. Finally, the rate and timing of
licensure in NJ has been relatively stable from 2006 to 2012, with at most a 1-3%
point decline in rates. These findings support the growing body of literature
suggesting that teens delay licensure primarily for economic reasons and that a
substantial proportion of potentially high-risk teens may be obtaining licenses
outside the auspices of a graduated driver licensing system. Finally, our finding
of a relatively stable trend in licensure in recent years is in contrast to
national-level reports of a substantial decline in licensure rates.
PMID- 25590922
TI - Atrial septal defect in adults: does repair always mean cure?
PMID- 25590923
TI - Effectiveness of biomarkers in cardiology.
PMID- 25590925
TI - Value of the Qrs-T angle in predicting the induction of ventricular
tachyarrhythmias in patients with Chagas disease.
AB - BACKGROUND: The QRS-T angle correlates with prognosis in patients with heart
failure and coronary artery disease, reflected by an increase in mortality
proportional to an increase in the difference between the axes of the QRS complex
and T wave in the frontal plane. The value of this correlation in patients with
Chagas heart disease is currently unknown. OBJECTIVE: Determine the correlation
of the QRS-T angle and the risk of induction of ventricular tachycardia /
ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in
patients with Chagas disease. METHODS: Case-control study at a tertiary center.
Patients without induction of VT / VF on EPS were used as controls. The QRS-T
angle was categorized as normal (0-105o), borderline (105-135o) or abnormal (135
180o). Differences between groups for continuous variables were analyzed with the
t test or Mann-Whitney test, and for categorical variables with Fisher's exact
test. P values < 0.05 were considered significant. RESULTS: Of 116 patients
undergoing EPS, 37.9% were excluded due to incomplete information / inactive
records or due to the impossibility to correctly calculate the QRS-T angle
(presence of left bundle branch block and atrial fibrillation). Of 72 patients
included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was
normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients
without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%,
borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients
with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of
inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio
(OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for
other variables such as age, ejection fraction (EF) and QRS size, there was a
trend for the abnormal QRS-T angle to identify patients with increased risk of
inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also
emerged as a predictor of induction of VT / VF: for each point increase in EF,
there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS.
CONCLUSIONS: Changes in the QRS-T angle and decreases in EF were associated with
an increased risk of induction of VT / VF on EPS.
PMID- 25590924
TI - Biomarkers in cardiology--part 1--in heart failure and specific cardiomyopathies.
AB - Cardiovascular diseases are the leading causes of mortality and morbidity in
Brazil. The primary and secondary preventions of those diseases are a priority
for the health system and require multiple approaches to increase their
effectiveness. Biomarkers are tools used to more accurately identify high-risk
individuals, to speed the diagnosis, and to aid in treatment and prognosis
determination. This review aims to highlight the importance of biomarkers in
clinical cardiology practice, and to raise relevant points of their use and the
promises for the coming years. This document was divided into two parts, and this
first one discusses the use of biomarkers in specific cardiomyopathies and heart
failure.
PMID- 25590926
TI - Late outcome of a randomized study on oral magnesium for premature complexes.
AB - BACKGROUND: Ventricular and supraventricular premature complexes (PC) are
frequent and usually symptomatic. According to a previous study, magnesium
pidolate (MgP) administration to symptomatic patients can improve the PC density
and symptoms. OBJECTIVE: To assess the late follow-up of that clinical
intervention in patients treated with MgP or placebo. METHODS: In the first phase
of the study, 90 symptomatic and consecutive patients with PC were randomized
(double-blind) to receive either MgP or placebo for 30 days. Monthly follow-up
visits were conducted for 15 months to assess symptoms and control electrolytes.
24-hour Holter was performed twice, regardless of symptoms, or whenever symptoms
were present. In the second phase of the study, relapsing patients, who had
received MgP or placebo (crossing-over) in the first phase, were treated with MgP
according to the same protocol. RESULTS: Of the 45 patients initially treated
with MgP, 17 (37.8%) relapsed during the 15-month follow-up, and the relapse time
varied. Relapsing patients treated again had a statistically significant
reduction in the PC density of 138.25/hour (p < 0.001). The crossing-over
patients reduced it by 247/hour (p < 0.001). Patients who did not relapse, had a
low PC frequency (3 PC/hour). Retreated patients had a 76.5% improvement in
symptom, and crossing-over patients, 71.4%. CONCLUSION: Some patients on MgP had
relapse of symptoms and PC, indicating that MgP is neither a definitive nor a
curative treatment for late follow-up. However, improvement in the PC frequency
and symptoms was observed in the second phase of treatment, similar to the
response in the first phase of treatment.
PMID- 25590927
TI - Prevalence of dyslipidemia according to the nutritional status in a
representative sample of Sao Paulo.
AB - BACKGROUND: Overweight is one of the major public health problems in Brazil; it
is associated with dyslipidemia, which is an important risk factor for
cardiovascular diseases. OBJECTIVE: To evaluate the lipid profile of residents of
the municipality of Sao Paulo, state of Sao Paulo, according to the nutritional
status. METHODS: Data from the population-based cross-sectional study ISA-Capital
2008 on a sample of residents of Sao Paulo were used. Participants were
categorized into groups according to body mass index and age range. The levels of
total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and non-HDL
cholesterol were measured. The association between lipid profile, nutricional
status, and waist circumference was investigated. The data were processed using
the survey mode of the Stata 11.0 software. RESULTS: The prevalence of any type
of dyslipidemia in the population was 59.74%, with low HDL-cholesterol
dyslipidemia being the most common type. Not overweight individuals had higher
mean levels of HDL-cholesterol and lower levels of LDL-cholesterol, total
cholesterol, triglycerides, and non-HDL cholesterol when compared with the
overweight group. The rate of inadequacy of these variables was higher in the
overweight individuals, regardless of the age group, to the exception of LDL
cholesterol in the adults and elderly. A higher prevalence of isolated
hypertriglyceridemia was observed in individuals with higher waist circumference
among the adults and the total population. CONCLUSION: The results indicate an
association between dyslipidemia and overweight in the population of the city of
Sao Paulo. The most prevalent dyslipidemia in this population was low HDL
cholesterol.
PMID- 25590928
TI - Impact of atrial fibrillation ablation on left ventricular filling pressure and
left atrial remodeling.
AB - BACKGROUND: Left ventricular (LV) diastolic dysfunction is associated with new
onset atrial fibrillation (AF), and the estimation of elevated LV filling
pressures by E/e' ratio is related to worse outcomes in patients with AF.
However, it is unknown if restoring sinus rhythm reverses this process.
OBJECTIVE: To evaluate the impact of AF ablation on estimated LV filling
pressure. METHODS: A total of 141 patients underwent radiofrequency (RF) ablation
to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days
before and 12 months after ablation. LV functional parameters, left atrial volume
index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and
E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was
present in 102 patients, and long-standing persistent AF in 21 patients. Follow
up included electrocardiographic examination and 24-h Holter monitoring at 3, 6,
and 12 months after ablation. RESULTS: One hundred seventeen patients (82.9%)
were free of AF during the follow-up (average, 18 +/- 5 months). LAVind reduced
in the successful group (30.2 mL/m(2) +/- 10.6 mL/m(2) to 22.6 mL/m(2) +/- 1.1
mL/m(2), p < 0.001) compared to the non-successful group (37.7 mL/m(2) +/- 14.3
mL/m(2) to 37.5 mL/m(2) +/- 14.5 mL/m(2), p = ns). Improvement of LV filling
pressure assessed by a reduction in the E/e' ratio was observed only after
successful ablation (11.5 +/- 4.5 vs. 7.1 +/- 3.7, p < 0.001) but not in patients
with recurrent AF (12.7 +/- 4.4 vs. 12 +/- 3.3, p = ns). The success rate was
lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001).
CONCLUSION: Successful AF ablation is associated with LA reverse remodeling and
an improvement in LV filling pressure.
PMID- 25590929
TI - Comparison of cardiovascular risk factors in different areas of health care over
a 20-year period.
AB - BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death
worldwide. Knowledge about cardiovascular risk factors (CVRFs) in young adults
and their modification over time are measures that change the risks and prevent
CVDs. OBJECTIVES: To determine the presence of CVRFs and their changes in
different health care professionals over a period of 20 years. METHODS: All
students of medicine, nursing, nutrition, odontology, and pharmacy departments of
Federal University of Goias who agreed to participate in this study were
evaluated when they started their degree courses and 20 years afterward.
Questionnaires on CVRFs [systemic arterial hypertension (SAH), diabetes mellitus,
dyslipidemia, and family history of early CVD, smoking, alcohol consumption, and
sedentarism] were administered. Cholesterol levels, blood sugar levels, blood
pressure, weight, height, and body mass index were determined. The Kolmogorov
Smirnov test was used to evaluate distribution, the chi-square test was used to
compare different courses and sexes, and the McNemar test was used for comparing
CVRFs. The significance level was set at a p value of < 0.05. RESULTS: The first
stage of the study included 281 individuals (91% of all the students), of which
62.9% were women; the mean age was 19.7 years. In the second stage, 215 subjects
were reassessed (76% of the initial sample), of which 59.07% were women; the mean
age was 39.8 years. The sample mostly consisted of medical students (with a
predominance of men), followed by nursing, nutrition, and pharmacy students, with
a predominance of women (p < 0.05). Excessive weight gain, SAH, and dyslipidemia
were observed among physicians and dentists (p < 0.05). Excessive weight gain and
SAH and a reduction in sedentarism (p < 0.05) were observed among pharmacists.
Among nurses there was an increase in excessive weight and alcohol consumption (p
< 0.05). Finally, nutritionists showed an increase in dyslipidemia (p < 0.05).
CONCLUSION: In general, there was an unfavorable progression of CVRFs in the
population under study, despite it having adequate specialized knowledge about
these risk factors.
PMID- 25590930
TI - Improving post-discharge medication adherence in patients with CVD: a pilot
randomized trial.
AB - BACKGROUND: Effective interventions to improve medication adherence are usually
complex and expensive. OBJECTIVE: To assess the impact of a low-cost intervention
designed to improve medication adherence and clinical outcomes in post-discharge
patients with CVD. METHOD: A pilot RCT was conducted at a teaching hospital.
Intervention was based on the four-item Morisky Medication Adherence Scale (MMAS
4). The primary outcome measure was medication adherence assessed using the eight
item MMAS at baseline, at 1 month post hospital discharge and re-assessed 1 year
after hospital discharge. Other outcomes included readmission and mortality
rates. RESULTS: 61 patients were randomized to intervention (n = 30) and control
(n = 31) groups. The mean age of the patients was 61 years (SD 12.73), 52.5% were
males, and 57.4% were married or living with a partner. Mean number of prescribed
medications per patient was 4.5 (SD 3.3). Medication adherence was correlated to
intervention (p = 0.04) and after 1 month, 48.4% of patients in the control group
and 83.3% in the intervention group were considered adherent. However, this
difference decreased after 1 year, when adherence was 34.8% and 60.9%,
respectively. Readmission and mortality rates were related to low adherence in
both groups. CONCLUSION: The intervention based on a validated patient self
report instrument for assessing adherence is a potentially effective method to
improve adherent behavior and can be successfully used as a tool to guide
adherence counseling in the clinical visit. However, a larger study is required
to assess the real impact of intervention on these outcomes.
PMID- 25590931
TI - Association between angiotensin-converting enzyme inhibitors and troponin in
acute coronary syndrome.
AB - BACKGROUND: Cardiovascular disease is the leading cause of mortality in the
western world and its treatment should be optimized to decrease severe adverse
events. OBJECTIVE: To determine the effect of previous use of angiotensin
converting enzyme inhibitors on cardiac troponin I measurement in patients with
acute coronary syndrome without ST-segment elevation and evaluate clinical
outcomes at 180 days. METHODS: Prospective, observational study, carried out in a
tertiary center, in patients with acute coronary syndrome without ST-segment
elevation. Clinical, electrocardiographic and laboratory variables were analyzed,
with emphasis on previous use of angiotensin-converting enzyme inhibitors and
cardiac troponin I. The Pearson chi-square tests (Pereira) or Fisher's exact test
(Armitage) were used, as well as the non-parametric Mann-Whitney's test.
Variables with significance levels of <10% were submitted to multiple logistic
regression model. RESULTS: A total of 457 patients with a mean age of 62.1 years,
of whom 63.7% were males, were included. Risk factors such as hypertension
(85.3%) and dyslipidemia (75.9%) were the most prevalent, with 35% of diabetics.
In the evaluation of events at 180 days, there were 28 deaths (6.2%). The
statistical analysis showed that the variables that interfered with troponin
elevation (> 0.5 ng / mL) were high blood glucose at admission (p = 0.0034) and
ST-segment depression >= 0.5 mm in one or more leads (p = 0.0016). The use of
angiotensin-converting inhibitors prior to hospitalization was associated with
troponin <= 0.5 ng / mL (p = 0.0482). The C-statistics for this model was 0.77.
CONCLUSION: This study showed a correlation between prior use of angiotensin
converting enzyme inhibitors and reduction in the myocardial necrosis marker
troponin I in patients admitted for acute coronary syndrome without ST-segment
elevation. However, there are no data available yet to state that this reduction
could lead to fewer severe clinical events such as death and re-infarction at 180
days.
PMID- 25590932
TI - Autologous transplantation of bone marrow adult stem cells for the treatment of
idiopathic dilated cardiomyopathy.
AB - BACKGROUND: Morbimortality in patients with dilated idiopathic cardiomyopathy is
high, even under optimal medical treatment. Autologous infusion of bone marrow
adult stem cells has shown promising preliminary results in these patients.
OBJECTIVE: Determine the effectiveness of autologous transplantation of bone
marrow adult stem cells on systolic and diastolic left ventricular function, and
on the degree of mitral regurgitation in patients with dilated idiopathic
cardiomyopathy in functional classes NYHA II and III. METHODS: We administered
4,54 x 10(8) +/- 0,89 x 10(8) bone marrow adult stem cells into the coronary
arteries of 24 patients with dilated idiopathic cardiomyopathy in functional
classes NYHA II and III. Changes in functional class, systolic and diastolic left
ventricular function and degree of mitral regurgitation were assessed after 3
months, 6 months and 1 year. RESULTS: During follow-up, six patients (25%)
improved functional class and eight (33.3%) kept stable. Left ventricular
ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p =
0.024; 0.017 and 0.018), respectively. There were no significant changes neither
in diastolic left ventricular function nor in mitral regurgitation degree. A
combined cardiac resynchronization and implantable cardioversion defibrillation
was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and
four patients died due to terminal cardiac failure. Average survival of these
eight patients was 2.6 years. CONCLUSION: Intracoronary infusion of bone marrow
adult stem cells was associated with an improvement or stabilization of
functional class and an improvement in left ventricular ejection fraction,
suggesting the efficacy of this intervention. There were no significant changes
neither in left ventricular diastolic function nor in the degree of mitral
regurgitation.
PMID- 25590936
TI - Case 6/2014--A case of a 61-year-old woman with diastolic heart failure.
PMID- 25590933
TI - Focused cardiac ultrasound using a pocket-size device in the emergency room.
AB - BACKGROUND: Cardiovascular urgencies are frequent reasons for seeking medical
care. Prompt and accurate medical diagnosis is critical to reduce the morbidity
and mortality of these conditions. OBJECTIVE: To evaluate the use of a pocket
size echocardiography in addition to clinical history and physical exam in a
tertiary medical emergency care. METHODS: One hundred adult patients without
known cardiac or lung diseases who sought emergency care with cardiac complaints
were included. Patients with ischemic changes in the electrocardiography or fever
were excluded. A focused echocardiography with GE Vscan equipment was performed
after the initial evaluation in the emergency room. Cardiac chambers dimensions,
left and right ventricular systolic function, intracardiac flows with color,
pericardium, and aorta were evaluated. RESULTS: The mean age was 61 +/- 17 years
old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients,
arrhythmia to evaluate the left ventricular function in ten patients,
hypotension/dizziness in five patients and edema in one patient. In 28 patients,
the focused echocardiography allowed to confirm the initial diagnosis: 19
patients with heart failure, five with acute coronary syndrome, two with
pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the
echocardiography changed the diagnosis: ten with suspicious of heart failure, two
with pulmonary embolism suspicious, two with hypotension without cause, one
suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic
dissection. CONCLUSION: The focused echocardiography with pocket-size equipment
in the emergency care may allow a prompt diagnosis and, consequently, an earlier
initiation of the therapy.
PMID- 25590934
TI - Development of anatomophysiologic knowledge regarding the cardiovascular system:
from Egyptians to Harvey.
AB - Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS)
has progressed since the fourth millennium BC. In Egypt (3500 BC), it was
believed that a set of channels are interconnected to the heart, transporting
air, urine, air, blood, and the soul. One thousand years later, the heart was
established as the center of the CVS by the Hippocratic Corpus in the medical
school of Kos, and some of the CVS anatomical characteristics were defined. The
CVS was known to transport blood via the right ventricle through veins and the
pneuma via the left ventricle through arteries. Two hundred years later, in
Alexandria, following the development of human anatomical dissection, Herophilus
discovered that arteries were 6 times thicker than veins, and Erasistratus
described the semilunar valves, emphasizing that arteries were filled with blood
when ventricles were empty. Further, 200 years later, Galen demonstrated that
arteries contained blood and not air. With the decline of the Roman Empire, Greco
Roman medical knowledge about the CVS was preserved in Persia, and later in Islam
where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of
dissection of the human body in Europe in the 14th century was associated with
the revival of the knowledge pertaining to the CVS. The main findings were the
description of pulmonary circulation by Servetus, the anatomical discoveries of
Vesalius, the demonstration of pulmonary circulation by Colombo, and the
discovery of valves in veins by Fabricius. Following these developments, Harvey
described blood circulation.
PMID- 25590937
TI - Severe coronary vasospasm complicated with ventricular tachycardia.
PMID- 25590938
TI - Cardiac tamponade caused by compression of right cardiac chamber: a hidden enemy.
PMID- 25590939
TI - Effectiveness of a fotonovela for reducing depression and stress in Latino
dementia family caregivers.
AB - The clinical need to address stress and depression in Latino dementia caregivers
(CGs) combined with low health literacy and less accurate knowledge of dementia
motivated the development of a pictorial tool [called a fotonovela (FN)] to teach
(a) coping skills for caregiver (CG) stress; (b) self-assessment of depression;
and (c) encourage improved utilization of available resources. To test the
effectiveness of the FN, 110 of 147 Latino CGs, who were randomly assigned to the
Fotonovela Condition (FNC) or the Usual Information Condition (UIC), were
included in the final analyses. Self-report measures were given at baseline and
post intervention. Results showed that FNC CGs demonstrated significantly greater
reductions in level of depressive symptoms than UIC CGs. A significant decrease
in level of stress due to memory and behavioral problems exhibited by their loved
ones was similar in both groups. The FNC CGs reported that the FN was more
helpful and that they referred to it more often than the UIC CGs did with regard
to the informational materials they were provided about dementia. In conclusion,
a culturally tailored FN can be an effective tool for Latino CGs given their high
unmet needs for assistance and various barriers in accessing resources.
PMID- 25590940
TI - Deficits in Everyday Function Differ in AD and FTD.
AB - Alzheimer disease (AD) and frontotemporal dementia (FTD) are 2 neurodegenerative
diseases with differing cognitive and neuropathologic profiles. Although both
diseases ultimately result in functional disability, differences in the profiles
of everyday functioning between the 2 groups have not been well characterized.
The present study examines potential differences in the types of everyday
functional limitations present in these 2 dementias. The present study compared
individuals with AD (N=240) or FTD (N=13). The Everyday Cognition (ECog) scale
was used to measure distinct domains of everyday cognition: everyday memory,
everyday language, everyday visuospatial ability, and a variety of everyday
executive abilities. A total ECog score was used to represent global disability
level. The groups showed equivalent levels of global disability. However, AD
group exhibited worse Everyday Memory and Everyday Visuospatial abilities than
the FTD group. Contrary to expectation, FTD was not more impaired in everyday
executive abilities. Results remained similar when accounting for severity of
cognitive impairment or disease duration. Findings suggest that a somewhat
different pattern of everyday functional difficulties can be seen across dementia
types.
PMID- 25590941
TI - Study on the pharmacokinetics profiles of polyphyllin I and its bioavailability
enhancement through co-administration with P-glycoprotein inhibitors by LC-MS/MS
method.
AB - Polyphyllin I (PPI), one of the steroidal saponins in Paris polyphylla, is a
promising natural anticancer candidate. Although the anticancer activity of PPI
has been well demonstrated, information regarding the pharmacokinetics and
bioavailability is limited. In this study, a series of reliable and rapid liquid
chromatography-tandem mass spectrometry methods were developed and successfully
applied to determinate PPI in rat plasma, cell incubation media and cell
homogenate. Then the pharmacokinetics of PPI in rats was studied and the result
revealed that PPI was slowly eliminated with low oral bioavailability (about
0.62%) at a dose of 50 mg/kg, and when co-administrated with verapamil (VPL) and
cyclosporine A (CYA), the oral bioavailability of PPI could increase from 0.62%
to 3.52% and 3.79% respectively. In addition, in vitro studies showed that with
the presence of VPL and CYA in Caco-2 cells, the efflux ratio of PPI decreased
from 12.5 to 2.96 and 2.22, and the intracellular concentrations increased 5.8-
and 5.0-fold respectively. These results demonstrated that PPI, with poor oral
bioavailability, is greatly impeded by P-gp efflux, and inhibition of P-gp can
enhance its bioavailability.
PMID- 25590942
TI - Multi-responses extraction optimization combined with high-performance liquid
chromatography-diode array detection-electrospray ionization-tandem mass
spectrometry and chemometrics techniques for the fingerprint analysis of Aloe
barbadensis Miller.
AB - A quality control strategy using high-performance liquid chromatography-diode
array detector-electrospray ionization-tandem mass spectrometry (HPLC-DAD-ESI
MS/MS) coupled with chemometrics analysis was proposed for Aloe barbadensis
Miller. Firstly, the extraction conditions including methanol concentration,
extraction time and solvent-to-material ratio were optimized by multi-responses
optimization based on response surface methodology (RSM). The optimum conditions
were achieved by Derringer's desirability function and experimental validation
implied that the established model exhibited favorable prediction ability. Then,
HPLC fingerprint consisting of 27 common peaks was developed among 15 batches of
A. barbadensis samples. 25 common peaks were identified using HPLC-DAD-ESI-MS/MS
method by their spectral characteristics or comparison with the authentic
standards. Chemometrics techniques including similarity analysis (SA), principal
components analysis (PCA) and hierarchical clustering analysis (HCA) were
implemented to classify A. barbadensis samples. The results demonstrated that all
A. barbadensis samples shared similar chromatographic patterns as well as
differences. These achievements provided an effective, reliable and comprehensive
quality control method for A. barbadensis.
PMID- 25590943
TI - Profiling and multivariate statistical analysis of Panax ginseng based on ultra
high-performance liquid chromatography coupled with quadrupole-time-of-flight
mass spectrometry.
AB - An ultra-high-performance liquid chromatography coupled with quadrupole-time-of
flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed for the detection
and structural analysis of ginsenosides in white ginseng and related processed
products (red ginseng). Original neutral, malonyl, and chemically transformed
ginsenosides were identified in white and red ginseng samples. The aglycone types
of ginsenosides were determined by MS/MS as PPD (m/z 459), PPT (m/z 475), C-24,
25 hydrated-PPD or PPT (m/z 477 or m/z 493), and Delta20(21)-or Delta20(22)
dehydrated-PPD or PPT (m/z 441 or m/z 457). Following the structural
determination, the UHPLC-Q-TOF-MS-based chemical profiling coupled with
multivariate statistical analysis method was applied for global analysis of white
and processed ginseng samples. The chemical markers present between the processed
products red ginseng and white ginseng could be assigned. Process-mediated
chemical changes were recognized as the hydrolysis of ginsenosides with large
molecular weight, chemical transformations of ginsenosides, changes in malonyl
ginsenosides, and generation of 20-(R)-ginsenoside enantiomers. The relative
contents of compounds classified as PPD, PPT, malonyl, and transformed
ginsenosides were calculated based on peak areas in ginseng before and after
processing. This study provides possibility to monitor multiple components for
the quality control and global evaluation of ginseng products during processing.
PMID- 25590944
TI - The effect of excipients on the stability and phase transition rate of xylazine
hydrochloride and zopiclone.
AB - The compatibility of thermodynamically unstable polymorph of two active
pharmaceutical compounds (xylazine hydrochloride form X and zopiclone form C)
with different excipients was investigated. The effects of the excipient and its
amount in the sample on the thermal properties and possible chemical interactions
were studied. The most commonly used excipients in the pharmaceutical industry -
calcium carbonate, lactose hydrate, cellulose, magnesium stearate hydrate and
calcium stearate hydrate were selected for this study. The dependence of the
phase transition rate from an unstable to a more stable polymorph on the
excipients and their amounts in the initial sample was analysed at 80 degrees C,
and the corresponding phase transition rate constants were calculated.
PMID- 25590945
TI - Prediction of hydrolysis pathways and kinetics for antibiotics under
environmental pH conditions: a quantum chemical study on cephradine.
AB - Understanding hydrolysis pathways and kinetics of many antibiotics that have
multiple hydrolyzable functional groups is important for their fate assessment.
However, experimental determination of hydrolysis encounters difficulties due to
time and cost restraint. We employed the density functional theory and transition
state theory to predict the hydrolysis pathways and kinetics of cephradine, a
model of cephalosporin with two hydrolyzable groups, two ionization states, two
isomers and two nucleophilic attack directions. Results showed that the
hydrolysis of cephradine at pH = 8.0 proceeds via opening of the beta-lactam ring
followed by intramolecular amidation. The predicted rate constants at different
pH conditions are of the same order of magnitude as the experimental values, and
the predicted products are confirmed by experiment. This study identified a
catalytic role of the carboxyl group in the hydrolysis, and implies that the
carboxyl group also plays a catalytic role in the hydrolysis of other
cephalosporin and penicillin antibiotics. This is a first attempt to quantum
chemically predict hydrolysis of an antibiotic with complex pathways, and
indicates that to predict hydrolysis products under the environmental pH
conditions, the variation of the rate constants for different pathways with pH
should be evaluated.
PMID- 25590946
TI - Probability in reasoning: a developmental test on conditionals.
AB - Probabilistic theories have been claimed to constitute a new paradigm for the
psychology of reasoning. A key assumption of these theories is captured by what
they call the Equation, the hypothesis that the meaning of the conditional is
probabilistic in nature and that the probability of If p then q is the
conditional probability, in such a way that P(if p then q)=P(q|p). Using the
probabilistic truth-table task in which participants are required to evaluate the
probability of If p then q sentences, the present study explored the
pervasiveness of the Equation through ages (from early adolescence to adulthood),
types of conditionals (basic, causal, and inducements) and contents. The results
reveal that the Equation is a late developmental achievement only endorsed by a
narrow majority of educated adults for certain types of conditionals depending on
the content they involve. Age-related changes in evaluating the probability of
all the conditionals studied closely mirror the development of truth-value
judgements observed in previous studies with traditional truth-table tasks. We
argue that our modified mental model theory can account for this development, and
hence for the findings related with the probability task, which do not
consequently support the probabilistic approach of human reasoning over
alternative theories.
PMID- 25590947
TI - Income deprivation and mental well-being: the role of non-cognitive skills.
AB - We show that the positive relation between income deprivation and mental health
is affected by an individual's non-cognitive skills. Income deprivation is
operationalized as the Yitzhaki index, i.e., as a function of the sum of income
differences between an individual and others in her reference group who are more
affluent. Non-cognitive skills are extracted from a Locus of Control
questionnaire and the Big Five Inventory, a self-report measurement of an
individual in regard to five aspects of personality: conscientiousness,
neuroticism, extraversion, agreeableness and open-mindedness. The results, based
on the 2002-2010 waves of the German Socio-Economic Panel dataset (SOEP), show
that deprivation is negative and significantly related with mental health.
However, neurotic individuals are more deprivation-sensitive than are others.
Compared to the mean effect, a one standard deviation rise in neuroticism is
associated with a deprivation effect that is 36.6% and 51.9% larger among men and
women, respectively. Although to a lesser extent, extraverted men and
conscientious women are also found to be more deprivation-sensitive than are
others, the corresponding figures being 31.1% and 45.9%, respectively. These
findings suggest that personality differences should be taken into account in the
design of policies, practices and initiatives aimed at alleviating the well-being
costs of income deprivation.
PMID- 25590948
TI - OCT1 in hepatic steatosis and thiamine disposition.
PMID- 25590949
TI - Modulation of charge transport across double-stranded DNA by the site-specific
incorporation of copper bis-phenanthroline complexes.
AB - The site-specific incorporation of transition-metal complexes within DNA
duplexes, followed by their immobilization on a gold surface, was studied by
electrochemistry to characterize their ability to mediate charge. Cyclic
voltammetry, square-wave voltammetry, and control experiments were carried out on
fully matched and mismatched DNA strands that are mono- or bis-labeled with
transition-metal complexes. These experiments are all consistent with the ability
of the metal centers to act as a redox probe that is well coupled to the DNA pi
stack, allowing DNA-mediated charge transport.
PMID- 25590950
TI - The Glycemic Index of Rice and Rice Products: A Review, and Table of GI Values.
AB - Rice is the principle staple and energy source for nearly half the world's
population and therefore has significant nutrition and health implications. Rice
is generally considered a high glycemic index (GI) food, however, this depends on
varietal, compositional, processing, and accompaniment factors. Being a major
contributor to the glycemic load in rice eating populations, there is increasing
concern that the rising prevalence of insulin resistance is as a result of the
consumption of large amounts of rice. Devising ways and means of reducing the
glycemic impact of rice is therefore imperative. This review gathers studies
examining the GI of rice and rice products and provides a critical overview of
the current state of the art. A table collating published GI values for rice and
rice products is also included.
PMID- 25590952
TI - Vitamin D deficiency predisposes to adherent-invasive Escherichia coli-induced
barrier dysfunction and experimental colonic injury.
AB - BACKGROUND: Adherent-invasive Escherichia coli (AIEC) colonization has been
strongly implicated in the pathogenesis of Crohn's disease. Environmental
triggers such as vitamin D deficiency have emerged as key factors in the
pathogenesis of inflammatory bowel diseases. The aim of this study was to
investigate the effects of 1,25(OH)2D3 on AIEC infection-induced changes in vivo
and in vitro. METHODS: Barrier function was assessed in polarized epithelial Caco
2-bbe cells grown in medium with or without vitamin D and challenged with AIEC
strain LF82. Weaned C57BL/6 mice were fed either a vitamin D-sufficient or
deficient diet for 5 weeks and then infected with AIEC, in the absence and
presence of low-dose dextran sodium sulphate. Disease severity was assessed by
histological analysis and in vivo intestinal permeability assay. Presence of
invasive bacteria was assessed by transmission electron microscopy. RESULTS: Caco
2-bbe cells incubated with 1,25(OH)2D3 were protected against AIEC-induced
disruption of transepithelial electrical resistance and tight-junction protein
redistribution. Vitamin D-deficient C57BL/6 mice given a course of 2% dextran
sodium sulphate exhibited pronounced epithelial barrier dysfunction, were more
susceptible to AIEC colonization, and showed exacerbated colonic injury.
Transmission electron microscopy of colonic tissue from infected mice
demonstrated invasion of AIEC and fecal microbiome analysis revealed shifts in
microbial communities. CONCLUSIONS: These data show that vitamin D is able to
mitigate the deleterious effects of AIEC on the intestinal mucosa, by maintaining
intestinal epithelial barrier homeostasis and preserving tight-junction
architecture. This study highlights the association between vitamin D status,
dysbiosis, and Crohn's disease.
PMID- 25590954
TI - Size-based microfluidic multimodal microparticle sorter.
AB - Microfluidic sorting of synthetic and biological microparticles has attracted
much interest in recent years. Inertial microfluidics uses hydrodynamic forces to
manipulate migration of such microparticles in microfluidic channels to achieve
passive sorting based on size with high throughput. However, most inertial
microfluidic devices are only capable of bimodal separation with a single cutoff
diameter and a well-defined size difference. These limitations inhibit efficient
separation of real-world samples that often include heterogeneous mixtures of
multiple microparticle components. Our design overcomes these challenges to
achieve continuous multimodal sorting of microparticles with high resolution and
high tunability of separation cutoff diameters. We demonstrate separations with
flexible modulation of the separation bandwidth and the passband location. Our
approach offers a number of benefits, including straightforward system design,
easily and precisely tuned cutoff diameters, high separation resolution, and high
throughput. Ultimately, the unique multimodal separation functionality
significantly broadens applications of inertial microfluidics in sorting of
complex microparticle samples.
PMID- 25590955
TI - Chronic obstructive pulmonary disease in nonsmokers by occupation and exposure: a
brief review.
AB - PURPOSE OF REVIEW: This review gives an overview on recent reports of various
occupations associated with chronic obstructive pulmonary disease (COPD) and
exposures to associate with COPD among nonsmokers. RECENT FINDINGS: Recent
research has focused on identifying occupations with increased risk of COPD and
exposures associated with COPD among nonsmokers based on national health survey
data in the United States and studies in other countries. Recently reported
prevalence of COPD among nonsmokers was 2.8% in the United States and the
prevalence in other countries varied from 2% to 4.2%. The newly identified
occupations with high COPD prevalence include machine operators, construction
trades, financial record processing, cotton workers, farm machinery workers,
construction workers, and bus drivers. SUMMARY: The results of various studies
among nonsmokers show that some occupations are associated with an increased risk
of developing COPD, but no exact causes are reported. More research is needed to
confirm the newly identified occupations associated with an increased risk of
COPD and to identify causal risk factors. To reduce the prevalence of COPD in the
workplace, etiologic research and preventive interventions should focus on
occupations at risk for occupational exposures.
PMID- 25590953
TI - Biologic concentration testing in inflammatory bowel disease.
AB - Anti-TNF medications have revolutionized the care of patients with inflammatory
bowel disease. However, despite an initial robust effect, loss of response is
common and long-term results are disappointing. Much of this lack of durability
may be due to inadequate dose optimization, and recent studies suggest a
correlation between serum drug concentrations and clinical outcomes. Currently,
in clinical practice, measurement of drug concentrations and antibodies to drug
are typically performed only when a patient presents with active inflammatory
bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF
("reactive" setting). However, proactive monitoring of anti-TNF concentrations
with titration to a therapeutic window (i.e., therapeutic concentration
monitoring) represents a new strategy with many potential clinical benefits
including prevention of immunogenicity, less need for IFX rescue therapy, and
greater durability of IFX treatment. This review will cover the salient features
of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach
for the use of anti-TNF concentration testing in both the reactive and proactive
settings.
PMID- 25590956
TI - Optical coherence tomography evaluation of overlapping everolimus-eluting
bioresorbable vascular scaffold implantation guided by enhanced stent
visualization system.
PMID- 25590957
TI - Risk of myocardial contusion in cardiac arrest patients resuscitated with
mechanical chest compression device.
PMID- 25590958
TI - Body size and high intake of salt is associated with elevated blood pressure
among children and adolescents in Shandong, China.
PMID- 25590959
TI - Cardioprotection with melatonin in the acute myocardial infarction: awaiting
results of MARIA trial?
PMID- 25590960
TI - Thrombosis in Fontan patient on apixaban.
PMID- 25590962
TI - Mechanism of PKC activity affecting the adhesion reaction of endothelial cells
with monocytes.
PMID- 25590961
TI - Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a
reservoir of anti-apoptotic microRNAs for cardioprotection.
AB - BACKGROUND: Exosomes play an important role in intercellular signaling and exert
regulatory function by carrying bioactive molecules. This study investigated (1)
the cardioprotective capabilities of exosomes derived from mesenchymal stem cells
(MSCs) overexpressing GATA-4 (MSC(GATA-4)) and (2) its underlying regulatory
mechanisms for expression of target proteins in recipient cells. METHODS AND
RESULTS: Exosomes were isolated and purified from MSC(GATA-4) (Exo(GATA-4)) and
control MSCs (Exo(Null)). Cell injury was investigated in primary cultured rat
neonatal cardiomyocytes (CM) and in the rat heart. Exosomes contributed to
increased CM survival, reduced CM apoptosis, and preserved mitochondrial membrane
potential in CM cultured under a hypoxic environment. Direct intramyocardial
transplantation of exosomes at the border of an ischemic region following
ligation of the left anterior descending coronary artery significantly restored
cardiac contractile function and reduced infarct size. Real-time PCR revealed
that several anti-apoptotic miRs were highly expressed in Exo(GATA-4). Rapid
internalization of Exo(GATA-4) by CM was documented using time-lapse imaging.
Subsequent expression of these miRs, particularly miR-19a was higher in CM and in
the myocardium treated with Exo(GATA-4) compared to those treated with Exo(Null).
The enhanced protective effects observed in CM were diminished by the inhibition
of miR-19a. The expression level of PTEN, a predicted target of miR-19a, was
reduced in CM treated with Exo(GATA-4), which resulted in the activation of the
Akt and ERK signaling pathways. CONCLUSIONS: Exo(GATA-4) upon transplantation in
the damaged tissue mediate protection by releasing multiple miRs responsible for
activation of the cell survival signaling pathway.
PMID- 25590963
TI - Comparison of strain measurement from multimodality tissue tracking with strain
encoding MRI and harmonic phase MRI in pulmonary hypertension.
AB - BACKGROUND: Pixel-based multimodality tissue tracking (MTT) is a new noninvasive
method for the quantification of cardiac deformation from cine image of MRI. The
aim of this study is to validate bi-ventricular strain measurement by MTT
compared to strain-encoding (SENC) MRI and harmonic phase (HARP) MRI in pulmonary
hypertension (PH) patients. METHODS: In 45 subjects (30 PH patients and 15 normal
subjects), RV and LV peak global longitudinal strains (Ell) were measured from
long axis 4 chamber view using MTT. LV peak global circumferential strains (Ecc)
by MTT were measured from short axis. For validation, RV and LV Ell by MTT were
compared to measures by SENC-MRI from short axis, and LV Ecc by MTT was compared
to measures by short axis tagged MRI analysis (HARP). Reproducibility of MTT was
also determined. RESULTS: MTT quantified RV Ell correlated closely to those of
SENC (r=0.72, p<0.001), with good limits of agreement. LV Ell quantified by MTT
showed moderate correlation with SENC (r=0.57, p=0.001), and LV Ecc by MTT also
showed moderate correlation with HARP (-16.9+/-4.1 vs -14.3+/-3.5, p<0.001 for
all, r=0.60, p<0.001). RV Ell negatively correlated with RVEF (r=-0.53, p=0.001)
and also positively correlated with mean PAP in PH patients (r=0.60, p=0.001).
Strain measurement by MTT showed high reproducibility. CONCLUSIONS: We
demonstrate that MTT is a reproducible tool for quantification of cardiac
deformation using cine images in PH patients. Hence, it could serve as a new
rapid and comprehensive technique for clinical assessment of regional cardiac
function.
PMID- 25590965
TI - Corrigendum. Noise effect on comfort in open-space offices: development of an
assessment questionnaire.
PMID- 25590964
TI - A phenotypic screen identifies microtubule plus end assembly regulators that can
function in mitotic spindle orientation.
AB - Proper regulation of microtubule dynamics during mitosis is essential for
faithful chromosome segregation. In fact, recently we discovered increased
microtubule plus end assembly rates that are frequently observed in human cancer
cells as an important mechanism leading to whole chromosome missegregation and
chromosomal instability (CIN). However, the genetic alterations responsible for
increased microtubule polymerization rates in cancer cells remain largely
unknown. The identification of such lesions is hampered by the fact that
determining dynamic parameters of microtubules usually involves analyses of
living cells, which is technically difficult to perform in large-scale screening
settings. Therefore, we sought to identify alternative options to systematically
identify regulators of microtubule plus end polymerization. Here, we introduce a
simple and robust phenotypic screening assay that is based on the analyses of
monopolar mitotic spindle structures that are induced upon inhibition of the
mitotic kinesin Eg5/KIF11. We show that increased microtubule polymerization
causes highly asymmetric monoasters in the presence of Eg5/KIF11 inhibition and
this phenotype can be reliably assessed in living as well as in fixed cells.
Using this assay we performed a siRNA screen, in which we identify several
microtubule plus end binding proteins as well as centrosomal and cortex
associated proteins as important regulators of microtubule plus end assembly.
Interestingly, we demonstrate that a subgroup of these regulators function in the
regulation of spindle orientation through their role in dampening microtubule
plus end polymerization.
PMID- 25590966
TI - The effects of the atypical antipsychotic asenapine in a strain-specific battery
of tests for mania-like behaviors.
AB - Asenapine is indicated for the treatment of schizophrenia and manic episodes in
bipolar disorder (BPD). There is a paucity of information on the effects of
asenapine in animal models of BPD, but such work is essential to discover its
scope of effects and its mechanisms of therapeutic action. This study evaluated
the effects of asenapine in a validated test battery for manic-like behaviors in
Black Swiss mice. Male Black Swiss mice received asenapine at 0.03, 0.1, and 0.3
mg/kg twice daily for 7 days and were tested for spontaneous activity, sweet
solution preference, forced-swim test, social interaction, and amphetamine
induced hyperactivity. Asenapine treatment resulted in dose-dependent, clinically
relevant plasma levels. Asenapine, at the 0.1 and 0.3 mg/kg doses, reduced
activity, with the 0.3 mg/kg dose also resulting in increased time in the center
of an open field, increased immobility in the forced-swim test, and reduced
amphetamine-induced hyperactivity. Asenapine exerted no effects in the social
interaction or sweet solution preference tests. The results suggest that
asenapine exerts antimanic-like effects in some of the behavioral tests performed
in Black Swiss mice. These data support the utilization of asenapine in the
treatment of BPD.
PMID- 25590967
TI - Fluvoxamine alleviates seizure activity and downregulates hippocampal GAP-43
expression in pentylenetetrazole-kindled mice: role of 5-HT3 receptors.
AB - Epilepsy has been documented to lead to many changes in the nervous system
including cell loss and mossy fiber sprouting. Neuronal loss and aberrant
neuroplastic changes in the dentate gyrus of the hippocampus have been identified
in the pentylenetetrazole (PTZ) kindling model. Antiseizure activity of selective
serotonin reuptake inhibitors has been reported in several studies. In the
current study, the protective effect of fluvoxamine against PTZ-kindling was
investigated in terms of seizure scores, neuronal loss, and regulation of
hippocampal neuroplasticity. Further, the role of 5-HT3 receptors was determined.
Kindling was induced by repeated injections of PTZ (35 mg/kg) thrice weekly, for
a total of 13 injections. One hundred male albino mice were allocated into 10
groups: (1) saline, (2) PTZ, (3) diazepam (1 mg/kg)+PTZ, (4-6) fluvoxamine (5, 10
or 20 mg/kg)+PTZ, (7) ondansetron+fluvoxamine (20 mg/kg)+PTZ, (8) ondansetron+PTZ
group, (9) ondansetron (2 mg/kg, i.p.)+saline, and (10) fluvoxamine (20
mg/kg)+saline. PTZ-kindled mice showed high seizure activity, hippocampal
neuronal loss, and expression of growth-associated phosphoprotein (GAP-43)
compared with saline-treated mice. Repeated administration of fluvoxamine (20
mg/kg) in PTZ-kindled mice suppressed seizure scores, protected against
hippocampal neuronal loss, and downregulated GAP-43 expression, without producing
any signs of the 5-HT syndrome in healthy rats. Importantly, pretreatment with a
selective 5-HT3 receptor blocker (ondansetron) attenuated the aforementioned
effects of fluvoxamine. In conclusion, the ameliorating effect of fluvoxamine on
hippocampal neurons and neuroplasticity in PTZ-kindled mice was, at least in
part, dependent on enhancement of hippocampal serotoninergic transmission at 5
HT3 receptors.
PMID- 25590969
TI - Redox-tagged peptide for capacitive diagnostic assays.
AB - Early detection assays play a key role in the successful treatment of most
diseases. Redox capacitive biosensors were recently introduced as a potential
electroanalytical assay platform for point-of-care applications but alternative
surfaces (besides a mixed layer containing ferrocene and antibody receptive
component) for recruiting important clinical biomarkers are still needed. Aiming
to develop alternative receptive surfaces for this novel electrochemical
biosensing platform, we synthesized a ferrocene redox-tagged peptide capable of
self-assembly into metallic interfaces, a potentially useful biological surface
functionalization for bedside diagnostic assays. As a proof of concept we used C
reactive protein (CRP), as a model biomarker, and compared the obtained results
to those of previously reported capacitive assays. The redox-tagged peptide
approach shows a limit of detection of 0.8 nmol L(-1) (same as 94 ng mL(-1)) and
a linear range (R(2)~98%) with the logarithm of the concentration of the analyte
comprising 0.5-10.0 nmol L(-1), within a clinical relevant range for CRP.
PMID- 25590968
TI - Postmarketing analysis of aflibercept-related sterile intraocular inflammation.
AB - IMPORTANCE: Aflibercept-related sterile inflammation, an event that is poorly
understood, has been the subject of ongoing postmarketing reports. OBJECTIVE: To
analyze cases of aflibercept-related sterile inflammation reported to the
American Society of Retina Specialists (ASRS) Therapeutic Surveillance Committee
(TSC), an independent task force formed to monitor drug- and device-related
safety events. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 56
cases in 55 patients was performed of all cases of sterile inflammation after
aflibercept injection that were voluntarily reported by 12 practices throughout
the United States to the ASRS TSC from December 1, 2011, through February 12,
2014. MAIN OUTCOMES AND MEASURES: Cases of aflibercept-related sterile
inflammation were analyzed for baseline and demographic information, presenting
symptoms and findings, visual acuity changes, injection technique, and management
details. RESULTS: Among 56 reported cases of sterile inflammation, mean time to
onset was 3.5 days (median, 2 days; range, 0-30 days). Most cases consisted of
initial loss of vision and intraocular inflammation without prominent redness,
severe pain, or hypopyon. Thirty-seven cases (66%) were treated with topical
corticosteroids and/or observation alone. Mean time to resolution was 28.6 days
(median, 28 days; range, 4-84 days). Although final vision was overall unchanged,
some patients developed permanent vision loss, which may have resulted from
inflammation and/or progression of the underlying disease. Age older than 80
years was associated with worse visual outcomes. No difference in visual outcome
was detected in patients with sterile inflammation undergoing topical therapy
alone vs invasive procedures (vitreous biopsy and/or intravitreal antibiotic
administration and/or vitrectomy). CONCLUSIONS AND RELEVANCE: With the largest
number of reported cases of aflibercept-related sterile inflammation to our
knowledge, this analysis suggests typical findings and an often favorable
prognosis of this event. Analysis of real-world, postmarketing data has
limitations, and these findings should be considered as hypothesis-generating
assessments rather than a definitive reflection of this event or its typical
course. Distinguishing sterile inflammation and infectious endophthalmitis at the
time of presentation may often be difficult, and cautious evaluation and
management of these patients are warranted. The ASRS TSC encourages active
postmarketing surveillance by all physicians.
PMID- 25590970
TI - Cyclodextrin supramolecular inclusion-enhanced pyrene excimer switching for time
resolved fluorescence detection of biothiols in serum.
AB - We report here an efficient pyrene excimer signaling-based time-resolved
fluorescent sensor for the measurement of biothiols (cysteine (Cys), homocysteine
(Hcy), glutathione (GSH)) in human serum based on thymine-Hg(2+)-thymine (T
Hg(2+)-T) coordination chemistry and the inclusion interaction of cyclodextrin.
The sensing mechanism of the approach is based on the competitive ligation of
Hg(2+) ions by Hcy/Cys/GSH and T-T mismatches in a bis-pyrene-labeled DNA strand
with the self-complementary 5' and 3' ends. The introduction of gamma
cyclodextrin can provide cooperation for the molecular level space proximity of
the two labeled pyrene molecules, moreover the hydrophobic cavity of gamma
cyclodextrin can also offer protection for the pyrene dimer's emission from the
quenching effect of environmental conditions and enhance the fluorescence
intensity of the pyrene excimer. When the biothiols are not presented, the
sensing ensemble is in the "off" state due to the long distance between the two
labeled pyrene molecules resulted from the formation of a more stable T-Hg(2+)-T
structure. While in the presence of biothiols, Hg(2+) interacts very strongly
with thiol groups and the T-Hg(2+)-T structure is dehybridized, and then the
pyrene excimer will be formed due to the self-complementary 5' and 3' ends of the
DNA probe and the cooperation interaction of gamma-cyclodextrin to pyrene dimer,
thus resulting in switching the sensing ensemble to the "on" state. In the
optimum conditions described, the linear concentration range of 1.0-100 MUM with
the limit of detection (LOD) of 0.36 MUM for GSH was obtained. Moreover, due to
the much longer lifetime of the pyrene excimer fluorescence than those of the
ubiquitous endogenous fluorescent components, the time-resolved fluorescence
technique has been successfully used for application in complicated biological
samples.
PMID- 25590971
TI - Multiplex electrochemical DNA platform for femtomolar-level quantification of
genetically modified soybean.
AB - Current EU regulations on the mandatory labeling of genetically modified
organisms (GMOs) with a minimum content of 0.9% would benefit from the
availability of reliable and rapid methods to detect and quantify DNA sequences
specific for GMOs. Different genosensors have been developed to this aim, mainly
intended for GMO screening. A remaining challenge, however, is the development of
genosensing platforms for GMO quantification, which should be expressed as the
number of event-specific DNA sequences per taxon-specific sequences. Here we
report a simple and sensitive multiplexed electrochemical approach for the
quantification of Roundup-Ready Soybean (RRS). Two DNA sequences, taxon (lectin)
and event-specific (RR), are targeted via hybridization onto magnetic beads. Both
sequences are simultaneously detected by performing the immobilization,
hybridization and labeling steps in a single tube and parallel electrochemical
readout. Hybridization is performed in a sandwich format using signaling probes
labeled with fluorescein isothiocyanate (FITC) or digoxigenin (Dig), followed by
dual enzymatic labeling using Fab fragments of anti-Dig and anti-FITC conjugated
to peroxidase or alkaline phosphatase, respectively. Electrochemical measurement
of the enzyme activity is finally performed on screen-printed carbon electrodes.
The assay gave a linear range of 2-250 pM for both targets, with LOD values of
650 fM (160 amol) and 190 fM (50 amol) for the event-specific and the taxon
specific targets, respectively. Results indicate that the method could be applied
for GMO quantification below the European labeling threshold level (0.9%),
offering a general approach for the rapid quantification of specific GMO events
in foods.
PMID- 25590972
TI - Label-free colorimetric detection of Hg2+ based on Hg2+-triggered exonuclease III
assisted target recycling and DNAzyme amplification.
AB - This work reported a label-free colorimetric assay for sensitive detection of
Hg(2+) based on Hg(2+)-triggered hairpin DNA probe (H-DNA) termini-binding and
exonuclease SH (Exo SH)-assisted target recycling, as well as hemin/G-quadruplex
(DNAzyme) signal amplification. The specific binding of free Hg(2+) with the
thymine-thymine (T-T) mismatches termini of H-DNA could immediately trigger the
Exo SH digestion, and then set free G-quadruplex segments and Hg(2+). The Exo SH
impellent recycling of ultratrace Hg(2+) produced numerous G-quadruplexes. The
corresponding DNAzymes catalyzed efficiently the H2O2-mediated oxidation of the
ABTS(2-) to the colored product in the presence of hemin. Using the color change
as the output signal, and the Exo SH-aided Hg(2+) recycling and DNAzyme as the
signal amplifier, the ultrasensitive assay system successfully achieved visual
detection of Hg(2+) as low as 1.0 nM by the naked eye, and was suitable for field
monitoring. The calibration curve was linear in the range of 50.0 pM to 20.0 nM
for Hg(2+) (R=0.9962) with a detection limit of 10.0 pM. Moreover, this proposed
strategy showed excellent selectivity, portability and low-cost, and was
successfully applied to colorimetric detection of Hg(2+) in laboratory tap water
and Jialing river water samples.
PMID- 25590974
TI - Correction to "amyloid fibril nucleation: effect of amino Acid hydrophobicity".
PMID- 25590973
TI - Analytical bioconjugates, aptamers, enable specific quantitative detection of
Listeria monocytogenes.
AB - As a major human pathogen in the Listeria genus, Listeria monocytogenes causes
the bacterial disease listeriosis, which is a serious infection caused by eating
food contaminated with the bacteria. We have developed an aptamer-based sandwich
assay (ABSA) platform that demonstrates a promising potential for use in pathogen
detection using aptamers as analytical bioconjugates. The whole-bacteria SELEX
(WB-SELEX) strategy was adopted to generate aptamers with high affinity and
specificity against live L. monocytogenes. Of the 35 aptamer candidates tested,
LMCA2 and LMCA26 reacted to L. monocytogenes with high binding, and were
consequently chosen as sensing probes. The ABSA platform can significantly
enhance the sensitivity by employing a very specific aptamer pair for the
sandwich complex. The ABSA platform exhibited a linear response over a wide
concentration range of L. monocytogenes from 20 to 2*10(6) CFU per mL and was
closely correlated with the following relationship: y=9533.3x+1542.3 (R(2)=0.99).
Our proposed ABSA platform also provided excellent specificity for the tests to
distinguish L. monocytogenes from other Listeria species and other bacterial
genera (3 Listeria spp., 4 Salmonella spp., 2 Vibrio spp., 3 Escherichia coli and
3 Shigella spp.). Improvements in the sensitivity and specificity have not only
facilitated the reliable detection of L. monocytogenes at extremely low
concentrations, but also allowed for the development of a 96-well plate-based
routine assay platform for multivalent diagnostics.
PMID- 25590975
TI - The effect of polydioxanone absorbable plates in septorhinoplasty for stabilizing
caudal septal extension grafts.
AB - IMPORTANCE: Caudal septal extension grafts (CSEGs) can be used to alter and
secure nasal projection and length. Graft position and thickness play an
important role in terms of both function and aesthetics. The limitations of
harvesting cartilage from additional sites necessitate development of a more
efficient method for securing CSEGs. OBJECTIVE: To assess the efficacy and safety
of polydioxanone absorbable plates used in primary and revision septorhinoplasty.
DESIGN, SETTING, AND PARTICIPANTS: We investigated all patients who underwent
primary or revision septorhinoplasty with the use of absorbable plates to secure
CSEGs at a tertiary academic medical center from 2010 to 2014. To standardize and
objectify the symptoms of nasal obstruction, a validated quality-of-life
instrument called the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire,
with 5 questions on a scale of 0 to 4, was implemented preoperatively and
postoperatively. Preoperative and multiple successive postoperative measurements
of nasal length and projection were taken using 3dMDvultus imaging software. MAIN
OUTCOMES AND MEASURES: Change in NOSE questionnaire score, change in nasal length
and projection, and complications. RESULTS: There were no absorbable plate
related complications in the 95 included patients. Comparing preoperative and
postoperative NOSE questionnaire scores, there was a statistically significant
improvement in all 5 categories: mean (SD) change of -1.42 (1.59) in congestion,
1.56 (1.53) in blockage or obstruction, -1.60 (1.54) in breathing through nose,
0.90 (1.54) in trouble sleeping, and -1.28 (1.46) in breathing during exercise (P
< .001 for all) in the 50 patients with available data. In the 24 patients with
greater than 180 days of follow-up, follow-up ranged from 183 to 717 days, and
mean (SD) change in nasal length and projection was 0.64 (2.19) and 0.26 (0.96)
mm, respectively, showing no statistically significant change over time (P = .17
and .21, respectively). CONCLUSIONS AND RELEVANCE: In our study population, nasal
length and projection maintained position over time when absorbable plates were
used to secure CSEGs. Absorbable plates appear safe and effective when used to
secure CSEGs and limit the requirement of harvesting additional cartilage. Nasal
airway improvement can be obtained when absorbable plates are used to secure
CSEGs. LEVEL OF EVIDENCE: 4.
PMID- 25590976
TI - Symptom-driven idiopathic disease gene identification.
AB - PURPOSE: Rare genetic variants are the major cause of Mendelian disorders, yet
only half of described genetic diseases have been causally linked to a gene. In
addition, the total number of rare genetic diseases is projected to be far
greater than that of those already described. Whole-genome sequencing of patients
with subsequent genetic and functional analysis is a powerful way to describe
these gene anomalies. However, this approach results in tens to hundreds of
candidate disease-causative genes, and the identification of additional
individuals suffering from the same disorder can be difficult because of rarity
and phenotypic heterogeneity. METHODS: We describe a genetic network-based method
to rank candidate genes identified in family-based sequencing studies, termed
phenotype informed network (PIN) ranking. Furthermore, we present a case study as
an extension of the PIN ranking method in which disease symptoms drive the
network ranking and identification of the disease-causative gene. RESULTS: We
demonstrate, through simulation, that our method is capable of identifying the
correct disease-causative gene in a majority of cases. PIN-rank is available at
https://genomics.scripps.edu/pinrank/. CONCLUSION: We have developed a method to
prioritize candidate disease-causative genes based on symptoms that would be
useful for both the prioritization of candidates and the identification of
additional subjects.
PMID- 25590977
TI - Assessing the utility of confirmatory studies following identification of large
scale genomic imbalances by microarray.
AB - PURPOSE: The identification of clinically relevant genomic dosage anomalies
assists in accurate diagnosis, prognosis, and medical management of affected
individuals. Technological advancements within the field, such as the advent of
microarray, have markedly increased the resolution of detection; however,
clinical laboratories have maintained conventional techniques for confirmation of
genomic imbalances identified by microarray to ensure diagnostic accuracy. In
recent years the utility of this confirmatory testing of large-scale aberrations
has been questioned but has not been scientifically addressed. METHODS: We
retrospectively reviewed 519 laboratory cases with genomic imbalances meeting
reportable criteria by microarray and subsequently confirmed with a second
technology, primarily fluorescence in situ hybridization. RESULTS: All genomic
imbalances meeting reportable criteria detected by microarray were confirmed with
a second technology. Microarray analysis generated no false-positive results.
CONCLUSION: Confirmatory testing of large-scale genomic imbalances (deletion of
>=150 kb, duplication of >=500 kb) solely for the purpose of microarray
verification may be unwarranted. In some cases, however, adjunct testing is
necessary to overcome limitations inherent to microarray. A recommended clinical
strategy for adjunct testing following identified genomic imbalances using
microarray is detailed.
PMID- 25590978
TI - Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169
individuals undergoing genetic testing.
AB - PURPOSE: The aim of this study was to assess whether differences in frequency and
phenotype of APC and MUTYH mutations exist among racially/ethnically diverse
populations. METHODS: We studied 6,169 individuals with a personal and/or family
history of colorectal cancer (CRC) and polyps. APC testing involved full
sequencing/large rearrangement analysis (FS/LRA); MUTYH involved "panel testing"
(for Y165C, G382D mutations) or FS/LRA performed by Myriad Genetics, a commercial
laboratory. Subjects were identified as Caucasian, Asian, African American (AA),
or other. Statistical tests included chi(2), Fisher's exact test, analysis of
variance, and z approximation. RESULTS: Among participants, 17.5% had pathogenic
APC mutations and 4.8% were biallelic MUTYH carriers. With regard to
race/ethnicity, 18% were non-Caucasian, with >100 adenomas and younger ages at
adenoma or CRC diagnosis (P < 0.0001) than Caucasians. The overall APC mutation
rate was higher in Asians, AAs, and others as compared with Caucasians (25.2,
30.9, 24, and 15.5%, respectively; P < 0.0001) but was similar in all groups when
adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or other
than Asian or AA (5, 7, 2.7, and 0.3%, respectively; P < 0.0001). Among
Caucasians, 5% were biallelic carriers identified by panel testing versus 2%
identified by sequencing/large rearrangement analysis (LRA) (P = 0.002). Among
non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10%
identified by sequencing/LRA (P < 0.0002). CONCLUSION: Non-Caucasians undergo
genetic testing at more advanced stages of polyposis and/or are younger at
CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of
biallelic carriers, particularly in non-Caucasians.
PMID- 25590980
TI - Acceptability and feasibility of a virtual counselor (VICKY) to collect family
health histories.
AB - PURPOSE: To overcome literacy-related barriers in the collection of electronic
family health histories, we developed an animated Virtual Counselor for Knowing
your Family History, or VICKY. This study examined the acceptability and accuracy
of using VICKY to collect family histories from underserved patients as compared
with My Family Health Portrait (MFHP). METHODS: Participants were recruited from
a patient registry at a safety net hospital and randomized to use either VICKY or
MFHP. Accuracy was determined by comparing tool-collected histories with those
obtained by a genetic counselor. RESULTS: A total of 70 participants completed
this study. Participants rated VICKY as easy to use (91%) and easy to follow
(92%), would recommend VICKY to others (83%), and were highly satisfied (77%).
VICKY identified 86% of first-degree relatives and 42% of second-degree
relatives; combined accuracy was 55%. As compared with MFHP, VICKY identified a
greater number of health conditions overall (49% with VICKY vs. 31% with MFHP;
incidence rate ratio (IRR): 1.59; 95% confidence interval (95% CI): 1.13-2.25; P
= 0.008), in particular, hypertension (47 vs. 15%; IRR: 3.18; 95% CI: 1.66-6.10;
P = 0.001) and type 2 diabetes (54 vs. 22%; IRR: 2.47; 95% CI: 1.33-4.60; P =
0.004). CONCLUSION: These results demonstrate that technological support for
documenting family history risks can be highly accepted, feasible, and effective.
PMID- 25590979
TI - Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.
AB - PURPOSE: Despite the recognized clinical value of exome-based diagnostics,
methods for comprehensive genomic interpretation remain immature. Diagnoses are
based on known or presumed pathogenic variants in genes already associated with a
similar phenotype. Here, we extend this paradigm by evaluating novel
bioinformatics approaches to aid identification of new gene-disease associations.
METHODS: We analyzed 119 trios to identify both diagnostic genotypes in known
genes and candidate genotypes in novel genes. We considered qualifying genotypes
based on their population frequency and in silico predicted effects we also
characterized the patterns of genotypes enriched among this collection of
patients. RESULTS: We obtained a genetic diagnosis for 29 (24%) of our patients.
We showed that patients carried an excess of damaging de novo mutations in
intolerant genes, particularly those shown to be essential in mice (P = 3.4 * 10(
8)). This enrichment is only partially explained by mutations found in known
disease-causing genes. CONCLUSION: This work indicates that the application of
appropriate bioinformatics analyses to clinical sequence data can also help
implicate novel disease genes and suggest expanded phenotypes for known disease
genes. These analyses further suggest that some cases resolved by whole-exome
sequencing will have direct therapeutic implications.
PMID- 25590984
TI - Design, synthesis, and characterization of fatty acid derivatives of a dimeric
peptide-based postsynaptic density-95 (PSD-95) inhibitor.
AB - Dimeric peptide-based inhibitors of postsynaptic density-95 (PSD-95) can reduce
ischemic brain damage and inflammatory pain in rodents. To modify the
pharmacokinetic profile, we designed a series of fatty acid linked dimeric
ligands, which potently inhibits PSD-95 and shows improved in vitro blood plasma
stability. Subcutaneous administration in rats showed extended stability and
sustained release of these ligands. This can facilitate new pharmacological uses
of PSD-95 inhibitors and further exploration of PSD-95 as a drug target.
PMID- 25590983
TI - Divergent, coexisting Pseudomonas aeruginosa lineages in chronic cystic fibrosis
lung infections.
AB - RATIONALE: Pseudomonas aeruginosa, the predominant cause of chronic airway
infections of patients with cystic fibrosis, exhibits extensive phenotypic
diversity among isolates within and between sputum samples, but little is known
about the underlying genetic diversity. OBJECTIVES: To characterize the
population genetic structure of transmissible P. aeruginosa Liverpool Epidemic
Strain in chronic infections of nine patients with cystic fibrosis, and infer
evolutionary processes associated with adaptation to the cystic fibrosis lung.
METHODS: We performed whole-genome sequencing of P. aeruginosa isolates and
pooled populations and used comparative analyses of genome sequences including
phylogenetic reconstructions and resolution of population structure from genome
wide allele frequencies. MEASUREMENTS AND MAIN RESULTS: Genome sequences were
obtained for 360 isolates from nine patients. Phylogenetic reconstruction of the
ancestry of 40 individually sequenced isolates from one patient sputum sample
revealed the coexistence of two genetically diverged, recombining lineages
exchanging potentially adaptive mutations. Analysis of population samples for
eight additional patients indicated coexisting lineages in six cases.
Reconstruction of the ancestry of individually sequenced isolates from all
patients indicated smaller genetic distances between than within patients in most
cases. CONCLUSIONS: Our population-level analysis demonstrates that coexistence
of distinct lineages of P. aeruginosa Liverpool Epidemic Strain within
individuals is common. In several cases, coexisting lineages may have been
present in the infecting inoculum or assembled through multiple transmissions.
Divergent lineages can share mutations via homologous recombination, potentially
aiding adaptation to the airway during chronic infection. The genetic diversity
of this transmissible strain within infections, revealed by high-resolution
genomics, has implications for patient segregation and therapeutic strategies.
PMID- 25590981
TI - Family history and the natural history of colorectal cancer: systematic review.
AB - PURPOSE: Family history of colorectal cancer (CRC) is a known risk factor for CRC
and encompasses both genetic and shared environmental risks. METHODS: We
conducted a systematic review to estimate the impact of family history on the
natural history of CRC and adherence to screening. RESULTS: We found high
heterogeneity in family-history definitions, the most common definition being one
or more first-degree relatives. The prevalence of family history may be lower
than the commonly cited 10%, and confirms evidence for increasing levels of risk
associated with increasing family-history burden. There is evidence for higher
prevalence of adenomas and of multiple adenomas in people with family history of
CRC but no evidence for differential adenoma location or adenoma progression by
family history. Limited data regarding the natural history of CRC by family
history suggest a differential age or stage at cancer diagnosis and mixed
evidence with respect to tumor location. Adherence to recommended colonoscopy
screening was higher in people with a family history of CRC. CONCLUSION:
Stratification based on polygenic and/or multifactorial risk assessment may
mature to the point of displacing family history-based approaches, but for the
foreseeable future, family history may remain a valuable clinical tool for
identifying individuals at increased risk for CRC.
PMID- 25590985
TI - Influence of functionalized pyridine ligands on the radio/chemical behavior of
[M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.
AB - While a number of chelate strategies have been developed for the organometallic
precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), a unique challenge has been
to improve the overall function and performance of these complexes for in vivo
and in vitro applications. Since its discovery, fac-[M(I)(OH2)3(CO)3](+) has
served as an essential scaffold for the development of new targeted (99m)Tc based
radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic
nature of the fac-[M(I)(CO)3](+) core can influence the in vivo pharmacokinetics
and biodistribution of the complexes. In an effort to understand and improve this
behavior, monosubstituted pyridine ligands were used to assess the impact of
donor nitrogen basicity on binding strength and stability of fac-[M(I)(CO)3](+)
in a 2 + 1 labeling strategy. A series of Re and (99m)Tc complexes were
synthesized with picolinic acid as a bidentate ligand and 4-substituted pyridine
ligands. These complexes were designed to probe the effect of pKa from the
monodentate pyridine ligand both at the macro scale and radiochemical
concentrations. Comparison of X-ray structural data and radiochemical solution
experiments clearly indicate an increase in overall yield and stability as
pyridine basicity increased.
PMID- 25590986
TI - Enforced expression of Hoxa5 in haematopoietic stem cells leads to aberrant
erythropoiesis in vivo.
AB - Hoxa5 is preferentially expressed in haematopoietic stem cells (HSCs) and
multipotent progenitor cells (MPPs), and is more highly expressed in expanding
HSCs. To date, little is known regarding the role of Hoxa5 in HSCs and downstream
progenitor cells in vivo. In this study, we show that increased expression of
Hoxa5 in haematopoietic stem cells leads to aberrant erythropoiesis in vivo.
Hoxa5 differentially modifies the cell cycle of HSCs and lineage committed
progenitor cells, depending on the cellular context. Hoxa5 drives HSCs, but not
MPPs, through the cell cycle and arrests erythroid progenitor cells in G0 phase.
Although the HSC pool shrinks after overexpression of Hoxa5, HSCs sustain the
abilities of self-renewal and multipotency. In vivo, Hoxa5 has two effects on
erythropoiesis: it causes a predominance of mature erythroid lineage cells and
the partial apoptosis of erythroid progenitors. RNA-seq indicates that multiple
biological processes, including erythrocyte homeostasis, cell metabolism, and
apoptosis, are modified by Hoxa5. The results of this study indicate that Hoxa5
is a key regulator of the HSC cell cycle, and the inappropriate expression of
Hoxa5 in lineage-committed progenitor cells leads to aberrant erythropoiesis.
PMID- 25590987
TI - Successful long-term management of invasive cerebral fungal infection following
liver transplantation.
AB - Central nervous system (CNS) infections after liver transplantation may be fungal
in aetiology, with involvement from either common organisms such as Cryptococcus
neoformans and Aspergillus spp. as well as less common organisms, such as the
Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections
was nearly 100% in early series, more recent data has suggested that good
outcomes can be achieved. This may be due to both improved diagnostic
capabilities, such as the ability to obtain fungal susceptibilities and
therapeutic drug levels, and improved therapeutic options, such as the newer
triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have
now arisen around the long-term tolerability of these agents. The following two
cases of invasive cerebral fungal infections following liver transplantation, one
with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum
highlight the success that can be seen with the modern management of a previously
fatal diagnosis. In particular, we highlight the issues around therapeutic
monitoring and discontinuation of therapy.
PMID- 25590988
TI - The role of TRPV1 channels in carrageenan-induced mechanical hyperalgesia in
mice.
AB - Peripheral inflammation leads to ipsilateral and contralateral mechanical
hyperalgesia. The transient receptor potential channel vanilloid type 1 (TRPV1),
a nonselective cation channel expressed in mammalian primary sensory neurons and
the spinal cord, may be involved in peripheral inflammation, but there is no
consensus on the role of this channel in inflammation-induced mechanical
hyperalgesia. Here, we examined the role of TRPV1 channels in carrageenan-induced
mechanical hyperalgesia using wild-type and TRPV1-knockout (KO) mice and compared
the results with those obtained in mice peripherally administered capsazepine, a
TRPV1 antagonist, or capsaicin, a TRPV1 agonist. In the TRPV1-KO mice,
ipsilateral mechanical hyperalgesia was significantly reduced during the acute
phase (10-60 min), and the contralateral mechanical hyperalgesia nearly
disappeared during both the acute and subacute phases. Blocking peripheral TRPV1
using capsazepine before carrageenan administration resulted in similar effects
as those observed in the TRPV1-KO mice, except that it was less effective against
contralateral mechanical hyperalgesia during the subacute phase. In contrast,
capsaicin remarkably decreased ipsilateral and contralateral mechanical
hyperalgesia throughout both phases, but this analgesic effect was not observed
in the TRPV1-KO mice. Thus, TRPV1 channels could be involved in the development
of both ipsilateral and contralateral mechanical hyperalgesia after inflammation.
Peripheral TRPV1 could participate in acute hyperalgesia, whereas central TRPV1
may participate in subacute secondary hyperalgesia. Capsaicin potentially acts on
both primary and secondary hyperalgesia in a TRPV1-dependent manner.
PMID- 25590989
TI - Surgical fixation of sternal fractures: preoperative planning and a safe surgical
technique using locked titanium plates and depth limited drilling.
AB - Different ways to stabilize a sternal fracture are described in literature.
Respecting different mechanisms of trauma such as the direct impact to the
anterior chest wall or the flexion-compression injury of the trunk, there is a
need to retain each sternal fragment in the correct position while neutralizing
shearing forces to the sternum. Anterior sternal plating provides the best
stability and is therefore increasingly used in most cases. However, many
surgeons are reluctant to perform sternal osteosynthesis due to possible
complications such as difficulties in preoperative planning, severe injuries to
mediastinal organs, or failure of the performed method. This manuscript describes
one possible safe way to stabilize different types of sternal fractures in a step
by step guidance for anterior sternal plating using low profile locking titanium
plates. Before surgical treatment, a detailed survey of the patient and a three
dimensional reconstructed computed tomography is taken out to get detailed
information of the fracture's morphology. The surgical approach is usually a
midline incision. Its position can be described by measuring the distance from
upper sternal edge to the fracture and its length can be approximated by the
summation of 60 mm for the basis incision, the thickness of presternal soft
tissue and the greatest distance between the fragments in case of multiple
fractures. Performing subperiosteal dissection along the sternum while reducing
the fracture, using depth limited drilling, and fixing the plates prevents
injuries to mediastinal organs and vessels. Transverse fractures and oblique
fractures at the corpus sterni are plated longitudinally, whereas oblique
fractures of manubrium, sternocostal separation and any longitudinally fracture
needs to be stabilized by a transverse plate from rib to sternum to rib. Usually
the high convenience of a patient is seen during follow up as well as a precise
reconstruction of the sternal morphology.
PMID- 25590990
TI - Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and
literature review.
AB - To date, there has been only one published report on the infectious
sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic
fungus. Regarding corneal infection, three reports have been published to date.
Although the prognoses of the corneal infections are favourable, prognosis when
scleral infection is involved is very poor. A 76-year-old patient presented with
foreign body sensation in the left eye. Microscopic examination with Fungi Flora
Y staining of the corneal scraping revealed fungal infection. The conjunctiva was
melted by the infection over a wide area. Although intensive medications were
administered, an emergency surgery was necessary because scleral thinning,
corneal perforation and lens prolapse occurred. The fungal isolate was identified
as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we
report the second known case worldwide of M. anisopliae sclerokeratitis, and we
review the literature related to the ocular infections.
PMID- 25590991
TI - Zebrafish (Danio rerio) eleutheroembryo-based procedure for assessing
bioaccumulation.
AB - This paper reports on the development and preliminary evaluation of a new
bioaccumulation test based on the use of zebrafish (Danio renio) eleutheroembryos
(72 h after hatching, corresponding to 144 h post fertilization, hpf) as an
alternative to adult fish-based procedures for regulatory purposes regarding
REACH application. The proposed test accomplished the OECD 305 guideline and
consists of a 48 h uptake period followed by a 24 h depuration step.
Bioaccumulation experiments were performed for a selected of hyper hydrophobic
chemicals (log Kow> 7.6), that is, PCB 136 and PBDE 154 at two concentration
levels corresponding roughly to 1% and 0.1% the chemicals LC50(nominal
concentrations of 4.0 and 12.0 MUg/L for PCB 136, and 1.0 and 5.0 MUg/L PBDE 154,
respectively). Toxicokinetic models were used to calculate the bioconcentration
factors (BCFs) based on of the chemical concentrations found in the contaminated
eleutheroembryos and their surrounding media. The experimentally determined
accumulation profiles show bioaccumulation by zebrafish eleutheroembryos of both
chemicals, and that the process is more complex than simple water-lipid
partition. Calculated log BCFs using a first-order accumulation model(3.97 and
3.73 for PCB 136, and 3.95 and 4.29 for PBDE 154) were in the range of those
previously reported in the literature. The suitability of this new nonprotected
life stage bioaccumulation protocol for BCF estimation was evaluated by
application to widely divergent micropollutants with different accumulation
mechanisms. The results were compared with those in the MITE-NITE database for
adult rice fish (Oryzias latipes).
PMID- 25590992
TI - Synthesis of unsymmetrical pyrazines based on alpha-diazo oxime ethers.
AB - Synthesis of unsymmetrically substituted pyrazines has been a challenge. The
reactivity of alpha-imino carbenoids derived from alpha-diazo oxime ethers has
been exploited for pyrazine synthesis, in which the reaction of alpha-diazo oxime
ethers with 2H-azirines provides highly substituted pyrazines in good to
excellent yields.
PMID- 25590993
TI - What's new in Shock? February 2015.
PMID- 25590995
TI - Vertical heterostructure of two-dimensional MoS2 and WSe2 with vertically aligned
layers.
AB - Two-dimensional (2D) layered materials consist of covalently bonded 2D atomic
layers stacked by van der Waals interactions. Such anisotropic bonding nature
gives rise to the orientation-dependent functionalities of the 2D layered
materials. Different from most studies of 2D materials with their atomic layers
parallel to substrate, we have recently developed layer vertically aligned 2D
material nanofilms. Built on these developments, here, we demonstrate the
synthesis of vertical heterostructure of n-type MoS2 and p-type WSe2 with
vertically aligned atomic layers. Thin film of MoS2/WSe2 vertical structure was
successfully synthesized without significant alloy formation. The heterostructure
synthesis is scalable to a large area over 1 cm(2). We demonstrated the pn
junction diode behavior of the heterostructure device. This novel device geometry
opens up exciting opportunities for a variety of electronic and optoelectronic
devices, complementary to the recent interesting vertical heterostructures with
horizontal atomic layers.
PMID- 25590994
TI - Evaluation of stem cell properties in human ovarian carcinoma cells using multi
and single cell-based spheres assays.
AB - Years of research indicates that ovarian cancers harbor a heterogeneous mixture
of cells including a subpopulation of so-called "cancer stem cells" (CSCs)
responsible for tumor initiation, maintenance and relapse following conventional
chemotherapies. Identification of ovarian CSCs is therefore an important goal. A
commonly used method to assess CSC potential in vitro is the spheres assay in
which cells are plated under non-adherent culture conditions in serum-free medium
supplemented with growth factors and sphere formation is scored after a few days.
Here, we review currently available protocols for human ovarian cancer spheres
assays and perform a side-by-side analysis between commonly used multi cell-based
assays and a more accurate system based on single cell plating. Our results
indicate that both multi cell-based as well as single cell-based spheres assays
can be used to investigate sphere formation in vitro. The more laborious and
expensive single cell-based assays are more suitable for functional assessment of
individual cells and lead to overall more accurate results while multi cell-based
assays can be strongly influenced by the density of plated cells and require
titration experiments upfront. Methylcellulose supplementation to multi cell
based assays can be effectively used to reduce mechanical artifacts.
PMID- 25590996
TI - Copy number variation detection using SNP genotyping arrays in three Chinese pig
breeds.
AB - We performed genome-wide CNV detection based on SNP genotyping data of 96 Chinese
native Tibetan, Dahe and Wuzhishan pigs. These pigs are particularly interesting
because of their excellent adaptation to hypoxia or small body size, which
facilitates the use of them as models of different human diseases in addition to
valuable agricultural animals. A total of 105 CNV regions (CNVRs) were
identified, encompassing 16.71 Mb of the pig genome. Seven of 10 (70%) CNVRs
selected randomly were validated by quantitative real-time PCR. Comparison with
previous studies revealed 25 (23.81%) novel CNVRs, indicating that CNV coverage
of the pig genome is still incomplete and there exists large diversity between
pig breeds. Functional analysis of genes located in these CNVRs confirmed the
high representation of genes involved in sensory perception, neurological system
processes and other basic metabolic processes. In addition, the majority of these
CNVRs were detected to span reported pig QTL that affect various traits, which
highlighted three biologically interesting genes with copy number changes (i.e.,
ANKRD34B, FAM110B and ABCG1). These genes may have economic importance in pig
breeding and are worth being further investigated. We also obtained some CNVRs
harboring genes that had human orthologs involved in human diseases such as
cardiovascular disease and Alzheimer's disease. The findings of this study are a
significant extension of the coverage of CNVRs in the pig genome and provide
valuable resources for follow-up-associated studies of CNVs in pig complex traits
as well as important implications of human diseases.
PMID- 25590997
TI - An analytical method for 14C in environmental water based on a wet-oxidation
process.
AB - An analytical method for (14)C in environmental water based on a wet-oxidation
process was developed. The method can be used to determine the activity
concentrations of organic and inorganic (14)C in environmental water, or total
(14)C, including in drinking water, surface water, rainwater and seawater. The
wet-oxidation of the organic component allows the conversion of organic carbon to
an inorganic form, and the extraction of the inorganic (14)C can be achieved by
acidification and nitrogen purging. Environmental water with a volume of 20 L can
be used for the wet-oxidation and extraction, and a detection limit of about 0.02
Bq/g(C) can be achieved for water with carbon content above 15 mg(C)/L, obviously
lower than the natural level of (14)C in the environment. The collected carbon is
sufficient for measurement with a low level liquid scintillation counter (LSC)
for typical samples. Extraction or recovery experiments for inorganic carbon and
organic carbon from typical materials, including analytical reagents of organic
benzoquinone, sucrose, glutamic acid, nicotinic acid, humic acid, ethane diol, et
cetera., were conducted with excellent results based on measurement on a total
organic carbon analyzer and LSC. The recovery rate for inorganic carbon ranged
tween 98.7%-99.0% with a mean of 98.9(+/- 0.1)%, for organic carbon recovery
ranged between 93.8% and 100.0% with a mean of 97.1(+/- 2.6)%. Verification and
an uncertainty budget of the method are also presented for a representative
environmental water. The method is appropriate for (14)C analysis in
environmental water, and can be applied also to the analysis of liquid effluent
from nuclear facilities.
PMID- 25590998
TI - Non-invasive imaging and analysis of cerebral ischemia in living rats using
positron emission tomography with 18F-FDG.
AB - Stroke is the third leading cause of death among Americans 65 years of age or
older(1). The quality of life for patients who suffer from a stroke fails to
return to normal in a large majority of patients(2), which is mainly due to
current lack of clinical treatment for acute stroke. This necessitates
understanding the physiological effects of cerebral ischemia on brain tissue over
time and is a major area of active research. Towards this end, experimental
progress has been made using rats as a preclinical model for stroke,
particularly, using non-invasive methods such as (18)F-fluorodeoxyglucose (FDG)
coupled with Positron Emission Tomography (PET) imaging(3,10,17). Here we present
a strategy for inducing cerebral ischemia in rats by middle cerebral artery
occlusion (MCAO) that mimics focal cerebral ischemia in humans, and imaging its
effects over 24 hr using FDG-PET coupled with X-ray computed tomography (CT) with
an Albira PET-CT instrument. A VOI template atlas was subsequently fused to the
cerebral rat data to enable a unbiased analysis of the brain and its sub
regions(4). In addition, a method for 3D visualization of the FDG-PET-CT time
course is presented. In summary, we present a detailed protocol for initiating,
quantifying, and visualizing an induced ischemic stroke event in a living Sprague
Dawley rat in three dimensions using FDG-PET.
PMID- 25591000
TI - Isolation and intravenous injection of murine bone marrow derived monocytes.
AB - As a subtype of leukocytes and progenitors of macrophages, monocytes are involved
in many important processes of organisms and are often the subject of various
fields in biomedical science. The method described below is a simple and
effective way to isolate murine monocytes from heterogeneous bone marrow. Bone
marrow from the femur and tibia of Balb/c mice is harvested by flushing with
phosphate buffered saline (PBS). Cell suspension is supplemented with macrophage
colony stimulating factor (M-CSF) and cultured on ultra-low attachment surfaces
to avoid adhesion-triggered differentiation of monocytes. The properties and
differentiation of monocytes are characterized at various intervals. Fluorescence
activated cell sorting (FACS), with markers like CD11b, CD115, and F4/80, is used
for phenotyping. At the end of cultivation, the suspension consists of 45%+/- 12%
monocytes. By removing adhesive macrophages, the purity can be raised up to 86%+/
6%. After the isolation, monocytes can be utilized in various ways, and one of
the most effective and common methods for in vivo delivery is intravenous tail
vein injection. This technique of isolation and application is important for
mouse model studies, especially in the fields of inflammation or immunology.
Monocytes can also be used therapeutically in mouse disease models.
PMID- 25591001
TI - Image-based flow cytometry technique to evaluate changes in granulocyte function
in vitro.
AB - Granulocytes play a key role in the body's innate immune response to bacterial
and viral infections. While methods exist to measure granulocyte function, in
general these are limited in terms of the information they can provide. For
example, most existing assays merely provide a percentage of how many
granulocytes are activated following a single, fixed length incubation.
Complicating matters, most assays focus on only one aspect of function due to
limitations in detection technology. This report demonstrates a technique for
simultaneous measurement of granulocyte phagocytosis of bacteria and oxidative
burst. By measuring both of these functions at the same time, three unique
phenotypes of activated granulocytes were identified: 1) Low Activation (minimal
phagocytosis, no oxidative burst), 2) Moderate Activation (moderate phagocytosis,
some oxidative burst, but no co-localization of the two functional events), and
3) High Activation (high phagocytosis, high oxidative burst, co-localization of
phagocytosis and oxidative burst). A fourth population that consisted of
inactivated granulocytes was also identified. Using assay incubations of 10, 20,
and 40-min the effect of assay incubation duration on the redistribution of
activated granulocyte phenotypes was assessed. A fourth incubation was completed
on ice as a control. By using serial time incubations, the assay may be able to
able to detect how a treatment spatially affects granulocyte function. All
samples were measured using an image-based flow cytometer equipped with a
quantitative imaging (QI) option, autosampler, and multiple lasers (488, 642, and
785 nm).
PMID- 25590999
TI - The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin
ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex.
AB - The MAGE (Melanoma-associated antigen) protein family members are structurally
related to each other by a MAGE-homology domain comprised of 2 winged helix
motifs WH/A and WH/B. This family specifically evolved in placental mammals
although single homologs designated NSE3 (non-SMC element) exist in most
eukaryotes. NSE3, together with its partner proteins NSE1 and NSE4 form a tight
subcomplex of the structural maintenance of chromosomes SMC5-6 complex.
Previously, we showed that interactions of the WH/B motif of the MAGE proteins
with their NSE4/EID partners are evolutionarily conserved (including the MAGEA1
NSE4 interaction). In contrast, the interaction of the WH/A motif of NSE3 with
NSE1 diverged in the MAGE paralogs. We hypothesized that the MAGE paralogs
acquired new RING-finger-containing partners through their evolution and form
MAGE complexes reminiscent of NSE1-NSE3-NSE4 trimers. In this work, we employed
the yeast 2-hybrid system to screen a human RING-finger protein library against
several MAGE baits. We identified a number of potential MAGE-RING interactions
and confirmed several of them (MDM4, PCGF6, RNF166, TRAF6, TRIM8, TRIM31, TRIM41)
in co-immunoprecipitation experiments. Among these MAGE-RING pairs, we chose to
examine MAGEA1-TRIM31 in detail and showed that both WH/A and WH/B motifs of
MAGEA1 bind to the coiled-coil domain of TRIM31 and that MAGEA1 interaction
stimulates TRIM31 ubiquitin-ligase activity. In addition, TRIM31 directly binds
to NSE4, suggesting the existence of a TRIM31-MAGEA1-NSE4 complex reminiscent of
the NSE1-NSE3-NSE4 trimer. These results suggest that MAGEA1 functions as a co
factor of TRIM31 ubiquitin-ligase and that the TRIM31-MAGEA1-NSE4 complex may
have evolved from an ancestral NSE1-NSE3-NSE4 complex.
PMID- 25591002
TI - Protein-protein interactions affect alpha helix stability in crowded
environments.
AB - The dense, heterogeneous cellular environment is known to affect protein
stability through interactions with other biomacromolecules. The effect of
excluded volume due to these biomolecules, also known as crowding agents, on a
protein of interest, or test protein, has long been known to increase the
stability of a test protein. Recently, it has been recognized that attractive
protein-crowder interactions play an important role. These interactions affect
protein stability and can destabilize the test protein. However, most
computational work investigating the role of attractive interactions has used
spherical crowding agents and has neglected the specific roles of crowding agent
hydrophobicity and hydrogen bonding. Here we use multicanonical molecular
dynamics and a coarse-grained protein model to study the folding thermodynamics
of a small helical test protein in the presence of crowding agents that are
themselves proteins. Our results show that the stability of the test protein
depends on the hydrophobicity of the crowding agents. For low values of crowding
agent hydrophobicity, the excluded volume effect is dominant, and the test
protein is stabilized relative to the dilute solution. For intermediate values of
the crowding agent hydrophobicity, the test protein is destabilized by favorable
side chain-side chain interactions stabilizing the unfolded states. For high
values of the crowding agent hydrophobicity, the native state is stabilized by
the strong intermolecular attractions, causing the formation of a packed
structure that increases the stability of the test protein through favorable side
chain-side chain interactions. In addition, increasing crowding agent
hydrophobicity increases the "foldability" of the test protein and alters the
potential energy landscape by simultaneously deepening the basins corresponding
to the folded and unfolded states and increasing the energy barrier between them.
PMID- 25591004
TI - Magnetic anisotropy in "scorpionate" first-row transition-metal complexes: a
theoretical investigation.
AB - In this work we have analyzed in detail the magnetic anisotropy in a series of
hydrotris(pyrazolyl)borate (Tp(-)) metal complexes, namely [VTpCl](+),
[CrTpCl](+), [MnTpCl](+), [FeTpCl], [CoTpCl], and [NiTpCl], and their substituted
methyl and tert-butyl analogues with the goal of observing the effect of the
ligand field on the magnetic properties. In the [VTpCl](+), [CrTpCl](+),
[CoTpCl], and [NiTpCl] complexes, the magnetic anisotropy arises as a consequence
of out-of-state spin-orbit coupling, and covalent changes induced by the
substitution of hydrogen atoms on the pyrazolyl rings does not lead to drastic
changes in the magnetic anisotropy. On the other hand, much larger magnetic
anisotropies were predicted in complexes displaying a degenerate ground state,
namely [MnTpCl](+) and [FeTpCl], due to in-state spin-orbit coupling. The
anisotropy in these systems was shown to be very sensitive to perturbations, for
example, chemical substitution and distortions due to the Jahn-Teller effect. We
found that by substituting the hydrogen atoms in [MnTpCl](+) and [FeTpCl] by
methyl and tert-butyl groups, certain covalent contributions to the magnetic
anisotropy energy (MAE) could be controlled, thereby achieving higher values.
Moreover, we showed that the selection of ion has important consequences for the
symmetry of the ground spin-orbit term, opening the possibility of achieving zero
magnetic tunneling even in non-Kramers ions. We have also shown that substitution
may also contribute to a quenching of the Jahn-Teller effect, which could
significantly reduce the magnetic anisotropy of the complexes studied.
PMID- 25591009
TI - Numerically testing phenomenological models for conductance of a solid-state
nanopore.
AB - The ionic conductance of a solid-state nanopore plays an important role in
analyzing biomolecules transported through the pore. The phenomenological pore
conductance is assumed to be a sum of three contributions: bulk, surface (for a
charged nanopore) and access ones. Despite being commonly used, phenomenological
results were not rigorously derived in theory and their accuracies have not been
tested yet. By carrying out numerical modeling on the nanopore conductance, I
show that both the ion concentration and the surface charge can affect the
accuracy. For a charged solid-state nanopore solvated in an intermediate-ion
concentration electrolyte (e.g. 50 mM), the phenomenological result can be
substantially larger than the numerically calculated one. The criteria for
properly applying phenomenological results are provided.
PMID- 25591003
TI - Structural convergence of unstructured p53 family transactivation domains in MDM2
recognition.
AB - The p53, p63, and p73 proteins belong to the p53 family of transcription factors,
which play key roles in tumor suppression. Although the transactivation domains
(TADs) of the p53 family are intrinsically disordered, these domains are commonly
involved in the regulatory interactions with mouse double minute 2 (MDM2). In
this study, we determined the solution structure of the p73TAD peptide in complex
with MDM2 using NMR spectroscopy and biophysically characterized the interactions
between the p53 family TAD peptides and MDM2. In combination with mutagenesis
data, the complex structures revealed remarkably close mimicry of the MDM2
recognition mechanism among the p53 family TADs. Upon binding with MDM2, the
intrinsically disordered p73TAD and p63TAD peptides adopt an amphipathic alpha
helical conformation, which is similar to the conformation of p53TAD, although
the alpha-helical content induced by MDM2 binding varies. With isothermal
titration calorimetry (ITC) and circular dichroism (CD) data, our biophysical
characterization showed that p73TAD resembles p53TAD more closely than p63TAD in
terms of helical stability, MDM2 binding affinity, and phosphorylation effects on
MDM2 binding. Therefore, our structural information may be useful in establishing
alternative anticancer strategies that exploit the activation of the p73 pathway
against human tumors bearing p53 mutations.
PMID- 25591008
TI - Heliotropium europaeum poisoning in cattle and analysis of its pyrrolizidine
alkaloid profile.
AB - Pyrrolizidine alkaloids (PAs) are carcinogenic and genotoxic phytochemicals found
exclusively in angiosperms. The ingestion of PA-containing plants often results
in acute and chronic toxicities in man and livestock, targeting mainly the liver.
During February 2014, a herd of 15-18-month-old mixed-breed beef cattle (n = 73)
from the Galilee region in Israel was accidently fed hay contaminated with 12%
Heliotropium europaeum (average total PA intake was 33 mg PA/kg body weight/d).
After 42 d of feed ingestion, sudden death occurred over a time period of 63 d
with a mortality rate of 33%. Necropsy and histopathological examination revealed
fibrotic livers and moderate ascites, as well as various degrees of hyperplasia
and fibrosis of bile duct epithelial cells. Elevated gamma-glutamyl-transferase
and alkaline phosphatase levels were indicative of severe liver damage.
Comprehensive PA profile determination of the contaminated hay and of native H.
europaeum by LC-MS/MS revealed the presence of 30 PAs and PA-N-oxides, including
several newly reported PAs and PA-N-oxides of the rinderine and heliosupine
class. Heliotrine- and lasiocarpine-type PAs constituted 80% and 18% of the total
PAs, respectively, with the N-oxides being the most abundant form (92%). The PA
profile of the contaminated hay showed very strong resemblance to that of H.
europaeum.
PMID- 25591010
TI - One-pot chemical synthesis of small ubiquitin-like modifier protein-peptide
conjugates using bis(2-sulfanylethyl)amido peptide latent thioester surrogates.
AB - Small ubiquitin-like modifier (SUMO) post-translational modification (PTM) of
proteins has a crucial role in the regulation of important cellular processes.
This protocol describes the chemical synthesis of functional SUMO-peptide
conjugates. The two crucial stages of this protocol are the solid-phase synthesis
of peptide segments derivatized by thioester or bis(2-sulfanylethyl)amido (SEA)
latent thioester functionalities and the one-pot assembly of the SUMO-peptide
conjugate by a sequential native chemical ligation (NCL)/SEA native peptide
ligation reaction sequence. This protocol also enables the isolation of a SUMO
SEA latent thioester, which can be attached to a target peptide or protein in a
subsequent step. It is compatible with 9-fluorenylmethoxycarbonyl (Fmoc)
chemistry, and it gives access to homogeneous, reversible and functional SUMO
conjugates that are not easily produced using living systems. The synthesis of
SUMO-peptide conjugates on a milligram scale takes 20 working days.
PMID- 25591011
TI - A 12-step user guide for analyzing voxel-wise gray matter asymmetries in
statistical parametric mapping (SPM).
AB - Voxel-based morphometry (VBM) has been proven capable of capturing cerebral gray
matter asymmetries with a high (voxel-wise) regional specificity. However, a
standardized reference on how to conduct voxel-wise asymmetry analyses is
missing. This protocol provides the scientific community with a carefully
developed guide describing, in 12 distinct steps, how to take structural images
from data pre-processing, via statistical analysis, to the final interpretation
of the significance maps. Key adaptations compared with the standard VBM workflow
involve establishing a voxel-wise hemispheric correspondence, capturing the
direction and degree of asymmetry and preventing a blurring of information across
hemispheres. The workflow incorporates the most recent methodological
developments, including high-dimensional spatial normalization and partial volume
estimations. Although the protocol is primarily designed to enable relatively
inexperienced users to conduct a voxel-based asymmetry analysis on their own, it
may also be useful to experienced users who wish to efficiently adapt their
existing scripts or pipelines.
PMID- 25591013
TI - Efficiency of hole transfer from photoexcited quantum dots to covalently linked
molecular species.
AB - Hole transfer from high photoluminescence quantum yield (PLQY) CdSe-core CdS
shell semiconductor nanocrystal quantum dots (QDs) to covalently linked molecular
hole acceptors is investigated. (1)H NMR is used to independently calibrate the
average number of hole acceptor molecules per QD, N, allowing us to measure PLQY
as a function of N, and to extract the hole transfer rate constant per acceptor,
kht. This value allows for reliable comparisons between nine different donor
acceptor systems with variant shell thicknesses and acceptor ligands, with kht
spanning over 4 orders of magnitude, from single acceptor time constants as fast
as 16 ns to as slow as 0.13 ms. The PLQY variation with acceptor coverage for all
kht follows a universal equation, and the shape of this curve depends critically
on the ratio of the total hole transfer rate to the sum of the native
recombination rates in the QD. The dependence of kht on the CdS thickness and the
chain length of the acceptor is investigated, with damping coefficients beta
measured to be (0.24 +/- 0.025) A(-1) and (0.85 +/- 0.1) A(-1) for CdS and the
alkyl chain, respectively. We observe that QDs with high intrinsic PLQYs (>79%)
can donate holes to surface-bound molecular acceptors with efficiencies up to 99%
and total hole transfer time constants as fast as 170 ps. We demonstrate the
merits of a system where ill-defined nonradiative channels are suppressed and
well-defined nonradiative channels are engineered and quantified. These results
show the potential of QD systems to drive desirable oxidative chemistry without
undergoing oxidative photodegradation.
PMID- 25591012
TI - Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d
and CYP125A1.
AB - Azoles and pyridines are commonly incorporated into small molecule inhibitor
scaffolds that target cytochromes P450 (CYPs) as a strategy to increase drug
binding affinity, impart isoform-dependent selectivity, and improve metabolic
stability. Optical absorbance spectra of the CYP-inhibitor complex are widely
used to infer whether these inhibitors are ligated directly to the heme iron as
catalytically inert, low-spin (type II) complexes. Here, we show that the low
spin complex between a drug-metabolizing CYP2C9 variant and 4-(3-phenylpropyl)-1H
1,2,3-triazole (PPT) retains an axial water ligand despite exhibiting elements of
"classic" type II optical behavior. Hydrogens of the axial water ligand are
observed by pulsed electron paramagnetic resonance (EPR) spectroscopy for both
inhibitor-free and inhibitor-bound species and show that inhibitor binding does
not displace the axial water. A (15)N label incorporated into PPT is 0.444 nm
from the heme iron, showing that PPT is also in the active site. The reverse type
I inhibitor, LP10, of CYP125A1 from Mycobacterium tuberculosis, known from X-ray
crystal structures to form a low-spin water-bridged complex, is found by EPR and
by visible and near-infrared magnetic circular dichroism spectroscopy to retain
the axial water ligand in the complex in solution.
PMID- 25591015
TI - Oral potentially malignant disorders in a large dental population.
AB - OBJECTIVES: Oral cancer (OC) may be preceded by clinically evident oral
potentially malignant disorders (OPMDs). Oral carcinogenesis is a multistep
process that begins as epithelial hyperplasia and progresses to oral epithelial
dysplasia and finally to fully malignant phenotypes. The aim of our study was to
estimate the prevalence of OPMDs in a large population of dental patients.
METHODS: Patients were seen in the Oral Diagnosis and Oral Medicine clinics at
Boston University Henry M. Goldman School of Dental Medicine between July 2013
and February 2014 and received a comprehensive oral examination to identify any
possible mucosal lesions. Patients with a suspected OPMD (submucous fibrosis,
oral lichen planus, leukoplakia and erythroplakia) that did not resolve in 2-3
weeks received a biopsy for definitive diagnosis. Logistic regression models were
used to explore the relationship between OPMDs and associated risk factors.
RESULTS: A total of 3,142 patients received a comprehensive oral examination
[median age: 43 (range: 18-97); 54.3% females]. Among these, 4.5% had an oral
mucosal lesion with 0.9% being an OPMD (one submucous fibrosis, three epithelial
dysplasias, fourteen with hyperkeratosis/epithelial hyperplasia and nine with
oral lichen planus). Males and current smokers were associated with higher odds
of having OPMD (OR 1.7, 95% CI 0.8-3.8; OR 1.9, 95% CI 0.8-4.1). Increasing age
was associated with having OPMDs (p<0.01). CONCLUSION: Optimal oral visual
screening for OC remains a simple and essential tool to identify any suspicious
lesions and potentially increase survival. Although OPMDs were rare, our results
confirm the importance of a thorough chairside screening by dentists and dental
students to detect any mucosal changes.
PMID- 25591016
TI - Telegenetics: application of a tele-education program in genetic syndromes for
Brazilian students.
AB - With the high occurrence of genetic anomalies in Brazil and the manifestations of
communication disorders associated with these conditions, the development of
educative actions that comprise these illnesses can bring unique benefits in the
identification and appropriate treatment of these clinical pictures. Objective
The aim of this study was to develop and analyze an educational program in
genetic syndromes for elementary students applied in two Brazilian states, using
an Interactive Tele-education model. Material and Methods The study was carried
out in 4 schools: two in the state of Sao Paulo, Southeast Region, Brazil, and
two in the state of Amazonas, North Region, Brazil. Forty-five students, both
genders, aged between 13 and 14 years, of the 9th grade of the basic education of
both public and private system, were divided into two groups: 21 of Sao Paulo
Group (SPG) and 24 of Amazonas Group (AMG). The educational program lasted about
3 months and was divided into two stages including both classroom and distance
activities on genetic syndromes. The classroom activity was carried out
separately in each school, with expository lessons, graphs and audiovisual
contents. In the activity at a distance the educational content was presented to
students by means of the Interactive Tele-education model. In this stage, the
students had access a Cybertutor, using the Young Doctor Project methodology. In
order to measure the effectiveness of the educational program, the Problem
Situation Questionnaire (PSQ) and the Web Site Motivational Analysis Checklist
adapted (FPM) were used. Results The program developed was effective for
knowledge acquisition in 80% of the groups. FPM showed a high satisfaction index
from the participants in relation to the Interactive Tele-education, evaluating
the program as "awesome course". No statistically significant differences between
the groups regarding type of school or state were observed. Conclusion Thus, the
Tele-Education Program can be used as a tool for educational purposes in genetic
syndromes of other populations, in several regions of Brazil.
PMID- 25591017
TI - Evaluation of caries-associated virulence of biofilms from Candida albicans
isolated from saliva of pediatric patients with sickle-cell anemia.
AB - A previous study demonstrated that the amount of Candida spp. in saliva is higher
in children with sickle-cell disease. The results from a recent study demonstrate
its participation in the etiology of dental caries. Objective This study assessed
caries-associated virulence (production of acid, extracellular polysaccharides,
proteins and metabolic activity) of biofilms from Candida albicans isolated from
saliva of patients with sickle-cell anemia in comparison to isolates obtained
from matched healthy children. Material and Methods The isolates were previously
obtained from 25 children (4-6 years) and their matched controls (healthy
children). One isolate of C. albicans per children was used, totaling 25 isolates
per group. The C. albicans biofilms were grown for five days and analyzed
regarding the production of lactic acid, extracellular polysaccharides, proteins
and metabolic activity. The production of lactic acid was determined by the
enzymatic method. The concentration of extracellular polysaccharides was
determined by the phenol-sulphuric acid method, and the concentration of the
protein was analyzed using the QuantiPro BCA kit. The XTT reduction was used to
verify the metabolic activity. The data were analyzed with GraphPad Prism at 5%.
Results The Mean+/-standard deviation for acid production, extracellular
polysaccharides, proteins and metabolic activity of isolates from sickle-cell
group was, respectively: 7.1+/-5.0 mmol/L; 15.6+/-2.5 MUg glucose/mg biofilm;
7,503+/-3,097 MUg/mL; A490 3.5+/-0.7. For isolates from control group the values
obtained were: 3.5+/-3.3 mmol/L; 12.8+/-3.4 MUg glucose/mg biofilm; 4,995+/-682
MUg/mL; A490 3.4+/-0.5. The C. albicans isolates from patients with sickle-cell
anemia produced a significantly greater quantity of acids (p=0.025),
polysaccharides (p=0.025) and proteins (p=0.047) compared with the isolates from
control group. However, there was no difference in metabolic activity (XTT)
between groups (p=0.750). Conclusion The C. albicans biofilms from patients with
sickle-cell anemia presented a greater caries-associated virulence than isolates
from healthy children.
PMID- 25591018
TI - A castor oil-containing dental luting agent: effects of cyclic loading and
storage time on flexural strength.
AB - Favorable results in the use of castor oil polyurethane (COP) as pulp capping,
membrane material, sealer, mouthwash and in bone repair, associated with the fact
that Ricinus communis is not derived from petroleum and it is abundant in Brazil,
encourage researches in the development of luting agents. Objectives This study
compared the flexural strength (FS) of a castor oil-containing dental luting
agent with a weight percentage of 10% (wt%) of calcium carbonate (COP10) with
RelyX ARC (RX) after mechanical cycling (MC) and distilled water storage.
Material and Methods Sixty-four specimens (25x2x2 mm) were fabricated and divided
into two groups, COP10 and RX (control). Each group was divided into 4 subgroups
(n=8) according to the storage time, 24 hours (24 h) or 60 days (60 d), and the
performance (MC+FS) or not (only FS) of the mechanical cycling test. The FS (10
kN; 0.5 mm/min) and MC tests (10,000 cycles, 5 Hz, 0.5 mm/min) were carried out
using an MTS-810 machine. The data were analyzed using ANOVA (alpha=0.05).
Results The obtained FS (MPa) values were: COP10 24h- 19.04+/-2.41; COP10 60d-
17.92+/-3.54; RX 24h- 75.19+/-3.43; RX 60d- 88.77+/-6.89. All the RX specimens
submitted to MC fractured, while the values for COP10 after MC were as follows:
COP10 24h- 17.90+/-1.87 and COP10 60d- 18.60+/-1.60. Conclusions A castor oil
containing dental luting agent with a weight percentage of 10% (wt%) of calcium
carbonate is resistant to mechanical cycling without decreases in flexural
strength. However, mean COP10 showed only about 25% of the RelyX ARC mean
flexural strength.
PMID- 25591019
TI - Evaluation of technical quality and periapical health of root-filled teeth by
using cone-beam CT.
AB - OBJECTIVE: This study aimed to assess the quality of root fillings, coronal
restorations, complications of all root-filled teeth and their association with
apical periodontitis (AP) detected by cone-beam computed tomography (CBCT) images
from an adult Turkish subpopulation. MATERIAL AND METHODS: The sample for this
study consisted of 242 patients (aging from 15 to 72 years) with 522
endodontically treated teeth that were assessed for technical quality of the root
canal filling and periapical status of the teeth. Additionally, the apical status
of each root-filled tooth was assessed according to the gender, dental arch,
tooth type and age classification, undetected canals, instrument fracture, root
fracture, apical resorption, apical lesion, furcation lesion and type and quality
of the coronal structure. Statistical analysis was performed using percentages
and chi-square test. RESULTS: The success rate of the root canal treatment was of
54.4%. The success rates of adequate and inadequate root canal treatment were not
significantly different (p>0.05). Apical periodontitis was found in 228 (45.6%)
teeth treated for root canals. Higher prevalence of AP was found in patients
aging from 20 to 29 years [64 (27%) teeth] and in anterior (canines and incisors)
teeth [97 (41%) teeth]. CONCLUSIONS: The technical quality of root canal filling
performed by dental practitioners in a Turkish subpopulation was consistent with
a high prevalence of AP. The probable reasons for this failure are
multifactorial, and there may be a need for improved undergraduate education and
postgraduate courses to improve the clinical skills of dental practitioners in
endodontics.
PMID- 25591020
TI - Thickness and marking quality of different occlusal contact registration strips.
AB - OBJECTIVES: Evaluate the thickness and the marking quality of different occlusal
contact registration strips (OCRS) and a possible correlation between them.
MATERIAL AND METHODS: The following OCRS were selected: Accufilm II, BK20, BK21,
BK22, BK23, BK28, and BK31. The thickness was measured in three points of the
OCRS with an electronic measuring device (TESA), and the mean was calculated. To
produce the marks on the strips, composite resin specimens were adapted to a
universal testing machine (Versat 2000) with 40 kgf load cell at a speed of 1.0
mm/min. The mark images were photographed with a stereoscopic microscope (Stemi
SV11) and processed and analyzed by the 550-Leica Qwin analyzer. RESULTS: Values
(MUm) found in the 1st and 2nd thickness measurements were: Accufilm II - 16.4
and 14.2; BK20 - 10.0 and 8.1; BK21 - 9.5 and 8.0; BK22 - 9.7 and 8.7; BK23 - 9.8
and 7.9; BK28 - 12.8 and 10.0; and BK31 - 8.4 and 8.0, respectively. The mean
(mm2) values found in the mark areas were: Accufilm II - 0.078; BK20 - 0.035;
BK21 - 0.045; BK22 - 0.012; BK23 - 0.022; BK28 - 0.024; and BK31 - 0.024. The
results were submitted to the Kruskal-Wallis (p<0.05) and Pearson's correlation
tests. CONCLUSIONS: Only in the 2nd measurement, the OCRS thickness observed was
similar to the value indicated by the manufacturers; the Accufilm II and the BK28
strips showed the better marks; and no correlation was found between the
thickness and the marking area.
PMID- 25591021
TI - Association between periodontal condition and subgingival microbiota in women
during pregnancy: a longitudinal study.
AB - OBJECTIVE: In this study, the gingival conditions and the quantitative detection
for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas
gingivalis and Prevotella intermedia in pregnant women were determined. MATERIAL
AND METHODS: Quantitative determinations of periodontal bacteria by using a SyBr
green system in women during pregnancy were performed. Women at the 2nd and 3rd
trimesters of pregnancy and non-pregnant women were included in this study. A.
actinomycetemcomitans was observed in high numbers in women at the 2nd and 3rd
trimesters of pregnancy with a significant difference (p<0.05). F. nucleatum and
P. intermedia were also observed in high levels. RESULTS AND CONCLUSION: Our
results show that pregnant women are more susceptible to gingivitis, and the
presence of A. actinomycetemcomitans in subgingival biofilm might be taken into
account for the treatment of periodontal disease.
PMID- 25591022
TI - Immunolocalization of markers for bone formation during guided bone regeneration
in osteopenic rats.
AB - OBJECTIVE: The aim of this paper was to evaluate the repair of onlay autogenous
bone grafts covered or not covered by an expanded polytetrafluoroethylene (e
PTFE) membrane using immunohistochemistry in rats with induced estrogen
deficiency. MATERIAL AND METHODS: Eighty female rats were randomly divided into
two groups: ovariectomized (OVX) and with a simulation of the surgical procedure
(SHAM). Each of these groups was again divided into groups with either placement
of an autogenous bone graft alone (BG) or an autogenous bone graft associated
with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and
60. The specimens were subjected to immunohistochemistry for bone sialoprotein
(BSP), osteonectin (ONC), and osteocalcin (OCC). RESULTS: All groups (OVX+BG,
OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7
and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone
graft showed direct bonding to the recipient bed in all specimens. The ONC and
OCC showed more expressed in granulation tissue, in the membrane groups,
independently of estrogen deficiency. CONCLUSIONS: The expression of bone forming
markers was not negatively influenced by estrogen deficiency. However, the
markers could be influenced by the presence of the e-PTFE membrane.
PMID- 25591025
TI - Preventing falls.
PMID- 25591023
TI - Radiopacity and cytotoxicity of Portland cement associated with niobium oxide
micro and nanoparticles.
AB - OBJECTIVE: Mineral Trioxide Aggregate (MTA) is composed of Portland Cement (PC)
and bismuth oxide (BO). Replacing BO for niobium oxide (NbO) microparticles (Nbu)
or nanoparticles (Nbeta) may improve radiopacity and bioactivity. The aim of this
study was to evaluate the radiopacity and cytotoxicity of the materials: (1) PC;
(2) White MTA; (3) PC+30% Nbu; (4) PC+30% Nbeta. MATERIAL AND METHODS: For the
radiopacity test, specimens of the different materials were radiographed along an
aluminum step-wedge. For cell culture assays, Saos-2 osteoblastic-cells (ATCC HTB
85) were used. Cell viability was evaluated through MTT assay, and bioactivity
was assessed by alkaline phosphatase activity assay. RESULTS: The results
demonstrated higher radiopacity for MTA, followed by Nbu and Nbeta, which had
similar values. Cell culture analysis showed that PC and PC+NbO associations
promoted greater cell viability than MTA. CONCLUSIONS: It was concluded that the
combination of PC+NbO is a potential alternative for composition of MTA.
PMID- 25591026
TI - Member profile.
PMID- 25591024
TI - Alkali production in the mouth and its relationship with certain patient's
characteristics.
AB - OBJECTIVES: To assess the relationships among alkali production, diet, oral
health behaviors, and oral hygiene. METHODS: Data from 52 subjects including
demographics, diet, and oral hygiene scores were analyzed against the level of
arginine and urea enzymes in plaque and saliva samples. An oral habit survey was
completed that included: use of tobacco (TB), alcohol (AH), sugary drinks (SD),
and diet. Alkali production through arginine deiminase (ADS) and urease
activities were measured in smooth-surface supragingival dental plaque and un
stimulated saliva samples from all subjects. ADS and urease activities were
measured by quantification of the ammonia generated from the incubation of plaque
or saliva samples. Spearman correlations were used to compute all associations.
RESULTS: Participants in the lowest SES (Socio-economic status) group had the
habit of consuming sugary drinks the most and had the highest rate of tobacco
use. Males consumed significantly more alcohol than females. No significant
relationship was found between age or gender and alkali production. Higher rates
of sugary drink consumption and tobacco use were significantly related to lower
alkali production. CONCLUSION: The study showed a relationship between alkali
production and oral hygiene, diet, and certain oral health behaviors. Poor oral
hygiene was significantly associated with age, lower SES, tobacco use, and
alcohol, and sugary drinks consumption. Clinical relevance Certain oral health
behaviors have an impact on oral hygiene and on alkali production; it is
important to address these factors with patients as a strategy for caries
control.
PMID- 25591027
TI - Rescheduling of combination hydrocodone products: problems for long-term care
practitioners.
AB - The Drug Enforcement Administration recently announced the final rule to
reschedule hydrocodone combinations from schedule III of the Controlled
Substances Act to the more restrictive schedule II category. This regulatory
change will have broad operational implications for practitioners serving the
health care needs of long-term care residents. Stakeholders will need to work
collectively to identify possible efficiencies to counter some of the anticipated
costs as well as its effect on patient care.
PMID- 25591028
TI - Statins for the primary prevention of cardiovascular disease in the elderly.
AB - OBJECTIVE: The objective is to review the evidence evaluating the efficacy of
statin therapy for primary prevention of cardiovascular (CV) disease in the
elderly. DATA SOURCES: A literature search of MEDLINE and PubMed (1966-January
2013) using the terms HMG-CoA reductase inhibitor, statin, primary prevention,
elderly, and geriatrics was performed. The search was limited to clinical trials,
meta-analyses, and subanalyses, including primary prevention patients.
Bibliographies of selected articles were examined to identify additional clinical
trials. STUDY SELECTION: Fourteen clinical trials, subanalyses, and meta-analyses
were reviewed. A total of seven clinical trials and subanalyses evaluating statin
therapy versus placebo in the elderly primary prevention patients with a primary
endpoint of hard coronary heart disease were included. DATA EXTRACTION: Data
collected from the clinical trials and subanalyses included number of elderly
patients randomized, therapy, duration of follow-up, and the incidence of
coronary events. DATA SYNTHESIS: The average annual rates of first CV event
increases as patients age. There is strong evidence that supports the use of
statins for secondary prevention; although primary prevention, specifically in
the elderly, is less defined. This paper reviews the literature specifically for
primary prevention, for which the results have shown a trend toward decreased
first occurrence of coronary heart disease with statin therapy in elderly
patients. CONCLUSION: Statin therapy should be considered as a primary prevention
therapy against coronary disease for elderly patients. Evidence-based clinical
benefits are seen in this patient population. However, clinical judgment and
consideration of comorbidities that may impact life expectancy should be assessed
to determine appropriateness for individual patients.
PMID- 25591029
TI - Expanding clinical and information services to the ambulatory older adult through
community outreach programs.
AB - OBJECTIVE: To share successful techniques pharmacists can use to educate
community-based older adults about health and medications. SETTING: Events
coordinated through MCPHS University Pharmacy Outreach Program and offered at
Massachusetts senior centers. PRACTICE DESCRIPTION: The MCPHS University Pharmacy
Outreach Program, staffed with pharmacists, caseworkers, and pharmacy students,
under the supervision of licensed pharmacists, provides free medication-related
information to Massachusetts residents. Clients also receive assistance with cost
minimizing programs and insurance benefits. Seventy percent of contacts are older
adults. Services are provided through a toll-free number and outreach programs.
PRACTICE INNOVATION: Focus on expanding educational health services and includes
selecting Medicare D plans, working with support groups, providing medication
management for diverse cultures, educating older adults on how to search for
health information on the Internet, and discussing medication safety and
adherence. MAIN OUTCOME MEASUREMENTS: Participant and pharmacy student knowledge
assessed utilizing survey tools. Additional measurements include savings for
Medicare beneficiaries and improvements in medication management. RESULTS:
Observed results of the Pharmacy Outreach Program include decreased out-of-pocket
costs for Medicare beneficiaries, improved medication adherence resulting in
reduction of glycated hemoglobin and blood pressure, identifying and recommending
medication treatment changes to reduce patient fall risk, and increased
confidence in locating Web-based health information. Pharmacy students
demonstrated increased knowledge of and ability to communicate Medicare benefits.
CONCLUSION: Outreach programs can improve older adults' understanding about their
health and medications. Pharmacists can increase visibility in the community by
engaging in effective outreach programs.
PMID- 25591030
TI - Treating recurrent postmenopausal vasomotor symptoms in a patient with a positive
family history for breast cancer.
AB - OBJECTIVE: To report a case of recurrent hot flashes unresponsive to gabapentin
in a postmenopausal patient with a positive family history of breast cancer. CASE
SUMMARY: A 69-year-old Caucasian female experienced a recurrence of debilitating
hot flashes for the past eight months. More recently, she failed a two-month
trial of gabapentin 600 mg by mouth at bedtime after she previously received
effective hormone replacement therapy (HRT) seven years ago with near-complete
resolution of her symptoms. The patient had a sister and a niece who developed
breast cancer in their 40s. DISCUSSION: The treatment of postmenopausal hot
flashes in a patient with a positive family history of breast cancer represents a
clinical challenge for many clinicians. This case is an example in which
gabapentin was ineffective in the treatment of severe hot flashes in a
postmenopausal woman. The risks and benefits of HRT compared with nonhormonal
alternatives were assessed. CONCLUSION: In this case, a two-month trial of
gabapentin 600 mg/day failed to demonstrate efficacy in reducing the severity,
frequency, and duration of hot flashes. Controlled trials are necessary to
evaluate the safety and efficacy of other therapeutic alternatives.
PMID- 25591031
TI - Evaluation of pharmacy resident and student recommendations made before and after
home-based primary care patient visits.
AB - OBJECTIVE: To compare the types of recommendations documented in pharmacy
resident and student home-visit notes with those made in the electronic medical
record-based drug regimen review (DRR) notes. SETTING: San Francisco Veterans
Affairs Medical Center (SFVAMC), San Francisco, California. PRACTICE DESCRIPTION:
The SFVAMC Home-Based Primary Care (HBPC) program provides primary care services
through an interdisciplinary team. The pharmacist performs a DRR-a federally
required, quarterly retrospective review of the medications for each patient
enrolled in the HBPC program and acts as a preceptor for pharmacy residents and
students helping to provide patient care. PRACTICE INNOVATION: Starting in 2008,
residents and students began making home visits with the HBPC primary care
providers. Activities and recommendations were documented in a home visit
clinical note. MAIN OUTCOME MEASURES: Number and types of recommendations
documented during the DRR and in the home visit notes as well as the clinical
change in disease states based on the accepted recommendations. RESULTS: Ninety
three recommendations were accepted: 27 DRR recommendations and 66 home visit
recommendations from August 1, 2008, to July 31, 2009. The most commonly accepted
DRR recommendations were to evaluate response to therapy (29%) and home visit
recommendations to document medications not listed in the medication profile
(26%). Clinical change in disease state based on the majority of the accepted
recommendations remained unchanged for both DRR and home visit recommendations.
CONCLUSION: Home visits by pharmacy residents and students resulted in a greater
number and different type of recommendations documented in their home visit notes
compared with those in the DRR notes.
PMID- 25591032
TI - What do the 2014 midterm election results mean for ASCP?
PMID- 25591033
TI - Toward ultraflat surface morphologies during focused electron beam induced
nanosynthesis: disruption origins and compensation.
AB - Emerging applications for nanoscale materials demand precise deposit shape
retention from design to deposition. This study investigates the effects that
disrupt high-fidelity shapes during focused electron beam induced nanosynthesis.
It is shown that process parameters, patterning strategies and deposit topography
can impose lateral precursor coverage gradients during growth resulting in
unwanted topographic artifacts. The study classifies the evolving surface shapes
into four general types and explains the formation and transition from a
fundamental point of view. Continuum model calculations and simulations expand
the experimental results to provide a comprehensive insight into understand the
disruption mechanism. The findings demonstrate that the well-established concept
of growth regimes has to be expanded by its lateral gradients as they strongly
influence final shape fidelities. Finally, the study is complemented by a
compensation strategy that improves the edge fidelity on the lower nanoscale to
further push this technique toward the intrinsic limitations.
PMID- 25591034
TI - Percutaneous clamping of spiral and oblique fractures of the tibial shaft: a safe
and effective reduction aid during intramedullary nailing.
AB - The reduction of tibial shaft fractures during intramedullary nailing is
important if limb alignment is to be restored and successful clinical outcomes
are expected. We have used a percutaneously applied (or open) clamp or clamps to
achieve and maintain reduction during nailing of all amendable tibial shaft
fractures. In this article, we describe the technique and preliminary results
comparing closed, simple spiral and oblique tibial shaft fractures (OTA 42-A1 and
A2) managed with percutaneous clamp-assisted nailing (CAN) versus nailing using
manual reduction (MRN) held by the surgical team. In the MRN group, there were an
increased fracture gap (P = 0.04) and trends toward malalignment (P = 0.07) and
healing time (P = 0.06) compared with the CAN group. There were also trends in
clinical; no wound complications occurred in either group. We have found that
percutaneous CAN of closed, simple spiral and oblique tibial shaft fractures
seems safe and allows for early predictable union with reproducible alignment
compared with nailing using MRN.
PMID- 25591035
TI - A Biomechanical Study of Posteromedial Tibial Plateau Fracture Stability: Do They
All Require Fixation?
AB - OBJECTIVES: Although the posteromedial fragment in tibial plateau fractures is
often considered unstable, biomechanical evidence supporting this view is
lacking. We aimed to evaluate the stability of the fragment in a cadaver model.
Our hypothesis was that under the expected small axial force during
rehabilitation and the combined effects of this force with shear force, internal
rotation torque, and varus moment, the most common posteromedial tibial fragment
morphology could maintain stability in early flexion. METHODS: Axial compression
force alone or combined with posterior shear, internal rotation torque, or varus
moment was applied to the femurs of 5 fresh cadaveric knees. A Tekscan pressure
mapping system was used to measure pressure and contact area between the femoral
condyles, meniscus, and tibial plateau. A Microscribe 3D digitizer was used to
define the 3-dimensional positions of the femur and tibia. A 10-mm and then a 20
mm osteotomy was created with a saw at an angle of 30 degrees in the axial plane
with respect to the tangent of the posterior tibial plateau and 75 degrees in the
sagittal plane, representing a typical posteromedial fracture fragment. At each
flexion angle (15, 30, 60, 90, and 120 degrees) and loading condition (axial
compression only, compression with shear force, torque, and varus moment), distal
displacement of the medial femoral condyle and the tibial fracture fragments was
determined. RESULTS: For the 10-mm fragment, medial femoral condyle displacement
was little affected up to approximately 30-degree flexion, after which it
increased. For the 20-mm fragment, there was progressive medial femoral condyle
displacement with increasing flexion from baseline. However, for the 10- and 20
mm fragments themselves, displacements were noted at every flexion angle,
starting at 1.7 mm inferior displacement with 15 degrees of flexion and internal
rotation torque and up to 10.2 mm displacement with 90 degrees of flexion and
varus bending moment. CONCLUSIONS: In this cadaveric model of a posteromedial
tibial plateau fracture, both fracture fragments studied displaced with knee
flexion, even at low flexion angles. Although such fragments may initially seem
nondisplaced after injury, posteromedial fragments similar to these tested are
likely to displace during knee range of motion exercises in non-weight-bearing
conditions.
PMID- 25591036
TI - Volar subluxation of the ulnar head in dorsal translation deformities of distal
radius fractures: an in vitro biomechanical study.
AB - OBJECTIVES: To quantify the effects of dorsal translation deformities of the
distal radius with and without dorsal angulation on volar displacement of the
ulnar head during simulated active forearm rotation, both with the triangular
fibrocartilage complex (TFCC) intact and sectioned conditions. METHODS: Eight
fresh-frozen cadaveric upper extremities were mounted in an active forearm motion
simulator, and distal radial deformities of 0, 5, and 10 mm of dorsal translation
with 0, 10, 20, and 30 degrees of dorsal angulation were simulated. Volar
displacement of the ulnar head at the distal radioulnar joint as a result of each
distal radial deformity was quantified during simulated active supination. The
data were collected with the TFCC intact and after sectioning the TFCC at its
ulnar insertion. RESULTS: Increasing isolated dorsal translation deformities
increased volar displacement of the ulnar head when the TFCC was intact (P <
0.001). Increasing dorsal translation combined with dorsal angulation increased
volar displacement of the ulnar head compared with isolated dorsal angulation
deformities (P < 0.001). Sectioning the TFCC increased the volar displacement of
the ulnar head caused by each distal radial deformity (P = 0.001). CONCLUSIONS:
These results emphasize the clinical importance of evaluating the magnitude of
both dorsal translation and dorsal angulation when managing displaced distal
radius fractures and malunions.
PMID- 25591037
TI - Passively scattered proton beam entrance dosimetry with a plastic scintillation
detector.
AB - We tested the feasibility of using plastic scintillation detectors (PSDs) for
proton entrance dosimetry. A PSD built with BCF-12 scintillating fiber was used
to measure the absolute entrance dose of a passively scattered proton beam for
energies ranging from 140 to 250 MeV, and for a range of spread out Bragg peak
(SOBP) widths at two energies, to quantify the effect of ionization quenching on
the response of the detector and to determine the necessity of Cerenkov radiation
correction in proton beams. The overall accuracy and precision of the PSD was
evaluated by measuring lateral beam profiles and comparing the results with
profiles measured using film. The PSD under-responded owing to ionization
quenching, exhibiting approximately a 7% loss of signal at the highest energy
studied (250 MeV) and a 10% loss of signal at the lowest energy studied (140
MeV). For a given nominal energy, varying the SOBP width did not significantly
alter the response of the PSD. Cerenkov radiation contributed negligibly to the
PSD signal and can be safely ignored without introducing more than 1% error in
the measured dose. Profiles measured with the PSD and film agreed to within the
uncertainty of the detector, demonstrating good relative accuracy. Although
correction factors were necessary to account for ionization quenching, the
magnitude of the correction varied minimally over a broad range of energies; PSDs
therefore represent a practical detector for proton entrance dosimetry.
PMID- 25591038
TI - Light-responsive iron(III)-polysaccharide coordination hydrogels for controlled
delivery.
AB - Visible-light responsive gels were prepared from two plant-origin polyuronic
acids (PUAs), alginate and pectate, coordinated to Fe(III) ions. Comparative
quantitative studies of the photochemistry of these systems revealed unexpected
differences in the photoreactivity of the materials, depending on the
polysaccharide and its composition. The roles that different functional groups
play on the photochemistry of these biomolecules were also examined. Mannuronic
rich alginates were more photoreactive than guluronic acid-rich alginate and than
pectate. The microstructure of alginates with different mannuronate-to-guluronate
ratios changed with polysaccharide composition. This influenced the gel
morphology and the photoreactivity. Coordination hydrogel beads were prepared
from both Fe-alginate and Fe-pectate. The beads were stable carriers of molecules
as diverse as the dye Congo Red, the vitamin folic acid, and the antibiotic
chloramphenicol. The photoreactivity of the hydrogel beads mirrored the
photoreactivity of the polysaccharides in solution, where beads prepared with
alginate released their cargo faster than beads prepared with pectate. These
results indicate important structure-function relationships in these systems and
create guidelines for the design of biocompatible polysaccharide-based materials
where photoreactivity and controlled release can be tuned on the basis of the
type of polysaccharide used and the metal coordination environment.
PMID- 25591039
TI - Asperlones A and B, dinaphthalenone derivatives from a mangrove endophytic fungus
Aspergillus sp. 16-5C.
AB - Racemic dinaphthalenone derivatives, (+/-)-asperlone A (1) and (+/-)-asperlone B
(2), and two new azaphilones, 6'-hydroxy-(R)-mitorubrinic acid (3) and
purpurquinone D (4), along with four known compounds, (-)-mitorubrinic acid (5),
(-)-mitorubrin (6), purpurquinone A (7) and orsellinic acid (8), were isolated
from the cultures of Aspergillus sp. 16-5C. The structures were elucidated using
comprehensive spectroscopic methods, including 1D and 2D NMR spectra and the
structures of 1 further confirmed by single-crystal X-ray diffraction analysis,
while the absolute configuration of 3 and 4 were determined by comparing their
optical rotation and CD with those of the literature, respectively. Compounds 1,
2 and 6 exhibited potent inhibitory effects against Mycobacterium tuberculosis
protein tyrosine phosphatase B (MptpB) with IC50 values of 4.24 +/- 0.41, 4.32 +/
0.60 and 3.99 +/- 0.34 MUM, respectively.
PMID- 25591040
TI - Combination of trabectedin and gemcitabine for advanced soft tissue sarcomas:
results of a phase I dose escalating trial of the German Interdisciplinary
Sarcoma Group (GISG).
AB - BACKGROUND: Evaluation of the potential efficacy and safety of combination
therapies for advanced soft tissue sarcomas (STS) has increased substantially
after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe
in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and
leiomyosarcoma); combination of trabectedin with other chemotherapies used in STS
seems of particular interest. METHODS: We initiated within the German
Interdisciplinary Sarcoma Group (GISG) a phase I dose escalating trial evaluating
the combination of trabectedin and gemcitabine in patients with advanced and/or
metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633). Patients were
treated with increasing doses of trabectedin and gemcitabine. The primary
endpoint was to determine the maximum tolerated dose. RESULTS: Five patients were
included in the study. Two patients were treated on dose level 1 comprising
trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3
weeks. Due to dose-limiting toxicity (DLT) in both patients (elevated
transaminases and thrombocytopenia), an additional three patients were treated on
dose level -1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these
three patients, two demonstrated another DLT; therefore, the trial was stopped
and none of the dose levels could be recommended for phase II testing.
CONCLUSION: The GISG-02 phase I study was stopped with the conclusion that the
combination of gemcitabine and trabectedin is generally not recommended for the
treatment of patients with advanced and/or metastatic leiomyosarcoma or
liposarcoma. Also, this phase I study strongly supports the necessity for careful
evaluation of combination therapies.
PMID- 25591043
TI - Impaired autophagosome clearance contributes to local anesthetic bupivacaine
induced myotoxicity in mouse myoblasts.
AB - BACKGROUND: The current study examined the role(s) of autophagy in myotoxicity
induced by bupivacaine in mouse myoblast C2c12 cells. METHODS: C2c12 cells were
treated with bupivacaine. Myotoxicity was evaluated by 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide assay (n = 3 to 30), live/dead assay (n = 3
to 4), and morphological alterations (n = 3). Autophagosome formation was
reflected by microtubule-associated protein light chain 3 conversion (n = 4 to
12) and light chain 3 punctation (n = 4 to 5). Autophagosome clearance was
evaluated by p62 protein level (n = 4) and autolysosomes generation (n = 3).
RESULTS: Bupivacaine induced significant cell damage. Notably, there was a
significant increase in autophagosome generation as evidenced by light chain 3
puncta formation (72.7 +/- 6.9 vs. 2.1 +/- 1.2) and light chain 3 conversion
(2.16 +/- 0.15 vs. 0.33 +/- 0.04) in bupivacaine-treated cells. Bupivacaine
inactivated the protein kinase B/mammalian target of rapamycin/p70 ribosomal
protein S6 kinase signaling. However, cellular levels of p62 protein were
significantly increased upon bupivacaine treatment (1.29 +/- 0.15 vs. 1.00 +/-
0.15), suggesting that the drug impaired autophagosome clearance. Further
examination revealed that bupivacaine interrupted autophagosome-lysosome fusion
(10.87% +/- 1.48% vs. 32.94% +/- 4.22%). Administration of rapamycin increased
autophagosome clearance and, most importantly, improved the survival in
bupivacaine-treated cells. However, knockdown of autophagy-related protein 5
(atg5) exacerbated bupivacaine-induced impairment of autophagosome clearance and
myotoxicity. CONCLUSIONS: The data suggest that autophagosome formation was
induced as a stress response mechanism after bupivacaine challenge; however,
autophagosome clearance was impaired due to inadequate autophagosome-lysosome
fusion. Therefore, impairment of autophagosome clearance appears to be a novel
mechanism underlying bupivacaine-induced myotoxicity.
PMID- 25591041
TI - [I Guidelines of heart failure and heart transplantation in the fetus, in
children and adults with congenital cardiopathy, The Brazilian Society of
Cardiology].
PMID- 25591042
TI - Synergistic Inhibition of beta2-adrenergic Receptor-mediated Alveolar Epithelial
Fluid Transport by Interleukin-8 and Transforming Growth Factor-beta.
AB - BACKGROUND: Patients with acute respiratory distress syndrome who retain maximal
alveolar fluid clearance (AFC) have better clinical outcomes. The release of
endogenous catecholamines associated with shock or the administration of beta2
adrenergic receptor (beta2AR) agonists enhances AFC via a 3'-5'-cyclic adenosine
monophosphate-dependent mechanism. The authors have previously reported that
transforming growth factor-beta1 (TGF-beta1) and interleukin-8 (IL-8), two major
mediators of alveolar inflammation associated with the early phase of acute
respiratory distress syndrome, inhibit AFC upregulation by beta2AR agonists via a
phosphoinositol-3-kinase (PI3K)-dependent mechanism. However, whether TGF-beta1
and IL-8 cause an additive or synergistic inhibition of AFC is unclear. Thus, the
central hypothesis of the study was to determine whether they synergistically
inhibit the beta2AR-stimulated AFC by activating two different isoforms of PI3K.
METHODS: The effects of TGF-beta1 or IL-8 on beta2AR agonist-stimulated net
alveolar fluid transport were studied using short-circuit current studies.
Molecular pathways of inhibition were confirmed by pharmacologic inhibitors and
Western blotting of p-Akt, G-protein-coupled receptor kinase 2, protein kinase C
zeta, and phospho-beta2AR. Finally, our observations were confirmed by an in vivo
model of AFC. RESULTS: Combined exposure to TGF-beta1 and IL-8/cytokine-induced
neutrophil chemoattractant-1 caused synergistic inhibition of beta2AR agonist
stimulated vectorial Cl across alveolar epithelial type II cells (n = 12 in each
group). This effect was explained by activation of different isoforms of PI3K by
TGF-beta1 and IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each
group). Furthermore, the inhibitory effect of TGF-beta1 on 3'-5'-cyclic adenosine
monophosphate-stimulated alveolar epithelial fluid transport required the
presence of IL-8/cytokine-induced neutrophil chemoattractant-1 (n = 12 in each
group). Inhibition of cytokine-induced neutrophil chemoattractant-1 prevented TGF
beta1-mediated heterologous beta2AR downregulation and restored physiologic
beta2AR agonist-stimulated AFC in rats (n = 6 in each group). CONCLUSIONS: TGF
beta1 and IL-8 have a synergistic inhibitory effect on beta2AR-mediated
stimulation of pulmonary edema removal by the alveolar epithelium. This result
may, in part, explain why a large proportion of the patients with acute
respiratory distress syndrome have impaired AFC.
PMID- 25591044
TI - Sleep problems and cognitive behavior therapy in pediatric obsessive-compulsive
disorder have bidirectional effects.
AB - OBJECTIVES: To investigate the presence of sleep problems and their reaction to
CBT in pediatric obsessive compulsive disorder (OCD). Moreover, we investigated
whether sleep problems predict the outcome of CBT on OCD-symptoms. METHODS: 269
children and adolescents, age 7-17 years, with DSM-IV primary OCD that took part
in the first step of a stepwise treatment trial, were assessed with regard to
both individual sleep problems and a sleep composite score (SCS) using the Child
Behavior Checklist (CBCL). Their OCD symptoms were rated using the Children Yale
Brown Obsessive Compulsive Scale (CY-BOCS). RESULTS: We found elevated symptoms
of sleep deprivation and nightmares before treatment. However most sleep problems
(e.g. nightmares (p=.03), too little sleep (p<.001), trouble sleeping (p<.001)
and parasomnias p=.03)) as well as being over-tired (p<.001) reduced during CBT
treatment. Co-morbidities had no effect on the reduction of SCS. Moreover,
elevated levels of sleep problems using the SCS (p<.001), as well as any sleep
problem at baseline (p<.001) predicted less effect of CBT on the OCD symptoms.
CONCLUSION: Sleep problems in paediatric OCD are frequent and interfere with
treatment outcome. They need to be assessed using better methods in future
trials. Moreover, lack of resolution of sleep problems need to be recognized and
treated as it seems probable that continued sleep problems may have a negative
impact on CBT efficacy.
PMID- 25591045
TI - Serum docosahexaenoic acid (DHA) is inversely associated with anxiety disorders
in early pregnancy.
AB - Little is known about the association between polyunsaturated fatty acids (PUFAs)
and anxiety disorders during pregnancy. We evaluated this association at the
first pregnancy trimester in 228 women. The study endpoint was the diagnosis of
any anxiety disorder assessed by the Mini International Neuropsychiatric
Interview. The independent variables were the serum concentrations of total n-3
and fractions (18:2, 20:5, 22:5, 22:6), total n-6 and fractions (18:2, 18:3,
20:2, 20:3, 20:4, 22:4, 22:5) and the n-6/n-3 ratio PUFAs. The prevalence of any
anxiety disorders was 25%. The first tertile of the docosahexaenoic acid (DHA,
22:6 n-3) distribution represented 1.95 (95% CI: 1.00-3.77) higher chance of
having an anxiety disorder diagnosis, compared to those in the second and third
tertiles after adjusting the analyses for parity, family income, early pregnancy
BMI and gestational age at the blood sampling. Serum concentrations of DHA were
inversely associated with the occurrence of early pregnancy anxiety disorders.
PMID- 25591046
TI - Excoriation disorder: impulsivity and its clinical associations.
AB - Excoriation disorder is the repetitive scratching or picking of skin that leads
to physical damage, distress, and functional impairment. Skin picking has been
associated with impulsivity and problems with inhibition. We hypothesized that
problems in these areas could be disease severity markers. We recruited 73 adults
meeting DSM-5 criteria for excoriation disorder, and 50 adult controls. Those
with excoriation disorder were categorized as either "high impulsive" (HI) or
"low impulsive" (LI) using either a neurocognitive task of motor impulsivity
(Stop Signal Task) or the Barratt Impulsiveness Scale's (BIS-11) motor
impulsivity subscale. The HI subjects, based on the BIS-11, showed higher urges
scores, anxiety, and depressive symptoms. These data suggest that impulsivity may
reflect a specific clinical presentation among those with excoriation disorder,
but the clinical characteristics differ depending upon the impulsivity measure
used. Agreement on how to measure various domains of impulsivity may be important
in better understanding the disorder psychopathology and so improve future
treatments.
PMID- 25591047
TI - Mercury in little brown bat (Myotis lucifugus) maternity colonies and its
correlation with freshwater acidity in Nova Scotia, Canada.
AB - Insectivorous little brown bats are exposed to elevated concentrations of mercury
(Hg) through their preference for aquatic-based prey. Here we investigated
spatial patterns of total Hg (THg) in fur from 10 little brown bat maternity
colonies across Nova Scotia, and assessed relationships with the acidity of
nearby lakes and rivers. Total Hg concentrations were measured in fur samples
from 149 adult female little brown bats. Values showed significant variation
among colonies (mean range 3.76-27.38 MUg/g, dry weight), and 48% of individuals
had Hg concentrations in excess of the 10 MUg/g threshold associated with
neurochemical changes in Chiroptera conspecifics (n = 26) from Virginia. Average
surface water acidity parameters (pH and acid neutralization capacity) within an
8 km radius of each maternity roost showed strong negative associations with
average colony fur THg concentrations. This suggests that freshwater acidity in
foraging grounds explains much of the variation in average fur THg concentrations
in little brown bat colonies. These findings highlight the significant role that
water quality may have on Hg bioaccumulation within terrestrial species that feed
on aquatic prey.
PMID- 25591048
TI - Indicators of hypertriglyceridemia from anthropometric measures based on data
mining.
AB - BACKGROUND: The best indicator for the prediction of hypertriglyceridemia derived
from anthropometric measures of body shape remains a matter of debate. The
objectives are to determine the strongest predictor of hypertriglyceridemia from
anthropometric measures and to investigate whether a combination of measures can
improve the prediction accuracy compared with individual measures. METHODS: A
total of 5517 subjects aged 20-90 years participated in this study. The numbers
of normal and hypertriglyceridemia subjects were 3022 and 653 females,
respectively, and 1306 and 536 males, respectively. We evaluated 33
anthropometric measures for the prediction of hypertriglyceridemia using
statistical analysis and data mining. RESULTS: In the 20-90-year-old groups, age
in women was the variable that exhibited the highest predictive power; however,
this was not the case in men in all age groups. Of the anthropometric measures,
the waist-to-height ratio (WHtR) was the best predictor of hypertriglyceridemia
in women. In men, the rib-to-forehead circumference ratio (RFcR) was the
strongest indicator. The use of a combination of measures provides better
predictive power compared with individual measures in both women and men.
However, in the subgroups of ages 20-50 and 51-90 years, the strongest indicators
for hypertriglyceridemia were rib circumference in the 20-50-year-old group and
WHtR in the 51-90-year-old group in women and RFcR in the 20-50-year-old group
and BMI in the 51-90-year-old group in men. CONCLUSIONS: Our results demonstrated
that the best predictor of hypertriglyceridemia may differ according to gender
and age.
PMID- 25591049
TI - The poro-viscoelastic properties of trabecular bone: a micro computed tomography
based finite element study.
AB - Bone is a porous structure with a solid phase that contains hydroxyapatite and
collagen. Due to its composition, bone is often represented either as a
poroelastic or as a viscoelastic material; however, the poro-viscoelastic
formulation that allows integrating the effect of both the fluid flow and the
collagen on the mechanical response of the tissue, has not been applied yet. The
objective of this study was to develop a micro computed tomography (uCT)-based
finite element (FE) model of trabecular bone that includes both the poroelastic
and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from
human distal tibia were scanned with uCT and stress relaxation experiments were
conducted. The uCT images were the basis for sample specific FE models, and the
stress relaxation experiments were simulated applying a poro-viscoelastic
formulation. The model considers two scales of the tissue: the intertrabecular
pore and the lacunar-canalicular pore scales. Independent viscoelastic and
poroelastic models were also developed to determine their contribution to the
poro-viscoelastic model. All the experiments exhibited a similar relaxation
trend. The average reaction force before relaxation was 9.28 * 10(2)N (SD +/-
5.11 * 10(2)N), and after relaxation was 4.69 * 10(2)N (SD +/- 2.88 * 10(2)N).
The slope of the regression line between the force before and after relaxation
was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the
variability of the experimental data before relaxation and 33% after relaxation.
The relaxation predicted with viscoelastic models was similar to the poro
viscoelastic ones; however, the poroelastic formulation underestimated the
reaction force before relaxation. These data suggest that the contribution of
viscoelasticity (fluid flow-independent mechanism) to the mechanical response of
the tissue is significantly greater than the contribution of the poroelasticity
(fluid flow-dependent mechanism).
PMID- 25591050
TI - One step closer to targeting RAS.
PMID- 25591051
TI - On the self-assembly of TiOx into 1D NP network nanostructures.
AB - Here, we report for the first time a 'ligand free' method of designing 1D TiOx
supramolecular network materials, which starts from Ti bare metal powder. Each
TiOx oxidation step has been carefully investigated with different analytical
techniques, including high resolution transmission electron microscopy/high
resolution scanning electron microscopy (HRTEM/HRSEM), x-ray photoelectron
spectroscopy (XPS), Raman spectroscopy and superconducting quantum interference
device (SQUID) measurements. The self-assembly of TiOx nanoparticles (NPs) into
1D supramolecular nanoparticle networks is induced by the formation of mixed
valent Ti(II,III) species. The synthesis starts with etching a bare Ti surface,
followed by a continuous oxidation of TiOx clusters and NPs, and it finally ends
with the self-assembly into rigid 1D NPs chains. Today, such self-assembled 1D NP
TiOx network materials are bridging the gap between the nanoscale and the
macroscopic material world and will further provide interesting research
opportunities.
PMID- 25591052
TI - Analyzing B-vitamins in Human Milk: Methodological Approaches.
AB - According to the World Health Organization (WHO), infants should be exclusively
breastfed for the first six months of life. However, there is insufficient
information about the concentration of nutrients in human milk. For some
nutrients, including B-vitamins, maternal intake affects their concentration in
human milk but the extent to which inadequate maternal diets affect milk B
vitamin content is poorly documented. Little is known about infant requirements
for B-vitamins; recommendations are generally set as Adequate Intakes (AI)
calculated on the basis of the mean volume of milk (0.78 L/day) consumed by
infants exclusively fed with human milk from well-nourished mothers during the
first six months, and the concentration of each vitamin in milk based on reported
values. Methods used for analyzing B-vitamins, commonly microbiological,
radioisotope dilution or more recently chromatographic, coupled with UV,
fluorometric and MS detection, have rarely been validated for the complex human
milk matrix. Thus the validity, accuracy, and sensitivity of analytical methods
is important for understanding infant requirements for these nutrients, the
maternal intakes needed to support adequate concentrations in breast milk. This
review summarizes current knowledge on methods used for analyzing the B-vitamins
thiamin, riboflavin, niacin, vitamin B-6 and pantothenic acid, vitamin B-12,
folate, biotin, and choline in human milk, their chemical and physical
properties, the different forms and changes in concentration during lactation,
and the effects of deficiency on the infant.
PMID- 25591053
TI - Effects of therapeutic Tai Chi on balance, gait, and quality of life in chronic
stroke patients.
AB - The aim of this study was to analyze the effects of therapeutic Tai Chi on
balance, gait, and quality of life in chronic stroke patients. Twenty-two
inpatients diagnosed with stroke were divided randomly into two groups: one
treated with both general physical therapy and Tai Chi exercise (11 patients) and
one treated with only general physical therapy (11 patients). Therapeutic Tai Chi
included 10 different movements and was performed for 60 min, twice per week, for
6 weeks. Pretest and post-test measurements were recorded for sway length and
sway velocity using Gaitview, the functional reach test, the dynamic gait index,
the 10-m walking test, the timed up-and-go test, and SF-36 survey. Both the Tai
Chi group and the control group showed a significant improvement in sway length
and sway velocity, and the Tai Chi group showed greater improvement than the
control group in degree of variation. In addition, only the Tai Chi group showed
a significant result for functional reach test, the dynamic gait index, the 10-m
walking test, the timed up-and-go test, and the Tai Chi group improved. In the
quality of life, the therapeutic Tai Chi group showed a significant improvement
in five items (physical function, pain, vitality, general health, mental health)
among eight items in SF-36. This study confirmed that therapeutic Tai Chi
influences the balance, gait, and life quality of stroke patients. Therefore,
therapeutic Tai Chi can be used as an effective exercise in combination with
general physical therapy to improve the balance, gait, and quality of life in
stroke patients.
PMID- 25591054
TI - Robotic tilt table reduces the occurrence of orthostatic hypotension over time in
vegetative states.
AB - The aim of this study is to evaluate the effects of verticalization with or
without combined movement of the lower limbs in patients in a vegetative state or
a minimally conscious state. In particular, we aimed to study whether, in the
group with combined movement, there was better tolerance to verticalization. This
was a randomized trial conducted in a neurorehabilitation hospital. Twelve
patients with vegetative state and minimally conscious state 3-18 months after
acute acquired brain injuries were included. Patients were randomized into A and
B treatment groups. Study group A underwent verticalization with a tilt table at
65 degrees and movimentation of the lower limbs with a robotic system for 30 min
three times a week for 24 sessions. Control group B underwent the same
rehabilitation treatment, with a robotic verticalization system, but an inactive
lower-limb movement system. Systolic and diastolic blood pressure and heart rate
were determined. Robotic movement of the lower limbs can reduce the occurrence of
orthostatic hypotension in hemodynamically unstable patients. Despite the small
number of patients involved (only eight patients completed the trial), our
results indicate that blood pressures and heart rate can be stabilized better
(with) by treatment with passive leg movements in hemodynamically unstable
patients.
PMID- 25591056
TI - Longevity through DNA damage tolerance.
PMID- 25591057
TI - Find me the evidence: connecting the practitioner with the evidence on
bereavement care.
AB - Care practices change as knowledge emerges and research findings challenge
current approaches. Access to evidence has challenges. Bereavement care is
diverse: practitioners often work alone or in small teams, terminology can be
diffuse, and practitioners may not have time and skills for effective search
strategies. CareSearch, an online palliative care resource, is hosting the
Bereavement Search Filter, a validated search strategy to facilitate access to
bereavement care evidence. The service connects practitioners to global best
practice evidence; it is free and trustworthy. This article outlines the
development of the Medline Bereavement Search Filter, translating it for PubMed
and deploying it online.
PMID- 25591058
TI - Role of catecholamines in acute hypertensive response: subarachnoid hemorrhage
versus spontaneous intracerebral hemorrhage.
AB - BACKGROUND AND OBJECTIVE: Acute hypertensive response, defined as systolic blood
pressure (SBP) 140 mmHg or more within 24 h of onset, is frequently observed in
hemorrhagic stroke patients. Although catecholamine surge is pivotal in its
pathogenesis, few studies have evaluated the relationship between admission SBP
and plasma catecholamine levels. PATIENTS AND METHODS: A prospective
observational study was carried out to investigate potential differences in the
acute hypertensive reaction between subarachnoid hemorrhage (SAH) and spontaneous
intracerebral hemorrhage (SICH) by analyzing 200 SAH and 200 SICH patients. In
each category, patients were quadrichotomized on the basis of their SBPs in
emergency department: less than 140 mmHg, 140-184 mmHg, 185-219 mmHg, and 220
mmHg or more. The plasma catecholamine levels were compared among the four
groups. Furthermore, multivariate regression analyses were carried out to
identify variables correlated with hypertensive emergency (SBP>=185 mmHg).
RESULTS: In SAH patients, there was a proportional increase in norepinephrine
levels relative to the graded SBPs, and norepinephrine levels in the 220 mmHg or
more group were significantly higher than those in the less than 140 mmHg group
(1596+/-264 vs. 853+/-124 pg/ml, P=0.03). By contrast, no proportional increase
in norepinephrine levels to the graded SBPs was observed in SICH patients.
Multivariate regression analyses showed that the initial Glasgow Coma Scale
scores of 8 or less (odds ratio 2.251, 95% confidence interval 1.002-5.117) and
plasma norepinephrine levels (odds ratio 1.002, 95% confidence interval 1.001
1.003) were correlated with hypertensive emergency in SAH patients. By contrast,
none of the variables evaluated were correlated with hypertensive emergency in
SICH patients. CONCLUSION: An acute hypertensive response may be more complex,
multifactorial, and less catecholamine dependent in SICH patients compared with
SAH patients.
PMID- 25591059
TI - Identifying masked uncontrolled hypertension in the community pharmacy setting.
AB - Masked uncontrolled hypertension (MUCH) is associated with an increased
cardiovascular risk. This condition is frequent in the community pharmacy (i.e.,
CP-MUCH), but there is no evidence on the factors associated with its presence in
that setting. The aim of this analysis was to explore these factors. A sample of
98 treated hypertensive patients from the MEPAFAR study, with normal community
pharmacy blood pressure (CPBP <135/85 mmHg), were analyzed. Blood pressure (BP)
was also measured at home (4 days) and monitored for 24 h. CP-MUCH was identified
when either ambulatory (daytime) or home BP averages were equal to or higher than
135/85 mmHg. A multivariate logistic regression analysis was carried out to
identify the factors associated with CP-MUCH. The prevalence of CP-MUCH tends to
be higher as systolic and diastolic CPBP increase, reaching 47% in patients with
both systolic and diastolic CPBP equal to or higher than 123 mmHg and 79 mmHg,
respectively. The multivariate regression analysis showed only systolic CPBP as
an independent factor of CP-MUCH [>=123 mmHg: odds ratio=16.46 (P=0.012); from
115 to 122.9 mmHg: odds ratio=10.74 (P=0.036); systolic CPBP <115 mmHg as the
reference]. Further assessment, using ambulatory and/or home BP monitoring, is
recommended in patients with normal CPBP, but systolic CPBP equal to or higher
than 115 mmHg. A more feasible approach would be evaluating patients with
systolic CPBP equal to or higher than 123 mmHg and diastolic CPBP equal to or
higher than 79 mmHg.
PMID- 25591060
TI - Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory,
and Episodic Memory: A Meta-analysis.
AB - The use of prescription stimulants to enhance healthy cognition has significant
social, ethical, and public health implications. The large number of enhancement
users across various ages and occupations emphasizes the importance of examining
these drugs' efficacy in a nonclinical sample. The present meta-analysis was
conducted to estimate the magnitude of the effects of methylphenidate and
amphetamine on cognitive functions central to academic and occupational
functioning, including inhibitory control, working memory, short-term episodic
memory, and delayed episodic memory. In addition, we examined the evidence for
publication bias. Forty-eight studies (total of 1,409 participants) were included
in the analyses. We found evidence for small but significant stimulant
enhancement effects on inhibitory control and short-term episodic memory. Small
effects on working memory reached significance, based on one of our two
analytical approaches. Effects on delayed episodic memory were medium in size.
However, because the effects on long-term and working memory were qualified by
evidence for publication bias, we conclude that the effect of amphetamine and
methylphenidate on the examined facets of healthy cognition is probably modest
overall. In some situations, a small advantage may be valuable, although it is
also possible that healthy users resort to stimulants to enhance their energy and
motivation more than their cognition.
PMID- 25591061
TI - Varieties of standard-of-care treatment randomized trials: ethical implications.
PMID- 25591062
TI - Nanostructured sensors for biomedical applications--a current perspective.
AB - Nanostructured sensors have unique capabilities that can be tailored to advantage
in advancing the diagnosis, monitoring and cure of several diseases and health
conditions. This report aims at providing a current perspective on, (a) the
emerging clinical needs that defines the challenges to be addressed by
nanostructured sensors, with specific emphasis on early stage diagnosis, drug
diagnostic combinations, and predictive models to design therapy, (b) the
emerging industry trends in in vitro diagnostics, mobile health care, high
throughput molecular and cell-based diagnostic platforms, and (c) recent
instances of nanostructured biosensors, including promising sensing concepts that
can be enhanced using nanostructures that carry high promise towards catering to
the emerging clinical needs, as well as the market/industry trends.
PMID- 25591063
TI - What are health-related users tweeting? A qualitative content analysis of health
related users and their messages on twitter.
AB - BACKGROUND: Twitter is home to many health professionals who send messages about
a variety of health-related topics. Amid concerns about physicians posting
inappropriate content online, more in-depth knowledge about these messages is
needed to understand health professionals' behavior on Twitter. OBJECTIVE: Our
goal was to characterize the content of Twitter messages, specifically focusing
on health professionals and their tweets relating to health. METHODS: We
performed an in-depth content analysis of 700 tweets. Qualitative content
analysis was conducted on tweets by health users on Twitter. The primary
objective was to describe the general type of content (ie, health-related versus
non-health related) on Twitter authored by health professionals and further to
describe health-related tweets on the basis of the type of statement made.
Specific attention was given to whether a tweet was personal (as opposed to
professional) or made a claim that users would expect to be supported by some
level of medical evidence (ie, a "testable" claim). A secondary objective was to
compare content types among different users, including patients, physicians,
nurses, health care organizations, and others. RESULTS: Health-related users are
posting a wide range of content on Twitter. Among health-related tweets, 53.2%
(184/346) contained a testable claim. Of health-related tweets by providers,
17.6% (61/346) were personal in nature; 61% (59/96) made testable statements.
While organizations and businesses use Twitter to promote their services and
products, patient advocates are using this tool to share their personal
experiences with health. CONCLUSIONS: Twitter users in health-related fields
tweet about both testable claims and personal experiences. Future work should
assess the relationship between testable tweets and the actual level of evidence
supporting them, including how Twitter users-especially patients-interpret the
content of tweets posted by health providers.
PMID- 25591064
TI - Transcutaneous securing technique for nasal onlay grafts.
PMID- 25591066
TI - Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment
of all stages of prostate cancer.
AB - In our effort to discover potent and specific inhibitors of 17alpha
hydroxylase/17,20-lyase (CYP17), the key enzyme which catalyzes the biosynthesis
of androgens from progestins, 3beta-(hydroxy)-17-(1H-benzimidazole-1-yl)androsta
5,16-diene (Galeterone or TOK-001, formerly called VN/124-1) was identified as a
selective development candidate which modulates multiple targets in the androgen
receptor (AR) signaling pathway. This drug annotation summarizes the mechanisms
of action, scientific rationale, medicinal chemistry, pharmacokinetic properties,
and human efficacy data for galeterone, which has successfully completed phase II
clinical development in men with castration resistant (advanced) prostate cancer
(CRPC). Phase III clinical studies in CRPC patients are scheduled to begin in
early 2015.